Radioimmunoassay: (RIA) is a very sensitive technique used to measure concentrations

of antigens (for example, hormone levels in the blood) without the need to use a bioassay.

Although the RIA technique is extremely sensitive and extremely specific, it requires specialized

equipment, but remains the least expensive method to perform such tests. It requires special precautions

and licensing, since radioactive substances are used. Today it has been supplanted by

the ELISA method, where the antigen-antibody reaction is measured using colorimetric signals instead of

a radioactive signal. However, because of it's robustness, consistent results and low price per test , RIA

methods are again becoming popular.

The RAST test (radio allergosorbent test) is an example of radioimmunoassay. It is used to detect the

causative allergen for an allergy.

Contents

 [hide]

1     Method   

2     History   

3     References   

4     External links   

Method

To perform a radioimmunoassay, a known quantity of an antigen is made radioactive, frequently by

labeling it with gamma-radioactive isotopes of iodine attached to tyrosine. This radiolabeled antigen is

then mixed with a known amount of antibody for that antigen, and as a result, the two chemically bind to

one another. Then, a sample of serum from a patient containing an unknown quantity of that same

antigen is added. This causes the unlabeled (or "cold") antigen from the serum to compete with the radio

labeled antigen ("hot") for antibody binding sites.

As the concentration of "cold" antigen is increased, more of it binds to the antibody, displacing the radio

labeled variant, and reducing the ratio of antibody-bound radiolabeled antigen to free radiolabeled

antigen. The bound antigens are then separated from the unbound ones, and the radioactivity of the free

antigen remaining in the supernatant is measured using a gamma counter. Using known standards,

a binding curve can then be generated which allows the amount of antigen in the patient's serum to be

derived.

Thyroid Nuclear Medicine Scan

DefinitionA thyroid nuclear medicine scan is a diagnostic procedure to evaluate the thyroid gland, which is located in the front of the neck and controls the body's metabolism. A radioactive substance that concentrates in the thyroid is taken orally or injected into a vein (intravenously), or both. A special camera is used to take an image of the distribution of the radioactive substance in and around the thyroid gland. This is interpreted to evaluate thyroid function and to diagnose abnormalities.

PurposeA thyroid scan may be ordered by a physician when the gland becomes abnormally large, especially if the enlargement is greater on one side, or when hard lumps (nodules) are felt. The scan can be helpful in determining whether the enlargement is caused by a diffuse increase in the total amount of thyroid tissue or by a nodule or nodules.

When other laboratory studies show an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism), a radioactive iodine uptake scan is often used to confirm the diagnosis. It is frequently done along with a thyroid scan.

PrecautionsWomen who are pregnant should not have this test.

DescriptionThis test is performed in a radiology facility, either in an outpatient x ray center or a hospital department. Most often, the patient is given the radioactive substance in the form of a tasteless liquid or capsule. It may be injected into a vein (intravenously) in some instances. Images will be taken at a specified amount of time after this, depending on the radioisotope used. Most often, scanning is done 24 hours later, if the radioisotope is given orally. If it is given intravenously, the scan is performed approximately 20 minutes later.

For a thyroid scan, the patient is positioned lying down on his or her back, with the head tilted back. The radionuclide scanner, also called a gamma camera, is positioned above the thyroid area as it scans. This takes 30-60 minutes.

The uptake study may be done with the patient sitting upright in a chair or lying down. The procedure is otherwise the same as described for the thyroid scan. It takes approximately 15 minutes. There is no discomfort involved with either study.

A thyroid scan may also be referred to as a thyroid scintiscan. The name of the radioactive substance used may be incorporated and the study called a technetium thyroid scan or an iodine thyroid scan. The radioactive iodine uptake scan may be called by its initials, an RAIU test, or an iodine uptake test.

PreparationCertain medications can interfere with iodine uptake. These include certain cough medicines, some oral contraceptives, and thyroid medications. The patient is usually instructed to stop taking these medicines for a period of time before the test. This period may range from several days up to three to four weeks, depending on the amount of time the medicine takes to clear from the body.

Other nuclear medicine scans and x ray studies using contrast material performed within the past 60 days may affect this test. Therefore, patients should tell their doctors if they have had either of these types of studies before the thyroid scan is begun, to avoid inaccurate results.

Some institutions prefer that the patient have nothing to eat or drink after midnight on the day before the radioactive liquid or capsule is to be taken. A normal diet can usually be resumed two hours after the radioisotope is taken. Dentures, jewelry, and other metallic objects must be removed before the scanning is performed. No other physical preparation is needed.

The patient should understand that there is no danger of radiation exposure to themselves or others. Only very small amounts of radioisotope are used. The total amount of radiation absorbed is often less than the dose received from ordinary x rays. The scanner or camera does not emit any radiation, but detects and records it from the patient.

Normal resultsA normal scan will show a thyroid of normal size, shape, and position. The amount of radionuclide uptake by the thyroid will be normal according to established laboratory figures. There will be no areas where radionuclide uptake is increased or decreased.

Abnormal resultsAn area of increased radionuclide uptake may be called a hot nodule or "hot spot." This means that a benign growth is overactive. Despite the name, hot nodules are unlikely to be caused by cancer.

An area of decreased radionuclide uptake may be called a cold nodule or "cold spot." This indicates that this area of the thyroid gland is under active. A variety of conditions, including cysts, nonfunctioning benign growths, localized inflammation, or cancer may produce a cold spot.

A thyroid nuclear medicine scan is rarely sufficient to establish a clear diagnosis. Frequently, the information revealed will need to be combined with data from other studies to determine the problem.

Positron emission tomography

Positron emission tomography (PET) is a nuclear medicine imaging technique which produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Images of tracer concentration in 3-dimensional or 4-dimensional space (the 4th dimension being time) within the body are then reconstructed by computer analysis. In modern scanners, this reconstruction is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine.

If the biologically active molecule chosen for PET is FDG,   an   analogue   of   glucose,   the concentrations of tracer imaged then give tissue metabolic activity, in terms of regional glucose uptake. Although use of this tracer results in the most common type of PET scan, other tracer molecules are used in PET to image the tissue concentration of many other types of molecules of interest.

Contents

1 Description

1.1 Operation

1.2 Localization of the positron annihilation event

1.3 Image reconstruction using coincidence statistics

1.4 Combination of PET with CT and MRI

1.5 Radio nuclides

1.6 Limitations

1.7 Image reconstruction

2 History

3 Applications

4 Pulse Shape Discrimination

5 Safety

Description

Schematic view of a detector block and ring of a PET scanner

Operation

To conduct the scan, a short-lived radioactive tracer isotope is injected into the living subject (usually into blood circulation). The tracer is chemically incorporated into a biologically active molecule. There is a waiting period while the active molecule becomes concentrated in tissues of interest; then the research subject or patient is placed in the imaging scanner. The molecule most commonly used for this purpose is fluorodeoxyglucose (FDG), a sugar, for which the waiting period is typically an hour. During the scan a record of tissue concentration is made as the tracer decays.

Schema of a PET acquisition process

PET - Positron Emission Tomography System Block Diagram

As the radioisotope undergoes positron emission decay (also known as positive beta decay), it emits a positron, an antiparticle of the electron with opposite charge. After travelling up to a few millimeters [1] the positron encounters an electron. The encounter annihilates them both, producing a pair of annihilation (gamma) photons moving in opposite directions. These are detected when they reach a scintillator in the scanning device, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons moving in approximately opposite direction (it would be exactly opposite in their center of mass frame, but the scanner has no way to know this, and so has a built-in slight direction-error tolerance). Photons that do not arrive in temporal "pairs" (i.e. within a timing-window of few nanoseconds) are ignored.

Localization of the positron annihilation event

The most significant fraction of electron-positron decays result in two 511 keV gamma photons being emitted at almost 180 degrees to each other; hence it is possible to localize their source along a straight line of coincidence (also called formally the line of response or LOR). In practice the LOR has a finite width as the emitted photons are not exactly 180 degrees apart. If the resolving time of the detectors is less than 500 picoseconds rather than about 10 nanoseconds, it is possible to localize the event to a segment of a chord, whose length is determined by the detector timing resolution. As the timing resolution improves, the signal-to-noise ratio (SNR) of the image will improve, requiring fewer events to achieve the same image quality. This technology is not yet common, but it is available on some new systems.[2]

Image reconstruction using coincidence statistics

More commonly, a technique much like the reconstruction of computed tomography (CT) and single photon emission computed tomography (SPECT) data is used, although the data set collected in PET is much poorer than CT, so reconstruction techniques are more difficult (see Image reconstruction of PET).

Using statistics collected from tens-of-thousands of coincidence events, a set of simultaneous equations for the total activity of each parcel of tissue along many LORs can be solved by a number of techniques, and thus a map of radio activities as a function of location for parcels or bits of tissue (also called voxels), may be constructed and plotted. The resulting map shows the tissues in which the molecular probe has become concentrated, and can be interpreted by a nuclear medicine physician or radiologist in the context of the patient's diagnosis and treatment plan.

A complete body PET / CT Fusion image

A Brain PET / MRI Fusion image

Combination of PET with CT and MRI

PET scans are increasingly read alongside CT or magnetic resonance imaging (MRI) scans, the combination ("co-registration") giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners. Because the two scans can be performed in

immediate sequence during the same session, with the patient not changing position between the two types of scans, the two sets of images are more-precisely registered, so that areas of abnormality on the PET imaging can be more perfectly correlated with anatomy on the CT images. This is very useful in showing detailed views of moving organs or structures with higher anatomical variation, which is more common outside the brain.

PET-MRI: At the Jülich Institute of Neurosciences and Biophysics, the world's largest PET/MRI device began operation in April 2009: a 9.4-tesla magnetic resonance tomograph (MRT) combined with a positron emission tomograph (PET). Presently, only the head and brain can be imaged at these high magnetic field strengths.[3]

Radio nuclides

Radio nuclides used in PET scanning are typically isotopes with short half lives such as carbon-11 (~20 min), nitrogen-13 (~10 min), oxygen-15 (~2 min), and fluorine-18 (~110 min). These radio nuclides are incorporated either into compounds normally used by the body such as glucose (or glucose analogues), water or ammonia, or into molecules that bind to receptors or other sites of drug action. Such labeled compounds are known as radiotracers. It is important to recognize that PET technology can be used to trace the biologic pathway of any compound in living humans (and many other species as well), provided it can be radio labeled with a PET isotope. Thus the specific processes that can be probed with PET are virtually limitless, and radiotracers for new target molecules and processes are being synthesized all the time; as of this writing there are already dozens in clinical use and hundreds applied in research. Presently, however, by far the most commonly used nuclide in clinical PET scanning is fluorine-18 in the form of FDG.

Due to the short half lives of most radioisotopes, the radiotracers must be produced using a cyclotron and radiochemistry laboratory that are in close proximity to the PET imaging facility. The half life of fluorine-18 is long enough such that fluorine-18 labeled radiotracers can be manufactured commercially at an offsite location.

Limitations

The minimization of radiation dose to the subject is an attractive feature of the use of short-lived radio nuclides. Besides its established role as a diagnostic technique, PET has an expanding role as a method to assess the response to therapy, in particular, cancer therapy, [4] where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation.

Limitations to the widespread use of PET arise from the high costs of cyclotrons needed to produce the short-lived radio nuclides for PET scanning and the need for specially adapted on-site chemical synthesis apparatus to produce the radiopharmaceuticals. Few hospitals and universities are capable of maintaining such systems, and most clinical PET is supported by third-party suppliers of radiotracers which can supply many sites simultaneously. This limitation

restricts clinical PET primarily to the use of tracers labeled with fluorine-18, which has a half life of 110 minutes and can be transported a reasonable distance before use, or to rubidium-82, which can be created in a portable generator and is used for myocardial perfusion studies. Nevertheless, in recent years a few on-site cyclotrons with integrated shielding and hot labs have begun to accompany PET units to remote hospitals. The presence of the small on-site cyclotron promises to expand in the future as the cyclotrons shrink in response to the high cost of isotope transportation to remote PET machines [5]

Because the half-life of fluorine-18 is about two hours, the prepared dose of a radiopharmaceutical bearing this radionuclide will undergo multiple half-lives of decay during the working day. This necessitates frequent recalibration of the remaining dose (determination of activity per unit volume) and careful planning with respect to patient scheduling.

Image reconstruction

The raw data collected by a PET scanner are a list of 'coincidence events' representing near-simultaneous detection of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred. Modern systems with a high time resolution also use a technique (called "Time-of-flight") where they more precisely decide the difference in time between the detection of the two photons and can thus limit the length of the earlier mentioned line to around 10 cm.

Coincidence events can be grouped into projections images, called sinograms. The sinograms are sorted by the angle of each view and tilt, the latter in 3D case images. The sinogram images are analogous to the projections captured by computed tomography (CT) scanners, and can be reconstructed in a similar way. However, the statistics of the data is much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for the whole acquisition, while the CT can reach a few billion counts. As such, PET data suffer from scatter and random events much more dramatically than CT data does.

In practice, considerable pre-processing of the data is required - correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time correction (after the detection of a photon, the detector must "cool down" again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence).

Filtered back projection (FBP) has been frequently used to reconstruct images from the projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. However, shot noise in the raw data is prominent in the reconstructed images and areas of high tracer uptake tend to form streaks across the image.

Iterative expectation-maximization algorithms are now the preferred method of reconstruction. The advantage is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is higher computer resource requirements.

Attenuation correction: As different LORs must traverse different thicknesses of tissue, the photons are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, however earlier equipment offered a crude form of CT using a gamma ray (positron emitting) source and the PET detectors.

While attenuation-corrected images are generally more faithful representations, the correction process is itself susceptible to significant artifacts. As a result, both corrected and uncorrected images are always reconstructed and read together.

2D/3D reconstruction: Early PET scanners had only a single ring of detectors, hence the acquisition of data and subsequent reconstruction was restricted to a single transverse plane. More modern scanners now include multiple rings, essentially forming a cylinder of detectors.

There are two approaches to reconstructing data from such a scanner: 1) treat each ring as a separate entity, so that only coincidences within a ring are detected, the image from each ring can then be reconstructed individually (2D reconstruction), or 2) allow coincidences to be detected between rings as well as within rings, then reconstruct the entire volume together (3D).

3D techniques have better sensitivity (because more coincidences are detected and used) and therefore less noise, but are more sensitive to the effects of scatter and random coincidences, as well as requiring correspondingly greater computer resources. The advent of sub-nanosecond timing resolution detectors affords better random coincidence rejection, thus favoring 3D image reconstruction.

Applications

Maximum intensity projection (MIP) of a F-18 FDG whole body PET acquisition, showing abnormal focal uptake in the region of the stomach. Normal physiological isotope uptake is seen in the brain, renal collection systems and bladder. In this animation, it is important to view the subject as rotating clockwise (note liver position).

PET is both a medical and research tool. It is used heavily in clinical oncology (medical imaging of tumors and the search for metastases), and for clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is also an important research tool to map normal human brain and heart function.

PET is also used in pre-clinical studies using animals, where it allows repeated investigations into the same subjects. This is particularly valuable in cancer research, as it results in an increase

in the statistical quality of the data (subjects can act as their own control) and substantially reduces the numbers of animals required for a given study.

Alternative methods of scanning include x-ray computed tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI), ultrasound and single photon emission computed tomography (SPECT).

While some imaging scans such as CT and MRI isolate organic anatomic changes in the body, PET and SPECT are capable of detecting areas of molecular biology detail (even prior to anatomic change). PET scanning does this using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Changing of regional blood flow in various anatomic structures (as a measure of the injected positron emitter) can be visualized and relatively quantified with a PET scan.

PET imaging is best performed using a dedicated PET scanner. However, it is possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. The quality of gamma-camera PET is considerably lower, and acquisition is slower. However, for institutions with low demand for PET, this may allow on-site imaging, instead of referring patients to another center, or relying on a visit by a mobile scanner.

PET is a valuable technique for some diseases and disorders, because it is possible to target the radio-chemicals used for particular bodily functions.

Oncology: PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), called FDG-PET, is widely used in clinical oncology. This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly growing malignant tumours). A typical dose of FDG used in an oncological scan is 200-400 mBq for an adult human. Because the oxygen atom which is replaced by F-18 to generate FDG is required for the next step in glucose metabolism in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the phosphate added by hexokinase. This means that FDG is trapped in any cell which takes it up, until it decays, since phosphorylated sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the brain, the liver, and most cancers. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's lymphoma, non-Hodgkin lymphoma, and lung cancer. Many other types of solid tumors will be found to be very highly labeled on a case-by-case basis—a fact which becomes especially useful in searching for tumor metastasis, or for recurrence after a known highly active primary tumor is removed. Because individual PET scans are more expensive than "conventional" imaging with computed tomography (CT) and magnetic resonance imaging (MRI), expansion of FDG-PET in cost-constrained health services will depend on proper health technology assessment; this problem is a difficult one because structural and functional imaging often cannot be directly compared, as

they provide different information. Oncology scans using FDG make up over 90% of all PET scans in current practice.

PET scan of the human brain.

Neurology: PET neuro imaging is based on an assumption that areas of high radioactivity are associated with brain activity. What is actually measured indirectly is the flow of blood to different parts of the brain, which is generally believed to be correlated, and has been measured using the tracer oxygen-15. However, because of its 2-minute half-life O-15 must be piped directly from a medical cyclotron for such uses, and this is difficult. In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer's disease from other dementing processes, and also to make early diagnosis of Alzheimer's disease. The advantage of FDG-PET for these uses is its much wider availability. PET imaging with FDG can also be used for localization of seizure focus: A seizure focus will appear as hypo metabolic during an interracial scan. Several radiotracers (i.e. radio ligands) have been developed for PET that are ligands for specific neuro receptor subtypes such as [11C] raclopride and [18F] fallypride for dopamine D2/D3 receptors, [11C]McN 5652 and [11C]DASB for serotonin transporters, or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuro receptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. A novel probe developed at the University of Pittsburgh termed PIB (Pittsburgh Compound-B) permits the visualization of amyloid plaques in the brains of Alzheimer's patients. This technology could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [11C]PMP (N-[11C] methylpiperidin-4-yl propionate) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetyl cholinergic neurotransmitter system by acting as a substrate for acetyl cholinesterase. Post-mortem examinations of AD patients have shown

decreased levels of acetyl cholinesterase. [11C]PMP is used to map the acetyl cholinesterase activity in the brain which could allow for pre-mortem diagnosis of AD and help to monitor AD treatments.[9]

Cardiology, atherosclerosis and vascular disease study: In clinical cardiology, FDG-PET can identify so-called "hibernating myocardium", but its cost-effectiveness in this role versus SPECT is unclear. Recently, a role has been suggested for FDG-PET imaging of atherosclerosis to detect patients at risk of stroke [3].

Neurophysiology / Cognitive neuroscience: To examine links between specific psychological processes or disorders and brain activity.

Psychiatry: Numerous compounds that bind selectively to neuro receptors of interest in biological psychiatry have been radio labeled with C-11 or F-18. Radio ligands that bind to dopamine receptors (D1, D2, and reuptake transporter), serotonin receptors (5HT1A, 5HT2A, reuptake transporter) opioid receptors (mu) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia, substance abuse, mood disorders and other psychiatric conditions.

Pharmacology: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. Such scans are referred to as bio distribution studies. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. Much more commonly, however, drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and radio labeled compounds known apriori to bind with specificity to the site. A single radioligand can be used this way to test many potential drug candidates for the same target. A related technique involves scanning with radio ligands that compete with an endogenous (naturally occurring) substance at a given receptor to demonstrate that a drug causes the release of the natural substance.

PET technology for small animal imaging: A miniature PET tomography has been constructed that is small enough for a fully conscious and mobile rat to wear on its head while walking around.[10] This Rat CAP (Rat Conscious Animal PET) allows animals to be scanned without the confounding effects of anesthesia. PET scanners designed specifically for imaging rodents or small primates are marketed for academic and pharmaceutical research.

Pulse Shape Discrimination

The pulse Shape Discrimination (PSD) is a technique used to define which pulse is related to each crystal. Different Techniques were introduced to discriminate between two-types of pulses according to its shape (indeed due to the decay time).

Safety

PET scanning is non-invasive, but it does involve exposure to ionizing radiation. The total dose of radiation is not insignificant, usually around 11 mSv.[citation needed] When compared to the classification level for radiation workers in the UK, of 6 mSv it can be seen that PET scans need proper justification. This can also be compared to 2.2 mSv average annual background radiations in the UK, 0.02 mSv for a chest x-ray and 6.5 - 8 mSv for a CT scan of the chest, according to the Chest Journal and ICRP.[11][12] A policy change suggested by the IFALPA member associations in year 1999 mentioned that an aircrew member is likely to receive a radiation dose of 4–9 mSv per year.[13]

Positron Emission Tomography – Computed Tomography (PET/CT)

Products and Applications

What is Positron Emission Tomography – Computed Tomography (PET/CT) Scanning?

What are some common uses of the procedure?

How should I prepare for a PET and PET/CT scan?

What does the equipment look like?

How does the procedure work?

How is the procedure performed?

What will I experience during and after procedure?

Who interprets the results and how do I get them?

What are the benefits vs. risks?

What are the limitations of Positron Emission Tomography – Computed Tomography (PET/CT)?

What is Positron Emission Tomography – Computed Tomography (PET/CT) Scanning?

Sample image obtained using a combination of PET and CT imaging technology.

Positron emission tomography, also called PET imaging or a PET scan, is a type of nuclear medicine imaging.

Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material to diagnose or treat a variety of diseases, including many types of cancers, heart disease and certain other abnormalities within the body.

Nuclear medicine or radionuclide imaging procedures are noninvasive and, with the exception of intravenous injections, are usually painless medical tests that help physicians diagnose medical conditions. These imaging scans use radioactive materials called radiopharmaceuticals or radiotracers.

Depending on the type of nuclear medicine exam you are undergoing, the radiotracer is either injected into a vein, swallowed or inhaled as a gas and eventually accumulates in the organ or area of your body being examined, where it gives off energy in the form of gamma rays. This energy is detected by a device called a gamma camera, a (positron emission tomography) PET scanner and/or probe. These devices work together with a computer to measure the amount of radiotracer absorbed by your body and to produce special pictures offering details on both the structure and function of organs and tissues.

In some centers, nuclear medicine images can be superimposed with computed tomography (CT) or magnetic resonance imaging (MRI) to produce special views, a practice known as image fusion or co-registration. These views allow the information from two different studies to be correlated and interpreted on one image, leading to more precise information and accurate diagnoses. In addition, manufacturers are now making single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT) units that are able to perform both imaging studies at the same time.

A PET scan measures important body functions, such as blood flow, oxygen use, and sugar (glucose) metabolism, to help doctors evaluate how well organs and tissues are functioning.

CT imaging uses special x-ray equipment, and in some cases a contrast material, to produce multiple images or pictures of the inside of the body. These images can then be interpreted by a radiologist on a computer monitor as printed images. CT imaging provides excellent anatomic information.

Today, most PET scans are performed on instruments that are combined PET and CT scanners. The combined PET/CT scans provide images that pinpoint the location of abnormal metabolic activity within the body. The combined scans have been shown to provide more accurate diagnoses than the two scans performed separately.

What are some common uses of the procedure?

PET and PET/CT scans are performed to:

Detect cancer.

Determine whether a cancer has spread in the body.

Assess the effectiveness of a treatment plan, such as cancer therapy.

Determine if a cancer has returned after treatment.

Determine blood flow to the heart muscle.

Determine the effects of a heart attack, or myocardial infarction, on areas of the heart.

Identify areas of the heart muscle that would benefit from a procedure such as angioplasty or coronary artery bypass surgery (in combination with a myocardial perfusion scan).

Evaluate brain abnormalities, such as tumors, memory disorders and seizures and other central nervous system disorders.

To map normal human brain and heart function.

How should I prepare for a PET and PET/CT scan?

You may be asked to wear a gown during the exam or you may be allowed to wear your own clothing.

Women should always inform their physician or technologist if there is any possibility that they are pregnant or if they are breastfeeding their baby.

You should inform your physician and the technologist performing your exam of any medications you are taking, including vitamins and herbal supplements. You should also inform them if you have any allergies and about recent illnesses or other medical conditions.

You will receive specific instructions based on the type of PET scan you are undergoing. Diabetic patients will receive special instructions to prepare for this exam.

If you are breastfeeding at the time of the exam, you should ask your radiologist or the doctor ordering the exam how to proceed. It may help to pump breast milk ahead of time and keep it on hand for use after the PET radiopharmaceutical and CT contrast material are no longer in your body.

Metal objects including jewelry, eyeglasses, dentures and hairpins may affect the CT images and should be left at home or removed prior to your exam. You may also be asked to remove hearing aids and removable dental work.

Generally, you will be asked not to eat anything for several hours before a whole body PET/CT scan since eating may alter the distribution of the PET tracer in your body and can lead to a suboptimal scan. This could require the scan to be repeated on another day, so following instructions regarding eating is very important. You should not drink any liquids containing sugars or calories for several hours before the scan. Instead, you are encouraged to drink water. If you are diabetic, you may be given special instructions. You should inform your physician of any medications you are taking and if you have any allergies, especially to contrast materials, iodine, or seafood.

You will be asked and checked for any conditions that you may have that may increase the risk of using intravenous contrast material.

What does the equipment look like?

A positron emission tomography (PET) scanner is a large machine with a round, doughnut shaped hole in the middle, similar to a CT or MRI unit. Within this machine are multiple rings of detectors that record the emission of energy from the radiotracer in your body.

The CT scanner is typically a large, box like machine with a hole, or short tunnel, in the center. You will lie on a narrow examination table that slides into and out of this tunnel. Rotating around you, the x-ray tube and electronic x-ray detectors are located opposite each other in a ring, called a gantry. The computer workstation that processes the imaging information is located in a separate room, where the technologist operates the scanner and monitors your examination.

Combined PET/CT scanners are combinations of both scanners and look similar to both the PET and CT scanners.

A computer aids in creating the images from the data obtained by the camera or scanner.

How does the procedure work?

With ordinary x-ray examinations, an image is made by passing x-rays through your body from an outside source. In contrast, nuclear medicine procedures use a radioactive material called a radiopharmaceutical or radiotracer, which is injected into your bloodstream, swallowed or inhaled as a gas. This radioactive material accumulates in the organ or area of your body being examined, where it gives off a small amount of energy in the form of gamma rays. A gamma camera, PET scanner, or probe detects this energy and with the help of a computer creates pictures offering details on both the structure and function of organs and tissues in your body.

Unlike other imaging techniques, nuclear medicine imaging studies are less directed toward picturing anatomy and structure, and more concerned with depicting physiologic processes within the body, such as rates of metabolism or levels of various other chemical activity. Areas of greater intensity, called "hot spots", indicate where large amounts of the radiotracer have accumulated and where there is a high level of chemical activity. Less intense areas, or "cold spots", indicate a smaller concentration of radiotracer and less chemical activity.

How is the procedure performed?

Nuclear medicine imaging is usually performed on an outpatient basis, but is often performed on hospitalized patients as well.

You will be positioned on an examination table. If necessary, a nurse or technologist will insert an intravenous (IV) line into a vein in your hand or arm.

Depending on the type of nuclear medicine exam you are undergoing, the dose of radiotracer is then injected intravenously, swallowed or inhaled as a gas.

It will take approximately 60 minutes for the radiotracer to travel through your body and to be absorbed by the organ or tissue being studied. You will be asked to rest quietly, avoiding movement and talking.

You may be asked to drink some contrast material that will localize in the intestines and help the radiologist interpreting the study.

You will then be moved into the PET/CT scanner and the imaging will begin. You will need to remain still during imaging. The CT exam will be done first, followed by the PET scan. On occasion, a second CT scan with intravenous contrast will follow the PET scan. The actual CT scanning takes less than two minutes. The PET scan takes 20-30 minutes.

Total scanning time is approximately 30 minutes.

Depending on which organ or tissue is being examined, additional tests involving other tracers or drugs may be used, which could lengthen the procedure time to three hours. For example, if you are being examined for heart disease, you may undergo a PET scan both before and after exercising or before and after receiving intravenous medication that increases blood flow to the heart.

When the examination is completed, you may be asked to wait until the technologist checks the images in case additional images are needed. Occasionally, more images are obtained for clarification or better visualization of certain areas or structures. The need for additional images does not necessarily mean there was a problem with the exam or that something abnormal was found, and should not be a cause of concern for you. You will not be exposed to more radiation during this process.

If you had an intravenous line inserted for the procedure, it will usually be removed unless you are scheduled for an operating room procedure that same day.

What will I experience during and after the procedure?

Except for intravenous injections, most nuclear medicine procedures are painless and are rarely associated with significant discomfort or side effects.

If the radiotracer is given intravenously, you will feel a slight pin prick when the needle is inserted into your vein for the intravenous line. When the radioactive material is injected into your arm, you may feel a cold sensation moving up your arm, but there are generally no other side effects.

When swallowed, the radiotracer has little or no taste. When inhaled, you should feel no differently than when breathing room air or holding your breath.

With some procedures, a catheter may be placed into your bladder, which may cause temporary discomfort.

It is important that you remain still while the images are being recorded. Though nuclear imaging itself causes no pain, there may be some discomfort from having to remain still or to stay in one particular position during imaging.

If you are claustrophobic, you may feel some anxiety while you are being scanned.

Unless your physician tells you otherwise, you may resume your normal activities after your nuclear medicine scan. If any special instructions are necessary, you will be informed by a technologist, nurse or physician before you leave the nuclear medicine department.

Through the natural process of radioactive decay, the small amount of radiotracer in your body will lose its radioactivity over time. It may also pass out of your body through your urine or stool during the first few hours or days following the test. You may be instructed to take special precautions after urinating, to flush the toilet twice and to wash your hands thoroughly. You should also drink plenty of water to help flush the radioactive material out of your body as instructed by the nuclear medicine personnel.

Who interprets the results and how do I get them?

A radiologist who has specialized training in nuclear medicine will interpret the images and forward a report to your referring physician.

If your physician has ordered a diagnostic CT, a radiologist with specialized training in interpreting CT exams will report the findings of the CT and forward a report to your referring physician.

What are the benefits vs. risks?

Benefits

The information provided by nuclear medicine examinations is unique and often unattainable using other imaging procedures.

For many diseases, nuclear medicine scans yield the most useful information needed to make a diagnosis or to determine appropriate treatment, if any.

Nuclear medicine is less expensive and may yield more precise information than exploratory surgery.

By identifying changes in the body at the cellular level, PET imaging may detect the early onset of disease before it is evident on other imaging tests such as CT or MRI.

The benefits of a combined PET/CT scanner include:

greater detail with a higher level of accuracy; because both scans are performed at one time without the patient having to change positions, there is less room for error.

Greater convenience for the patient who undergoes two exams (CT & PET) at one sitting, rather than at two different times.

Risks

Because the doses of radiotracer administered are small, diagnostic nuclear medicine procedures result in low radiation exposure, acceptable for diagnostic exams. Thus, the radiation risk is very low compared with the potential benefits.

Nuclear medicine diagnostic procedures have been used for more than five decades, and there are no known long-term adverse effects from such low-dose exposure.

Allergic reactions to radiopharmaceuticals may occur but are extremely rare and are usually mild. Nevertheless, you should inform the nuclear medicine personnel of any allergies you may have or other problems that may have occurred during a previous nuclear medicine exam.

Injection of the radiotracer may cause slight pain and redness which should rapidly resolve.

Women should always inform their physician or radiology technologist if there is any possibility that they are pregnant or if they are breastfeeding their baby.

What are the limitations of Positron Emission Tomography – Computed Tomography (PET/CT)?

Nuclear medicine procedures can be time-consuming. It can take hours to days for the radiotracer to accumulate in the part of the body under study and imaging may take up to several hours to perform, though in some cases, newer equipment is available that can substantially shorten the procedure time. You will be informed as to how often and when you will need to return to the nuclear medicine department for further procedures.

The resolution of structures of the body with nuclear medicine may not be as clear as with other imaging techniques, such as CT or MRI. However, nuclear medicine scans are more sensitive than other techniques for a variety of indications, and the functional information gained from nuclear medicine exams is often unobtainable by any other imaging techniques.

PET scanning can give false results if chemical balances within the body are not normal. Specifically, test results of diabetic patients or patients who have eaten within a few hours prior to the examination can be adversely affected because of altered blood sugar or blood insulin levels.

Because the radioactive substance decays quickly and is effective for only a short period of time, it is important for the patient to be on time for the appointment and to receive the radioactive material at the scheduled time. Thus, late arrival for an appointment may require rescheduling the procedure for another day.

A person who is very obese may not fit into the opening of a conventional PET/CT unit.

Image of a typical positron emission tomography (PET) facility

PET/CT-System with 16-slice CT; the ceiling mounted device is an injection pump for CT contrast agent

LSO Crystal Technology

Since we know that the highest PET image quality is achieved by collecting the greatest number of true counts, we designed new systems that could collect more counts and process those counts faster.

3-D Count-Rate Improvement with LSO

The faster LSO detectors dramatically increase system count-rate performance at activity levels relevant to patient scanning. This improvement brings significant speed and quality advantages for clinical and research applications.

PET Detector Material Properties 

Property Characteristic Desired Value Value

Density (g/cc) Defines detection efficiency of detector and scanner sensitivity

High LSO = 7.4BGO = 7.1GSO = 6.7NaI = 3.7

Effective Atomic Number Defines detection efficiency of detector and scanner sensitivity

High LSO = 65BGO = 75GSO = 59NaI = 51

Decay Time (nsec) Defines detector dead time and randoms rejection

Low LSO = 40BGO = 300GSO = 60NaI = 230

Relative Light Output(%) Impacts spatial and energy resolution

High LSO = 75BGO = 15GSO = 35NaI = 100

Energy Resolution (%) Influences scatter rejection Low LSO = 10.0BGO = 10.1GSO = 9.5NaI = 7.8

Nonhygroscopic Simplifies manufacturing, improves reliability and reduces service costs

Yes LSO = YesBGO = YesGSO = YesNaI = No

Ruggedness Simplifies manufacturing, improves reliability and reduces service costs

Yes LSO = YesBGO = YesGSO = NoNaI = No

LSO Crystal Detector

The performance of a PET scanner depends greatly upon the physical and scintillation properties of the crystal detector material. LSO offers the best combination of properties of any PET scintillator known today.

LSO exhibits the fastest scintillation decay time of all PET scintillator currently in use. This allows fast coincidence timing with efficient rejection of random events to provide the very high count rates that are essential to high-speed PET scanning. LSO also has high density and a high atomic number for good detection efficiency and a high light output for improved energy and position determination.

The lightning speed of LSO crystal technology brings significant advantages to high-throughput 3-D acquisition. In combination with high-speed electronics, accurate data correction and fast reconstruction techniques, Siemens LSO-based scanners deliver exceptional image quality in the shortest scanning time possible today.

HOT LAB EQUIPMENT

1. Syringe and vial shields

Staff preparing and injecting radiopharmaceuticals in hospitals may receive significant radiation doses to their hands. These doses may be high enough to warrant that they be classified as radiation workers. The influence of local shielding on finger doses has been investigated. Staff preparing radioactive liquids in a radionuclide dispensary and drawing up and injecting radiopharmaceuticals in a nuclear medicine department have been studied. Measurements have been recorded with an electronic extremity dose monitor, an advanced extremity gamma instrumentation system (AEGIS), worn near to the finger tip. The electronic dosimeter allows the pattern of doses received during different procedures to be determined. Doses received for individual manipulations during many routine sessions have been recorded for different staff members. Dose distributions around shielded vials and syringes have also been measured using AEGIS. In the radionuclide dispensary the vials from which radioactive liquids are dispensed are

held in tungsten shields, whereas in nuclear medicine simple lead pots are used. Syringe shields are employed for some parts of dispensing and patient injections. Data on dose distributions have been used in interpretation of results from monitoring. Use of syringe shields during dispensing reduced the finger dose by 75-85%. The peaks in dose rate were 60% lower, and periods of exposure to high dose rates were reduced in length by a third because of the restriction in the region of high dose rate. The extremity doses to staff dispensing and injecting radiopharmaceuticals in nuclear medicine were of similar magnitude. Doses received during dispensing varied from 10 to 555 microGy depending upon whether the vial containing the radiopharmaceutical was directly handled or not. Doses received from individual injections varied from 1 to 150 microGy depending on the degree of difficulty experienced during the injection.

Shielding and Storage Products (L block shield)

Space-saving design – Ideal for mobile units

1.5" thick lead shielding in front, 1" in base

8" x 8" x 4" adjustable lead glass window

1" thick lead shield surrounds calibration chamber

Optional Lead Brick Cave for complete lateral shielding

The unique Compact L-Block with Dose Calibrator Shield is designed to maximize space in facilities receiving and preparing doses of high-energy nuclides such as FDG F-18. This unit provides convenient access and viewing of the work area and incorporates a built-in calibration chamber shield. The special shield is designed to accommodate a chamber that is through-mounted in a countertop (customer responsible for installation). The chamber shield accommodates all Atom lab chambers and many others (check chamber shield specifications to determine fit). This combination of L-Block and dose calibrator shield eliminates the need to purchase interlocking shielding rings. This unit is constructed of lead encased in steel. It features a large 8" x 8" x 4" lead glass window with adjustable window angle, 1.5" thickness lead shielding in front, and 1" thick lead in the base and in the chamber shield. A special plate with a hex-shaped recess is mounted on the L-Block base to facilitate one-handed loading and unloading of dose pigs incorporating hex-shaped bottoms. The optional 042-434 Lead Brick Cave fits neatly into the sides of the vertical section to provide lateral shielding around the full

perimeter of the L-Block’s base. For hot labs in mobile vans, the optional Brick Cave Cover will prevent the cave from shifting when the vehicle is in motion.

Dose Calibrators and Wipe Test Counters

The Atom lab Dose Calibrators are used to measure the Radioactivity of a known radioisotope. Their primary applications the measurement of the dose administered to a patient in nuclear imaging. The design for both units incorporates unique electronics and software which surpassStringent regulatory performance standards and provide fast and accurate results. The Detector Unit uses an ionization chamber for radiation detection and an electrometer for ion current measurement. The chamber bias is generated with an electronic high voltage supply, eliminating the need for expensive battery changes. An optional Multi-Chamber Manual Interface is also available. The Display Unit communicates with the Detector Unit through a serial port. An optional RS-232 computer interface is available. This interface will allow the user to send data and commands between the dose calibrator and a remote PC.

THE DETECTORThe Atom lab Detector Unit is a well type ionization chamber capable of measuring activity as low as 0.01 μCi and as high as 9999. mCi of Tc-99m. The chamber is surrounded on all sides and on the bottom with .25-inch lead to both shield you from the source you are measuring and shield the dose calibrator from any ambient radiation.THE CHAMBERThe well type chamber was carefully selected to provide a nearly "4 pi" measuring geometry which means that the radiation detector nearly surrounds the radionuclide. This allows the Atom lab Dose Calibrator to measure the activity of a sample no matter what its volume or shape, as long as it fits into the Chamber Well. This is necessary, for example, when measuring syringe doses when the volume is unimportant.CHAMBER WELL LINERPlaced within the well is a plastic liner to protect the chamber from contamination in the event of the source leaking during measurement.CURRENT MEASUREMENTThe ionization current is measured by a microprocessor controlled high impedance electrometer located within the base of the Detector Unit.REAR PANELOn the rear panel of the Detector Unit are the connectors for power and data communication with the Display Unit. The Detector Unit can be located up to three meters away from the Display Unit.RESPONSEThe response of this type of ionization chamber has been carefully studied using radio nuclides calibrated at the National Institute of Standards & Technology. The result is a well-defined energy response curve which is used to determine the calibration values for many different isotopes with high accuracy. Each chamber has been calibrated with a National Institute of Standards & Technology traceable source. The corresponding Calibration Value has been stored in the memory of the Detector Unit. After calibration, the chamber's accuracy is tested with several sources of differing

gamma energies whose activity values are traceable to the National Institute of Standards & Technology.THE DISPLAY UNITThe Atom lab Dose Calibrator Display Unit consists of control keys and displays that allow you to make activity measurements. A built-in microprocessor executes commands input via the front panel keys and computes activity values from Detector data. The Display Unit, with a molded plastic case housing the electronics, has been specifically designed to perform Activity Measurements in a laboratory setting. To allow easy fingertip control of the keys, the front panel slopes gradually. The Activity Display slopes as well, providing an optimum viewing angle. On the rear panel of the unit are the power and communication connectors, and the power switch, which remain out of the way as they are infrequently needed.

THEORY OF RADIO ISOTOPE PRODUCTIONINTRODUCTIONThe production of radioisotopes for use in biomedical procedures, such as diagnostic imaging and/or therapeutic treatments, is achieved through nuclear reactions in reactors or from charged particle bombardment in accelerators. In reactors, the nuclear reactions are initiated with neutrons, while in accelerators the typical charged particle reactions utilize protons, although deuterons and helium nuclei (3He2+ and alpha particles) play a role. While 99Mo for the 99Mo/99mTc generator is produced in reactors and the procedures using this generator account for nearly 90% of all nuclear medicine procedures, this chapter will focus on utilization of low energy (<50 MeV protons/20 MeV deuterons) accelerators for the production of radioisotopes.One clear advantage that accelerators possess is the fact that, in general, the target and product are different chemical elements. This makes it possible to: (a)Find suitable chemical or physical means for separation; (b)Obtain high SA preparations, owing to the target and product being different elements; (c)Produce fewer radio isotopic impurities by selecting the energy window for irradiation. The available accelerators fit into three categories (see Chapter 3):(1)Firstly, there are university based cyclotrons, which are typically multi particle machines with energies around 30–50 MeV.(2)Secondly, there are hospital based machines, which are generally dedicated to the production of the standard PET radioisotopes (11C, 13N, 15O and 18F). These cyclotrons accelerate protons in the 10–19 MeV range, and some also produce deuterons with an energy of about half that of the protons (5–9 MeV). (3)Thirdly, there are the cyclotrons used by industry for large scale production. These are typically 30 MeV proton-only machines, although some use lower energies for dedicated production of 103Pd.There are three major reasons that accelerator produced radioisotopes are used widely and that they are becoming ever more popular. These are: (1)Accelerator produced radioisotopes have more favorable decay characteristics (particle emission, half-life, gamma rays, etc.) in comparison with reactor produced radioisotopes.(2)Radioisotopes cannot usually be produced in reactors with high SAs.

(3)Access to reactors is often very limited (perhaps the most important reason). The number of reactors available to the scientific community has become significantly less than the number of cyclotrons available. This reduction in the number of available reactors is a problem that was already predicted in 1983 to become more severe. This prediction has been borne out over the last 20 years.There are literally hundreds of radioisotopes that can be produced with charged particle accelerators. The cyclotron is the most frequent choice of accelerator, but the linac and other accelerators may become more common with the development of smaller, more reliable, machines. This chapter will deal only with targetry for a small subset of the radionuclides produced with charged particle accelerators.The goal of cyclotron targetry is to place the target material into the beam, keep it there during irradiation, and remove the product radionuclide from the target material quickly and efficiently. The specific design of the target is what allows this goal to be achieved. Unless care is taken in the design and fabrication of the target, the production of the radioisotope can be far from optimal and may even be impossible. Over time, many facilities will need to increase the number of radioisotopes being produced or to optimize the yields of their currently produced radioisotopes. If an increase in production with commercial targets is being sought, modifications of existing targets and procedures or development of new targets may be ways of accomplishing this objective.The purpose of this chapter will be to explore some of the problems in the design and construction of cyclotron targets, and to demonstrate with practical examples how to evaluate some of the solutions to the numerous problems encountered in achieving the optimal design of a cyclotron target. An attempt has been made to present some useful formulas and ‘rules of thumb’ that may be used in the design of cyclotron targetry. Even if the reader is not concerned with the design of cyclotron targets, these equations may provide an insight into the processes occurring in targets. The formulas are taken from a number of textbooks on nuclear physics, nuclear chemistry and engineering, and compiled here merely for easy access.One of the challenges to those involved with the design of targets is that not all cyclotrons are the same. The design of targetry associated with one cyclotron may not be optimal for a different cyclotron. In addition to the characteristics of mechanical design, beam energy and beam current, the major variables are the beam size and profile. An uncontrolled or unstable beam profile may result in an unreliable radioisotope yield. If the beam profile Can not be controlled, then allowances must be made in the targetry in order to obtain predictable yields. There are often significant differences in the characteristics of the beam profile between a positive ion cyclotron and a negative ion cyclotron. Negative ion cyclotrons usually have a more uniform beam profile incident on the target. This is a result of the extraction process through a stripping foil that will scatter and, therefore, tend to eliminate hot spots in the beam [5.1–5.3]. Focusing magnets and steering them along the transport line, if there is one, can alter the beam shape to a more homogeneous one. Positive ion cyclotrons may have a uniform beam profile, or the profile may be quite ‘hot’ in spots and not uniform at all, depending on the extraction characteristics and focusing magnets used to transport the beam. In general, the extraction process for positive ions tends to create areas of high intensity in the beam. Most of the newer, commercially available cyclotrons for PET are negative ion cyclotrons and have targets mounted directly on the cyclotron without any focusing or steering magnets to alter the beam shape.Other factors that are important for effective radioisotope production are whether or not an internal beam is available, and whether or not multiple targets can be irradiated simultaneously.

Internal targets were first developed because the extraction efficiency of older cyclotrons was quite low. The extraction efficiency of a cyclotron is defined as the beam current extracted from the machine divided by the beam current circulating before extraction. In older positive ion cyclotrons, most of the beam was lost inside the machine (an extraction efficiency of 10% being thought quite acceptable, although more modern positive ion machines are capable of extracting more than 60% of the beam). The use of negative ion cyclotrons and the greatly improved extraction efficiency of newer positive ion cyclotrons have reduced the need for internal targets, but they are still quite common since they work well. Internal targets are usually set as grazing incidence targets, because this allows the heat generated from the target to be dispersed over a wider area. Negative ion cyclotrons allow for irradiation of multiple targets simultaneously. This is not usually possible with positive ion cyclotrons, unless the targets are ‘piggyback’ or tandem targets with one target following another along the same beam line.TARGET TYPESFor production of radioisotopes, the target material may be either gas, liquid or solid. Targets are, consequently, designed to accommodate the material being irradiated. The design of the target will also depend upon whether the target is placed inside (internal) or outside (external) the cyclotron.Internal targetsInternal targets were the first targets to be used in cyclotrons. The real advantage of these targets at present is that the target may be built to exactly match the beam curvature and, therefore, spread the power of the beam over the maximum area and increase the amount of beam current that may be applied to the target. A schematic diagram of an internal target is shown in Fig. 5.1.Water CoolingTarget MaterialBase PlateRamTrailingEdge MonitorLeading Edge MonitorWater CoolingWater CoolingFIG. 5.1. Schematic diagram of an internal target, showing a plated surface on a base plate for cooling.These targets are very widely used at present for the production of non-volatile solid radioisotopes such as 123I, 124I, 201Tl, 67Ga and 111In. The target material is typically a solid, usually in the form of a thin metal layer, although internal targets using powders and liquids have been designed and used.Figure 5.2 shows a typical internal target used for the production of radioisotopes in nuclear medicine. This particular target was used for production of 201Tl. The thallium is electroplated onto the copper surface and then dissolved after irradiation [5.6].CHAPTER 5 76

An example of an internal powder target is shown in Fig. 5.3 [5.7]. FIG. 5.2. An internal target used for production of 201Tl.FIG. 5.3. An example of an internal target using 122Te powder to produce 123I. This particular target was used to produce 123I from 122Te, using deuterons as the bombarding particle. The 123I is swept out of the target by the helium gas flow, and the target never has to be removed from the cyclotron except for maintenance.5.2.2. External targetsThere is a very wide variety of external targets that can be used for irradiation of solids, liquids and gases. Solid targetsBecause the density of solids is typically higher than that of liquids or gases, the path length of the beam is shorter, and the target somewhat smaller. The solid can be in the form of a foil or a powder. If the solid is a good heat conductor, then the beam can be aligned to be perpendicular to the solid. A typical solid target for conductive powders is shown in Fig. A typical solid powder target for use with low beam current or with thermally conductive solids.A photograph of a typical external solid target is shown in Fig. Photograph of the solid powder target used at BNL. The powder is held in the small cavity in the target. The cover foil is shown next to the cavity.If the solid is not a good thermal conductor, or when very high beam currents are used, it is typical to form the solid on an inclined plane (Section 5.5.4).

Liquid targetsIn the case of liquids, targets have similar dimensions to those of solid targets, since the target material occupies a specific volume unless the liquid volatilizes. The difference is that the liquid is typically added and removed from the target while it is in place on the cyclotron. A typical liquid target for the production of 18F from 18O in water is shown in Figs

Gas targetsGas targets are widely used and are usually some type of cylinder to hold the gas under pressure, with a thin beam entry foil usually referred to as a window. The principal constraint on gas targets is removal of heat from the gas, since gases are not very good heat conductors and the targets must be quite large in comparison with solid or liquid targets in order to hold the necessary amount of material. A schematic diagram of a typical gas target is shown in fig and a photograph is shown in the cold finger on the bottom of the target allows the gas to be transferred into the target more efficiently. The large volume at the front of the target was used to capture the xenon if the front foil ruptured.

APPLICATION OF PHYSICS TO TARGETRYA major concern in target design is the generation and dissipation of heat during irradiation. Efficient cooling not only ensures that the target material will remain in the target but also allows

the target to be irradiated at higher beam currents, which in turn allows production of more radioisotopes in a given time. Factors to be considered in relation to thermodynamics include:—Interactions of charged particles with matter; —Stopping power and ranges; —Energy straggling; —Small angle multiple scattering. Each of these factors will be described in some detail in Sections 5.3.1–5.3.4.Interactions of charged particles with matter As a charged particle moves through a surrounding medium, it interacts through ionization, scattering and various types of radioactive losses. There are four main modes of interaction involved. In the first mode of interaction, the particles undergo inelastic collisions with the atomic electrons of the surrounding medium. In this case, the electrons are promoted to a higher energy level (excitation), or an unbound state (ionization) [5.1]. If ionization occurs, then the ions and electrons recombine to form an excited neutral atom or molecule. In either case, the excited atom or molecule must transfer the excess energy to the surrounding molecules. The transfer of energy from the charged particle to the surrounding medium in this fashion is the primary energy loss mechanism for the charged particle beam and the major source of heat in the target material.In the second mode of interaction, the particles undergo inelastic collisions with nuclei of the target material. In this case, the charged particle is deflected by an amount depending on the proximity of the encounter and the charges involved. In some of these deflections, a quantum of energy is lost from radiation (bremsstrahlung) and a corresponding amount of kinetic energy is lost from the colliding pair. The total bremsstrahlung intensity varies inversely with the square of the mass of the charged particle, so that it is not usually important for protons or more massive particles.In the third mode of interaction, the particles undergo elastic collisions with the nuclei of the target material. In an elastic collision, the incident particle is deflected but neither radiates nor results in any excitation of the target nucleus. The only kinetic energy lost is due to conservation of momentum by the deflection of the particle. This process is common for electrons, but is much less probable for charged particles.In the last mode of interaction, the particles undergo elastic collisions with atomic electrons. This process usually occurs only at low energy when the charged particle does not transfer enough energy to the atomic electron to promote it to the lowest excited state energy level.The charged particle loses energy as a result of all four of these processes as it moves through the target material. At energies typical for radioisotope production, a particle will undergo more than a million collisions before it comes to rest. Of course, the type of collisions and the exact path of an individual particle cannot be predicted. However, since the probabilities can be calculated and the number of particles is large, the overall behaviour of the beam can be predicted with high accuracy and reliability.

RADIO NUCLIDES: The use of radionuclides in the physical and biological sciences can be broken down into three general categories; imaging, radiotherapy and radiotracers. Imaging can be further divided into PET and SPECT. All of these uses rely on the fact that radionuclides are used at tracer concentrations. In order to be used as tracers, the radionuclides and the compounds to which they are attached must obey the tracer principles, which state that:(1)The tracer behaves or interacts with the system to be probed in a known and reproducible fashion.(2)The tracer does not alter or perturb the system in any measurable fashion.(3)The tracer concentration can be measured.In internal radiotherapy for treating cancer and other diseases, the second principle is, in a strict sense, broken since the purpose of delivering the radiotoxic substance is to have the emitted radiation cause damage to the tumor tissues. However, in order for the radiotoxic substance to be localized, it must follow the known chemical behaviour without perturbing that pathway. The following are some typical radionuclides used in each of the broad categories:(a)Carbon-11 is a positron emitting radionuclide with a half-life of 20.3 min used for PET imaging. It is generally produced as 11CO2, which can be converted into a wide variety of labelling agents, such as 11CH3I or H11CN. Since almost all biological compounds contain carbon, 11C finds widespread use as a tracer in PET. In fact, more than 200 compounds have been labelled with 11C [2.1].(b)Nitrogen-13, with a half-life of 10 min, is also a positron emitting radionuclide. However, in addition to its use as a cardiac blood flow agent (as 13NH4+), it is used in applications other than PET imaging. For example, it is widely used in botany studies to determine the kinetics of nitrogen uptake in a variety of plant systems under a variety of conditions [2.2, 2.3].(c)Iodine-123, with a half-life of 13.1 h, emits gamma rays with an energy of 159 keV, which is ideally suited to imaging in SPECT cameras that have been optimized for use with 99mTc (with a gamma ray energy of 140 keV). In addition, the ease with which an iodine atom can be inserted into a compound makes 123I extremely versatile as a radiotracer in SPECT [2.4–2.6].(d)Rhenium-186 is a b– emitter with a low abundance 140 keV gamma ray. The 1 MeV b– ray and its 90 h half-life make it a promising radiotoxic nuclide for therapy. As a chemical analogue of technetium, rhenium possesses similar chemical properties as 99mTc and can be used with some of the same compounds that have been developed for imaging tumours.

USES OF ACCELERATOR PRODUCED RADIOISOTOPES 15

TABLE 2.2. TYPICAL RADIOISOTOPES AND THEIR USES FOR IMAGINGRadioisotope Half-life Uses

Technetium-99m

6 h, derived from Mo-99 parent (66 h)

Used to image the skeleton and heart muscle, in particular; but also used for brain, thyroid, lungs (perfusion and ventilation), liver, spleen, kidneys (structure and filtration rate), gall bladder, bone marrow, salivary and lachrymal glands, heart blood pool, infections and numerous specialized medical studies.

Cobalt-57 272 d Used as a marker to estimate organ size and forin vitro diagnostic kits.

Gallium-67 78 h Used for tumour imaging and localization of inflammatory lesions (infections).

Indium-111 67 h Used for specialist diagnostic studies; e.g. for the brain, infections and colon transit.

Iodine-123 13 h Increasingly used for diagnosis of thyroid function,it is a gamma emitter without the beta radiation ofI-131.

Krypton-81m 13 s fromRb-81 (4.6 h)

Kr-81m gas can yield functional images of pulmonary ventilation, e.g. in asthmatic patients, and for the early diagnosis of lung diseases and function.

Rubidium-82 65 h Convenient PET agent for myocardial perfusion imaging.

Strontium-92 25 d Used as the ‘parent’ in a generator to produce Rb-82.

Thallium-201 73 h Used for diagnosis of coronary artery disease and other heart conditions, such as heart muscle death and for location of low grade lymphomas.

Carbon-11Nitrogen-13Oxygen-15Fluorine-18

20.4 min9.97 min2 min110 min

These are the positron emitters used in PET for studying brain physiology and pathology, in particular for localizing epileptic focus, and in dementia, psychiatry and neuropharmacology studies. They also have a significant role in cardiology. Fluorine-18 in FDG has become very important in detecting cancers and in monitoring progress in their treatment, using PET.

TABLE 2.5. RADIONUCLIDES THAT HAVE BEEN PROPOSED FOR USE AS POSSIBLE RADIOTOXIC ISOTOPES FOR TREATMENT OF CANCERSc-47 Cu-

64Cu-67

Br-77

Y-90

Rh-105 Pd-103

Ag-111

I-124

Pr-142

Pm-149

Sm-153

Gd-159

Ho-166

Lu-177

Re-186/188

Ir-194

Pt-199

At-211

Bi-213

Question bankOnPositron emission tomographyShort answer questions:

1. Define nuclear medicine and mention its applications?2. What is meant by a tracer and mention its properties?3. List out 4 radionuclides used for PET imaging?4. List out 4 radionuclides used for SPECT imaging?5. Differentiate PET and SPECT?6. Differentiate Nuclear Medicine from general imaging techniques?7. Mention few detectors used in PET?8. What is the need of PET-CT?9. Define annihilation, and mention its significance in PET imaging?10. Define LOR, mention its significance?11. List out the reconstruction techniques used in PET?12. Define coincidence events, and sinogram?13. What is the need of attenuation correction in PET?14. What is meant by FDG-PET, and where it is used?15. Name the radionuclide used in Neuro imaging, mention its half life?16. Name the radionuclide used in psychiatry, mention its half life?17. What are the benefits Vs Risks?18. What are the limitations of PET?19. Write the indications and contraindications of PET scan?20. Differentiate PET, PET-CT?21. What is scanning time for PET?22. Name few hot lab equipments?23. Write the principle of Cyclotron?24. Classify accelerators in cyclotron?25. Name the targets used for production of radionuclides?26. Define radioimmunoassay?27. Write short notes on thyroid scanning?28. Name the radionuclides used in radiotherapy?29. Mention the specifications of processors used in PET?30. Mention the role of FPGA’s in PET?31. List out the hardware details of PET?

Long Answer questions?1. Discuss in detail about PET with a neat block diagram?2. Write short notes on nuclear medicine, and differentiate PET from SPECT?3. Discuss in detail about the reconstruction techniques of images in PET?4. Describe in detail about cyclotron?5. Name the hot lab equipment and discuss in detail about any two?6. List out the radionuclides used for PET and mention their characteristics?7. Write in detail about the principle of PET, and mention its applications?8. Differentiate PET from other imaging techniques?

9. write short notes ona. Thyroid scanning b. Radioimuno assay