Positron Emission Tomography

in Clinical Oncology

Chun Ki Kim, M.D.Chun Ki Kim, M.D.

Mount Sinai School of MedicineMount Sinai School of Medicine

New York, New YorkNew York, New York

Commonly used PET Radiotracers

• [F-18] FDG - Glucose metabolism

• [C-11] Methionine - Amino acid transport- Incorporation of amino acid into protein fractions

• [O-15] Water - Blood flow• [N-13] Ammonia - Blood flow• Rb-82 - Blood flow

• [C-11] Thymidine Tumor cellular proliferation rate• [C-11] Aminoisobutyric acid Tumor amino acid uptake• [F-18] 5-FU Prediction/evaluation of

ChemoTx• [C-11] Tyrosine Tumor metabolism• [N-13] Glutamate Tumor metabolism

• [C-11] Acetate Myocardial oxidative metabolism• [C-11] Palmitate Myocardial fatty acid metabolism

• [F-18] FluoroDOPA Dopamine synthesis• Many other receptor agents Dopamine, serotonin, opiate etc.

Potential PET Radiotracers

PET Radiotracer approved by FDA

• [F-18] FDG (fluoro deoxyglucose)

Malignancy ~ Glucose / FDG uptake

NORMAL TUMOR

• Overexpression of Glucose transporters• Higher levels of Hexokinase• Down-regulation of Glucose-6-phosphatase• Anaerobic glycolysis, less ATP per glucose molecule, more glucose molecules needed for ATP production• General increase in metabolism from high growth rates

Malignancy

Glucose/FDG uptake

Gallium PET

Metastatic Thyroid Ca. to Lung, Mediastinum, and Skeleton

General Indications for FDG-PET Tumor Imaging

DDx: Benign versus Malignant Staging & Restaging Metastatic work up: Rising tumor markers Monitoring treatment response Scar/necrosis/fibrosis vs. Recurrent/residual disease Grading/Prognosis Detection of unknown primary

New Medicare Coverage Policy for FDG PET

• Lung Ca (NSC): Dx, Staging & restaging• Esophgeal Ca: Dx, Staging & restaging• Colorectal Ca: Dx, Staging & restaging• Lymphoma: Dx, Staging & restaging• Melanoma: Dx, Staging & restaging,

Non-covered for evaluating regional nodes• Head & Neck Ca: Dx, Staging & restaging

Lung Cancer

Dx: Solitary Pulmonary NoduleStagingMetastatic work-up

Solitary Pulmonary Nodule

• Incidence detected by CXR: 130,000/year.

50-60%: Benign

20-40%: Invasive nodule biopsy

Resection.

CT: an indeterminant LUL nodule.

Efficacy of PET Solitary Pulmonary Nodule

• Sensitivity = 97%• Specificity = 78%

(Meta-analysis of >40 articles: Gould et al. JAMA 2001)

False Positives:

Active Infection/Inflammation

TB

PneumoniaCryptococcosisHistoplasmosis

AspergillosisInflammatory

Staging

60/M: Lung Ca.

62y/o Lung Ca. with adrenal mass

Colorectal Cancer:Clinical Indications for PET

Imaging Staging before primary resection? Detection of Lesions after Primary Resection

Staging before resection of recurrent disease.Rising CEA in the absence of a known source.Equivocal/residual lesion on conventional imaging.Patient is clinically symptomatic, but CEA is normal.

Monitoring treatment response (pre-op & post-op)

Staging before resection of recurrent disease

63 y/o woman with a H/O Colon Ca. and liver metastases

79/M. Resection of Rectal Ca (Dukes B) 4 mos earlier,

CEA, CT: possible local relapse.

T1 T2

T1 enhanced T1 enhanced

• F/68• H/O Colon Ca.• Rising CEA• CT/MRI;

multiple cysts

Sagittal Transverse Coronal

YW: Colon Ca• 3/00: (-) CT • 5/00: rising CEA

• 6/00: (+) PET

• 7/00: CT

58/M - S/P Colon CaRising CEA

Coronal Coronal Transverse

58/M - S/P Colon CaRising CEA

Local recurrence

Hemangioma

• 48y/o with Colon Ca.• S/P Primary resection.• S/P Resection of liver lesion

• Now with CEA • CT: (-) for mets

• 48y/o with Colon Ca.• S/P Primary resection.• S/P Resection of liver lesion

• Now with CEA • CT: (-) for mets

N. G. 8/15/00Colon cancer with a Hx of UCProven mesenteric carcinomatosis

1756441

Huebner et al. J Nucl Med 2000;41:1177-1189

Huebner et al. J Nucl Med 2000;41:1177-1189

Colorectal Cancer: A possible algorithm

CT evidence of resectable disease in patient suitable for surgery

WholeBodyPET imaging

Colorectal Cancer: A possible algorithm

CT evidence of resectable disease in patient suitable for surgery

WholeBodyPET imaging

Further evaluation of CT abnormality

All sites negative

Colorectal Cancer: A possible algorithm

CT evidence of resectable disease in patient suitable for surgery

WholeBodyPET imaging

Further evaluation of CT abnormality

Surgery

All sites negative

PET = CT and other sites negative

Colorectal Cancer: A possible algorithm

CT evidence of resectable disease in patient suitable for surgery

WholeBodyPET imaging

Further evaluation of CT abnormality

Non-surgical management

Surgery

All sites negative

+ ve at multipleSites

PET = CT and other sites negative

44/F with Colon Ca, S/P primary resection.CT: multiple liver mets and a lung nodule

Treated with systemic chemoTx instead of intra-arterial chemoTx.

Staging:

Colorectal Cancer:Clinical Indications for PET Imaging

Detection of Lesions Staging before resection of recurrent disease. Rising CEA in the absence of a known source. Equivocal/residual lesion on conventional imaging. Patient is clinically symptomatic, but CEA is normal.

Monitoring treatment response (pre-op & post-op) Staging before primary resection?

S/P ChemoRx

Before 2mo after Adjuvant chemo and radioTxPrior to surgery for rectal Ca.

Optimal time to scan after treatment??

Uptake may be seen in inflammatory tissue / macrophages.

Residual FDG activity after treatment:Not always active tumor

• 1 month after Chemo.

PET findings at 1 mo ~ CT findings at 3 mosFindlay et al. J Clin Oncol 1996

• Several months after RT?

Lymphoma: Indications for PET Imaging

Dx Staging Monitoring treatment response Recurrence?

Evaluation of early therapeutic response:

Is treatment effective?FDG uptake represents cell viability.

FDG uptake can be markedly decreased or even completely suppressed after 1 or 2 cycles of chemotherapy

Early determination is important: To avoid the toxicity of ineffective therapy. To allow selection of a new therapeutic regimen.

1846641Lymphoma

Before

After2 cylcles ofChemo

Lymphoma

Before

After2 cylcles ofChemo

56y/o : Lymphoma

Before 1 month after XRT

Esophageal/Gastro-esophageal Cancer:

Clinical Indications for PET Imaging

Pre-op stagingMonitoring treatment responseSuspected recurrence Prognostication

Esophageal/ Gastro-esophageal Cancer:Clinical Indications for PET Imaging

Pre-op stagingCT: Limited sensitivityEUS: More accurate for assessing local

invasion and regional nodal mets.

Limitations: stenosis,

celiac,

right hepatic lobe, peritoneum

(Choi et al: J Nucl Med 2000)

Evaluation of N stage of patients with Esophageal Cancer: 48 patients underwent esohagectomy and lymph node dissection (2 field=35pts, 3 field=13pts)

Evaluation of metastases in Esophageal Cancer: CT versus PET

CT PET

Kole 1998 Lymph nodes 62% 90%Resectability 65% 88%

Choi 2000 Lymph nodes 78% 86%N staging 60% 83%

Luketich 1999 Distant mets 63% 84%

Rt. Paratracheal

Subcarinal

Lt. Gastric

Common hepatic& Celiac

Rt. Paratracheal

Subcarinal

Lt. Gastric

Common hepatic& Celiac

62F: Gastric Ca. S/P ResectionCT: RecurrencePET performed to exclude other sites of tumor

Ultrasound: confirmed a liver metsSurgery cancelled and the patient treated with Chemo

Gastro-esophageal Cancer:Clinical Indications for PET

Imaging

Pre-op stagingMonitoring treatment responseSuspected recurrence Prognostication

Before

sagittal coronal

AfterRadiochemo

49M: large squamous esophageal Ca.Echo-endoscopy – an enlarged node

Gastro-esophageal Cancer:Clinical Indications for PET

Imaging

Pre-op stagingMonitoring treatment responseSuspected recurrencePrognostication

45M: S/P esophagectomy, Patient is clinically asymptomatic alkaline phosphatase

Gastro-esophageal Cancer:Clinical Indications for PET

Imaging

Pre-op stagingMonitoring treatment responseSuspected recurrencePrognostication

Surviavl based on initial PET scan identification of distant versus local disease only: (Luketich et al: Ann Thorac Surg 1999;68)

Pancreatic Cancer:Potential Indications for PET Imaging

DDx: Chronic pancreatic mass vs. Cancer Staging: Nodal mets and liver mets. Monitoring treatment response Prognostication

53/F: Pancreatic mass

51F: CT: (1) Mass forming pancreatitis vs Cancer (2) Hepatic Hemangioma vs Metastasis

Coronal Sagittal

Pancreatic Cancer:DDx: Chronic pancreatic mass vs. Cancer

Delbeke et al: J Nucl Med 1999

Brain Tumor

Grading Prognosis/Survival.Necrosis or Residual disease after

radiation therapy?

High Grade

Low Grade

Kim CK et al. J Neuro-Oncol 1991

Thyroid Cancer Thyroglobulin (+)

Iodine-131 scan (-)

FDG PET scan is useful.

IV

ML

FDG-PET I-131

Anterior Posterior

M

2 Coronal slices

62 y/o male S/P Resection of transglottic right laryngeal cancerR/O Recurrence

FDG PET Imaging

Determination of the site of unknown primary tumor

20~30%

Prediction of tumor response to treatment:

Will the tumor respond to treatment?

Labeled Estrogen [F-18] 5-Fluorouracil (5-FU)

FDG-PET Tumor Imaging

DDx: Is the lesion benign or malignant? Staging:

Re-staging: Evaluation of early therapeutic response: Scar/Necrosis vs recurrent/residual disease after surgery.

Scar/Necrosis vs recurrent/residual disease after XRT. Histologic grading / Prognosis.

Detection of unknown primary.

Summary: PET

• Safe.• Shows all the organ systems of the body with one image.• Decreases the number of diagnostic (imaging) procedures.• Diagnoses disease often before it shows up on other tests.• Shows the progress of disease and how the body responds

to treatment.• Reduces or eliminates ineffective or unnecessary surgical

or medical treatments and hospitalization.• Significantly reduces multiple medical costs and avoids

needless pain to the patient.

The influence of blood glucose levels

on 18FDG uptake in cancer(Crippa et al. Tumori 1997:83:748-752)

8 patients - 20 liver metastases on CT• PET 1: Fasting (92.4±10.2)

All 20 were (+) on PET.

• PET 2: Glucose infusion (158±13.8)6/20 undetected, and 10 lesions localized less clearly.

• 70-years-old female smoker • CT showed Rt mid lung mass and inhomogeneity

throughout the liver

Coronal Sagittal

55 y/o womanDx’ed with colon ca.S/P resection 2 yrs agoCEA level is risingNo evidence of recurrence. CT: normal.