An Overview of Molecular Imaging

byDr Lohith T GMMST 2nd year

Indian Institute of TechnologyKharagpur

Central Dogma of life

Transcription

Translation

• 1953: Watson-Crick DNA model

• 1976: Genentech

• 1997: Dolly

• 2000: Book of Life

• 1972: Computerized Tomography

• 1975: Clinical PET

• 1978: Clinical MRI

• 2000: Fusion Imaging

Genetic Revolution Imaging Revolution

Dr Harvey Herschman Dr Sanjiv Sam Gambhir

“There’s always something unsatisfactory about studying genes in vitro”

Molecular Imaging Pioneers

Molecular ImagingRemote sensing of Cellular processes at molecular level in-vivo without affecting system.

APPLICATIONS:

Early detection of functional abnormalities at Cellular level.

In-vivo imaging of Gene delivery and expression.

Study of pathogenesis of diseases in intact microenvironments of living systems.

Oncology- Angiogenesis, Apoptosis, Cell tracking etc.

Monitor effectiveness of Gene therapy.

We are curious how we, other people, We are curious how we, other people, animals, etc, look inside…...animals, etc, look inside…...

… … but we don’t like to (be) hurt !but we don’t like to (be) hurt !

We are also curious We are also curious how organs...how organs...

……..are ..are functioningfunctioning

in vivoin vivo

Major Approaches: PET, Gamma scintigraphy

Magnetic Resonance Imaging

Magnetic Resonance Spectroscopy

Optical Imaging

Key Elements: Use of special Imaging Probes with high specificity

Signal Amplification strategies

Sensitive Imaging modalities with high resolution

Mechanisms for molecular imaging at the organ, tissue, cellular, and genetic levels.

Use of PET

Emission Tomography

High sensitivity (nano to picomolar range)

10,000 targets per cell

F-18, O-15, C-11, N-13, Cu-64, I-124

Poor spatial and Temporal resolution

Low Dosage

What area in the brain is responsible for a task?

PET and SPECT imaging enables mapping of of radio-labeled molecule distributions

Molecular imaging of MDR1 Pgp transport activity in vivo.

MDR1Pgp – Multi drug Resistant membrane receptor P-glycoprotien

PSC 833 – Pgp blocking agent (MDR modulator)

Use of MRI

Magnetic field and radiofrequency pulses

Low sensitivity (milli to micromolar range)

Requires amplification mechanisms

Good spatial and Temporal resolution

Standard Imaging (1.5T) gives 1 mm resolution

Three-dimensional T1-weighted gradient-echo MR imaging reconstruction (repetition time, 150 msec; echo time, 3.6 msec;flip angle, 34°; voxel size, 39 3 39 3 78 µm) shows tracking ofimmune cells with magnetically labeled lymphocytes homed to ahuman glioblastoma tumor (9L tumor model) xenograft in a mouse.Cell were labeled ex vivo by using a magnetic particle with membranetranslocation signals. Approximately 10,000 cells are distributedthroughout the elongated tumor

Optical Techniques

Optical coherence tomography

Fluorescence or Luminescence imaging

Infrared Imaging

Reporter probes

Luciferase tagged cells

Green fluorescent protein (GFP) encoding cDNA

Protease-activatable probes

Optical imaging with proteolytically (cathepsin B and H) activatable near-infrared fluorescent (NIRF) probe.