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.