Molecular Imaging by liaoqinmei


									 An Overview of
Molecular Imaging
        Dr Lohith T G
        MMST 2nd year
Indian Institute of Technology
Central Dogma of life


Genetic Revolution      Imaging Revolution

• 1953: Watson-        • 1972: Computerized
  Crick DNA model        Tomography
• 1976: Genentech      • 1975: Clinical PET
• 1997: Dolly          • 1978: Clinical MRI
• 2000: Book of Life   • 2000: Fusion Imaging
Molecular Imaging Pioneers

Dr Harvey Herschman       Dr Sanjiv Sam Gambhir

“There’s always something unsatisfactory about
studying genes in vitro”
         Molecular Imaging
Remote sensing of Cellular processes at molecular
level in-vivo without affecting system.

  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
  Monitor effectiveness of Gene therapy.
We are curious how we, other people,
    animals, etc, look inside…...

      … but we don’t like to (be) hurt !
We are also curious
  how organs...

                      …..are functioning
                            in 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
   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
 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 of
immune cells with magnetically labeled lymphocytes homed to a
human glioblastoma tumor (9L tumor model) xenograft in a mouse.
Cell were labeled ex vivo by using a magnetic particle with membrane
translocation signals. Approximately 10,000 cells are distributed
throughout 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.

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