An Overview of Molecular Imaging by Dr Lohith T G MMST 2nd year Indian Institute of Technology Kharagpur Central Dogma of life Transcription Translation 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. 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, 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 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 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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