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Molecular Imaging “101” Martin G. Pomper, MD, PhD Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University The Role of Molecular Imaging in Cancer Briefing and Roundtable Washington, DC July 22, 2008 The evolution of diagnostic imaging PAST PRESENT Anatomic Functional Hybrid plain films, CT, MRI, US angiography, doppler US, NM, MRI, PET PET/CT, SPECT/CT, PET/MR “FUTURE” Molecular NM, PET, SPECT, MRS, optical, PET/MRI contrast-enhanced MRI/US/CT What is molecular imaging? “Viewing” the Body’s Biological Processes Uses imaging technologies to assess biological activity in the body Shows what cells are doing and how they are functioning over time Different than x-rays or CT scans that show anatomical pictures of the body’s organs and tissues Changes in physiology and biochemistry occur prior to changes in anatomy Why is molecular imaging important? Enables early detection and/or identification of changes occurring in tissue Enables changes in individual patient management in real time (personalized medicine) Facilitates drug development Allows researchers to explore new ways to manage and treat illnesses Serves as a noninvasive diagnostic and monitoring tool Molecular imaging modalities Sensitivity Modality Agents H R Primary uses Examples FMT fluorescent proteins x X gene expression, tagging superficial structures GFP, RFP, NIRF probes BLI luciferin X gene expression, therapeutic monitoring fLuc rLuc X site-selectivity, protein labeling 99mTc-annex Optical pM Nuclear SPECT nM 99mTc, 123/5I, 111In X in V, 123I- A85380 PET 11C, 18F, 124I, X X 64/62/60Cu site-selectivity, gene expression, drug development 11C-RAC, 124I-FIAU, 64Cu-ATSM MRI M spectroscopy endogenous metabolites X X CNS, prostate , heart , breast NAA, Cr, Cho, Glx, mI, 31P contrast agents Gd, Mn, FeO x X cell trafficking, enzymatic activation poly-L-lysine, dendrimers, MION X drug-delivery, gene transfection human albumin (Optison) Ultrasound one bubble contrast agents perfluorinated microbubbles H=human, R=rodent Molecular imaging modalities MR Spectroscopy PET/CT Optical Imaging SPECT/CT Targeted ultrasound Positron emission tomography: PET 18FDG 511 kev+ -o 180 511 kev Radiotracer PET-CT image How is molecular imaging relevant to cancer patient care? metastasis Imaging cellular and molecular phenomena in vivo malignant M. Harisinghani Patient selection by genotype D. Artemov Diagnostic and therapeutic agents combine as “theranostics” S. Gambhir Molecular imaging and cancer Optical: Activatable fluorescence for intestinal adenoma MR: Amide proton transfer imaging to assess brain tumor characteristics U. Mahmood Nuclear: PSMA imaging for prostate cancer Nuclear: [18F]FHBG for tracking T cells J. Babich S. Gambhir P. Van Zijl What is the state of molecular imaging now? ~90 % of clinical molecular imaging is PET and SPECT Optical, other modalities on the horizon Nanoparticles, bacteria, new probes used to image critical cancer processes (cell death, tumor proliferation, angiogenesis, hypoxia) on the horizon Reporter-probe pairs are being generated for molecular-genetic imaging