A.3.II. Molecular Imaging Chemistry Core (MICC)The MICC serves as a crucial interface for various interdisciplinary projects, In addition to ensuringthe timely availability of imaging probes necessary for bioassays proposed by various investigators, thechemistry core also provides a training environment for students and post-doctoral fellows in chelationchemistry, radio-pharmaceutical synthesis, optical probe conjugation and preparation of MR relaxivityagents. The following represent areas of progress in service and discovery research:1) PET and SPECT Radiopharmaceuticals for Molecular Imaging of Reporter Gene Expression.Reporter genes have been used to evaluate promoter or regulatory elements that participate in geneexpression, inducible promoters to analyze the induction of gene expression, and transgenes comprisingendogenous promoters coupled to a reporter to evaluate endogenous gene expression. The WU ICMICsupports many projects that exploit the utility of noninvasive imaging techniques in probing transgene aswell as endogenous gene expression. Radiolabeled compounds and fluorophores constitute many of thesereporter probes and require a steady effort for synthesis, validation and quality control. A variety of projectsuse various mutant HSV1-tk reporter genes and radiolabeled nucleosides as PET reporter probes. TheMICC routinely synthesizes various nucleoside pyrimidine and purine derivatives (e.g., [18F]FHBG).Research Project 4 requires 18F-FHBG for both small animal imaging and the clinical PET imaging trial.The synthesis and validation of several novel nucleosides as reporter substrates remains under activeinvestigation.2) Peptide-Based Radiopharmaceuticals for Imaging and Therapy.Several transduction sequences capable of permeating the plasma membrane of cells and thereby enablingdelivery of biomolecules and various 'cargos' have been synthesized as both single labeled conjugates(99mTc) and as dual labeled conjugates (99mTc and fluorescein). Peptide transduction sequences have beenrecently evaluated for ophthalmic applications as well as novel applications in the imaging and therapy ofpancreatic and brain tumors. These Core activities may lead to novel Tc-99m-based imaging agents foranalysis of brain tumors.3) Peptide-Based Radiopharmaceuticals for Selective Imaging of Cell-Based Targeting.We continue to evaluate the ability of fIuorescent-TAT-permeation peptides conjugated with the antiapoptoticBH4 domain to penetrate lymphocytes for targeted therapy. Preliminary fluorescence experimentsindicate that peptide conjugates effectively penetrate lymphocytes.4) Peptide-Based 'Smart' Probes for Molecular Imaging.Biocompatible, far-red and near-infrared fluorescence (NIRF) imaging probes capable of generating astrong signal upon enzyme activation within intracellular compartments have become increasingly exploitedto evaluate biochemical pathways and in vivo imaging. Using a membrane permeant TAT peptide motif asdelivery vehicle, Alexa Fluor and NIRF probes have now been synthesized which can be activated throughan enzyme-cleavable amino acid sequence. Novel small activatable probes with QSY21-Alexa Fluor 647quenching strategies have recently been synthesized and validated. We continue to co-develop with thelaboratory of Sam Achilefu, Ph.D., new peptide conjugates for ICMIC projects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA094056-07
Application #
7287035
Study Section
Special Emphasis Panel (ZCA1-SRRB-9 (J1))
Project Start
2007-09-28
Project End
2011-12-31
Budget Start
2007-09-28
Budget End
2007-12-31
Support Year
7
Fiscal Year
2007
Total Cost
$201,879
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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