Core 1

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Core #1 Chemistry Dr. Wei Wang, Ph.D. The Chemistry core functions in the Division of Molecular Imaging and in this NTR consortium to (i) provide the ability to develop new molecularly targeting entities for both nuclear and optical imaging; (ii) develop the validated analytical tools necessary for new agents; and (iii) provide assistance in manufacture. New targeting entities Dr. Wei Wang's expertise and demonstrated innovation is evident in the small animal imaging results presented in Section 5.C.4,5 regarding the c(KRGD) and c(KAHWGFLD) dual labeled imaging agents. The following provides an example of her emerging work with Dr. Charles Brunicardi to develop an optical substrate for imaging vTK gene expression. [18F]-FHBG and other isotope substrates have been used along with several other TK substrates [143-145]. Although [18F]-FHBG is currently approved as an investigational drug for human studies [146], its short half life (2 h) may be responsible for the high background in small animal imaging. For example, in studies to track vTK expressing tumor cells, investigators routinely use subcutaneous tumor implantation on the shoulder of animals. One hour after administration, incomplete clearance prevents distinguishing tumor cells within the trunk of the animal. In addition, isotopically labeled agents are not widely available to the biomedical research community. For this reason, Dr. Wei Wang developed three optical analogs of FHBG depicted in Fig. 43 that are conjugated to NIR dye IR783 that is synthesized in-house. It is noteworthy that the second compound, could be developed as a potential dual labeled PET and optical imaging agent by replacing cold fluorine with 18F.