This application proposes to develop techniques to synthesize new radiopharmaceuticals labeled with the positron emitting radionuclides carbon-11, copper-60, and fluorine-18. Four sub-projects are proposed and include: 1) the synthesis of palmitic acid labeled in the carboxyl, omega and omega-1 positions, which will be evaluated in a transgenic mouse model to determine their efficacy in understanding genetic metabolic defects in cardiac disease; 2) the labeling of the copper-ATSM complex with copper-60 for use as a hypoxic tissue tracer in anima models of ischemic myocardium and human use approval will be obtained to conduct an initial patient study; 3) the radiolabeling of inhibitors of the inducible isoform of the enzyme nitric oxide synthase which is known to be upregulated in allograft rejection, and studies will be carried out in order t obtain human use approval for the most promising of these agents in patients with lung transplants experiencing episodes of rejection; and 4) the evaluatio of the potential efficacy of the synthon C-11-methylhypofluorite, which has potential for the preparation of C-11-methoxy-labeled radiopharmaceuticals. In addition, new approaches for radiolabeling of model peptides with fluorine-18 are proposed. The overall goal of this application is to develop and evaluate new PET radiopharmaceuticals that have potential for evaluating diseases of th heart, lung, and vasculature.
