Metabolic imaging techniques, such as positron emission tomography (PET), hold particular promise for diagnostic imaging of neoplasms. The central hypothesis of this project is that F-18 labeled choline analogs may serve as useful probes for PET imaging of cancer because they are good tracers of choline transport and phosphorylation are upregulated in cancer cells. We also believe their oxidative metabolism to betaine derivatives is very low, resulting in a simplification of their in-vivo kinetics. Preliminary work with C-11 and F-18 labeled choline analogs have shown promising utility in patients with prostate and breast cancer, brain tumors, and pulmonary nodules. The proposed work seeks to clarify the mechanisms that determine the disposition of the F-18 choline radiotracers in normal and malignant tissues, and compare the biochemical properties of three leading F-18 labeled choline tracer candidates: fluoromethylcholine (FCH), fluoroethylcholine (FECH), and fluoromethylallylcholine (FMAC). The work should provide a stronger basis for interpreting PET imaging studies of cancer with radiolabeled choline analogs and provide useful data for the selection of an optimal radiotracer for further development as a clinical imaging agent. The proposed research has the three specific aims: 1) to characterize the transport and metabolism of F-18 labeled choline analogs in relationship to C-14 choline in tumor and several normal tissues in 9L glioma-bearing rats, and also by in-vitro studies with recombinant human CK enzyme; 2) to clarify the relationship of tumor uptake of choline analog to tumor perfusion, and choline transport in 9L glioma-bearing rats; and 3) to evaluate the uptake of F-18 choline analogs in 2 animal models of inflammation in comparison with radiolabeled 2-fluoro-2-deoxy-glucose (FDG) and thymidine.
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