ASSESSMENT OF TUMOR-CELL PROLIFERATION USING [F-18] FLUORODEOXYADENOSINE AND [F-18] FLUOROETHYLURACIL

This study was to develop radiofluorinated ethyluracil (FEU) and deoxy adenosine analogues (FAD) for noninvasive assessment of tumor prolifer ative potential by positron emission tomography (PET). 5-(2-Fluoroethy l)uracil ([F-18]FEU) was prepared by treating 2,4-dimethoxy-5-(2-hydro xyethyl)pyrimidine with (KF)-F-18, followed by hydrolysis with HBr. Fl uorodeoxyadenosine ([F-18]FAD) was prepared by treating a triacetylate d analogue of adenosine with (KF)-F-18. In vitro cell proliferation as say of [F-18]- FEU was performed using human peripheral blood mononucl eus cells. Tissue distributions were studied in breast tumor-bearing r ats at 0.5, 1, 2 and 4 h along with autoradiography at 45 min postinje ction. PET imaging studies were conducted in VX-2 tumor-bearing rabbit s. In vitro assay indicated that [F-18]FEU incorporated into DNA/RNA d uring cell proliferation. Tumor-to-tissue count density ratios of [F-1 8]FAD and [F-18]. FEU increased as a function of time. [F-18]FAD had h igher tumor-to-nontumor tissue count density ratios than [F-18]FEU. Au toradiograms of [F-18]FEU and [F-18]FAD, and PET images of [F-18]FEU, showed that the tumors could be well visualized. The results suggest t hat [F-18]FEU and [F-18]FAD have potential use in evaluating tumor cel l proliferation by PET.