DRUG-SPECIFIC F-19 NMR AND DYNAMIC F-18 PET IMAGING OF THE CYTOSTATICAGENT 5-FLUOROURACIL

The spatial distribution of the antineoplastic agent 5-fluorouracil (5 -FU) has been mapped both with F-19 NMR and F-18 PET imaging technique s. For F-19 NMR imaging of 5-FU and its major catabolite alpha-fluoro- beta-alanine (FBAL), a fast gradient-echo pulse sequence was employed. A chemical-shift selective saturation pulse was used to suppress eith er the 5-FU or the FBAL resonance before the other component of the F- 19 NMR spectrum was imaged. This approach yielded selective 5-FU and F BAL NMR images free of chemical-shift artifacts in readout and slice-s election direction. In phantom experiments, F-19 5-FU and FBAL images with a spatial resolution of 12.5 X 12.5 X 20 mm(3) were obtained in 3 2 min from model solutions with drug and catabolite concentrations sim ilar to those estimated in animals and patients undergoing i.v. chemot herapy with 5-FU. The PET experiments were carried out using F-18-labe led 5-FU. The biodistribution of 5-[F-18]FU in rats shortly after admi nistration of the drug demonstrated the good vascularization of the tr ansplanted tumors. The metabolic turnover of the cytostatic agent star ted about 10-20 min p.i. and was predominant in the tumor and liver ti ssue. The rapid adjustment of the F-18 metabolite concentrations in th e transplanted tumors to a steady state provides evidence of anabolic tumor activity, which supports the hypothesis of 5-FU trapping in mali gnant cells based on F-19 NMR spectroscopy data. The high uptake of 5- [F-18]FU in the liver, on the other hand, mainly reflects the cataboli zation of 5-FU to the noncytotoxic FBAL, which leads to a reduced bioa vailability of the drug. The chemical-shift selective F-19 NMR techniq ue and the F-18 PET imaging method yield complementary metabolic and k inetic information on 5-FU. They are thus well suited for the noninvas ive observation of the uptake and the turnover of the cytostatic agent in normal and neoplastic tissues.