Drug-specific /sup 19/F NMR and dynamic /sup 18/F PET imaging of the cytostatic agent 5-fluorouracil

The spatial distribution of the antineoplastic agent 5-fluorouracil (5-FU) has been mapped both with /sup 19/F NMR and /sup 18/F PET imaging techniques. For /sup 19/F NMR imaging of 5-FU and its major catabolite /spl alpha/-fluoro-/spl beta/-alanine (FBAL), a fast gradient-echo pulse sequence was employed. A chemical-shift selective saturation pulse was used to suppress either the 5-FU or the FBAL resonance before the other component of the /sup 19/F NMR spectrum was imaged. This approach yielded selective 5-FU and FBAL NMR images free of chemical-shift artifacts in readout and slice-selection direction. In phantom experiments, /sup 19/F 5-FU and FBAL images with a spatial resolution of 12.5/spl times/12.5/spl times/20 mm/sup 3/ were obtained in 32 min from model solutions, with drug and catabolite concentrations similar to those estimated in animals and patients undergoing i.v. chemotherapy with 5-FU. The PET experiments were carried out using /sup 18/F-labeled 5-FU. The biodistribution of 5-[/sup 18/F]FU in rats shortly after administration of the drug demonstrated the good vascularization of the transplanted tumors. The metabolic turnover of the cytostatic agent started about 10-20 min p.i. and was predominant in the tumor and liver tissue. The rapid adjustment of the /sup 18/F metabolite concentrations in the transplanted tumors to a steady state provides evidence of anabolic tumor activity, which supports the hypothesis of 5-FU trapping in malignant cells based on /sup 19/F NMR spectroscopy data. The high uptake of 5-[/sup 18/F]FU in the liver, on the other hand, mainly reflects the catabolization of 5-FU to the noncytotoxic FBAL, which leads to a reduced bioavailability of the drug. The chemical-shift selective /sup 19/F NMR technique and the /sup 18/F PET imaging method yield complementary metabolic and kinetic information on 5-FU. They are thus well suited for the noninvasive observation of the uptake and the turnover of the cytostatic agent in normal and ne- - oplastic tissues.<>