Tumor uptake studies of D,L-[5-14C]ornithine and D,L-2-difluoromethyl [5-14C]ornithine

Abstract

The feasibility of D,L-[5-14C]ornithine ([14C]ornithine), a precursor for polyamine synthesis, and D,L-2-difluoromethyl[5-14C]ornithine ([14C]DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) were investigated for tumor localization. As an animal model, mice bearing mammary carcinoma, FM3A, were used. After i.v. injection of [14C]ornithine accumulation of radioactivity was observed in the FM3A, in which 43% of the 14C radioactivity was measured in the polyamine pool and 41% in the amino acid pool at 60 min after injection. Tumor uptake of [14C]DFMO was relatively low but constant during 60 min after injection. At 60 min after injection, 11% of the 14C was present in the acid-precipitable fraction of the FM3A, which suggests the formation of an irreversible complex of [14C]DFMO with ODC. For both compounds rapid blood clearance and high tumor-to-organ ratios were observed. Our results indicate that in connection with an enhanced polyamine synthesis in the tumors, the compounds investigated have potential as tracers for tumor detection.