Ishiwata K, Abe Y, Matsuzawa T, Ido T
Division of Radioisotope Research, Tohoku University, Sendai, Japan.
Int J Rad Appl Instrum B. 1988;15(2):119-22. doi: 10.1016/0883-2897(88)90076-1.
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.
对多胺合成前体D,L-[5-¹⁴C]鸟氨酸（[¹⁴C]鸟氨酸）和鸟氨酸脱羧酶（ODC）的不可逆抑制剂D,L-2-二氟甲基[5-¹⁴C]鸟氨酸（[¹⁴C]DFMO）用于肿瘤定位的可行性进行了研究。以携带乳腺癌FM3A的小鼠作为动物模型。静脉注射[¹⁴C]鸟氨酸后，在FM3A中观察到放射性积累，注射后60分钟时，¹⁴C放射性的43%在多胺池中测得，41%在氨基酸池中测得。[¹⁴C]DFMO的肿瘤摄取相对较低，但在注射后60分钟内保持恒定。注射后60分钟时，¹⁴C的11%存在于FM3A的酸沉淀部分，这表明[¹⁴C]DFMO与ODC形成了不可逆复合物。对于这两种化合物，均观察到快速的血液清除率和高肿瘤与器官比值。我们的结果表明，鉴于肿瘤中多胺合成增强，所研究的化合物有潜力作为肿瘤检测的示踪剂。
