Preparation and in-vivo evaluation of (188)Re(CO)(3)-colchicine complex for use as tumor-targeting agent.

The Re(I)-tricarbonyl synthon, [(188)Re(H(2)O)(3)(CO)(3)](+), was prepared by using carbon monoxide gas and amine-borane as the reducing agent. Colchicine, a naturally occurring cytotoxic alkaloid, was derivatized to iminodiacetic acid, the required array for the tridentate ligand system for coordination to the Re(I)-tricarbonyl core. (188)Re(CO)(3)-colchicine iminodiacetic acid (IDA) complex could be prepared in >95% radiochemical purity, as determined by high-performance liquid chromatography. The chemical characterization of (188)Re(CO)(3)-colchicine-IDA complex has been carried out by preparing the corresponding cold Re(CO)(3)-complex. The radiolabeled complex was stable at room temperature, even after 48 hours postpreparation, as well as against histidine and cysteine ligand exchange studies. Biodistribution studies were carried out in the murine fibrosarcoma tumor model. Tumor uptake of 1.7 +/- 0.03 percent injected dose per g (%ID/g) was observed at 3 hours postinjection (h.p.i.), which increased to 4.1 +/- 1.3 %ID/g at 24 h.p.i. Tumor-blood and tumor-muscle ratios were 0.14 and 1 at 1 h.p.i. that increased to 0.95 and 4 at 24 h.p.i., respectively. Retention of the complex in tumor for more than one half-life of (188)Re(t(1/2) = 17 hours) indicates its potentiality for tumor therapy.