Synthesis and evaluation of a 99mTc-labeled tubulin-binding agent for tumor imaging

Cholchicine and its derivatives are very potent tubulin-binding compounds and can be used as a potential tumor targeting agents. In this study, colchicine was labeled with Tc-99m via hydrazinonicotinic acid (HYNIC) and was investigated further. HYNIC/cholchicine was synthesized and labeling with Tc-99m was performed at 95 C for 15 min and radiochemical analysis included HPLC method. The stability of radiconjugate was checked in the presence of human serum at 37 degrees C up to 24 h. Biodistribution was studied in breast tumor-bearing mice. Labeling yield of 95.8 +/- 0.54% was obtained corresponding to a specific activity of 54 MBq/mu mol. Radioconjugate showed good stability in the presence of human serum. Biodistribution studies in tumor-bearing mice showed that Tc-99m/HYNIC/colchicine conjugate accumulated in tumor with good uptake (3.17 +/- 0.14% g/g at 1 h post-injection). The radioconjugate was cleared fast from normal organs and showed clearance through urinary and hepatobiliary systems with accumulation of activity in kidneys and intestine. This radioconjugate may be useful to assess the presence of tumor by imaging.