Synthesis of [Tc-99m]ethylenedicysteine-colchicine for evaluation of antiangiogenic effect

Angiogenesis is in part responsible for tumor growth and the development of metastasis. Radiolabeled angiongenesis inhibitors would be useful to asses s tumor microvasculature density, Colchicine (COL), a potent antiangiogenic agent, is known to inhibit microtubule polymerization and cell arrest at m etaphase. This study aimed to develop Tc-99m-labeled COL (EC-COL) using eth ylenedicysteine (EC) as a chelator to assess tumor microvascular density, E C was conjugated to trimethylcolchicinic acid using N-hydroxysuccinimide an d 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling agents with a yiel d of 50-60%, In vivo stability was analyzed in rabbit serum at 0.5-4 h. Tis sue distribution and planar imaging studies of [Tc-99m]EC-COL were evaluate d in breast tumor-bearing rats at 0.5, 2 and 4 h. The data was compared to that using [Tc-99m]EC (control). The radiochemical yield of [Tc-99m]EC-COL was greater than 95%, [Tc-99m]EC-COL was stable in rabbit serum, In vivo bi odistribution of [Tc-99m]EC-COL in breast tumor-bearing rats showed increas ed tumor-to-blood (0.52+/-0.12 to 0.72+/-0.07) and tumor-to-muscle (3.47+/- 0.40 to 7.97+/-0.93) ratios as a function of time. Conversely, tumor-to-blo od values showed a time-dependent decrease with [Tc-99m]EC over the same ti me period, Planar images confirmed that the tumors could be visualized clea rly with [Tc-99m]EC-COL from 0.5 to 4 h, [Tc-99m]EC-COL may be useful to as sess antiangiogenic and therapeutic effects during chemotherapy, [(C) 1999 Lippincott Williams & Wilkins.].