Synthesis and biological evaluation of 99mTc(CO)3(IDA-CPT) for tumor imaging

This work reports the synthesis, radiolabeling, and preliminary biodistribution results in tumor-bearing mice of Tc-99m(CO)(3)(IDA-CPT). The novel camptothecin (CPT) derivate was successfully synthesized by conjugation of iminodiacetic acid (IDA) to camptothecin via a short carbonyl-methylene linker. Radiolabeling was performed in high yield with [Tc-99m(CO)(3)](+) core to get Tc-99m(CO)(3)(IDA-CPT), which was hydrophilic and stable at room temperature. Biodistribution studies in tumor-bearing mice showed that Tc-99m(CO)(3)(IDA-CPT) accumulated in the tumor with good uptake and retention. However, its clearance from normal organs was slow, resulting in poor T/NT ratios. Further modification on the linker or/and Tc-99m-chelate to improve the tumor-targeting efficacy and in vivo kinetic profiles is currently in progress.