Preparation and biological evaluation of 99mTcN‐labeled pteroyl‐lys derivative as a potential folate receptor imaging agent

In order to develop a novel ^99mTc‐labeled folate receptor (FR) imaging agent, a dithiocarbamate derivative, pteroyl‐lys‐DTC, was synthesized and radiolabeled with ^99mTc through the [^99mTcN]²⁺ intermediate. The radiochemical purity of the corresponding ^99mTc‐complex, ^99mTcN‐pteroyl‐lys‐DTC, was over 95% as measured by reversed‐phase HPLC. The ^99mTcN complex was stable under physiological conditions. ^99mTcN‐pteroyl‐lys‐DTC exhibited specific FR binding in FR‐positive KB cells in vitro. The biodistribution in tumor‐bearing mice showed that the ^99mTcN‐labeled radiotracer had good uptake (3.56 ± 0.09%ID/g at 2 h postinjection) in FR‐positive KB tumors, as well as in the kidneys (30.34 ± 3.53%ID/g at 2 h postinjection). After coinjection with excess folic acid, the uptake in tumor and kidneys was significantly blocked. The results indicated that ^99mTcN‐pteroyl‐lys‐DTC was able to target the FR‐positive tumor cells and tissues specifically both in vitro and in vivo. Copyright © 2013 John Wiley & Sons, Ltd.