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

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 57; no. 1; pp. 12 - 17
• Main Authors: Chen, Yuan, Guo, Hongjuan, Xie, Fang, Lu, Jie
• Format: Journal Article
• Language: English; French; German
• Published: Bognor Regis Blackwell Publishing Ltd 01.01.2014; Wiley Subscription Services, Inc
• Subjects: 99mTc-nitrido complex; folate receptor; pteroyl-lys; tumor uptake
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3116

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. In order to develop a novel 99mTc‐labeled FR imaging agent, a dithiocarbamate derivative, pteroyl‐lys‐DTC, was synthesized and radiolabeled with 99mTc through the [99mTcN]2+ intermediate in high yield. The 99mTcN complex was stable under physiological conditions. The results of biological evaluation indicated that 99mTcN‐pteroyl‐lys‐DTC was able to target the FR‐positive tumor cells and tissues specifically both in vitro and in vivo.