Preparation and biological evaluation of (99m) TcN-labeled pteroyl-lys derivative as a potential folate receptor imaging agent.
In order to develop a novel (99m) Tc-labeled folate receptor (FR) imaging agent, a dithiocarbamate derivative, pteroyl-lys-DTC, was synthesized and radiolabeled with (99m) Tc through the [(99m) TcN](2+) intermediate. The radiochemical purity of the corresponding (99m) Tc-complex, (99m) TcN-pteroyl-lys-DTC, was over 95% as measured by reversed-phase HPLC. The (99m) TcN complex was stable under physiological conditions. (99m) TcN-pteroyl-lys-DTC exhibited specific FR binding in FR-positive KB cells in vitro. The biodistribution in tumor-bearing mice showed that the (99m) TcN-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 (99m) TcN-pteroyl-lys-DTC was able to target the FR-positive tumor cells and tissues specifically both in vitro and in vivo.
Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education; College of Chemistry, Beijing Normal University, Beijing, 100875, China.
Yuan
Y
Chen
Hongjuan
H
Guo
Fang
F
Xie
Jie
J
Lu
D000818:Animals; D001692:Biological Transport; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D058972:Folic Acid Transporters / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D007624:KB Cells; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011854:Radiochemistry; D013859:Thiocarbamates / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
D002219:Carbamates; D058972:Folic Acid Transporters; D015609:Organotechnetium Compounds; D013859:Thiocarbamates; C000592137:technetium 99m pteroyl-lysine-dithiocarbamate
99mTc-nitrido complex; folate receptor; pteroyl-lys; tumor uptake