99mTc labeled macrocyclic aza-oxa and aza-thia probes: synthesis, characterization and in vitro & in vivo biological studies

Abstract

Macrocyclic chelating agents 1-oxa-4,7,10-triazacyclopentadecane-3,11-dione (OTDD) and 1-thia-4,7, 10-triazacyclododecane-3,11-dione (TTDD) have been synthesized and labeled with radionuclide (99mTc), with radiolabeling efficiency 97.6 and 98.4 % respectively. The radiochemical purity of labeled complex (99mTc-OTDD and 99mTc-TTDD) was determined 97.5 and 98.1 %, respectively. The in vitro stability of the labeled chelates in human serum exhibited only <8 % dissociation upto 24 h. The in vivo distribution pattern of the labeled chelators in BALB/c mice suggested that major route of excretion in 99mTc-TTDD is hepatobilliary and minor is renal, while in case of 99mTc-OTDD hepatobilliary as well as renal both comparable. The in vivo blood kinetic studies of radio-complexes of 99mTc-OTDD and 99mTc-TTDD showed 99.26 and 99.4 % blood clearance over 24 h post injection. The biological half-life of 99mTc-OTDD and 99mTc-TTDD with t1/2(F) 1 h 10 min, t1/2(S) 18 h 50 min and t1/2(F) 1 h 42 min, t1/2(S) 18 h 20 min respectively. In vitro cytotoxicity study of OTDD and TTDD did not exhibit any significant antiproliferative property against cancer cells of human glioblastoma U-87, U373 and cervical SW756, HeLa cell lines.