Evaluation of methionine and tryptophan derivatised vehicles: Met-ac-TE3A/Trp-ac-TE3A for tumor imaging

Abstract

Two novel amino acid (methionine and tryptophan) appended 1,4,8,11-tetraazacyclotetradecane triacetate (TE3A) compounds Met-ac-TE3A and Trp-ac-TE3A were synthesized and evaluated for imaging applications. The pharmacokinetics of these compounds was analyzed by ^99mTc labeled tracer methods. In vitro human serum stability of ^99mTc labeled Met-ac-TE3A/Trp-ac-TE3A was found to be 96.5% and 96.0% after 24 h respectively. Blood kinetics of both the labeled probes on normal rabbits showed biphasic clearance. The tumor (EAT cell line) grafted in balb/c mice were readily identifiable in the gamma images. Biodistribution revealed significant tumor uptake and good contrast in the EAT tumor bearing mice and also showed high tumor/muscles ratio which is a requisite condition to work as SPECT-radiopharmaceutical for tumor imaging. To look its future applicability for therapy using M⁺² and M⁺³ metal ions, we performed thermodynamic stability constants of complexes derived from Met-ac-TE3A and Trp-ac-TE3A with Cu^II and Ln^III metal ions.