Novel Tcradiolabeled quinazolinone derivative [Qn-In]: synthesis, evaluation and biodistribution studies in mice and rabbit

A quinazolinone derivative as a novel non-peptidic CCK-B receptor antagonist designated as Qn-In, was synthesized, characterized by spectroscopic techniques and evaluated for radiopharmaceutical potential. The efficiency of labeling with ^99mTc was greater than 98% and the complex was stable for about 7 hours at 37°C in presence of serum. Affinity of Qn-In was determined to be in nanomolar range by competitive binding studies on cancer cell line MDA-MB-468. Bio-distribution of ^99mTc labeled Qn-In in mice was examined by intravenous administration and time-activity curves were generated. The ligand showed binding to most of the organs, known to express CCK-B receptor. The lack of uptake in brain may be due to the inability of the complex to cross the blood-brain barrier. Our results show that ^99mTc labeled Qn-In ligand provides a new template for further development of non-peptidic ligands for diagnosis and therapy of diseases related with CCK-B receptor.