title: Novel 99mTc radiolabeled quinazolinone derivative [Qn-In]: synthesis, evaluation and biodistribution studies in mice and rabbit.
abstract: 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 (99m)Tc was greater than 98% and the complex was stable for about 7 hours at 37 degrees 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 (99m)Tc 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 (99m)Tc 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.
authors.affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Kumari
authors.forename: Neetu
authors.initials: N
authors.lastname: Kalra
authors.forename: Pushpa
authors.initials: P
authors.lastname: Mishra
authors.forename: Krishna
authors.initials: K
authors.lastname: Chutani
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
authors.forename: Madhu
authors.initials: M
authors.lastname: Chopra
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D006835:Hydrazones / Q000737:chemistry / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011799:Quinazolines / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D043887:Receptor, Cholecystokinin B / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D006835:Hydrazones; D011799:Quinazolines; D019275:Radiopharmaceuticals; D043887:Receptor, Cholecystokinin B; C501652:technetium 99m 3-(4-methylphenyl)-2-(2-(2-oxo-2,3-dihydro-1H-indol-3-yl)hydrazino)quinazol-4(3H)-one