title: Synthesis, characterization and pre-clinical evaluation of (99m) Tc-tricarbonyl complexes as potential myocardial perfusion imaging agents.
abstract: Myocardial perfusion imaging is an established Nuclear Medicine investigation. Current myocardial perfusion imaging agents sestamibi and tetrofosmin have number of drawbacks; low heart uptake coupled with uptake into the surrounding tissues leads to a poorer image quality. There is a need for continued research into designing and evaluating potentially superior myocardial imaging agents. Tri-carbonyl-technetium and rhenium complexes were prepared by combination with mono-dentate and bi-dentate ligands. Complexes were characterized by HPLC, MAS, nuclear magnetic resonance, infrared, single-crystal X-ray diffraction and partition coefficient determinations. (99m) Tc(CO)3 complexes were administered intravenously to Sprague Dawley rats, and tissue distribution studies were carried out at 15 min and 1 h p.i. Radiochemical purity was assessed as >90%. 1-10-phenanthroline, 2,2'-bipyridine and imidazole complexes gave the highest heart uptake. The percentage injected dose per gram (n = 3) at 1 h for 1-10-phenanthroline/imidazole was blood 0.21 ± 0.01, heart 1.12 ± 0.11, kidney 3.61 ± 1.13, liver 0.62 ± 0.06, lung 0.28 ± 0.12, spleen 0.24 ± 0.05, small intestine contents 1.87 ± 0.92; and for 2,2'-bipyridine /imidazole was blood 0.23 ± 0.02, heart 1.07 ± 0.18, kidney 3.31 ± 1.28, liver 0.56 ± 0.09, lung 0.14 ± 0.02, spleen 0.2 ± 0.1, small intestine content 1.05 ± 0.48. Further investigation to evaluate more complexes based on 1,10-phenanthroline, 2,2'-bipyridine and imidazole derivatives could potentially lead to agents with an increased heart uptake and faster clearance from the liver and gastrointestinal tract.
authors: Nuclear Medicine Centre, Central Manchester University Hospitals, Oxford Road, Manchester, M13 9WL, UK.
authors: Beverley L
authors: BL
authors: Ellis
authors: Nikolay I
authors: NI
authors: Gorshkov
authors: Alexander A
authors: AA
authors: Lumpov
authors: Alexander E
authors: AE
authors: Miroslavov
authors: Anatoly N
authors: AN
authors: Yalfimov
authors: Vladislav V
authors: VV
authors: Gurzhiy
authors: Dmitrii N
authors: DN
authors: Suglobov
authors: Rattana
authors: R
authors: Braddock
authors: Joanne C
authors: JC
authors: Adams
authors: Anne-Marie
authors: AM
authors: Smith
authors: Mary C
authors: MC
authors: Prescott
authors: Harbans L
authors: HL
authors: Sharma
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000000981:diagnostic imaging; D055414:Myocardial Perfusion Imaging; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012211:Rhenium / Q000737:chemistry / Q000493:pharmacokinetics; D013667:Technetium / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012211:Rhenium; D013667:Technetium
keywords: 99mTc precursor; 99mTc-carbonyl; myocardial perfusion agent; technetium-99m tri-carbonyl