title: Synthesis of 99mTc-DOTMP and its preclinical evaluation as a multidentate imaging agent for skeletal metastases.
abstract: The convenient synthetic methodology and in vivo stability of the bone-seeking gamma-radiation-emitting compound, (99m)Tc-DOTMP are described in this paper. The radiolabeling efficiency was found to be >97%, and the stability in serum indicated that (99m)Tc remained bound to the chelate, DOTMP, for up to 24 hours. Blood clearance showed a quick washout from the circulation, and biologic half-life was found to be t(1/2)(F) = 25 min; t(1/2)(S) = 6 hours 5 minutes. The LD(50) was found to be 70 mg/kg, as determined by toxicity studies in BALB/c mice. Biodistribution characteristics of (99m)Tc-DOTMP were examined in BALB/c mice. The drug was excreted mainly through renal routes and the accumulation of (99m)Tc-DOTMP in bone was 9.06 +/- 0.75 percent injected dose per gram at 1 hour. Visual image analysis of (99m)Tc-DOTMP was clinically comparable to the interpretation of imaging studies with conventional (99m)Tc-MDP and other phosphonate derivatives. (99m)Tc-DOTMP injected into Balb/c mice showed prominent bone localization and rapid clearance from blood and other organs, thereby making it a promising candidate as a diagnostic pharmaceutical of bone metastases.
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Anupama
authors.initials: A
authors.lastname: Datta
authors.forename: Puja
authors.initials: P
authors.lastname: Panwar
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D002614:Chelating Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D011877:Radionuclide Imaging / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013667:Technetium / Q000737:chemistry* / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C082084:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid); D013667:Technetium