title: Development of a conjugate of (99m)Tc-EC with aminomethylenediphosphonate in the search for a bone tracer with fast clearance from soft tissue.
abstract: For the currently used (99m)Tc-labeled diphosphonates such as (99m)Tc-MDP and (99m)Tc-HDP, the required interval of 2.5 to 3 h between injection and the scintigraphic bone imaging is an inconvenience. The present study was set up in an attempt to develop a technetium-99m-labeled diphosphonate with efficient bone uptake and more rapid clearance from blood and soft tissue by renal extraction and excretion so that it would be possible to start imaging as early as 1 h after injection. A conjugate of the new renal tracer agent (99m)Tc-ethylene dicysteine ((99m)Tc-L,L-EC), covalently bound via one of its carboxylates with aminomethylenediphosphonic acid (AMDP), was synthesized in seven steps. EC-AMDP could be labeled easily and efficiently with (99m)Tc at pH > or = 12 and room temperature. Analysis using ion pair reversed phase high performance liquid chromatography showed the formation of a mixture of two main compounds with reproducible relative ratios, which were stable as a function of time. In a baboon, the scintigraphic images obtained with the new agent showed good quality bone scans, with clear visualization of the skeleton and low soft tissue activity at respectively 1 and 2 h after injection.
authors.affiliation: Laboratory of Radiopharmaceutical Chemistry, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, and Rega Institute for Medical Research, University of Leuven, Belgium.
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.forename: Jef
authors.initials: J
authors.lastname: Rozenski
authors.forename: Bernard
authors.initials: B
authors.lastname: Cleynhens
authors.forename: Hubert
authors.initials: H
authors.lastname: Vanbilloen
authors.forename: Tjibbe
authors.initials: T
authors.lastname: de Groot
authors.forename: Nancy
authors.initials: N
authors.lastname: Weyns
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging*; D002855:Chromatography, Thin Layer; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry*; D004164:Diphosphonates / Q000737:chemistry*; D004285:Dogs; D005269:Femur / Q000000981:diagnostic imaging; D007202:Indicators and Reagents; D007553:Isotope Labeling; D015609:Organotechnetium Compounds / Q000737:chemistry*; D010215:Papio; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: D004164:Diphosphonates; D007202:Indicators and Reagents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C073806:technetium Tc 99m-ethylenedicysteine; D003545:Cysteine