INTRODUCTION: (68)Ga is a radionuclide of great interest as a positron emitter for positron emission tomography (PET). To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing (68)Ga-labeled bone imaging agents for PET, in these initial studies (67)Ga was used because of its longer half-life. METHODS: DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). (67)Ga-DOTA-Bn-SCN-HBP was prepared by coordination with (67)Ga, and its in vitro and in vivo evaluations were performed. RESULTS: (67)Ga-DOTA-Bn-SCN-HBP was prepared with a radiochemical purity of over 95% without purification. (67)Ga-DOTA-Bn-SCN-HBP had great affinity for hydroxyapatite in binding assay. In biodistribution experiments, (67)Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly observed in tissues other than bone. Pretreatment of an excess amount of alendronate inhibited the bone accumulation of (67)Ga-DOTA-Bn-SCN-HBP. CONCLUSIONS: (67)Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics as a bone-imaging agent. These findings should provide useful information on the drug design of bone imaging agents for PET with (68)Ga.
INTRODUCTION: (68)Ga is a radionuclide of great interest as a positron emitter for positron emission tomography (PET). To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing (68)Ga-labeled bone imaging agents for PET, in these initial studies (67)Ga was used because of its longer half-life. METHODS:DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). (67)Ga-DOTA-Bn-SCN-HBP was prepared by coordination with (67)Ga, and its in vitro and in vivo evaluations were performed. RESULTS: (67)Ga-DOTA-Bn-SCN-HBP was prepared with a radiochemical purity of over 95% without purification. (67)Ga-DOTA-Bn-SCN-HBP had great affinity for hydroxyapatite in binding assay. In biodistribution experiments, (67)Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly observed in tissues other than bone. Pretreatment of an excess amount of alendronate inhibited the bone accumulation of (67)Ga-DOTA-Bn-SCN-HBP. CONCLUSIONS: (67)Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics as a bone-imaging agent. These findings should provide useful information on the drug design of bone imaging agents for PET with (68)Ga.
Authors: Robert K Doot; Anthony J Young; Margaret E Daube-Witherspoon; David Alexoff; Kyle J Labban; Hwan Lee; Zehui Wu; Zhihao Zha; Seok R Choi; Karl H Ploessl; Erin K Schubert; Hsiaoju Lee; Lin Zhu; Janet S Reddin; Joel S Karp; Hank Kung; Daniel A Pryma Journal: Nucl Med Biol Date: 2020-04-20 Impact factor: 2.408
Authors: Bradley J Ahrens; Lin Li; Alexandra K Ciminera; Junie Chea; Erasmus Poku; James R Bading; Michael R Weist; Marcia M Miller; David M Colcher; John E Shively Journal: J Nucl Med Date: 2017-04-27 Impact factor: 10.057