title: Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent.
abstract: BACKGROUND
  (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: Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan. kogawa@p.kanazawa-u.ac.jp
authors: Kazuma
authors: K
authors: Ogawa
authors: Kenichiro
authors: K
authors: Takai
authors: Hiroya
authors: H
authors: Kanbara
authors: Tatsuto
authors: T
authors: Kiwada
authors: Yoji
authors: Y
authors: Kitamura
authors: Kazuhiro
authors: K
authors: Shiba
authors: Akira
authors: A
authors: Odani
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D002614:Chelating Agents / Q000737:chemistry; D004164:Diphosphonates / Q000737:chemistry*; D004355:Drug Stability; D017886:Durapatite / Q000378:metabolism; D005710:Gallium Radioisotopes; D006207:Half-Life; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D002614:Chelating Agents; D004164:Diphosphonates; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D017886:Durapatite