title: 188Re(CO)3-dipicolylamine-alendronate: a new bisphosphonate conjugate for the radiotherapy of bone metastases.
abstract: The palliation of pain due to bone metastases using targeted compounds containing beta-emitters such as rhenium-188 ((188)Re) is an accepted and effective form of treatment. Here, we describe the efficient synthesis and preclinical evaluation of (188)Re(CO)(3)-dipicolylamine(DPA)-alendronate, a novel bifunctional bisphosphonate for the palliative treatment of bone metastases. (188)Re(CO)(3)-DPA-alendronate can be easily synthesized with high specific activities and yields (18.8 GBq/mg, radiochemical yield > or =96%) in two steps using kit-based methodology, and in contrast with the clinically approved bisphosphonate (186/188)Re-HEDP, it forms inert, single species that have been well-characterized. In vivo imaging and biodistribution studies demonstrate that (188)Re(CO)(3)-DPA-alendronate is superior to (188)Re-HEDP in targeting and accumulating in areas of high metabolic bone activity while having low soft-tissue uptake. In addition to these studies, a simple and convenient new method for purifying its precursor, fac-[(188)Re(CO)(3)(H(2)O)(3)](+), is described.
authors.affiliation: King's College London, Division of Imaging Sciences, 4th Floor Lambeth Wing, St. Thomas' Hospital, SE1 7EH, London, United Kingdom.
authors.forename: Rafael
authors.initials: R
authors.lastname: Torres Martin de Rosales
authors.forename: Ciara
authors.initials: C
authors.lastname: Finucane
authors.forename: Julie
authors.initials: J
authors.lastname: Foster
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Mather
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Blower
mesh_terms: D019386:Alendronate / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011868:Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D012211:Rhenium / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D019386:Alendronate