title: 188Re-labeled bisphosphonates as potential bifunctional agents for therapy in patients with bone metastases.
abstract: Two new bisphosphonates have been examined for their ability to bind 188Re and deliver it selectively to bone. The bisphosphonates are prototype compounds with potential to deliver rhenium radionuclides and a second therapy modality to bone metastases. A conjugate between diethylenetriaminepentaacetic acid and bisphosphonate (DTPA/BP) and a conjugate between 5-fluorouracil and bisphosphonate (5-FU/BP) were prepared and labeled at high radiochemical purity with 188Re and biodistribution studies were carried out in normal Balb/C mice. The compounds showed rapid blood clearance and elimination from soft tissues with substantial retention of activity in the bone comparable to 188Re-hydroxyethylidine diphosphonate used as a control. At 8 h bone activity was 3.51% of injected dose for 188Re-DTPA/BP and 6.38% of injected dose for 188Re-5-FU/BP representing 69.6% and 80.6% of total body radioactivity, respectively. The two compounds show the potential for combination therapy of painful bone metastases.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, 3118 Dentistry Pharmacy Center, University of Alberta, Edmonton Alta, Canada T6G-2N8.
authors.forename: Amal
authors.initials: A
authors.lastname: El-Mabhouh
authors.forename: John R
authors.initials: JR
authors.lastname: Mercer
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary; D004164:Diphosphonates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011868:Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D012211:Rhenium / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D004164:Diphosphonates; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D004369:Pentetic Acid; D005472:Fluorouracil