188Re-labeled bisphosphonates as potential bifunctional agents for therapy in patients with bone metastases

Two new bisphosphonates have been examined for their ability to bind Re-188 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 Re-188 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 Re-188-hydroxyethylidine diphosphonate used as a control. At 8 h bone activity was 3.51% of injected dose for Re-188-DTPA/BP and 6.38% of injected dose for Re-188-5-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. (C) 2004 Elsevier Ltd. All rights reserved.