Therapeutic effects of a 186Re-complex-conjugated bisphosphonate for the palliation of metastatic bone pain in an animal model

J Nucl Med. 2007 Jan;48(1):122-7.


Previously, based on the concept of bifunctional radiopharmaceuticals, we developed a highly stable (186)Re-mercaptoacetylglycylglycylglycine (MAG3) complex-conjugated bisphosphonate, [[[[(4-hydroxy-4,4-diphosphonobutyl)carbamoylmethyl]carbamoylmethyl]carbamoylmethyl]carbamoylmethanethiolate] oxorhenium(V) ((186)Re-MAG3-HBP), for the treatment of painful bone metastases. This agent showed a superior biodistribution as a bone-seeking agent in normal mice when compared with (186)Re-1-hydroxyethylidene-1,1-diphosphonate ((186)Re-HEDP). In this study, we evaluated the therapeutic effects of (186)Re-MAG3-HBP using an animal model of bone metastasis.

Methods: The model was prepared by injecting syngeneic MRMT-1 mammary tumor cells into the left tibia of female Sprague-Dawley rats. (186)Re-MAG3-HBP (55.5, 111, or 222 MBq/kg) or (186)Re-HEDP (55.5 MBq/kg) was then administered intravenously 21 d later. To evaluate the therapeutic effects and side effects, tumor size and peripheral blood cell counts were determined. Palliation of bone pain was evaluated by a von Frey filament test.

Results: In the rats treated with (186)Re-HEDP, tumor growth was comparable with that in untreated rats. In contrast, when (186)Re-MAG3-HBP was administered, tumor growth was significantly inhibited. Allodynia induced by bone metastasis was attenuated by treatment with (186)Re-MAG3-HBP or (186)Re-HEDP, but (186)Re-MAG3-HBP tended to be more effective.

Conclusion: These results indicate that (186)Re-MAG3-HBP could be useful as a therapeutic agent for the palliation of metastatic bone pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / radiotherapy*
  • Bone and Bones / radiation effects*
  • Diphosphonates / chemistry
  • Diphosphonates / therapeutic use*
  • Disease Models, Animal
  • Female
  • Mammary Neoplasms, Animal / radiotherapy
  • Mice
  • Neoplasm Metastasis
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / therapeutic use*
  • Pain
  • Radioisotopes / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Rhenium / therapeutic use*
  • Time Factors


  • (((((4-hydroxy-4,4-diphosphonobutyl)carbamoylmethyl)carbamoylmethyl)carbamoylmethyl)carbamoylmethanethiolate)oxorhenium(V)
  • Diphosphonates
  • Organometallic Compounds
  • Radioisotopes
  • Rhenium