Comparison of systemic toxicities of 177Lu-DOTMP and 153Sm-EDTMP administered intravenously at equivalent skeletal doses to normal dogs

J Nucl Med Technol. 2009 Mar;37(1):45-52. doi: 10.2967/jnmt.108.054700. Epub 2009 Feb 17.

Abstract

Bone-seeking radiopharmaceuticals have been used to effectively treat cancer arising from and metastasizing to bone in humans and dogs. The rate of complete tumor control is low, and the geographic distribution of available compounds is limited by their half-lives. This experiment was done to evaluate in normal dogs the toxicity of (177)Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonate ((177)Lu-DOTMP) used as a potential therapeutic radiopharmaceutical.

Methods: Four normal purpose-bred dogs were administered (177)Lu-DOTMP at a dose of 8.14 MBq/kg and monitored for 84 d for evidence of toxicity in the bone marrow and vital organs.

Results: No statistically significant alterations in the biochemical profile, white blood cell count, or platelet count were observed in any dog. Very mild decreases in the red cell count were seen on day 84. No microscopic evidence of toxicity was present at necropsy.

Conclusion: The dogs receiving (177)Lu-DOTMP tolerated the administration and the effects of the compound without apparent clinical toxicity. The results of this experiment support the further evaluation in tumor-bearing dogs of (177)Lu-DOTMP as a potential therapy for metastatic bone cancer and primary bone tumors in humans and dogs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cell Count
  • Bone Marrow / radiation effects
  • Bone Neoplasms / radiotherapy
  • Dogs
  • Female
  • Lutetium*
  • Male
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / therapeutic use
  • Organometallic Compounds / toxicity*
  • Organophosphorus Compounds / therapeutic use
  • Organophosphorus Compounds / toxicity*
  • Radiation Dosage
  • Radioisotopes
  • Samarium*

Substances

  • 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid)
  • Organometallic Compounds
  • Organophosphorus Compounds
  • Radioisotopes
  • Samarium
  • Lutetium
  • samarium Sm-153 lexidronam