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


CONCLUSIONS
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.
Bryan
Jeffrey N
JN
Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, USA. bryanjn@vetmed.wsu.edu
Bommarito
David
D
Kim
Dae Young
DY
Berent
Linda M
LM
Bryan
Margaret E
ME
Lattimer
Jimmy C
JC
Henry
Carolyn J
CJ
Engelbrecht
Hendrik
H
Ketring
Alan
A
Cutler
Cathy
C
D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000528:radiation effects; D001859:Bone Neoplasms / Q000532:radiotherapy; D004285:Dogs; D005260:Female; D008187:Lutetium; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000627:therapeutic use / Q000633:toxicity*; D011829:Radiation Dosage; D011868:Radioisotopes; D012493:Samarium
C531954:177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid); D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D012493:Samarium; D008187:Lutetium; C061972:samarium Sm-153 lexidronam