Pre-clinical evaluation of 2,3-dimercaptosuccinic acid as a radiation nephrotoxicity protective agent during radiopeptide therapy of neuroendocrine malignancy.
OBJECTIVE
To determine if dimercaptosuccinic acid (DMSA), an agent originally developed as a safe non-toxic antidote for heavy metal poisoning, would be useful as a kidney radiation dose reduction agent in patients undergoing radiopeptide therapy for cancer.


METHODS
Thirty-six adult male Wistar rats were injected via the penile vein with 10 MBq of 177Lu-DOTA-tyr(3)-octreotate. At 30 min after the radiopeptide injection, 18 of the animals (intervention group) were injected with 0.15 mg x g(-1) of DMSA (i.p.). Samples were collected for gamma counting at 24 (n=12), 48 (n=12) and 72 h (n=12) after administration of the radiopeptide. At each time point, the percentage injected dose per gram of tissue in each sample of the six control animals was compared with that of the six animals from the DMSA injection regimen.


RESULTS
The i.p. injection of 0.15 mg x g(-1) of DMSA 30 min following the administration of the 177Lu-DOTATATE reduced the mean (95% CI) kidney retention of radiopeptide by 15.6% (2.6-24.6) at 72 h while not significantly affecting uptake in other organs. Statistical testing of the difference between the two groups of animals (DMSA versus controls) at 72 h post-administration of the radiopeptide indicated only a 3% chance that the magnitude of the reduction in kidney radiopeptide retention observed would be expected due to natural variation (i.e., if there was no difference between the groups).


CONCLUSIONS
This study has indicated that DMSA has the potential to selectively reduce radiopeptide kidney retention. Further work is necessary to determine the most effective dose of DMSA and the most effective timing regimen, and to examine the clinical efficacy of several other chelating agents.
Moorin
Rachael E
RE
School of Population Health, The University of Western Australia, Perth, Australia. rachael.moorin@uwa.edu.au
Meyrick
Danielle P
DP
Rose
Alison
A
D000818:Animals; D001822:Body Burden; D002614:Chelating Agents / Q000008:administration & dosage; D004353:Drug Evaluation, Preclinical; D007668:Kidney / Q000378:metabolism* / Q000528:radiation effects; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D017599:Neuroectodermal Tumors / Q000378:metabolism / Q000532:radiotherapy; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009928:Organ Specificity; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000008:administration & dosage*; D016896:Treatment Outcome
C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D002614:Chelating Agents; D010455:Peptides; D011837:Radiation-Protective Agents; D019275:Radiopharmaceuticals; D004113:Succimer; D015282:Octreotide