Toxicity and dosimetry of 177Lu-DOTA-Y3-octreotate in a rat model

Jason S. Lewis, Mu Wang, Richard Laforest, Fan Wang, Jack L. Erion, Joseph E. Bugaj, Ananth Srinivasan, Carolyn J. Anderson

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Radiolabeled somatostatin analogs have demonstrated effectiveness for targeted radiotherapy of somatostatin receptor-positive tumors in both tumor-bearing rodent models and humans. A radionuclide of interest for cancer therapy is reactor-produced 177Lu (t1/2 = 6.64 d; β-- [100%]). The high therapeutic efficacy of the somatostatin analog 177Lu-DOTA-Tyr3-octreotate (DOTA-Y3-TATE, where DOTA is 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) was previously demonstrated in a tumor-bearing rat model (Erion et al., J. Nucl. Med. 1999;40:223P; de Jong et al., Int. J. Cancer, 2001; 92:628-633). In the current study, the toxicity and dosimetry of 177Lu-DOTA-Y3-TATE were determined in both normal and tumor-bearing rats. Doses of 177Lu-DOTA-Y3-TATE ranging from 0 to 123 mCi/kg were administered to rats and complete blood counts (CBCs) and blood chemistries were analyzed out to 6 weeks. No overt signs of toxicity were observed with 177Lu-DOTA-Y3-TATE (i.e., lethargy, weight loss, scruffy coat or diarrhea) at any of the dose levels. Blood chemistries and CBCs were normal except for the white blood cell counts, which showed a dose-dependent decrease. The maximum tolerated dose was not reached at 123 mCi/kg. The biodistribution of 177Lu-DOTA-Y3-TATE was determined in CA20948 rat pancreatic tumor-bearing rats, and the data were used to estimate human absorbed doses to normal tissues. The dose-limiting organ was determined to be the pancreas, followed by the adrenal glands. The absorbed dose to the rat CA20948 tumor was estimated to be 336 rad/mCi (91 mGy/MBq). These data demonstrate that 177Lu-DOTA-Y3-TATE is an effective targeted radiotherapy agent at levels that show minimal toxicity in this rat model.

Original languageEnglish
Pages (from-to)873-877
Number of pages5
JournalInternational Journal of Cancer
Volume94
Issue number6
DOIs
StatePublished - Dec 15 2001

Keywords

  • Lutetium-177
  • Neuroendocrine cancer
  • Somatostatin
  • Targeted radiotherapy

Fingerprint

Dive into the research topics of 'Toxicity and dosimetry of 177Lu-DOTA-Y3-octreotate in a rat model'. Together they form a unique fingerprint.

Cite this