Research & Industry Reports

213Bi-[DOTA0, Tyr3]Octreotide Peptide Receptor Radionuclide Therapy of Pancreatic Tumors in a Preclinical Animal Model.

By Jeffrey P. Norenberg, University of New Mexico

Purpose: The somatostatin analogue [DOTA0, Tyr3]octreotide (DOTATOC) has previously been labeled with low linear energy transfer (LET) ß-emitters, such as 177Lu or 90Y, for tumor therapy. In this study, DOTATOC labeled with
the high-LET ?-emitter, 213Bi, was evaluated.

Experimental Design: The radiolabeling, stability, biodistribution, toxicity, safety, and therapeutic effi cacy of 213Bi-DOTATOC (specifi c activity 7.4 MBq/Ag) were investigated. Biodistribution studies to determine somatostatin receptor specificity were done in Lewis rats at 1 and 3 hours postinjection. Histopathology of various organs was used to evaluated toxicity and safety. Therapeutic efficacy of 4 to 22 MBq 213Bi-DOTATOC was determined in a rat pancreatic carcinoma
model.

Results: Radiolabeling of the 213Bi-DOTATOC was achieved with radiochemical purity >95% and an incorporation yield =99.9%. Biodistribution data showed specific binding to somatostatin receptor-expressing tissues. Administration of free 213Bi, compared with 213Bi-DOTATOC, resulted in higher radioactivity accumulation at 3 hours postinjection in the kidneys [34.47 ± 1.40% injected dose/g (ID/g) tissue versus 11.15 ± 0.46 %, P <0.0001] and bone marrow (0.31 ± 0.01% ID/g versus 0.06 ± 0.02 %, P <0.0324). A signifi cant decrease in tumor growth rate was observed in rats treated with <11 MBq of 213Bi-DOTATOC 10 days postinjection compared with controls (P<0.025). Treatment with <20 MBq of 213Bi-DOTATOC showed significantly greater tumor reduction when compared with animals receiving 11 MBq (P<0.02).

Conclusions: 213Bi-DOTATOC showed dose-related antitumor effects with minimal treatment-related organ toxicity. No acute or chronic hematologic toxicities were observed. Mild, acute nephrotoxicity was observed without evidence of chronic toxicity. 213Bi-DOTATOC is a promising therapeutic radiopharmaceutical for further evaluation.