In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 12, No. 3 ( 2006-02-01), p. 897-903
Kurzfassung:
Purpose: The somatostatin analogue [DOTA0, Tyr3]octreotide (DOTATOC) has previously been labeled with low linear energy transfer (LET) β-emitters, such as 177Lu or 90Y, for tumor therapy. In this study, DOTATOC labeled with the high-LET α-emitter, 213Bi, was evaluated. Experimental Design: The radiolabeling, stability, biodistribution, toxicity, safety, and therapeutic efficacy of 213Bi-DOTATOC (specific activity 7.4 MBq/μg) 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 & gt;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 & lt; 0.0001] and bone marrow (0.31 ± 0.01% ID/g versus 0.06 ± 0.02%, P & lt; 0.0324). A significant decrease in tumor growth rate was observed in rats treated with & gt;11 MBq of 213Bi-DOTATOC 10 days postinjection compared with controls (P & lt; 0.025). Treatment with & gt;20 MBq of 213Bi-DOTATOC showed significantly greater tumor reduction when compared with animals receiving & lt;11 MBq (P & lt; 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.
Materialart:
Online-Ressource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-05-1264
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2006
ZDB Id:
1225457-5
ZDB Id:
2036787-9
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