Experimental α-particle radioimmunotherapy of breast cancer using 227Th-labeled p-benzyl-DOTA-trastuzumabReport as inadecuate




Experimental α-particle radioimmunotherapy of breast cancer using 227Th-labeled p-benzyl-DOTA-trastuzumab - Download this document for free, or read online. Document in PDF available to download.

EJNMMI Research

, 1:18

First Online: 24 August 2011Received: 30 May 2011Accepted: 24 August 2011

Abstract

BackgroundThe aim of the present study was to explore the biodistribution, normal tissue toxicity, and therapeutic efficacy of the internalizing low-dose rate alpha-particle-emitting radioimmunoconjugate Th-trastuzumab in mice with HER2-expressing breast cancer xenografts.

MethodsBiodistribution of Th-trastuzumab and Th-rituximab in nude mice bearing SKBR-3 xenografts were determined at different time points after injection. Tumor growth was measured after administration of Th-trastuzumab, Th-rituximab, cold trastuzumab, and saline. The toxicity of Th-trastuzumab was evaluated by measurements of body weight, blood cell, and clinical chemistry parameters, as well as histological examination of tissue specimens.

ResultsThe tumor uptake reached peak levels of 34% ID-g 4.6 kBq-g 3 days after injection of 400 kBq-kg of Th-trastuzumab. The absorbed radiation dose to tumor was 2.9 Gy, while it was 2.4 Gy to femur due to uptake of the daughter nuclide Ra in bone; the latter already explored in clinical phases I and II trials without serious toxicity. A significant dose-dependent antitumor effect was observed for dosages of 200, 400, and 600 kBq-kg of Th-trastuzumab but no effect of 400 and 600 kBq-kg Th-rituximab non-tumor binding. No serious delayed bone marrow or normal organ toxicity was observed, but there was a statistical significant reduction in blood cell parameters for the highest-dose group of Th-trastuzumab treatment.

ConclusionInternalizing Th-trastuzumab therapy was well tolerated and resulted in a dose-dependent inhibition of breast cancer xenograft growth. These results warrant further preclinical studies aiming at a clinical trial in breast cancer patients with metastases to bone.

Keywordsalpha radiation radioimmunotherapy SKBR-3 trastuzumab thorium-227 Electronic supplementary materialThe online version of this article doi:10.1186-2191-219X-1-18 contains supplementary material, which is available to authorized users.

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Author: Nasir Abbas - Helen Heyerdahl - Øyvind S Bruland - Jørgen Borrebæk - Jahn Nesland - Jostein Dahle

Source: https://link.springer.com/



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