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Cancer Biother Radiopharm. 2010 Aug;25(4):387-94. doi: 10.1089/cbr.2010.0783.

A pretherapy biodistribution and dosimetry study of indium-111-radiolabeled trastuzumab in patients with human epidermal growth factor receptor 2-overexpressing breast cancer.

Author information

1
Department of Radiation Oncology and Radiation Research, Beckman Research Institute, Duarte, California 91010, USA. jwong@coh.org

Abstract

PURPOSE:

The purposes of this study were to evaluate the organ biodistribution, pharmacokinetics, immunogenicity, and tumor uptake of (111)Indium ((111)In)-MxDTPA-trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers and to determine whether (90)Y-MxDTPA-trastuzumab should be evaluated in subsequent clinical therapy trials.

EXPERIMENTAL DESIGN:

Patients with HER2-overexpressing breast cancers who were to undergo planned trastuzumab therapy first received unlabeled trastuzumab (4-8 mg/kg IV), followed 4 hours later by 5 mCi (111)In-MxDTPA-trastuzumab (10 mg antibody). Serial blood samples, 24-hour urine collections, and nuclear scans were performed at defined time points for 7 days.

RESULTS:

Eight (8) patients received (111)In-MxDTPA-trastuzumab, which was well tolerated with no adverse side-effects. Three (3) of 7 patients with known lesions demonstrated positive imaging on nuclear scans. No antiantibody responses were observed for 2 months postinfusion. Organ doses (cGy/mCi) assuming radiolabeling with (90)Y were 19.9 for heart wall, 17.6 for liver, 4.6 for red marrow, and 2.8 for the whole body. Tumor doses ranged from 24 to 172 cGy/mCi.

CONCLUSIONS:

In summary, results from this study indicate that (90)Y-MxDTPA-trastuzumab is an appropriate agent to evaluate in therapy trials. No evidence of an immune response to (111)In-MxDTPA-trastuzumab was detected, predicting for the ability to administer multiple cycles. With the exception of cardiac uptake, pharmacokinetics and organ biodistribution were comparable to other (90)Y-labeled monoclonal antibodies previously evaluated in the clinic. Cardiac uptake was comparable to hepatic uptake and therefore predicted to not be prohibitively high as to result in dose-limiting cardiotoxicity.

PMID:
20707718
PMCID:
PMC2958439
DOI:
10.1089/cbr.2010.0783
[Indexed for MEDLINE]
Free PMC Article

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