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Preclinical Evaluation of ⁶⁷Cu-labeled Intact and Fragmented Anti-Colon Carcinoma Monoclonal Antibody MAb35¹

Radiopharmacy Division, Paul Scherrer Institute, Wuerenlingen [A. S., R. A., P. B., I. N-H., P. A. S.], and Department of Nuclear Medicine, University Hospital, Basel, Switzerland

² To whom requests for reprints should be addressed, at Paul Scherrer Institute, 5232 Villigen/PSI, Switzerland.

The anti-carcinoembryonic antigen murine monoclonal antibody MAb35 and its F(ab')₂ fragment were labeled with ¹³¹I or the potential therapeutic nuclide ⁶⁷Cu. In vivo distribution patterns were compared in nude mice bearing human tumor xenografts by coinjection of the ¹³¹I- and ⁶⁷Cu-labeled materials, thereby minimizing variations due to xenograft and host animal. The results showed that the ⁶⁷Cu-labeled intact MAb35 achieved twice the percentage of injected dose/g tumor when compared to its ¹³¹I-labeled counterpart, without significant impairment of the wholebody distribution pattern. However, this effect was not evident in the case of F(ab')₂, where high uptake of ⁶⁷Cu was found in the kidney without any enhancement of accumulation in the target xenografts. To investigate the underlying causes of the different distribution patterns observed, iodine labeling was also performed using a more stable linkage, and the results indicated that the observed differences cannot be explained by simple deiodination of conventionally labeled preparations. We conclude that the intact form of the ⁶⁷Cu-labeled antibody may be superior to the F(ab')₂ fragment for use in our intended clinical studies. Our continuing work on the processing of radiometal-labeled F(ab')₂ fragments, at the systemic and cellular level, will hopefully lead to a strategy to circumvent the problem of high kidney accumulation.

¹ This work was supported by the Swiss Cancer League (Schweizerischer Krebsliga) Grant FOR.267 and by the Gertrud-Hagman Stiftung, Lommiswil.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/ 7/93. Accepted 9/24/93.

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