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Correlation of Vascular Permeability and Blood Flow with Monoclonal Antibody Uptake by Human Clouser and Renal Cell Xenografts

Medical Products Department, Immunopharmaceutical R & D, E. I. duPont de Nemours, Co., Inc., North Billerica, Massachusetts 01862 and University of Minnesota and V. A. Medical Center, Minneapolis, Minnesota 55417

The specific uptake of ¹²⁵I-A6H antibody by xenografts of the human renal cell carcinoma (RCC) TK177G in the athymic mouse was considerably greater than that seen for other human tumor xenografts and their associated antibodies (e.g., ¹²⁵I-B6.2 uptake by the human breast carcinoma, Clouser). In addition the A6H-RCC model also demonstrated both greater localization indices and absolute amount of antibody bound than did the B6.2-Clouser model.

Several physiological factors were studied to assess whether they might play a role in this greater specific uptake. Vascular volume was determined using the in situ labeling of red blood cells with ^99mTc. Vascular permeability was determined by measuring the amount of ¹²⁵I-labeled bovine serum albumin and ¹³¹I-labeled nonspecific IgG1 (anti-horseradish peroxidase) extravasated out of the tumor vasculature during 1 hr. Relative blood flow to the tumor was determined using the ⁸⁶Rb method.

Blood flow and vascular permeability were found to be significantly greater in the RCC tumor xenografts than in Clouser tumors. Differences in vascular permeability were especially dramatic, showing the vasculature of the RCC xenograft was twice as permeable as that of the Clouser tumor. Animals bearing either RCC or Clouser xenografts were injected with a monoclonal antibody to human major histocompatibility complexes (¹²⁵I-labeled anti-human histocompatibility complex A, B, C). Tumor uptake of ¹²⁵I-labeled anti-human histocompatibility complex A, B, C was found to be 5 times greater in RCC than Clouser xenografts. These results, therefore, suggest that the differences seen in the physiological factors studied can account for some of the greater specific ¹²⁵I-A6H uptake by the RCC tumor than ¹²⁵I-B6.2 uptake by the Clouser xenograft.

¹ To whom requests for reprints should be addressed, at Medical Products Department, E. I. Dupont de Nemours Co., Immunopharmaceuticals R & D, 331 Treble Cove Road, North Billerica, MA 01862.

Received 1/ 2/87. Revised 10/ 6/87. Accepted 10/14/87.

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