Abstract

The intratumor distribution of a new monoclonal antibody-hapten-based delivery system was examined. From two marine antibodies, Hybritech, Inc. has developed a bifunctional antibody (BPA) with specificities against CEA (ZCE-025 or GEM 231) and against one of two derivatives of [111In]-benzyl-EDTA (CHA 255), EOTUBE or BLEDTA IV, to form ZCE/CHA or CEM/CHA. BFA accumulates in CEA-expressing tissue and clears from non-antigenic tissues prior to administration of an [111In]-hapten.

Using five groups of nude mice bearing human colon tumor xenografts (T380), we evaluated different carriers of [111In]-EOTUBE to prelocalized ZCE/CHA. We administered all antibodies and haptens (230-240 µCi) by intraperitoneal injection. The ZCE/CHA was followed 24 h later by [111In]-EOTUBE. Each group was treated as follows: (1) 14 µg ZCE/CHA + 1 µg ZCE/CHA carrier of [111In]-EOTUBE; (2) 14 µg ZCE/CHA + 1 µg CHA 255 intact IgG carrier of [111In]-EOTUBE; (3) 14 µg ZCE/CHA + [111In]-EOTUBE (no carrier); (4) no ZCE/CHA + 20 µg [111In]-ZCE-025 intact IgG; (5) no ZCE/CHA + [111In]-EOTUBE (no carrier; control group). The mice were euthanized 22-24 h after injection of radiolabeled compounds. We excised tumors and kidneys for autoradiography. Using this BFA system we found a diffusion gradient pattern in tumors with nonspecific hapten localization, indicating a more homogeneous distribution when compared with ZCE-025 distribution. We observed increased uptake of [111In]-EOTUBE in the cortex of the kidney.

We evaluated water bath hyperthermia to determine if it enhanced distribution and binding of [111In]-EOTUBE or [111In]-BLEDTA IV (140-200 µCi) to prelocalized CEM/CHA or CHA 255 F(ab')2 within human colon tumor (T380 and T380h) xenografts with six groups of nude mice: (1) 14 µg CEM/CHA + hyperthermia + [111In] -BLEDTA IV; (2) 14 µg CEM/CHA + hyperthermia + [111In]-EOTUBE; (3) 7 µg CHA 255 F(ab')2 + hyperthermia + [111In]-EOTUBE (control); (4-6) treated as above, without hyperthermia. Twenty-two to twenty-four hours after the prelocalizing dose, we treated the hyperthermia groups (41.5°C, 45 min). The [111In]-hapten was administered 2 h after hyperthermia (22-24 h before euthanasia). We measured biodistribution of radiolabeled haptens in tumors, kidneys, and livers. Hyperthermia significantly increased [111In]-EOTUBE localization to prelocalized CEM/CHA in T380h tumors. Equivocal results were observed in kidneys and livers.

LLU Discipline

Microbiology

Department

Microbiology

School

Graduate School

First Advisor

Daila S. Gridley

Second Advisor

Benjamin H. S. Lau

Third Advisor

Dwight R. Stickney

Fourth Advisor

Robert W. Teel

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1989

Date (Title Page)

6-1989

Language

English

Library of Congress/MESH Subject Headings

Biological Transport; Hyperthermia, Induced; Antibodies, Neoplasm

Type

Thesis

Page Count

iv; 46

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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