| Publication Type |
dissertation |
| School or College |
College of Pharmacy |
| Department |
Medicinal Chemistry |
| Author |
Bhalgat, Mahesh Kantilal |
| Title |
Antibody-directed delivery of copper-67 to tumors |
| Date |
1995-06 |
| Description |
The advent of monoclonal antibodies led to the reawakening of the 'magic bullet' concept of Ehrlich, which suggests that antibodies against tumor-associated antigens could potentially be used for the delivery of cytotoxic agents specifically to tumors. The rationale for the use of such antibodies as selective carriers for the site-specific delivery of anticancer agents, and for increasing the therapeutic index of anticancer agents, is based on observations that antitumor antibodies or their immunologically reactive fragments do indeed selectively localize in vivo. Because in vivo localization of parenterally administered antitumor antibodies can be achieved, it has become feasible to investigate the efficiency and benefits of both diagnostic imaging as well as radiotherapy, using antibodies labeled with appropriate radioisotopes. Whole antibody molecules and their fragments were used for the synthesis of radioimmunoconjugates. A radioisotope with both therapeutic and diagnostic utility, copper-67, was attached to a renal cell carcinoma antibody, A6H, or its fragments, using a synthetic porphyrin for chelation. A panel of conjugates was synthesized, either by direct attachment of the porphyrin to the protein or via the use of intermediate polymeric molecules. Each of the synthesized conjugates was subjected to in vitro testing to determine the coupling yield, radiometalation yield, immunoreactivity, cell binding ability, and aggregation properties. The copper-67-A6H conjugate with the highest level of immunoreactivity was injected in nude mice and its biodistribution was studied. Although a respectable tumor to blood ratio of 16 was obtained 45 hours after injection, the liver and spleen radioactivity levels were unusually high. Further investigation led to the possibility that aggregates present in the injection solution may be responsible for the high uptake of the conjugates by the reticuloendothelial system. Dendrimer molecules used as polymeric intermediates in the immunoconjugates were subjected to preliminary biological evaluation to determine their toxicity, immunogenicity, carcinogenicity, and biodistribution pattern. Results from these experiments suggest that low doses of lower generation dendrimers are not associated with adverse effects that would preclude their use as intermediates in drug delivery. |
| Type |
Text |
| Publisher |
University of Utah |
| Subject |
Monoclonal Antibodies; Raiommunoconjugates |
| Subject MESH |
Antibiotics, Antineoplastic; Copper; Diagnostic Techniques and Procedures |
| Dissertation Institution |
University of Utah |
| Dissertation Name |
PhD |
| Language |
eng |
| Relation is Version of |
Digital reproduction of "Antibody-directed delivery of copper-67 to tumors Spencer S. Eccles Health Sciences Library. Print version of "Antibody-directed delivery of copper-67 to tumors". available at J. Willard Marriott Library Special Collection. RC39.5 1995 .B48. |
| Rights Management |
© Mahesh Kantilal Bhalgat. |
| Format Medium |
application/pdf |
| Format Extent |
3,339,215 bytes |
| Identifier |
undthes,4456 |
| Source |
Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available). |
| Funding/Fellowship |
The Elsa U. Paardee foundation, American Cancer Society and the University of Utah College of Pharmacy. |
| Master File Extent |
3,339,289 bytes |
| ARK |
ark:/87278/s6r78h2w |
| Setname |
ir_etd |
| ID |
191290 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6r78h2w |
