Research: Laboratory Program –
Habibe Karacay, Ph.D.

Dr. Karacay is currently a Junior Member of the GSCC. She received her Ph.D. in inorganic chemistry from Rutgers University in New Brunswick NJ working with Dr. Stephan Isied and did postdoctoral work in bioconjugate chemistry with Dr. Claude Meares at the University of California, Davis. She worked in radioimmuno- imaging and therapy in industry before joining GSCC three years ago.

Dr. Karacay's major research activities are directed towards development of new reagents/procedures for imaging and therapy of cancers using monoclonal antibodies and peptides. In order to improve the results of radioimmunotherapy, studies are in progress to examine a pretargeting approach involving bispecific antibodies. One arm of a bispecific antibody recognizes the tumor and the second arm recognizes a small molecular weight peptide or metal-chelate complex. The bispecific antibody is administered first and allowed to target to tumor and clear from the blood. Radioactive isotope conjugated to a small molecular weight peptide is then administered. The small molecular weight radiolabeled peptide rapidly binds to the antibody yielding high radiation dose to the tumor. In addition, the radiolabeled peptide clears rapidly from the blood preventing high level radiation exposure of the normal organs. For these studies, several different bispecific antibody systems have been examined with high tumor/ nontumor ratios observed with several different radioisotopes. These preclinical studies will be used to direct initial clinical trials for imaging and therapy of cancer.

1. Sharkey RM, Karacay H, Griffiths GL, Behr TM, Blumenthal RD, Mattes MJ, Hansen HJ, and Goldenberg DM. Development of a streptavidin-anti-carcinoembryonic antigen antibody, radiolabeled biotin pretargeting method for radioimmunotherapy of colorectal cancer. Studies in a human colon cancer xenograft model. Bioconjugate Chem 8: 595-604 (1997).
2. Karacay H, Sharkey RM, Griffiths GL, Govindan SV, McBride WJ, Goldenberg DM, and Hansen HJ. Development of a streptavidin-anti-carcinoembryonic antigen antibody, radiolabeled biotin pretargeting method for radioimmunotherapy of colorectal cancer: Reagent development. Bioconjugate Chem 8: 585-594 (1997).
3. Karacay H, Ong GL, Hansen HJ, Griffiths GL, Goldenberg DM, and Mattes MJ. Intracellular processing of ^99mTc-antibody conjugates. Nucl Med Commun 19: 971-979 (1998).
4. Govindan SV, Mattes, Stein R, McBride BJ, Karacay H, Goldenberg DM Hansen HJ, and Griffiths GL. Labeling of monoclonal antibodies with diethylenetriaminepentacetic acid-appended radioiodinated peptides containing D-amino acids. Bioconjugate Chem 10: 231-240 (1999).
5. Karacay H, McBride WJ, Griffiths GL, Sharkey RM, Barbet J, Hansen HJ, Goldenberg, DM. Experimental Pretargeting studies of cancer with a humanized anti-CEA x murine anti-[In-DTPA] Bispecific antibody construct and a ^99mTc-/¹⁸⁸Re-labeled peptide. Bioconjugate Chem 11: 842-854 (2000).