Biochemistry

Thomas P. Quinn

Professor of Biochemistry
Director, Structural Biology Core

E-mail:quinnt@missouri.edu

Office: 234A Schweitzer Hall

Mail: Biochemistry
117 Schweitzer Hall
University of Missouri
Columbia, MO 65211

Phone: 573-882-6099

Fax: 573-882-5635

Lab: 573-882-4956

Educational background

Notable honors and service

• Director, Structural Biology Core
• Gamma Sigma Delta teaching award
• University of Missouri Entrepreneur of the Year (2007)

Research description

We have established a research program to develop radiolabeled peptides and proteins as tumor specific diagnostic and therapeutic agents. Combinatorial peptide and antibody fragment libraries are being employed to identify molecules that preferentially bind tumor antigens. The tumor-avid peptides and antibody fragments are subsequently engineered to bind the medically important radionuclides into their structures. Finally, the radiolabeled peptides and proteins are investigated for their abilities to target tumor cells in vitro and in vivo.

Radiolabeled α-MSH Peptide Analogs: The goal of this project is to design radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs for melanoma imaging and therapy. α-MSH is a small tridecapeptide hormone that is involved in control of skin coloration. α-MSH receptors have been identified on human and mouse melanoma cells making them attractive targets for the development of new peptide imaging and/or therapeutic radiopharmaceuticals. We have developed an α-MSH analog (CCMSH) that is cyclized via site-specific Tc-99m, Re, or Re-188 metal coordination. The metal-cyclized CCMSH analog is radiochemically stable and retains α-MSH receptor affinity and specificity. In vivo, the Tc-99m-CCMSH complex was effective in imaging melanoma in both murine and human melanoma mouse tumor model systems. The Tc-99m-CCMSH complex exhibited high tumor uptake and retention values coupled with rapid whole body clearance kinetics. Similar biodistribution results were obtained for the Re-188-CCMSH complex in tumor bearing mice. We are currently evaluating the melanoma therapeutic efficacy of the Re-188-CCMSH and Pb-212-DOTA-ReCCMSH in vivo.

Tumor Binding Peptides Selected from Bacteriophage Display Libraries: A combinatorial approach is being used to search for small polypeptides that bind the cancer associated Thomsen-Friedenreich (T) glycoantigen and ErbB-2 receptor with high affinities and specificities. Random peptide bacteriophage display libraries were screened for molecules that bound T-antigen and ErbB-2. Two T-antigen binding peptide sequences, P30 and P10, have been shown to bind free T-antigen in solution, T-antigen displaying proteins, and breast carcinoma cells displaying T antigen on their surfaces. The P30 peptide has be shown to inhibit T-antigen mediated tumor cell adhesion between malignant melanoma cells and adhesion between tumor cells and endothelial cells. Bacteriophage libraries have also been employed to identify peptide sequences that bind the ErbB-2 receptor. The ErbB-2 receptor is upregulated in a number of cancers, including breast and prostate. A six amino acid peptide, p6.1, has been identified that binds the extracellular domain of ErbB-2. The p6.1 peptide is capable of distinguishing between tumor cells and normal cells. We are continuing to explore the molecular recognition properties and the biological activities of the T antigen and ErbB-2 binding peptides.

Selected publications

Kumar, S.R., Sauter, E.R., Quinn, T.P. and Deutscher, S.L. (2005) Thomsen-Friedenreich and Tn antigens in nipple fluid: carbohydrate biomarkers for breast cancer detection. Clin. Cancer Res. 11, 6868-6871.

Miao, Y., Hylarides, M., Fisher, D.R., Shelton, T., Moore, H., Wester, D.W., Fritzberg, A.R., Winkelmann, C.T., Hoffman, T.J. and Quinn, T.P. (2005) Melanoma Therapy via Peptide-Targeted Alpha-Radiation. Clinical Cancer Res. 11, 5616-5621.

Newton, J.R., Miao, Y., Deutscher, S.L. and Quinn, T.P. (2007) Melanoma imaging with pretargeted bivalent bacteriophage. J. Nucl. Med. 48, 429-436.

Miao, Y., Shelton, T., and Quinn, T.P. (2007) Therapeutic Efficacy of a 177Lu Labeled DOTA Conjugated Alpha-Melanocyte Stimulating Hormone Peptide in a Murine Melanoma-bearing Mouse Model. Cancer Biotherapy and Radiopharm 22:333-341.

Kumar SR, Quinn TP, Deutscher SL. Evaluation of an 111In-radiolabeeld peptide as a targeting and imaging agent for erbB-2 receptor-expressing breast carcinomas. Clin Cancer Res 13: 6070-79, 2007.

Miao Y and Quinn TP. (2008) Peptide-targeted radionuclide therapy for melanoma. Crit Rev Onc Hemat 67, 213-228.

Cantorias M.V., Figueroa S.D., Quinn T.P., Lever J.R., Hoffman T.J., Watkinson L.D., Carmack T.L., Cutler C.S. (2009) Development of high-specific-activity (68)Ga-labeled DOTA-rhenium-cyclized alpha-MSH peptide analog to target MC1 receptors overexpressed by melanoma tumors. Nucl. Med. Biol. 36(5): 505-13

Wei K, Zhang X, Gallazzi F, Miao Y, Jin Y, Brechbiel MW, Xu H, Clifford T, Welch MJ, Lewis JS, Quinn TP. (2009) Melanoma imaging using 111In-, 86Y- and 68Ga-labeled CHX-A″-Re(Arg11)CCMSH. Nucl Med Biol 36, 345-354.