Y OUNG I NNOVATORS 2009 Prostate-Specific Membrane Antigen (PSMA)-Targeted Imaging, Diagnosis, and Therapy of Prostate Cancer using a PSMA inhibitor as.

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Y OUNG I NNOVATORS 2009 Prostate-Specific Membrane Antigen (PSMA)-Targeted Imaging, Diagnosis, and Therapy of Prostate Cancer using a PSMA inhibitor as a Homing Ligand Sumith A. Kularatne Philip S. Low Purdue University Part II

Department of Chemistry 2 DUPA- 99m Tc Formulation Vials (c) (b) (a) K699 R210 R534 Zn Binding Mode of DUPA- 99m Tc Low, P. S. & Kularatne, S. A. PCT/WO

Department of Chemistry 3 Affinity and Specificity of DUPA- 99m Tc to PSMA-positive Human PCa (LNCaP) cells Competition with excess PMPA Kularatne, S. A., Wang, K., Santhapuram, H-K. R. & Low, P. S. Mol. Pharm. 6,

Department of Chemistry (a) LNCaP tumor (PSMA positive) (b) LNCaP tumors (blocked PSMA) (c) LNCaP tumor (PSMA positive) (d) LNCaP tumor (blocked PSMA) (e) A549 tumor (PSMA negative) (f) KB tumor (PSMA negative) K 4 Whole-body Radioimages of Mice Treated with DUPA- 99m Tc Blocked PSMA = xs PMPA + DUPA- 99m Tc A549 => a human lung cancer cell line K = Kidney KB => a human nasopharyngeal cancer cell line

Department of Chemistry 5 Biodistribution Studies of Mice Treated with DUPA- 99m Tc PSMA expression is:  High in murine kidneys ( Slusher, B.S. et al J. Comp. Neurol. 315, and Foss, C. A Clin. Cancer Res. 11, )  Minimal in human kidneys ( Bender, N.H. et al Seminars in Oncology 30, and Ghosh, A. et al Cell. Biochem. 91, )

Department of Chemistry 6 PSMA-positive Tumor-to-Normal Tissue Ratios (Biodistribution Studies of Mice Treated with DUPA- 99m Tc ) tumor-to-muscle ratio ProstaScint 3:1 ( Sodee, D.B. et al The Prostate 37, ) DUPA- 99m Tc 75:1

Department of Chemistry FITC 488 Events DUPA-FITC xs PMPA + DUPA-FITC Unlabelled LNCaP cells 7 Binding and Specificity of DUPA Fluorescent Conjugates Analysis of binding of DUPA-FITC to LNCaP cells by flow cytometry Confocal (LNCaP cells) Overlay of confocal Onto DIC DUPA-FITC xs PMPA + DUPA-FITC

Department of Chemistry 8 Overlay of confocal Onto DIC DUPA-rhodamine B Conjugate LNCaP cells Endocytosis

Department of Chemistry 9 DUPA-siRNA-Cy5 xs PMPA + DUPA-siRNA-Cy5 Delivery of DUPA-siRNA-Cy5 Conjugate Thomas, M. A. ;Kularatne, S. A., et. Al. Ann. N.Y. Acad. Sci. 2009, 1175: 32–39

Department of Chemistry 10 CTC Quantitation of Blood Samples from PCa Patients (Mean # of CTCs /mL) CTCs/ mL Healthy Donor Prostate Cancer Patient 26 (Threshold value) Low, P. S., Wei, H. & Kularatne, S. A. PCT/WO He, W., Kularatne, S. A., et. al. Int. J. Cancer, 2008, 123,

Department of Chemistry 11 Chemotherapeutic Agents Screening for LNCaP Cells Kularatne, S. A., Chelvam V., Low P. S. et al. (Manuscript in submission)