Theranostics 2016; 6(6):849-861. doi:10.7150/thno.14744

Research Paper

Towards Personalized Treatment of Prostate Cancer: PSMA I&T, a Promising Prostate-Specific Membrane Antigen-Targeted Theranostic Agent

Kristell L.S. Chatalic1,2,3*, Sandra Heskamp4*, Mark Konijnenberg1, Janneke D.M. Molkenboer-Kuenen4, Gerben M. Franssen4, Marian C. Clahsen-van Groningen5, Margret Schottelius6, Hans-Jürgen Wester6, Wytske M. van Weerden3, Otto C. Boerman4, Marion de Jong1,2✉

1. Department of Nuclear Medicine, Erasmus MC Rotterdam, The Netherlands;
2. Department of Radiology, Erasmus MC Rotterdam, The Netherlands;
3. Department of Urology, Erasmus MC, Rotterdam, The Netherlands;
4. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands;
5. Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
6. Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.
*These authors contributed equally to this work.


Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa). Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics—they rapidly and efficiently localize in tumor lesions. However, high tracer uptake in kidneys and salivary glands are major concerns for therapeutic applications. Here, we present the preclinical application of PSMA I&T, a DOTAGA-chelated urea-based PSMA inhibitor, for SPECT/CT imaging and radionuclide therapy of PCa. 111In-PSMA I&T showed dose-dependent uptake in PSMA-expressing tumors, kidneys, spleen, adrenals, lungs and salivary glands. Coadministration of 2-(phosphonomethyl)pentane-1,5-dioic acid (2-PMPA) efficiently reduced PSMA-mediated renal uptake of 111In-PSMA I&T, with the highest tumor/kidney radioactivity ratios being obtained using a dose of 50 nmol 2-PMPA. SPECT/CT clearly visualized subcutaneous tumors and sub-millimeter intraperitoneal metastases; however, high renal and spleen uptake in control mice (no 2-PMPA) interfered with visualization of metastases in the vicinity of those organs. Coadministration of 2-PMPA increased the tumor-to-kidney absorbed dose ratio during 177Lu-PSMA I&T radionuclide therapy. Hence, at equivalent absorbed dose to the tumor (36 Gy), coinjection of 2-PMPA decreased absorbed dose to the kidneys from 30 Gy to 12 Gy. Mice injected with 177Lu-PSMA I&T only, showed signs of nephrotoxicity at 3 months after therapy, whereas mice injected with 177Lu-PSMA I&T + 2-PMPA did not. These data indicate that PSMA I&T is a promising theranostic tool for PCa. PSMA-specific uptake in kidneys can be successfully tackled using blocking agents such as 2-PMPA.

Keywords: PSMA, imaging, SPECT, radionuclide therapy, prostate cancer, CRPC, 2-PMPA.

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How to cite this article:
Chatalic KLS, Heskamp S, Konijnenberg M, Molkenboer-Kuenen JDM, Franssen GM, Clahsen-van Groningen MC, Schottelius M, Wester HJ, van Weerden WM, Boerman OC, de Jong M. Towards Personalized Treatment of Prostate Cancer: PSMA I&T, a Promising Prostate-Specific Membrane Antigen-Targeted Theranostic Agent. Theranostics 2016; 6(6):849-861. doi:10.7150/thno.14744. Available from