13-18 May 2018
Casino Conference Centre
Europe/Prague timezone

Albumin-binding PSMA Ligands: Next Step Towards Improved Radionuclide Therapy of Prostate Cancer

15 May 2018, 15:30
Red Hall (Casino Conference Centre)

Red Hall

Casino Conference Centre

Reitenbergerova 4/95, Mariánské Lázně, Czech Republic
Verbal Radiopharmaceutical Chemistry, Labelled Compounds RPH 1


Dr Martina Benesova (Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ)


The prostate-specific membrane antigen (PSMA) has emerged as an attractive target for imaging and therapy of prostate cancer. Despite many advances in the past years, the treatment of metastatic castration-resistant prostate cancer (mCRPC) still remains challenging. The aim of this study was to optimize radionuclide therapy of mCRPC through the development of albumin-binding PSMA ligands with increased uptake of radioactivity in the tumor compared to the clinically employed Lu-177-PSMA-617.(1)
A variation of albumin-binding PSMA ligands was prepared using a solid phase synthetic approach and radiolabeled with lutetium-177 (Lu-177; T1/2 = 6.65 d) within 10 min at 95 °C. The Lu-177-labeled compounds were tested for stability, lipophilicity and potency of binding to human serum albumin (HSA). Cell uptake experiments were performed in PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu cells. In vivo time-dependent biodistribution up to 8 days post injection (p.i.) and SPECT/CT imaging studies were performed in BALB/c nude mice bearing PC-3 PIP/flu tumor xenografts.
Lu-177-labeled PSMA ligands (50 MBq/nmol, radiochemical purity ≥98%) were stable in the presence of L-ascorbic acid over 24 h (≥95%). In vitro investigations revealed significant binding of the novel radioligands to HSA (≥95%). PSMA-specific uptake in PC-3 PIP tumor cells was high (60–63%, 4 h incubation) and comparable to Lu-177-PSMA-617. Biodistribution studies showed enhanced blood circulation of all radioligands and, as a consequence, an increased tumor uptake over time. The most promising radioligand showed a more than 2-fold increased area under the curve (AUC) for the tumor uptake as compared to Lu-177-PSMA-617. The tumor-to-kidney (~5.9) and tumor-to-blood ratios of AUCs (~46) were generally high, however, somewhat lower than ratios obtained for Lu-177-PSMA-617 (~37 and ~71, respectively). Finally, SPECT/CT imaging confirmed the high accumulation and retention of activity in PSMA-positive tumors as well as increasing tumor-to-blood and tumor-to-kidney ratios over time.
Taken all of the characteristics into account, the herein applied concept of albumin-binding PSMA ligands may potentially enable more potent and convenient radionuclide therapy of mCRPC using lower quantities of activity and/or its less frequent applications.

(1) Benesova et al., (2015) J Nucl Med. 2015; 56(6): 914–920.

Primary authors

Dr Martina Benesova (Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ) Mr Christoph Umbricht (Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ) Prof. Roger Schibli (Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ) Dr Cristina Müller (Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ)

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