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Article

Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer

1
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
2
Department of Research and Development, Nucligen AS, 0379 Oslo, Norway
3
Institute for Clinical Medicine, University of Oslo, 0318 Oslo, Norway
4
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
5
Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Finn Edler von Eyben
Int. J. Mol. Sci. 2021, 22(9), 4815; https://doi.org/10.3390/ijms22094815
Received: 31 March 2021 / Revised: 27 April 2021 / Accepted: 29 April 2021 / Published: 1 May 2021
(This article belongs to the Special Issue PSMA in Prostate Cancer)
Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of 212Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of 212Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of 212Pb-NG001. View Full-Text
Keywords: prostate-specific membrane antigen; metastatic castration-resistant prostate cancer; targeted alpha therapy; p-SCN-Bn-TCMC-PSMA ligand (NG001); 212Pb prostate-specific membrane antigen; metastatic castration-resistant prostate cancer; targeted alpha therapy; p-SCN-Bn-TCMC-PSMA ligand (NG001); 212Pb
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MDPI and ACS Style

Stenberg, V.Y.; Larsen, R.H.; Ma, L.-W.; Peng, Q.; Juzenas, P.; Bruland, Ø.S.; Juzeniene, A. Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer. Int. J. Mol. Sci. 2021, 22, 4815. https://doi.org/10.3390/ijms22094815

AMA Style

Stenberg VY, Larsen RH, Ma L-W, Peng Q, Juzenas P, Bruland ØS, Juzeniene A. Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer. International Journal of Molecular Sciences. 2021; 22(9):4815. https://doi.org/10.3390/ijms22094815

Chicago/Turabian Style

Stenberg, Vilde Y., Roy H. Larsen, Li-Wei Ma, Qian Peng, Petras Juzenas, Øyvind S. Bruland, and Asta Juzeniene. 2021. "Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer" International Journal of Molecular Sciences 22, no. 9: 4815. https://doi.org/10.3390/ijms22094815

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