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J Labelled Comp Radiopharm. 2020 Jan 9. doi: 10.1002/jlcr.3825. [Epub ahead of print]

Preparation of the alpha-emitting PSMA targeted radioligand [212 Pb]Pb-NG001 for prostate cancer.

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Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Nucligen AS, Oslo, Norway.
Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
MedKoo Biosciences, Morrisville, NC, USA.
Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.


Prostate-specific membrane antigen (PSMA) is the most promising target for radioligand therapy of prostate cancer. The aim of this study was to prepare a small molecular ligand p-SCN-Bn-TCMC-PSMA ligand (NG001), and compare it with the commonly used DOTA-based PSMA-617. The PSMA-targeting ability of 212 Pb-labelled ligands was evaluated using PSMA-positive C4-2 human prostate cancer cells. Lead-212 is an in vivo generator of alpha particles by its daughter nuclides 212 Bi and 212 Po. NG001 was synthesized by conjugating the isothiocyanato group of p-SCN-Bn-TCMC to the amino group of a glutamate-urea-based PSMA binding entity. Molecular size, chelator unit and chelator linking method are different in NG001 and PSMA-617. Both ligands were efficiently labelled with 212 Pb using a 224 Ra/212 Pb-solution generator in transient equilibrium with progeny. Lead-212-labelled NG001 was purified with a yield of 85.9±4.7% and with 0.7±0.2% of 224 Ra. Compared with [212 Pb]Pb-PSMA-617, [212 Pb]Pb-NG001 displayed a similar binding and internalization in C4-2 cells, with comparable tumour uptake in mice bearing C4-2 tumours, but almost a 2.5-fold lower kidney uptake. Due to the rapid normal tissue clearance and tumour internalisation, any significant translocalization of 212 Bi was not detected in mice. In conclusion, the obtained results warrant further preclinical studies to evaluate the therapeutic efficacy of [212 Pb]Pb-NG001.


212Pb; DOTA; p-SCN-Bn-TCMC-PSMA-ligand, PSMA-617; prostate cancer


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