Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer
| Autor: | Øyvind S. Bruland, Roy H. Larsen, Asta Juzeniene, Petras Juzenas, Li-Wei Ma, Qian Peng, Vilde Yuli Stenberg |
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| Rok vydání: | 2021 |
| Předmět: |
Biodistribution
QH301-705.5 Catalysis 030218 nuclear medicine & medical imaging Inorganic Chemistry prostate-specific membrane antigen 03 medical and health sciences Prostate cancer 0302 clinical medicine In vivo Glutamate carboxypeptidase II Radioligand medicine Cytotoxic T cell Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy targeted alpha therapy Chemistry Organic Chemistry General Medicine medicine.disease In vitro Computer Science Applications metastatic castration-resistant prostate cancer 212Pb 030220 oncology & carcinogenesis Toxicity Cancer research p-SCN-Bn-TCMC-PSMA ligand (NG001) |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 4815, p 4815 (2021) International Journal of Molecular Sciences Volume 22 Issue 9 |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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