Dual targeting with Ra/Pb-conjugates for targeted alpha therapy of disseminated cancers: A conceptual approach.

Metastases are the primary cause of death among cancer patients and efficacious new treatments are sorely needed. Targeted alpha-emitting radiopharmaceuticals that are highly cytotoxic may fulfill this critical need. The focus of this paper is to describe and explore a novel technology that may improve the therapeutic effect of targeted alpha therapy by combining two radionuclides from the same decay chain in the same solution.

Targeted alpha therapy with the Ra/Pb-TCMC-TP-3 dual alpha solution in a multicellular tumor spheroid model of osteosarcoma.

Osteosarcoma patients with overt metastases at primary diagnosis have a 5-year survival rate of less than 20%. TP-3 is a murine IgG2b monoclonal antibody with high affinity for an epitope residing on the p80 osteosarcoma cell surface membrane antigen. The tumor-associated antigen p80 is overexpressed in osteosarcomas, and has very low normal tissue expression.

An Experimental Generator for Production of High-Purity Pb for Use in Radiopharmaceuticals.

The feasibility, performance, and radiation safety of an experimental generator were evaluated to efficiently produce Pb intended for radiopharmaceuticals. The generator consisted of a flask with a removable cap containing a source of Ra or Th absorbed on quartz wool. Gaseous Rn emanated from the decaying source, which subsequently decayed to Pb, which was adsorbed on the flask's interior surface.

Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand Pb-NG001.

This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of Pb-NG001 were investigated in two human prostate cancer cell lines with different PSMA levels: C4-2 (PSMA+) and PC-3 PIP (PSMA+++). Despite 10-fold higher PSMA expression on PC-3 PIP cells, cytotoxicity and therapeutic efficacy of the radioligand was only 1.

Evaluation of the PSMA-Binding Ligand Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of 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 Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer.