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

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Jun 10

PMID 35681766

Authors

Vilde Yuli Stenberg

Anna Julie Kjol Tornes

Hogne Roed Nilsen

Mona-Elisabeth Revheim

Oyvind Sverre Bruland

Roy Hartvig Larsen

Asta Juzeniene

Affiliations

Soon will be listed here.

Abstract

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 1.8-fold better than for the C4-2 model, possibly explained by lower cellular internalization and less blood-rich stroma in PC-3 PIP xenografts. Mice bearing subcutaneous PC-3 PIP xenografts were treated with 0.2, 0.4, and 0.8 MBq of Pb-NG001 that resulted in therapeutic indexes of 2.7, 3.0, and 3.5, respectively. A significant increase in treatment response was observed in mice that received repeated injections compared to the corresponding single dose (therapeutic indexes of 3.6 for 2 × 0.2 MBq and 4.4 for 2 × 0.4 MBq). The results indicate that Pb-NG001 can induce therapeutic effects at clinically transferrable doses, both in the C4-2 model that resembles solid tumors and micrometastases with natural PSMA expression and in the PC-3 PIP model that mimics poorly vascularized metastases.

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