@article{stenberg_cytotoxicity_2025,
	title = {Cytotoxicity and cell cycle changes in prostate cancer cells with differing {PSMA} expression and p53 status after treatment with {PSMA}-targeting radioligand [{212Pb}]{Pb}-{AB001}},
	copyright = {2025 The Author(s)},
	issn = {2045-2322},
	url = {https://www.nature.com/articles/s41598-025-29785-7},
	doi = {10.1038/s41598-025-29785-7},
	abstract = {Targeted alpha therapy holds promise for treating advanced prostate cancer, but the interplay between prostate-specific membrane antigen (PSMA) expression, p53 status, and downstream cell fate remains poorly defined. This study evaluates the cytotoxic and cell cycle effects of the alpha-emitting radioligand [212Pb]Pb-AB001 in prostate cancer cell lines with differing PSMA expression and p53 status: C4-2 (PSMA+/TP53-wild-type) and PC-3 PIP (PSMA+++/ TP53-null). [212Pb]Pb-AB001 significantly inhibited proliferation and clonogenic survival in both cell lines in an activity-dependent manner. At 95\% clonogenic inhibition, both cell lines exhibited G2-phase arrest, S-phase suppression and reduced mitotic entry on day 1. At higher activities, PC-3 PIP cells showed polyploidy, and features consistent with mitotic catastrophe and senescence. Cytotoxicity was more pronounced in C4-2 3D spheroid models than in 2D monolayers, suggesting contribution of crossfire and bystander effects. Total cell-bound activity, rather than added activity, better predicted radiotoxicity in both TP53-wild-type and TP53-null cell lines, indicating that its therapeutic effect is primarily governed by PSMA-mediated uptake rather than p53 status. These results support the therapeutic potential of [212Pb]Pb-AB001 across cells with varying TP53 status and suggest that combining [212Pb]Pb-AB001 with DNA repair or checkpoint inhibitors may enhance treatment efficacy.},
	language = {en},
	urldate = {2025-12-01},
	journal = {Scientific Reports},
	author = {Stenberg, Vilde Yuli and Liukaityte, Rugile and Kristiansen, Sandra Kvarsvik and Wangen-Riise, Rina and Kleinauskas, Andrius and Dunne, Victoria and Juzeniene, Asta},
	month = nov,
	year = {2025},
	note = {Publisher: Nature Publishing Group},
	keywords = {Cancer, Cell biology, Oncology, scientific-publication},
}