Radiobiological Assessment of Targeted Radionuclide Therapy with [¹⁷⁷Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models

Author(s)

Julia Raitanen, Bernadette Barta, Hermann Fuchs, Marcus Hacker, Theresa Balber, Dietmar Georg, Markus Mitterhauser

Abstract

In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [¹⁷⁷Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others.

Organisation(s)

Department of Inorganic Chemistry, Joint Applied Medicinal Radiochemistry Facility

External organisation(s)

Medizinische Universität Wien, Ludwig Boltzmann Institute, Vienna Doctoral School in Chemistry (DoSChem)

Journal

International Journal of Molecular Sciences

Volume

24

ISSN

1661-6596

DOI

https://doi.org/10.3390/ijms242317015

Publication date

12-2023

Peer reviewed

Yes

Austrian Fields of Science 2012

106023 Molecular biology, 104020 Radiochemistry, 301904 Cancer research

Keywords

ASJC Scopus subject areas

Catalysis, Molecular Biology, Spectroscopy, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/7d58e177-51a8-4a6b-9c0d-5f370c4c4772