Establishing In Vitro Dosimetric Models and Dose–Effect Relationships for177Lu-DOTATATE in Neuroendocrine Tumors

• DOI: 10.2967/jnumed.125.269470
• Publication Date: 2025-05-22T19:00:39Z
• Authors: Giulia Tamborino; Pleun Engbers; Tijmen H. de Wolf; Thom G.A. Reuvers; Rob Verhagen; Mark Konijnenberg; Julie Nonnekens

This study investigates the radiobiology of peptide receptor radionuclide therapy (PRRT) using clinically relevant cancer cell lines by developing a framework for realistic cellular dosimetry in 2- and 3-dimensional cluster-forming configurations. Methods: The radiobiologic responses GOT1 NCI-H69 tumor to PRRT external beam radiotherapy (EBRT) were compared. Viability at 7 d death multiple time points assessed. Image-based multicellular models developed reflect vitro exposure complexity compared with traditional approaches. Results: absorbed dose suspension was dominated medium during incubation cross-dose within small clusters after incubation. Our findings reveal that can underestimate doses up 90% plated setups overlooks heterogeneity, initial rates varying 2.3-fold based on cluster size arrangement. maximum relative biologic effectiveness EBRT loss viability 0.43 ± 0.07 cells 0.22 0.02 cells. showed greater resistance PRRT-induced than EBRT, whereas exhibited similar levels both treatments, albeit different dose-response dynamics. Conclusion: requires average an 3 times higher achieve equivalent effects vitro. Traditional overestimates underestimating dose.