Dose-Dependent Cellular Phenotypic Change Induced by <sup>177</sup>Lu-Oxodotreotide Treatment in IMR-32 Cells
<b>Objectives</b>: Beta-emitting radionuclide therapy, exemplified by <sup>177</sup>Lu-Oxodotreotide (Lutathera<sup>®</sup>), enables targeted treatment of neuroendocrine tumors by delivering β-radiation to tumor cells. However, the dose-dependent molecular mechan...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1543 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <b>Objectives</b>: Beta-emitting radionuclide therapy, exemplified by <sup>177</sup>Lu-Oxodotreotide (Lutathera<sup>®</sup>), enables targeted treatment of neuroendocrine tumors by delivering β-radiation to tumor cells. However, the dose-dependent molecular mechanisms underlying cellular damage remain insufficiently characterized. This study aimed to investigate the phenotypic changes in IMR-32 human neuroblastoma cells following Lutathera exposure, with a focus on the dose-dependent relationship between radiation and cellular damage. <b>Methods</b>: IMR-32 cells were allocated to control, low- (0.05 MBq/mL), medium- (0.5 MBq/mL), and high-dose (5 MBq/mL) groups and treated with <sup>177</sup>Lu-Oxodotreotide for 24 h. Flow cytometry was employed to assess cell viability, apoptosis, mitochondrial membrane potential, γ-H2AX expression (a marker of DNA damage), and proliferation. <b>Results</b>: Lutathera induced dose-dependent cytotoxic effects. Cell viability declined linearly with increasing dose (control: 100% vs. high-dose: 13.48%; r = −0.955, <i>p</i> < 0.001). Apoptosis was significantly elevated (control: 35.34% vs. high-dose: 88.12%; r = 0.999), accompanied by increased γ-H2AX levels (control: 5.26 × 10<sup>4</sup> vs. high-dose: 13.13 × 10<sup>4</sup>; r = 0.930), indicating DNA double-strand breaks. Mitochondrial membrane potential decreased (control: 6.06 × 10<sup>4</sup> vs. high-dose: 46.27 × 10<sup>4</sup>; r = 0.999), and proliferation was suppressed (control: 91.10 × 10<sup>4</sup> vs. high-dose: 103.84 × 10<sup>4</sup>; r = 0.954), both showing strong dose correlations (<i>p</i> < 0.001). <b>Conclusions</b>: <sup>177</sup>Lu-Oxodotreotide exerts dose-dependent cytotoxicity in IMR-32 cells via DNA damage, mitochondrial dysfunction, and apoptosis induction. These findings underscore the necessity of optimizing dosing regimens to balance therapeutic efficacy and safety in clinical settings, providing a foundation for personalized β-emitter therapies. |
|---|---|
| ISSN: | 2227-9059 |