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Evaluation of an 211At-labeled RGD peptide in an orthotopic glioblastoma model by targeted alpha therapy
Hiroaki Echigo1, Masayuki Munekane1, Takeshi Fuchigami1
1Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
Introduction:
Glioblastoma, the most aggressive and malignant glioma type, remains challenging to treat, necessitating novel therapeutic strategies. Building on our previous development of an 211At-labeled RGD peptide, Ga-DOTA-K([211At]APBA)-c(RGDfK) ([211At]1), that showed high tumor uptake and excellent therapeutic effects in subcutaneous tumor-bearing mice, we investigated its potential as a glioblastoma therapeutic agent in an orthotopic GL261 mouse model.
Methods:
Cellular uptake of [211At]1 and corresponding radioiodine-labeled compound, Ga-DOTA-K([125I]IPBA)-c(RGDfK) ([125I]2), was evaluated in GL261 cells. Glioblastoma model mice were prepared. Ex vivo autoradiography confirmed [211At]1 and [125I]2 accumulation in brain tumor sites. Therapeutic experiments with [211At]1 were conducted in these glioblastoma model mice.
Results:
[211At]1 and [125I]2 showed time-dependent uptake in GL261 cells. In glioblastoma model mice, [211At]1 and [125I]2 selectively accumulated in brain tumor regions, with a tumor-to-normal brain radioactivity ratio of 16.6 ± 4.1 and 9.7 ± 3.7, respectively. A single intravenous injection of [211At]1 (270 kBq) significantly prolonged survival in these mice.
Conclusion:
[211At]1 is a promising candidate for targeted alpha therapy in glioblastoma.
Insights
Astatine-211 labeled RGD peptide shows promise for glioblastoma treatment. This targeted alpha therapy agent demonstrated significant tumor uptake and prolonged survival in preclinical mouse models, offering a new therapeutic avenue.
Area of Science:
- Oncology
- Radiochemistry
- Nuclear Medicine
Background:
- Glioblastoma is an aggressive brain cancer with limited treatment options.
- Novel therapeutic strategies are urgently needed to improve patient outcomes.
- Previous studies showed efficacy of an 211At-labeled RGD peptide in subcutaneous tumors.
Purpose of the Study:
- To evaluate the therapeutic potential of an 211At-labeled RGD peptide (Ga-DOTA-K([211At]APBA)-c(RGDfK), [211At]1) in an orthotopic glioblastoma mouse model.
- To assess the tumor-targeting capabilities and therapeutic effects of [211At]1.
Main Methods:
- Cellular uptake studies of [211At]1 and a radioiodine-labeled control ([125I]2) in GL261 cells.
- Preparation of orthotopic GL261 glioblastoma mouse models.
- Ex vivo autoradiography to confirm tumor accumulation.
- Therapeutic efficacy assessment via survival studies after [211At]1 administration.
Main Results:
- [211At]1 and [125I]2 exhibited time-dependent uptake in GL261 cells.
- Selective accumulation of [211At]1 and [125I]2 in brain tumor regions was confirmed, with high tumor-to-normal brain ratios.
- A single dose of [211At]1 significantly extended survival in glioblastoma-bearing mice.
Conclusions:
- [211At]1 demonstrates significant potential as a targeted alpha therapy agent for glioblastoma.
- The RGD peptide's ability to target glioblastoma tumors offers a promising strategy for radionuclide therapy.
