Targeted alpha therapy for glioblastoma.

Area of Science:

• Oncology
• Radiochemistry
• Neuroscience

Background:

• Glioblastoma (GB) is an aggressive primary brain tumor with poor prognosis, characterized by infiltration and heterogeneity.
• Current treatments (surgery, radiotherapy, chemotherapy) offer limited survival benefits, with high recurrence rates (90% within 6 months).
• Local drug delivery is a promising strategy due to glioblastoma recurrence near the primary site.

Purpose of the Study:

• To evaluate the potential of local radioisotope therapy for glioblastoma (GB).
• To investigate the NK-1 receptor as a target for glioblastoma treatment.
• To summarize experience with alpha-emitting radioisotopes ([213Bi]Bi-DOTA-SP, [225Ac]Ac-DOTA-SP) for local glioblastoma therapy.

Main Methods:

• Targeting the overexpressed NK-1 receptor in glioblastoma using substance P (SP) as a ligand.
• Utilizing alpha-emitting radioisotopes (e.g., 213Bi, 225Ac) for targeted radiation delivery.
• Local administration of radiolabeled SP conjugates ([213Bi]Bi-DOTA-SP, [225Ac]Ac-DOTA-SP) for primary and secondary glioblastomas.

Main Results:

• Alpha particles offer advantages over beta radiation, including high linear energy transfer and short range, maximizing tumor cell dose while sparing healthy tissue.
• The biological effects of alpha radiation are independent of cell cycle, oxygenation, and MGMT methylation status.
• Local radioisotope therapy with [213Bi]Bi-DOTA-SP or [225Ac]Ac-DOTA-SP was explored for glioblastoma treatment.

Conclusions:

• Targeting the NK-1 receptor with alpha-emitting radioisotopes presents a promising approach for localized glioblastoma treatment.
• Local alpha-particle therapy demonstrates potential for improved efficacy and reduced toxicity compared to conventional systemic treatments.
• Further research into substance P-based alpha-radionuclide therapy is warranted for glioblastoma management.