Translational Theranostics in Glioblastoma: FAPI-46 as a Precision Medicine Tool

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Glioblastoma is a highly lethal brain cancer with poor prognosis.
• Fibroblast activation protein (FAP) is a promising target due to its expression in glioblastoma.
• Theranostic agents offer simultaneous diagnosis and therapy.

Purpose of the Study:

• To evaluate FAP-targeted molecular probes (FAPI-46) as theranostic agents for glioblastoma.
• To assess the efficacy of radiolabeled FAPI-46 in preclinical glioblastoma models.
• To investigate FAPI-46's potential in human glioblastoma patients.

Main Methods:

• Established glioblastoma cell lines (U-87 MG, SB28) in immunodeficient and immunocompetent models.
• Radiolabeled FAPI-46 with 68Ga for imaging, and 225Ac or 177Lu for therapy.
• Evaluated tumor uptake, therapeutic efficacy, immunomodulatory effects, and survival in preclinical studies and patient imaging.

Main Results:

• [68Ga]Ga-FAPI-46 showed high tumor uptake in subcutaneous xenografts.
• [225Ac]Ac-FAPI-46 combined with temozolomide improved survival in preclinical models.
• [68Ga]Ga-FAPI-46 exhibited low uptake in orthotopic models and patients, indicating poor blood-brain barrier penetration.

Conclusions:

• FAPI-46 shows theranostic potential for peripheral glioblastoma models.
• Limited blood-brain barrier penetration restricts FAPI-46's efficacy for orthotopic glioblastoma.
• Future research is needed to enhance FAPI-46's clinical applicability in brain tumors.