Folate Receptor Alpha Targeted Immuno-Positron Emission Tomography Probe for Noninvasive Imaging in Triple-Negative...

Area of Science:

• Oncology
• Nuclear Medicine
• Radiochemistry

Background:

• Triple-negative breast cancer (TNBC) is heterogeneous with poor chemotherapy response.
• Folate receptor alpha (FRα) is an emerging therapeutic target in epithelial cancers.
• FRα expression in TNBC is not well-characterized, impacting targeted therapy selection.

Purpose of the Study:

• To evaluate FRα expression in clinical TNBC specimens.
• To develop and validate an immunoPET probe for noninvasive FRα quantification in TNBC.

Main Methods:

• FRα expression analysis in 176 TNBC tissue specimens.
• Synthesis and characterization of ⁸⁹Zr-DFO-Mirvetuximab immunoPET probe.
• In vitro cell uptake and binding affinity assays.
• In vivo micro-PET/CT imaging and biodistribution studies in TNBC xenograft mouse models.

Main Results:

• 84% of TNBC specimens showed no FRα expression; remaining showed low to moderate positivity.
• ⁸⁹Zr-DFO-Mirvetuximab exhibited high radiochemical purity, stability, and FRα-specific targeting.
• In vivo studies showed significantly higher probe uptake in FRα-high tumors compared to FRα-low tumors.

Conclusions:

• ⁸⁹Zr-DFO-Mirvetuximab enables noninvasive quantification of FRα expression in TNBC.
• This probe can identify TNBC patients suitable for FRα-targeted therapies like Mirvetuximab soravtansine.
• The immunoPET probe aids in patient stratification and monitoring treatment response.