Automated Radiosynthesis of High-Molar-Activity 4-Borono-2-[18F]Fluorophenylalanine: Validation in Rodent Tumor...

Area of Science:

• Radiochemistry
• Medical Imaging
• Oncology

Background:

• Boron Neutron Capture Therapy (BNCT) efficacy depends on accurate patient stratification.
• The diagnostic tracer 4-borono-2-[18F]fluorophenylalanine ([18F]FBPA) is essential for this stratification.
• Current production methods for [18F]FBPA have limited capacity and low molar activity, hindering clinical use.

Purpose of the Study:

• To develop a fully automated, GMP-compliant radiosynthesis of [18F]FBPA.
• To achieve high molar activity and radiochemical yield for clinical-grade [18F]FBPA.
• To evaluate the in vivo performance and pharmacokinetic profile of the synthesized [18F]FBPA for BNCT.

Main Methods:

• Utilized a spirocyclic iodonium ylide (SCIDY) precursor on a commercial module for automated radiosynthesis.
• Assessed radiochemical yield, molar activity, and purity of the produced [18F]FBPA.
• Conducted in vivo studies in tumor xenograft and orthotopic models, and pharmacokinetic studies in nonhuman primates.

Main Results:

• Achieved a decay-corrected radiochemical yield of 15.5% ± 6.3% and high molar activity of 75.9 ± 20.0 GBq/μmol.
• Demonstrated high specificity for LAT1-positive tumors and effective blood-brain barrier penetration in glioma models.
• Showed rapid renal clearance, low background in head-and-neck organs, and a favorable effective dose of 0.012 mSv/MBq in primates.

Conclusions:

• Established a robust, clinical-ready automated radiosynthesis for high-molar-activity [18F]FBPA.
• The developed method addresses production limitations, facilitating wider clinical application of BNCT.
• This advancement supports precise patient stratification and optimized BNCT treatment planning.