Microfluidic-based production of [⁶⁸Ga]Ga-FAPI-46 and [⁶⁸Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic...

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Microfluidics

Background:

• Increasing demand for ⁶⁸Ga-labeled radiotracers like FAPI derivatives and PSMA-11 for theranostic applications.
• ⁶⁸Ga-labeled FAPI-46 for broad cancer diagnosis and ⁶⁸Ga-labeled DOTA-TOC for neuroendocrine tumors are key clinical probes.
• Need for efficient and reliable synthesis methods to meet clinical demand.

Purpose of the Study:

• To develop and validate a microfluidic synthesis method for ⁶⁸Ga-labeled FAPI-46 and ⁶⁸Ga-labeled DOTA-TOC.
• To utilize a dose-on-demand (DOD) approach with the iMiDEV radiosynthesizer.
• To optimize synthesis parameters for improved yield and purity.

Main Methods:

• Utilized a microfluidic cassette-based iMiDEV radiosynthesizer.
• Employed a dose-on-demand (DOD) approach for synthesis.
• Optimized ⁶⁸Ga trapping, elution, mixing, and purification (SPE).

Main Results:

• Achieved decay-corrected yields of 44 ± 5% for [⁶⁸Ga]Ga-FAPI-46 and 46 ± 7% for [⁶⁸Ga]Ga-DOTA-TOC in ~30 min.
• Obtained high radiochemical purities: 98.2 ± 0.2% for [⁶⁸Ga]Ga-FAPI-46 and 98.4 ± 0.9% for [⁶⁸Ga]Ga-DOTA-TOC.
• Reduced precursor and chemical usage by 2-3 times compared to conventional methods.
• All quality control results met European Pharmacopoeia standards.

Conclusions:

• The microfluidic approach on the iMiDEV module enables efficient radiosynthesis of [⁶⁸Ga]Ga-FAPI-46 and [⁶⁸Ga]Ga-DOTA-TOC.
• This method facilitates preclinical and clinical applications and reduces precursor requirements.
• Validated synthesis demonstrates the potential of microfluidics for routine radiopharmaceutical production.