High-Yielding Radiosynthesis of [68Ga]Ga-PSMA-11 Using a Low-Cost Microfluidic Device.

Abstract

Current PET radiotracer production models result in facility and operational costs that scale prohibitively with the number of tracers synthesized, particularly those made as a single dose-on-demand. Short of a paradigm shift in the technology and economics of radiotracer production, the impact of PET on precision medicine will be limited. Inexpensive, microfluidic radiochemistry platforms have the potential to significantly reduce costs associated with dose-on-demand production and expand the breadth of PET tracers accessible for molecular imaging. To produce a miniaturized dose-on-demand device for [68Ga]Ga-PSMA-11 production, a microfluidic chip was assembled in polydimethylsiloxane (PDMS), combining all components of tracer production in an integrated, compact, and easily utilized platform. On-chip radionuclide concentration, as well as radionuclide and precursor starting material mixing and reaction were incorporated. The radionuclide was sourced from a standard, commercially available 68Ge/68Ga generator. Optimal reaction conditions were determined, which included precursor concentration (5μg/mL), temperature (95°C), and reaction time (1min). The total trapping efficiency of combined on-chip SCX and SAX columns was greater than 70% and could be accomplished in ~ 12min. Under optimized conditions, [68Ga]Ga-PSMA-11 could be reliably synthesized starting from a complete generator elution (1100MBq [29.7mCi]) in ~ 12min, with an average radiochemical yield of 70%, radiochemical purity > 99%, and specific activity > 740MBq/μg (20mCi/μg). Quality control testing demonstrated that tracer produced using this platform met or exceeded all typical FDA requirements for human use. A simple, low-cost, dose-on-demand radiosynthesis strategy, such as the chip presented here, represents an opportunity to reduce the financial barriers associated with PET imaging. While this study focused on a device for [68Ga]Ga-PSMA-11, the technology is also applicable to a wide range of other tracers where low-cost, automated, dose-on-demand production is highly desirable.