A rapid prototyping platform for radiochemistry automation: experience with Ga-68 labeling (2018)

1037 Objectives: Five Eleven Pharma (511P) is developing a simple, low-cost device for automating the preparation of Ga-68 labeled drugs at any site that is performing PET imaging. The goals of this work are to describe the automation platform used, how it was applied to Ga-68 drug preparation using a commercial Ge-68/Ga-68 generator and to summarize experience from > 300 runs supporting both research and clinical trial dose production. Methods: Fully functional prototype devices were constructed based on the Maestro family of servo controllers (Pololu, Las Vegas, NV, USA) that are commonly used in consumer robot kits and remote controlled (RC) products. Maestro servo controllers are available in several standard input/output configurations (6 - 24 channel) that include a native USB interface and internal scripting control. The use of RC-compatible devices or RC-switched relays (Pololu) simplified interfacing of fluid control components including solenoid valves (NResearch, West Caldwell, NJ, USA; Parker, Hollis, NH, USA), diaphragm pumps (KNF Neuberger, Trenton, NJ, USA; Parker) and miniature linear actuators (Actuonix, Victoria BC, Canada). All prototype devices were based on industry-standard, single-use disposable stopcock components (Elcam, Hackensack, NJ, USA) that were interfaced to servomotors (Pololu) using custom 3D printed (Objet30, VeroBlack material) actuators. Devices supporting clinical trial dose production automate (1) generator elution (2) heating and cooling of Ga-68 labeling vial (3) solid phase cartridge purification (4) formulation and (5) sterilization by terminal filtration, and do not require a phone, tablet or laptop to operate. Ga-68 labeling of more than 9 different compounds including “generic” PSMA-11 and DOTATOC, as well as 511P’s proprietary compounds ([68Ga]P15-041; [68Ga]P16-093 - both HBED-CC based) under clinical investigation (NCT02826382; NCT03073395) was evaluated using the prototype devices. Results: Constraints for device development included accelerated prototyping cycle (3-4 months from concept to first “hot” run), low-cost, compact size and robust/self-contained “pushbutton” operation. At initial device development, 4 major design evolutions were achieved in ~ 11 months, meeting the cycle-time goal. In a period of ~39 months, 13 separate fully functional prototypes were constructed in-house, 9 of which were fully tested with Ga-68 and deployed among 4 sites. Cumulatively more than 300 runs have been completed with only 3 (early) component failures (same plastic bolt since replaced with metal). Production time including generator elution to final product formulation is 15 - 25 min. In one configuration, DOTATOC, PSMA-11 and [68Ga]P15-041 were produced back-to-back-to-back ~ 3 hours apart with decay corrected yields (24 minutes) of 78%, 83% and 87% respectively, using the same conditions but different purification cartridges. Decay corrected (17 min) production yields at one clinical trial site are 85% ± 3.3% (N=18) and 75% ± 16% (N=29) for [68Ga]P15-041 and [68Ga]P16-093 respectively. QC passes all requirements for human use including Ge-68 breakthrough