Multi-GBq production of the radiotracer [¹⁸F]fallypride in a droplet microreactor

Abstract

Using a micro-cartridge based radionuclide concentrator enables the production of multiple (10 s) of clinical doses of the PET tracer [18F]fallypride with a droplet micro-reactor platform (8 μL).

High-Efficiency Production of Radiopharmaceuticals via Droplet Radiochemistry: A Review of Recent Progress

“…The droplet-based synthesis is then carried out and the crude product collected, followed by downstream purification and formulation. Adapted from Wang et al 37 with permission from The Royal Society of Chemistry.…”

“…Inset photograph shows the detailed chip design (top view). Adapted from Wang et al 37 with permission from The Royal Society of Chemistry. E, Schematic of the Teflon coated glass chip and the heating setup.…”

“…More recently, the concentrator was integrated with the PT-based radiosynthesizer to scale up the starting activity for the synthesis of [ 18 F]Fallypride as shown in Figure 7. 37 An optimized method to transfer this volume to the chip was developed, consisting of delivery of the collected concentrated activity as a series of small (0.5 mL) droplets, followed by rinsing the activity collection vial and dispensing the rinse solution to the chip in the same fashion. Using this approach, 96% of the starting activity was loaded onto the chip and localized at the reaction site.…”

Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use

“…However, due to the disparity between the volume of radioisotope solutions (~ 1 mL) and reaction volumes of microscale systems (as low as 1–10 s of µL), relatively small amounts of product activity have been acquired, suitable only for preclinical imaging 19 , 24 , 25 . Nevertheless, clinically-relevant quantities of various diagnostic radiopharmaceuticals has been produced with such microscale systems: [ 13 N]NH 3 26 , [ 68 Ga]Ga-PSMA-11 27 , [ 89 Zr]Zr-DFO-Trastuzamab 28 , [ 18 F]FDG 29 , 30 , [ 18 F]FET 31 , [ 18 F]fallypride 32 , 33 , [ 18 F]FT807 34 , [ 18 F]FPEB 35 , [ 18 F]FLT 36 and [ 18 F]FMISO 36 , 37 . A summary of reports of the 18 F-labeled ones is included in Table 1 .…”

“…not reported. Reference This work Wang et al 33 Lebedev et al 32 Frank et al 29 Liang et al 34 Liang et al 35 Zheng et al 37 Akula et al 36 Awasthi 30 Iwata et al 31 Microfluidic synthesis platform Droplet-based radiosynthesizer Droplet-based radiosynthesizer PEEK/pDCPD chip with syringe-type microvalves GE ISAR Advion NanoTek Advion NanoTek Advion NanoTek Advion NanoTek ABT BG75 Disposable glass vials with a fused 300-μL insert Synthesis format Batch Batch Batch Batch Flow Flow Flow Flow Batch Batch Tracer(s) produced [ 18 F]FET [ 18 F]FBB [ 18 F]Fallypride [ 18 F]Fallypride [ 18 F]FDG [ 18 F]T807 [ 18 F]FPEB [ 18 F]FMISO [ 18 F]FLT [ 18 F]FMISO [ 18 F]FDG [ 18 F]FET Starting activity (GBq) …”