3D-printed automation for optimized PET radiochemistry

Abstract

Reproducible batch synthesis of radioligands for imaging by positron emission tomography (PET) in a manner that maximizes ligand yield, purity, and molar activity, and minimizes cost and exposure to radiation, remains a challenge, as new and synthetically complex radioligands become available. Commercially available automated synthesis units (ASUs) solve many of these challenges but are costly to install and cannot always accommodate diverse chemistries. Through a reiterative design process, we exploit the proliferation of three-dimensional (3D) printing technologies to translate optimized reaction conditions into ASUs composed of 3D-printed, electronic, and robotic parts. Our units are portable and robust and reduce radiation exposure, shorten synthesis time, and improve the yield of the final radiopharmaceutical for a fraction of the cost of a commercial ASU. These 3D-printed ASUs highlight the gains that can be made by designing a fit-for-purpose ASU to accommodate a synthesis over accommodating a synthesis to an unfit ASU.

From circular synthesis to material manufacturing: advances, challenges, and future steps for using flow chemistry in novel application area

“…For example, Babich and co-workers 3D-printed an automated synthesis unit (ASU) that allowed less radiation exposure for the synthesis of radioligands containing 68 Ga, 18 F, and 11 C (radioactive PET tracers). 134 Neumaier and co-workers explored the synthesis of PET tracers in a 3D-printed ASU made of PEEK. 135 The authors applied a Villermaux-Dushman protocol to estimate the mixing efficiency for the multistep synthesis of clofarabine precursor.…”

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

“…Alejandro Amor-Corasa et al . recently developed and reported the lightweight (4 kg) and fully automated 3D-printed cassette-based synthesis unit for 11 C-labeled fatty acid production, giving [ 11 C]palmitic acid with a RCYs 57.2 ± 12.4% to the EOS within 10 min. , …”

“…Adding acid to the solution, the Grignard reagent in excess was quenched, and [ 1 - 11 C]­palmitic acid obtained was solubilized with serum albumin (solution 4% in saline), providing [ 1 - 11 C]­palmitic acid in injectable form for the biological test. The entire procedure took 30 min from the carbonation and produced 400–700 MBq of [ 1 - 11 C]­palmitic acid starting from 7.4 GBq of [ 11 C]­CO 2 . , Further optimizations of this radiosynthetic procedure allowed increased isolated RCY, Am, and reaction time. ,,− A remote semiautomated chemical process system developed by Padgett et al . with a more accessible product purification, through column chromatography on acetic acid-treated neutral alumina oxide, in 30 min synthesis time obtained [ 1 - 11 C]­palmitic acid with A m higher than 0.259 GBq/μmol .…”

“…Furthermore, an automated SPE-based radiosynthesis achieved [ 1 - 11 C]­palmitic acid in 33% isolated RCY within 10 min from [ 11 C]­CO 2 trapping, which increased in a solid-based method obtaining [ 1 - 11 C]­palmitic acid in 8 min from EOB, 38% isolated RCY, and A m of 9.25–12.95 GBq/μmol and 50% isolated RCY in 15 min using column extraction method. − Recently, Amor-Coarasa et al . developed a 3D-printed automated synthesis unit able to produce [ 1 - 11 C]­palmitic acid with 57% isolated RCY within 6.5 min …”

Photocatalysis in the Life Science Industry

“…A year later, the same team published the use of an AllinOne synthesizer from Trasis for a fully automated synthesis of an 18 F-labeled acyclovir derivative 132. 293 The photoreactor element consisted of FEP tubing within a 3D-printed plate 380 that was irradiated by a Kessil lamp. Using this workflow, the three-step procedure for the synthesis of 2-(CHF 18 F)-acyclovir 132 was achieved in 95 min without manual intervention (Scheme 133).…”