Automated production of [⁶⁸Ga]Ga‐DOTANOC and [⁶⁸Ga]Ga‐PSMA‐11 using a TRACERlab FX_FN synthesis module

Abstract

The interest in gallium-68 labelled positron-emission tomography probes continues to increase around the world. However, one of the barriers for routine clinical use is the cost of the automated synthesis units for relatively simple labelling procedures. Herein, we describe the adaptation of a TRACERlab FX FN synthesis module for the automated production of gallium-68 radiopharmaceuticals using a cation-exchange cartridge for postprocessing of the 68 Ge/ 68 Ga generator eluate. The recovery of activity from the cartridge was 95.6% to 98.9% using solutions of acidified sodium chloride (5 M with pH = 1-3).The radiosyntheses of [ 68 Ga]Ga-DOTANOC and [ 68 Ga]Ga-PSMA-11 were performed using acetate sodium buffer or 4-(2-hydroxyethyl)piperazine-1ethanesulfonic acid, with a total duration of 21 and 23 minutes, respectively, including generator elution and radiopharmaceutical dispensing. Activity yields were 77% ± 2% for [ 68 Ga]Ga-PSMA-11 and 68% ± 3% for [ 68 Ga]Ga-DOTANOC (n > 100). The labelled peptides had a radiochemical purity exceeding 97%, and all quality control parameters were in conformity with the limits prescribed by the European Pharmacopoeia.

Fully Automated Macro- and Microfluidic Production of [68Ga]Ga-Citrate on mAIO® and iMiDEVTM Modules

“…This finding differs from Jensen's method using SCX to perform [ 68 Ga]Ga-citrate production. Nevertheless, SCX is often used to perform purification of 68 Ga eluate obtained from the 68 Ge/ 68 Ga generator by the Muller method (5M NaCl/HCl) [27,28]. AG 50W-X8 support was also reported for the purification of 68 Ga eluate using the Zhernosekov method (HCl/acetone) for 68 Ga elution [29].…”

Development of an automated production process of [64Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications

“…From a general radiotracer production perspective, modern facilities have growing focuses on using automated production modules that can be placed into a fully shielded hot cell for high efficiency, high consistency, and high specific activity productions, in addition to minimizing radiation exposure to the production personnel. 19 Such synthesis modules have been commercialized and deployed in hospitals and productions sites for the synthesis of PET tracers such as 2-deoxy-2-[ 18 F] fluoroglucose ([ 18 F]FDG) and 1-(2-nitro-imidazolyl)-3-[ 18 F]fluoro-2-propanol ([ 18 F]FMISO). [20][21][22] On the other hand, these automated synthesis modules also have some associated challenges, including reconfiguration of the synthesis modules between different tracers or usage of multiple synthesis modules for different types of radiopharmaceuticals.…”

“…23,25 Tracerlab FX FN has also been used for the radiosynthesis of generator produced gallium-68 radiopharmaceuticals with excellent results. [26][27][28] Recently reported sequential elution approach of 61/64 Cu 2+ produced in a liquid target also utilized both cationic and anionic resins with a drying step to remove HCl and further re-dissolve and elute the copper in buffered solution. This synthesis was performed on an IBA Synthera ® Extension synthesizer, which can also be used in the automated synthesis of [ 61/64 Cu][Cu (ATSM)] in a cassette-based synthesis 14 and also recently demonstrated on a Fastlab (GE Healthcare) cassette-based system with solid target produced Cu-61/Cu-64.…”

“…Among the various methods, the 64 Ni(p,n) 64 Cu route in a biomedical cyclotron attracted substantial popularity partly due to the simplicity of the reaction and isolation process using ion‐exchange column, and more importantly the increasing availability of biomedical cyclotron facilities in research and hospital facilities, in contrast to the much limited access of a reactor facility. From a general radiotracer production perspective, modern facilities have growing focuses on using automated production modules that can be placed into a fully shielded hot cell for high efficiency, high consistency, and high specific activity productions, in addition to minimizing radiation exposure to the production personnel 19 . Such synthesis modules have been commercialized and deployed in hospitals and productions sites for the synthesis of PET tracers such as 2‐deoxy‐2‐[ 18 F]fluoroglucose ([ 18 F]FDG) and 1‐(2‐nitro‐imidazolyl)‐3‐[ 18 F]fluoro‐2‐propanol ([ 18 F]FMISO) 20–22 .…”

Automated radiosynthesis of [68Ga]Ga‐PSMA‐11 and [177Lu]Lu‐PSMA‐617 on the iPHASE MultiSyn module for clinical applications

“…Protocols for the manual, semiautomatic and fully automatic production of [ 68 Ga]Ga‐PSMA‐11 have been published with overall radiochemical production yields for manual and semiautomatic processes generally >90% 17–22 and fully automated procedures including product formulation ranging between 57‐80% decay‐corrected (d.c.) radiochemical yield 23–28 . Manual and fully automated production of [ 177 Lu]Lu‐PSMA‐617 has been reported in >90% radiochemical yields 29–32 …”