Clinically Applicable Cyclotron-Produced Gallium-68 Gives High-Yield Radiolabeling of DOTA-Based Tracers

Abstract

By using solid targets in medical cyclotrons, it is possible to produce large amounts of 68GaCl3. Purification of Ga3+ from metal ion impurities is a critical step, as these metals compete with Ga3+ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting 68GaCl3could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. 68GaCl3 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The 68Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The 68GaCl3eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [68Ga]Ga-DOTATOC and [68Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of 68Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer

“…In the near future, the production of [ 68 Ga]Gallium chloride by cyclotron and a liquid target will likely improve the limited amounts of injectable radioligands by starting with activities 20-30 fold greater than those obtained with a generator [9,10]. RCY should be carefully evaluated in this new scenario.…”

Preclinical Evaluation of a Lead Specific Chelator (PSC) Conjugated to Radiopeptides for 203Pb and 212Pb-Based Theranostics

“…Upon purification, generator eluate was loaded on a SPE column filled with 50 mg RE2 resin. The RE2 resin was then rinsed with 1 mL of 2 M HCl containing 1 mg sodium ascorbate to remove Fe(III) by reducing it to Fe(II) [ 34 ]. Then, 7.4 MBq of purified 212 Bi was eluted into the reaction vessel containing 1 or 5 µM PSC-PEG-T in 1 M NaOAc buffer at final pH 5.4.…”

Good practices for 68Ga radiopharmaceutical production

“…Using this updated method, apparent molar activity (AMA) was determined to be in the range of 100 to 200 GBq/µmol for DOTA- based tracers. As a comparison, the clinical batches from generator 68 Ga had an AMA of 27.5–42.5 GBq/µmol for [ 68 Ga]Ga-PentixaFor (Spreckelmeyer et al 2020 ) or 13–30 GBq/µmol for [ 68 Ga]Ga-FAPI-46 (Spreckelmeyer et al 2020 ; Jussing et al 2021 ). In the case of potent ligands, the amount that can be administered without induction of pharmacological effects can be small.…”