Production of [⁶⁸Ga]Ga‐PSMA: Comparing a manual kit‐based method with a module‐based automated synthesis approach

Abstract

The labeling of peptides with gallium-68 is often initially performed by manual labeling, but with high clinical demand, other alternatives are needed. Coldkits or automated synthesis are viable options for standardized methods and deemed pharmaceutically more acceptable. This study compares these [ 68 Ga] Ga-PSMA-11 production methods. Data from 40 kit-based and 40 automated syntheses of [ 68 Ga]Ga-PSMA-11 were analyzed. Pre-set criteria were evaluated including radiochemical purity, radionuclidic purity, chemical purity, physiological acceptability and sterility. The operator time and radiation dose received were measured. The robustness and repeatability of each method were assessed and a comparison of the running costs of each method is also provided. For both the methods all the analyzed products met the release criteria. No differences were found in radiochemical purity, radiochemical identity, radionuclidic purity, and sterility. However, radiochemical yield and apparent molar activity showed significant differences. For both methods, whole body radiation exposure to operators was lower than with manual labeling (25-40 μSv). The exposure during kit-based labeling (14.5 ± μSv) was seven times higher than that of automated synthesis (2.05 ± 0.99 μSv). The automated synthesis was the more expensive method. Both methods are sound alternatives to manual synthesis and offer higher quality, better radiation protection and a more reliable manufacturing of radiopharmaceuticals.

Efficient Production of the PET Radionuclide 133La for Theranostic Purposes in Targeted Alpha Therapy Using the 134Ba(p,2n)133La Reaction

“…Compared with other diagnostically used tracers, the value is rated as high, especially for radiometal-based conjugates. For comparison, an apparent molar activity ≥ 18.5 GBq/µmol to 35.5 GBq/µmol is usually exhibited for clinically applied [ 68 Ga]Ga-PSMA-11 [ 34 , 35 ].…”

Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

“…On the other hand, this, plus shorter production time and higher radiolabeling yield with the kit than with automated module synthesis, might allow for multiple patient preparations, although kits are usually recommended as single-dose preparations ( 118 , 124 , 125 ). Regarding outcomes of both processes, in terms of product characteristics, quality control gave comparable results ( Figure 6A ), and both methods are reliable and comply with Good Manufacturing Practices and European Pharmacopeia specifications ( 113 , 124 , 126 , 127 ). In terms of clinical applications, a direct comparison on patients with prostate cancer found no significant differences in PET/CT image quality ( Figures 6B,C ) ( 126 ).…”

“…They reported 70 and 132 μSv for the automated labeling (left and right hand) and 179 and 152 μSv for the kit-based preparation. In the study by Kleynhans et al on [ 68 Ga]Ga-HBED-CC-PSMA-11 synthesis, whole-body exposure was found to be significantly lower for the automated synthesis with 2.05 ± 0.99 μSv vs. 14.32 ± 5.3 μSv per synthesis ( 127 ). However, automated synthesis was performed on a hot cell with 50-mm lead shielding, while the kit preparation was realized in a 3-mm lead-shielded class II biosafety cabinet, with a 10-mm lead shielded tabletop shield.…”

“…To detail more precisely the cost efficiency of 68 Ga cold kit labeling, besides savings on expensive synthesizer and its maintenance, and, according to local regulation, even the need for a shielded hot cell, cost per synthesis is significantly decreased. For instance, Kleynhans et al calculated that one [ 68 Ga]Ga-HBED-CC-PSMA-11 synthesis with a module and commercially available cassette and precursor costed 274 €, and that the cold-kit synthesis amounted for only 10 € with an in-house made kit ( 127 ). It should be noted that a commercial kit would be more expensive.…”

Recent Breakthrough in 68Ga-Radiopharmaceuticals Cold Kits for Convenient PET Radiopharmacy

“…The Kleynhans group recently compared kit- and module-based production of 68 Ga-PSMA-11 . The study analyzed 40 preparations of 68 Ga-PSMA-11 from each method.…”