Optimization of the radiosynthesis of [68Ga]Ga-PSMA-11 using a Trasis MiniAiO synthesizer: do we need to heat and purify?

Abstract

Introdution: [68Ga]Ga-prostate specific membrane antigen (PSMA)-11 showed a clear gain in sensitivity for lesion detection in the biological recurrence of prostate cancer as compared to the standard [18F]fluorocholine radiopharmaceutical. To meet the strong demand for [68Ga]Ga-PSMA-11, we aimed to optimize an automated radiolabeling process by evaluating the influence of different key parameters on radiochemical purity and radiochemical yield. Methods: The radiosynthesis of [68Ga]Ga PSMA-11 was performed using a Trasis MiniAio synthesizer and a 68Ge/68Ga GalliaPharm generator supplied by Eckert & Ziegler, Berlin, Germany. Optimized labeling parameters were evaluated by variation of sodium acetate concentrations and temperature of radiolabeling as well as the purification process. Results: For each condition tested, radiochemical purity was higher than 99% in the final vial without batch failure, indicating a robust and fast radiosynthesis process. Radiosynthesis without the solid phase extraction purification process at room temperature in less than 5 min resulted in a radiolabeling efficiency of over 99% and remained stable at least 4 h without manual processing to limit operator radiation exposure. Conclusion: The procedure was completely automated and provided a high radiochemical yield. It can be performed several times a day, facilitating the clinical demand of this radiopharmaceutical.

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

“…Then, washing solution was passed through R1 to the waste vial (Vial A, 1 mL, by opening microfluidic valves 6 and 2 towards the waste port by passing nitrogen at 1 bar for 2 min). Lastly, [ 68 Ga]Gacitrate was formed during elution-formulation step with 136 mmol sodium citrate solution from the R1 chamber (Vial B, 4 mL, by opening microfluidic valves 33,29,22,18,13,12,7, and 1 towards the formulation chamber using nitrogen gas at 1.5 bar for 3 min). The final product was collected from the formulation chamber and was passed through the syringe port and a 0.22 µm sterile filter into the collection vial.…”

“…Herein, we describe the production of [ 68 Ga]Ga-citrate on two commercial synthesizers. The first one is the macrofluidic miniAIO ® (Trasis), and it has been used for production of numerous 68 Ga-radiopharmaceuticals such as [ 68 Ga]Ga-PSMA-11 [22,23] and [ 68 Ga]Ga-NODAGA-RGD [24]. The second one is iMiDEV ™ (PMB Alcen), a new commercially available synthesizer using microfluidic technology for radiopharmaceutical production [25].…”

Synthesis of [68Ga]Ga-PSMA-11 using the iMiDEV™ microfluidic platform

“…4,5 A number of technics have been described for a GMP-compliant 68 Ga-labelling of PSMA-11 using the 68 Ge/ 68 Ga generator on conventional automated synthesis modules (Scintomics GRP, miniAiO, iPHASE MultiSyn, iQS® Ga-68 Fluidic Labeling Module). [6][7][8][9][10] Moreover, two ready to use kits are commercially available, the first is developed by Isotopia Molecular Imaging Ltd. (isoPROtrace-11; Petach Tikva, Israel) 11,12 and the second one is from Telix Pharmaceuticals (TLX591-CDx, Illumet™ or Illuccix®; Melbourne, Australia). 12 The broadening of the theranostic approach and personalized medicine, particularly [ 177 Lu]Lu-PSMA-617 (Pluvicto®) for prostate cancer treatment, 13,14 revealed an emerging need for onsite and on-demand production of PET probes.…”

Labelling via [Al18F]2+ Using Precomplexed Al-NODA Moieties

“…These chelators can easily be linked to peptides or small molecules, which allows 68 Ga labelling of almost any substrate. Since the complex formation at the optimal pH is robust and can be achieved quantitatively within minutes, this labelling approach gained broad application both in research and routine production [ 11 , 12 ]. Standard labelling procedures with 18 F, in contrast, are more complex when covalent C-F bonds are aimed at, as in the labelling process of [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) [ 13 , 14 ].…”