Fully Automated cGMP Preparation of ⁶⁸Ga-PSMA-11 at Curie Level Using Cyclotron-Produced ⁶⁸Ga

Objectives: ⁶⁸Ga-PSMA-11 is currently one of the most widely used PET agent for imaging both recurrent prostate cancer and relevant metastases. However, the production and distribution of ⁶⁸Ga-PSMA-11 are limited to a few daily doses by commercially available ⁶⁸Ge/⁶⁸Ga generators that nominally deliver a modest activity up to 1850 MBq (50 mCi) when new but decreases over time. In response to the need for a more economically viable alternative, we present a simple and fully automated method for producing ⁶⁸Ga-PSMA-11 using cyclotron-produced ⁶⁸Ga.

Methods: The entirety of the ⁶⁸Ga-PSMA-11 production process was performed using a commercially available module under cGMP controlled environment. The ⁶⁸Ga was initially produced via irradiation of a ⁶⁸Zn solid target (enrichment ≥ 99%, 80-100 mg) by a medical cyclotron for 1.0-1.5 h, with protons at 14.5 MeV energy and beam currents of 30 μA. The irradiated target was dissolved and processed by an automation module fitted with a unique single-column purification system that was developed in-house. Purified ⁶⁸Ga with activity of 25.9-55.5 GBq (0.7-1.5 Ci) was eluted from the column by low concentration HCl and transferred directly to a reactor pre-loaded with PSMA-11 precursor, sodium acetate buffer, and L-ascorbic acid. Radiolabeling was conducted at 95^oC for 10 min and product was eventually passed through a 0.22µm filter prior collection. All quality control tests were performed in accordance to the USP<823> guidelines.

Results: The fully-automated process from target dissolution to ⁶⁸Ga-PSMA-11 final formulation takes less than 45 minutes and typically yields 18.5-37.0 GBq (0.5-1.0 Ci) at the end of synthesis (EOS). The HPLC analysis of the combined diastereomers of ⁶⁸Ga-PSMA-11 product has consistently reported a radiochemical purity of greater than 99%, and the specific activity was up to 740 GBq (20 Ci)/μmol. Additionally, the final product was determined to be sterile, colorless, and remained radiochemically pure (≥ 99%) after 4 h of radiosynthesis at room temperature.

Conclusions: We have developed a reliable and fully automated method for the routine production of ⁶⁸Ga-PSMA-11 at curie level quantity. Whereas the in vitro cell uptake and in vivo small animal PET imaging studies are currently underway to further demonstrate the biological sameness, our data indicate the potential for large scale production of ⁶⁸Ga-PSMA-11 that in turn can meet the increasing demand and facilitate regional distribution.