Optimized Automated GMP compliant Production and Quality Control of [68Ga]Ga-PentixaFor for Clinical PET Imaging

Background [ ⁶⁸ Ga]Ga-PentixaFor is the most promising PET tracer for chemokine receptor-4 (CXCR4) imaging, and the increasing use of [ ⁶⁸ Ga]Ga-PertixaFor for diagnosis has amplified its clinical demand, however, the reported radiochemical yield (RCY) of automated synthesis was far from satisfactory. The purpose of this study is to improve the RCY by optimizing the precursor amount and product elution in the automated synthesis, and to establish a comprehensive and integrated quality assurance system of [ ⁶⁸ Ga]Ga-PentixaFor for clinical use. Results Two different precursor amounts with 30 or 50 µg of PentixaFor were tested for radiolabeling, and different elution conditions with the total volume of 1 mL or 2 mL and the ethanol concentration of 60% or 70% were evaluated for the product elution. Methods A to D were constructed by different combinations of the precursor amounts and elution conditions. The number of batches for Methods A-D was 7, 14, 13 and 51, respectively, and the radiochemical yields (RCYs) of each method was 78.15%, 76.36%, 82.40% and 85.63%. Increasing the precursor amount from 30 µg to 50 µg, could significantly improve the RCY of [ ⁶⁸ Ga]Ga-PentixaFor. The increase of ethanol concentration of 1 mL ethanol eluent from 60–70% was not conducive to the improvement of RCY. However, increasing the volume of 70% ethanol eluent from 1 mL to 2 mL, could significantly improve the elution efficiency of the product on C18 cartridge and filter membrane, and ultimately improve the RCY significantly. The radiochemical purity of each batch of [ ⁶⁸ Ga]Ga-PentixaFor was greater than 95%. Predefined acceptance criteria were met for all other tests like the sterility, endotoxins level, radionuclidic purity, residual solvent content etc. Conclusions High RCY of [ ⁶⁸ Ga]Ga-PentixaFor was successfully automated synthesized by using 50 µg precursor and 2 mL 70% ethanol eluent. The final product solutions were safe and suitable, passing full acceptance criteria of radiopharmaceuticals for clinical use.