Abstract
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Objectives: In recent years radiolabeled ligands targeting the prostate-specific membrane antigen (PSMA) have gained a significant impact on the diagnosis and therapy of prostate cancer [1]. Therefore, we have developed a fluorine-18 labeled PSMA-targeted imaging probe, 18F-PSMA-1007, which has been successfully applied in first-in-man study [2]. So far, the tracer is only available by a two-step procedure with approx. 10 % RCY [3]. Currently, we are aiming towards a GMP-compliant routine-production of this novel tracer using direct radiofluorination.
Methods: A precursor for nucleophilic [18F]fluoride substitution (quarternized ammonium salt) without protection of the carboxylic groups has been developed (Scheme 1). Until now, radiofluorinations have been carried out on a cassette-based automated radiosynthesizer with integrated HPLC have been carried out. Based on those experiments a simplified process on a TRACERlab FX synthesis module has been established. Product purification in the simplified procedure is accomplished by cartridge extraction. A GMP-compliant quality control comparable to the Eur. Ph. monograph of FDG has been established for the first-in-man study.
Results: In preliminary experiments the radiofluorination was accomplished successfully with RCY of approx. 20 % and a total synthesis time of one hour. The radiochemical purity of the product was approx. 95 % after HPLC separation. Based on these preliminary experiments a process suitable for our TRACERlab FX modules has been elaborated. This straight-forward and fully GMP-compliant process on the TRACERlab FX Module is currently under evaluation. The final purification of the product is carried out by simple cartridge extraction. The radiochemical purity is >95% while all chemical impurities are below 0.1 mg / V.
Conclusion: A process for the radiolabeling of a novel precursor for the synthesis of [18F]PSMA-1007 by direct radiofluorination has been established. The product is obtained in good radiochemical yields of approx. 20% (final injection solution, corrected for decay) after short synthesis time. Currently this process is applied for the routine production of 18F-PSMA-1007 for future clinical trials (phases 1 and 2). Research Support: [1] Rowe, SP, Gorin, MA, Allaf, ME, et al., Prostate Cancer and Prostatic Disease 2016, 19, 223-230. [2] Giesel, F. L., Hadaschik, B., Cardinale, J., et al. et al. Eur. J. Nucl. Med. Mol. Imaging, (Doi: 10.1007/s00259-016-3573-4).[3] Cardinale, J., Schäfer, M., Benesova, M., et al., J. Nucl. Med., (Doi: 10.2967/jnumed.116.181768).