RESUMO
For the PET imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. [18F]PSMA-1007, a radiopharmaceutical labeled with fluorine-18, has excellent properties for the detection of prostate cancer. Essential for the human use of a radiotracer is its production and quality control under GMP-compliance. For this purpose, all analytical methods have to be validated. [18F]PSMA-1007 is easily radiosynthesized in a one-step procedure and isolated using solid phase extraction (SPE) cartridges followed by formulation of a buffered injection solution and for the determination of its chemical and radiochemical purity a robust, fast and reliable quality control method using radio-HPLC is necessary. After development and optimizations overcoming problems in reproducibility, the here described radio-HPLC method fulfills all acceptance criteria-for e.g., specificity, linearity, and accuracy-and is therefore well suited for the routine quality control of [18F]PSMA-1007 before release of the radiopharmaceutical. Recently a European Pharmacopeia monograph for [18F]PSMA-1007 was published suggesting a different radio-HPLC method for the determination of its chemical and radiochemical purity. Since the here described method has certain advantages, not least of all easier technical implementation, it can be an attractive alternative to the monograph method. The here described method was successfully validated on several radio-HPLC systems in our lab and used for the analysis of more than 60 batches of [18F]PSMA-1007. Using this method, the chemical and radiochemical purity of [18F]PSMA-1007 can routinely be evaluated assuring patient safety.
RESUMO
Radiolabeled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection, we recently developed the fluorine-18-labelled PSMA-ligand [18F]PSMA-1007 as the next generation radiofluorinated Glu-ureido PSMA inhibitor after [18F]DCFPyL and [18F]DCFBC. Since radiosynthesis so far has been suffering from rather poor yields, novel procedures for the automated radiosyntheses of [18F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly-used radiosynthesisers. Using the novel one-step procedure, the [18F]PSMA-1007 was produced in good radiochemical yields ranging from 25 to 80% and synthesis times of less than 55 min. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and, at the same time, high yielding production pathway for the next generation PSMA radioligand [18F]PSMA-1007. Actually, it turned out that the radiosynthesis is as easily realised as the well-known [18F]FDG synthesis and, thus, transferable to all currently-available radiosynthesisers. Using the new procedures, the clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.