Procedures for the GMP-Compliant Production and Quality Control of [18F]PSMA-1007: A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer

Abstract

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.

Discovery of 18F-JK-PSMA-7, a PET Probe for the Detection of Small PSMA-Positive Lesions

“…68 Ga-PSMA-11 and 18 F-PSMA-1007 were synthesized according to Eder et al (11) and Cardinale et al (12), respectively. 18 F-DCFPyL ( 18 F-2), 18 F-JK-PSMA-7-9 ( 18 F-4-6), and 18 F-JK-PSMA-11-13 ( 18 F-8-10) were prepared using the minimalist approach (13) according to the modified protocol of Neumaier et al (14) (Fig.…”

Fine‐tuning of the automated [18F]PSMA‐1007 radiosynthesis

“…The current study adapted and evaluated the one‐step procedure for the previous reported [ 18 F]PSMA‐1007 radiosynthesis, on the Synthra RNplus and the GE TRACERlab FxFN automated modules. Initial conditions for radiolabeling and purification were maintained, as previously described . Briefly, after radiolabeling for 10 minutes, activity was loaded on the SPE cartridges using 18 mL of 5% ethanol (in HPLC water).…”

“…HPLC analysis of the product samples of three independent experiments, using the initial purification conditions and 10 minutes of radiolabeling, as previously reported…”

“…The obtained results agree with the previously published quality control tests. All the modifications made to the previously described one‐step [ 18 F]PSMA‐1007 radiosynthesis are detailed in Section . It should be noted that the above mentioned modifications were reproducible on both automated radiosynthesizers, Synthra RNplus, and GE TRACERlab FxFN.…”

“…One clear advantage of [ 18 F]PSMA‐1007 is the non‐urinary excretion, which can benefit clinical decision making in local recurrence . Here, we describe the implementation and optimization of the recently published one‐step radiosynthesis of [ 18 F]PSMA‐1007 using commercially available modules …”