Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

Abstract

BackgroundOverexpression of prostatic membrane antigen (PSMA) is associated with the progression and prognosis of prostate cancer. There are numerous studies using this peptide with the 68Ga radionuclide. Previous methods to synthetize 18F–labeled PSMA ligands with complexes [18F]AlF2+ have been achieved. However, these reported syntheses were performed manually, using small volumes. Therefore it is only possible to have the radiopharmaceutical on a small scale, for use in preclinical studies. 18F–labelled tracers allow higher doses increasing the number of examined patients. In addition, late images can be acquired in the case of uptake in lymph nodes, to discard inflammation. It is important to transfer the manual synthesis to an automatic module, producing a batch of the radiopharmaceutical with high activity in a safe and effective way. The aim of this work was to optimize the labeling of [18F]AlF-[GLU-UREA-LYS(AHX)-HBED-CC] in a Tracerlab FXFN® (GE) platform.ResultsThe labeling up to the reactor corroborates the formation of the complex [18F]AlF-PSMA. After purification by HPLC, the radiopharmaceutical was achieved with a radiochemical purity higher than 90%. The quality control of the final product fulfilled all the requirements in agreement with USP, such as radiochemical purity (greater than 90%) and residual solvents. [18F]AlF-PSMA was obtained with a yield of 18 ± 3% (n = 7), not decay corrected (NCD) starting off from 500 to 2000 mCi the 18F and with a radiochemical purity of 95 ± 3% (n = 7). The product verified stability in the final formulation vial during 4 hs and in human plasma up to 1 h.ConclusionThe proposed method allowed the production of [18F]AlF-PSMA with suitable radiochemical purity in a commercial platform. High activities were achieved, with a simple and robust methodology appropriate for clinical purposes.

18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

“…The favorable binding affinities to PCa has also been proven by investigating PSMA-high LNCaP vs. PSMA-low PC3 tumors, showing a 24-fold higher uptake for [ 18 F]AlF-PSMA-11 in the high LNCaP tumors in C57BL6 mice 82. Notably, a recently established automated synthesis of this compound will also allow for large scale production and gurantaee a high throughput of patients in a busy PET practice 83-85.…”

Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents

“…While the excellent properties of [Al 18 F]PSMA-11 with high SCG tracer accumulation and low liver retention (significantly higher and lower than those of [ 18 F]DCFPyL, respectively) could be confirmed, we also observed high radioactivity uptake in bones attributed to extensive tracer defluorination. Whereas no substantial defluorination of [Al 18 F]PSMA-11 in vivo had been reported in earlier studies [29, 30], Ginglio et al recently observed relatively rapid defluorination of the tracer in vitro in human serum with half-time of 2.5 h [31]. 18 F-Fluoride avidly accumulates in PCa bone lesions [37], but also in healthy bones.…”

“…We examinated the applicability of this model using two widely used PSMA specific PET probes: [ 68 Ga]PSMA-11 [27] and [ 18 F]DCFPyL [28]. As an example of a PSMA-ligand with low in vivo stability we used PSMA-11 labeled with Al 18 F [29–31]. Finally, we compared [ 18 F]DCFPyL PET-scans obtained in healthy rats with those from LNCaP tumor-bearing SCID mice.…”

A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

“…Giglio et al optimized the synthesis of [ 18 F]AlF-PSMA-11 on a Tracerlab FXFN ® (GE) platform and obtained USP-grade radiotracer in about 18% yield, with a molar activity up to 544 GBq/µmol [98]. The optimized labeling conditions involved only 60 µg peptide, compared to 200 µg used in Kersemans protocol [97].…”