Synthesis and preclinical evaluation of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand

Abstract

Purpose The aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined. Methods Several conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed. Results Quantitative labeling yields could be achieved with >97 % radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p < 4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv. Conclusion 18F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible.

Optimization of PET protocol and interrater reliability of 18F-PSMA-11 imaging of prostate cancer

“…In recent years, prostate-specific membrane antigen (PSMA) has been the most widely studied target for imaging of recurrent and metastatic prostate cancer. 18 F-PSMA-11, a fluorine-18 derivative of the frequently used 68 Ga-PSMA-11 PET radiotracer, was developed [1,2], automatized [3] and evaluated for safety, biodistribution and dosimetry in a previously published study [4]. Before comparing the clinical efficacy of 18 F-PSMA-11 to other PSMA tracers, a Phase 2 trial should be conducted to determine the scan protocol which will be applied in following studies and clinical practice.…”

Preclinical Evaluation and Pilot Clinical Study of Al18F-PSMA-BCH for Prostate Cancer PET Imaging

“…The increased positron yield (b 1 97%) and shorter positron range (R ave [average range] [b 1 ] = 0.69 mm) may potentially improve image quality (27,28). Al 18 F has been developed as an 18 F-labeling technique that allows convenient 18 F labeling in less time and under milder conditions that can also be combined with a kit (29)(30)(31). Some 18 F-labeled PSMA ligands have been studied for preclinical evaluation, but none have been applied in clinical practice (31,32).…”

“…Al 18 F has been developed as an 18 F-labeling technique that allows convenient 18 F labeling in less time and under milder conditions that can also be combined with a kit (29)(30)(31). Some 18 F-labeled PSMA ligands have been studied for preclinical evaluation, but none have been applied in clinical practice (31,32). Here, we report a novel Al 18 F-labeled PSMA ligand and a pilot clinical study for further investigation.…”

Targeting prostate cancer: Prostate‐specific membrane antigen based diagnosis and therapy

“…A first radiolabeling with 18 F and evaluation of the compound in CWR22Rv1 tumorbearing mice in PET/CT exhibited tumor uptake and-apart from the kidneys-low uptake into other organs. With the basis of the successful 68 Ga-labeled imaging agent,68 Ga-PSMA-HBED-CC (see chapter Gallium-68),107 Boschi et al evaluated a radiofluorinated version of the tracer 108. They reacted PSMA-11 with AlCl 3 and Na 18 F and were able to achieve stable complexation.…”