Automated radiosynthesis of Al[18F]PSMA-11 for large scale routine use.

Objectives: We report a reproducible automated radiosynthesis for large scale batch production of clinical grade Al[F-18]PSMA-11. Methods: A SynthraFCHOL module was optimized to synthesize Al[F-18]PSMA-11 by Al[F-18]-chelation. Results Al[F-18]PSMA-11 was synthesized within 35 min in a yield of 21 +/- 3% (24.0 +/- 6.0 GBq) and a radiochemical purity > 95%. Batches were stable for 4 h and conform the European Pharmacopeia guidelines. Conclusions: The automated synthesis of Al[F-18]PSMA-11 allows for large scale production and distribution of Al [F-18]PSMA-11

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

Background Several scan parameters for PET imaging with F-18-PSMA-11 such as dosage, acquisition time and scan duration were evaluated to determine the most appropriate scan protocol, as well as the effect of furosemide administration on lesion visualization. Forty-four patients were randomly assigned to a dosage group (2.0 +/- 0.2 or 4.0 +/- 0.4 MBq/kg F-18-PSMA-11). All patients received a full-body PET/CT 1 h and 3 h after radiotracer injection with a scan duration of 3 min/bed position. For comparison of the scan duration, images were reconstructed for 1.5 and 3 min/bed position. Patients were intravenously administered 0.5 mg/kg furosemide with a maximum dose of 40 mg. To evaluate the furosemide effect, 22 additional patients were recruited and received one full-body PET/CT 1 h after administration of 2.0 +/- 0.2 MBq/kg F-18-PSMA-11 with a scan duration of 3 min/bed position. To this group, no furosemide was administered. Images were scored on image quality using a 7-point scale and each suspicious lesion was described. To assess interrater reliability, two nuclear physicians scored all scans independently and described all observed suspicious lesions. Results The 4 MBq/kg group received for all reconstructed images (60 min p.i., 1.5 and 3 min/bed position and 180 min p.i., 1.5 and 3 min/bed position) the highest median image quality score compared to the 2 MBq/kg group (p values < 0.01). When comparing all reconstructed images, the highest image quality score was given to images at 60 min p.i., 3 min/bed position for both dosage groups (score 5 and 6 for 2 and 4 MBq/kg, respectively). The addition of furosemide administration decreased the interference score with one point (p = 0.01106) and facilitated the evaluation of lesions in proximity to the ureters. The interrater reliability for the comparison of each lesion separately after more than 40 F-18-PSMA-11 scan readings showed an increasing kappa value from 0.78 (95% CI, 0.65-0.92) to 0.94 (95% CI, 0.87-1). Conclusion Although the results indicate an administered activity of 4.0 +/- 0.4 MBq/kg, preference will be given to 2.0 +/- 0.2 MBq/kg due to the small difference in absolute score (max 1 point) and the ALARA principle. For evaluation of lesions in proximity to the ureters, the co-administration of a diuretic can be useful. The increase of the kappa value from 0.78 to 0.94 suggests a learning curve in the interpretation of F-18-PSMA-11 images

Radiosynthesis, in vitro and preliminary in vivo evaluation of the novel glutamine derived PET tracers [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamine

INTRODUCTION: Glucose has been deemed the driving force of tumor growth for decades. However, research has shown that several tumors metabolically shift towards glutaminolysis. The development of radiolabeled glutamine derivatives could be a useful molecular imaging tool for visualizing these tumors. We elaborated on the glutamine-derived PET tracers by developing two novel probes, namely [(18)F]fluorophenylglutamine and [(18)F]fluorobiphenylglutamine MATERIALS AND METHODS: Both tracers were labelled with fluorine-18 using our recently reported ruthenium-based direct aromatic fluorination method. Their affinity was evaluated with a [(3)H]glutamine inhibition experiment in a human PC-3 and a rat F98 cell line. The imaging potential of [(18)F]fluorophenylglutamine and [(18)F]fluorobiphenylglutamine was tested using a mouse PC-3 and a rat F98 tumor model. RESULTS: The radiosynthesis of both tracers was successful with overall non-decay corrected yields of 18.46 ± 4.18 % (n=10) ([(18)F]fluorophenylglutamine) and 8.05 ± 3.25 % (n=5) ([(18)F]fluorobiphenylglutamine). In vitro inhibition experiments showed a moderate and low affinity of fluorophenylglutamine and fluorobiphenylglutamine, respectively, towards the human ASCT-2 transporter. Both compounds had a low affinity towards the rat ASCT-2 transporter. These results were endorsed by the in vivo experiments with low uptake of both tracers in the F98 rat xenograft, low uptake of [(18)F]FBPG in the mice PC-3 xenograft and a moderate uptake of [(18)F]FPG in the PC-3 tumors. CONCLUSION: We investigated the imaging potential of two novel PET radiotracers [(18)F]FPG and [(18)F]FBPG. [(18)F]FPG is the first example of a glutamine radiotracer derivatized with a phenyl group which enables the exploration of further derivatization of the phenyl group to increase the affinity and imaging qualities. We hypothesize that increasing the affinity of [(18)F]FPG by optimizing the substituents of the arene ring can result in a high-quality glutamine-based PET radiotracer. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: We hereby report novel glutamine-based PET-tracers. These tracers are tagged on the arene group with fluorine-18, hereby preventing in vivo defluorination, which can occur with alkyl labelled tracers (e.g. (2S,4R)4-[(18)F]fluoroglutamine). [(18)F]FPG shows clear tumor uptake in vivo, has no in vivo defluorination and has a straightforward production. We believe this tracer is a good starting point for the development of a high-quality tracer which is useful for the clinical visualization of the glutamine transport

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

Recently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq 18F-PSMA-11 and 68Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq 18F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUVmean, SUVmax, TBRmean and TBRmax). Mice underwent ex vivo biodistribution where 18F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (Kd) of 18F-PSMA-11 and 68Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both 18F-PSMA-11 and 68Ga-PSMA-11, while no difference was found for 18F-FDG uptake (except for SUVmax). Tumor uptake of 18F-PSMA-11 showed a similar trend over time as 68Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBRmean and TBRmax were significantly higher at the later timepoint, as well as the SUVmax of 68Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for 18F-PSMA-11 compared to 68Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late 18F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of 18F-PSMA-11 as well as no significant increase in bone uptake

L'évolution juridique des conseils de prud'hommes en Belgique. Regards particuliers sur le conseil de Charleroi

Master [120] en droit, Université catholique de Louvain, 201

Exploring the potential of [18F]AlF-PSMA-11 for prostate cancer imaging

In men, prostate cancer (PCa) is the second most frequently occurring cancer and the fifth leading cause of cancer death. A major issue in the clinical management of PCa is the early detection of recurrent disease after radical prostatectomy or local therapy with curative intent. Approximately 30% of patients experience biochemical recurrence within ten years. For salvage therapy to be successful, the detection of recurrent disease and the precise localization of metastases is necessary to determine the most appropriate treatment. Positron emission tomography (PET) imaging allows to detect functional alternations before any morphological changes occur. Therefore, there is an increasing interest in reliable imaging biomarkers to accurately visualize the disease. Prostate specific membrane antigen (PSMA) is a promising target for the development of PET radioligands because of its overexpression on PCa cells. [18F]AlF-PSMA-11 was evaluated as a PSMA targeting PET tracer in a preclinical and clinical setting. In vivo experiments in PCa xenograft bearing mice allowed to extensively evaluate the influence of the molar activity and PSMA expression level on the biodistribution and tumor uptake of [18F]AlF-PSMA-11. These results highlighted the importance of taking into account the molar activity in PSMA imaging and its potential use in reducing uptake in dose-limiting organs during PSMA radioligand therapy. Comparing [18F]AlF-PSMA-11 to other PSMA radiotracers [68Ga]PSMA-11 and [18F]PSMA-1007 suggested [18F]AlF-PSMA-11 to be a suitable PSMA PET tracer. The phase I clinical trial demonstrated the safety and low radiation burden of [18F]AlF-PSMA-11. The following phase II clinical trial determined the recommended scan protocol to be imaging for 3 min/bed position at 1h post 2 MBq [18F]AlF-PSMA-11/kg body weight administration. Meanwhile, [18F]AlF-PSMA-11 has been successfully introduced into routine clinical practice and readily available for patient care

When citizens and scientists work together: a French collaborative science network on earthworms communities distribution

International audienc

When citizens and scientists work together: A French collaborative science network on earthworms communities (the OPVT)

International audienc