Prostate-specific membrane antigen (PSMA) is highly overexpressed in prostate cancer. Many PSMA analog radiotracers for PET/CT prostate cancer staging have been developed, such as 68 Ga-PSMA-11. This radiotracer has achieved good results in multiple clinical trials, but because of the superior imaging characteristics of 18 F-fluoride, 18 F-PSMA-11 was developed. The aim of this study was to evaluate the administration safety and radiation dosimetry of 18 F-PSMA-11. Methods: Six patients (aged 62-68 y; mean, 66 ± 2 y) with suspected prostate cancer recurrence after previous treatment were administered 2 MBq of 18 F-PSMA-11 per kilogram of body weight and then underwent low-dose PET/CT imaging at 0, 20, 50, 90, and 300 min after injection. To evaluate the safety of administration, vital parameters were monitored. To assess toxicity, full blood count and biochemical parameters were determined. According to the latest International Commission on Radiological Protection recommendations, radiation dosimetry analysis was performed using IDAC-Dose 2.1. For blood activity measurement, small samples of venous blood were collected at various time points after injection. The unbound 18 F-fluoride fraction was determined in plasma at 20, 50, and 90 min after administration to evaluate the defluorination rate of 18 F-PSMA-11. Results: After injection, 18 F-PSMA-11 cleared rapidly from the blood. At 5 h after injection, 29.0% ± 5.9% of the activity was excreted in urine. The free 18 F fraction in plasma increased from 9.7% ± 1.0% 20 min after injection to 22.2% ± 1.5% 90 min after injection. The highest tracer uptake was observed in kidneys, bladder, spleen, and liver. No study drug-related adverse events were observed. The calculated mean effective dose was 12.8 ± 0.6 μSv/MBq. Conclusion: 18 F-PSMA-11 can be safely administered and results in a mean effective dose of 12.8 ± 0.6 μSv/MBq. Therefore, the total radiation dose is lower than for other PSMA PET agents and in the same range as 18 F-DCFPyL.
A widely held view on consciousness is that it is related to the 'broadcasting' of sensory information to the whole brain [1-3]. Despite the fact that there is general support for this view, it remains unclear how exactly this broadcasting is established. It has been proposed [2,3] that thalamocortical circuits are an important mediator of such broadcasting, but empirical support for this claim is lacking. In the present study, we investigated this hypothesis by exploiting the well-established, but in this context neglected, fact that thalamocortical connectivity is modulated by dopaminergic activity in the striatum [4]. We used positron emission tomography (PET) to measure individual differences in striatal dopamine (DA) level and we correlated this with individual differences in visual consciousness. Our results show that visual awareness is related to the concentration of endogenous DA or DA receptors in striatal areas, supporting the importance of dopaminergic signalling in visual consciousness.
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.
Background: Several scan parameters for PET imaging with 18 F-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 18 F-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 18 F-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 18 F-PSMA-11 scan readings showed an increasing κ 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 κ value from 0.78 to 0.94 suggests a learning curve in the interpretation of 18 F-PSMA-11 images.
BackgroundIn humans, non-stereotactic frameless neuronavigation systems are used as a topographical tool for non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS). TMS studies in dogs may provide treatment modalities for several neuropsychological disorders in dogs. Nevertheless, an accurate non-invasive localization of a stimulation target has not yet been performed in this species.HypothesisThis study was primarily put forward to externally locate the left frontal cortex in 18 healthy dogs by means of a human non-stereotactic neuronavigation system. Secondly, the accuracy of the external localization was assessed.AnimalsA total of 18 healthy dogs, drawn at random from the research colony present at the faculty of Veterinary Medicine (Ghent University), were used.MethodsTwo sets of coordinates (X, Y, Z and X″, Y″, Z″) were compared on each dog their tomographical dataset.ResultsThe non-stereotactic neuronavigation system was able to externally locate the frontal cortex in dogs with accuracy comparable with human studies.Conclusion and clinical importanceThis result indicates that a non-stereotactic neuronavigation system can accurately externally locate the left frontal cortex and paves the way to use guided non-invasive brain stimulation methods as an alternative treatment procedure for neurological and behavioral disorders in dogs. This technique could, in analogy with human guided non-invasive brain stimulation, provide a better treatment outcome for dogs suffering from anxiety disorders when compared to its non-guided alternative.
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