Spotlight on:guideline on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8

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Other Radiopharmaceuticals for Imaging GEP‐NET

In GEP‐NETs, especially the catecholamine and serotonin biosynthetic pathways are upregulated. Therefore, increased biosynthesis of these specific amines in GEP‐NETs enables imaging with specific amine precursors. For the catecholamine pathway, 6‐18F ‐l‐3,4‐dihydroxyphenylalanine (18F‐DOPA) is available, while for the serotonin pathway, carbon‐11‐labeled 5‐hydroxy‐l‐tryptophan ([11C]‐5‐HTP) is available as tracer. 11C‐5‐HTP PET and 18F‐DOPA PET are excellent functional imaging techniques for evaluating patients with proven pancreatic islet cell tumors and carcinoids. For both tracers, the combination with CT further improves the detection rate of NET, which shows that performing PET scans with these tracers in PET/CT scanners is beneficial for patients.Since well‐differentiated GEP‐NETs generally have a low glucose metabolism, 18F‐fluorodexyglucose (18F‐FDG) PET scanning has limited value for the primary staging of patients with well‐differentiated GEP‐NETs. However, in patients with rapidly progressive disease, dedifferentiation of GEP‐NET tumors can lead to a higher glucose metabolism in tumor cells. In these patients, 18F‐FDG PET can be of benefit for tumor staging. Also, 18F‐FDG PET can be of value when other malignancies are suspected in patients with GEP‐NETs, since these patients experience a higher incidence of these malignancies compared to the general population.Nowadays, (GEP)‐NETs can also be imaged with 68Ga‐labeled analogues of somatostatin, which are also PET tracers. Advantages of 68Ga‐labeled somatostatin analogues are the relatively easy generator‐based synthesis and the possibility to evaluate whether peptide (somatostatin) receptor radionuclide therapy (PRRT) for NETs can be considered

Focused ultrasound for opening blood-brain barrier and drug delivery monitored with positron emission tomography

Focused ultrasound (FUS) is a minimally-invasive technology used for treatment of many diseases, including diseases related to the colon, uterus, prostate, and brain. Although it has been mainly used for ablative procedures, the ability of FUS to open the blood-brain barrier (BBB) presents a promising new application. However, the mechanism of BBB opening by FUS remains unclear. This review focuses on the use of FUS to open the BBB for enhancing drug delivery and investigating how Positron Emission Tomography (PET) provides insight into the underlying mechanism

In vivo evaluation of [F-18]FEAnGA-Me:a PET tracer for imaging beta-glucuronidase (beta-GUS) activity in a tumor/inflammation rodent model

Introduction: The PET tracer, 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-beta-D-glucopyronuronate ([F-18]FEAnGA), was recently developed for PET imaging of extracellularl beta-glucuronidase (beta-GUS). However,[F-18]FEAnGA exhibited rapid renal clearance, which resulted in a relatively low tracer uptake in the tumor. To improve the pharmacokinetics of [F-18]FEAnGA, we developed its more lipophilic methyl ester analog, [F-18]FEAnGA-Me. Methods: [F-18]FEAnGA-Me was obtained by alkylation of the O-protected glucuronide methyl ester precursor with [F-18]-fluoroethylamine ([F-18]FEA), followed by removal of the acetate protecting groups with NaOMe/MeOH. The PET tracer was evaluated by in vitro and in vivo studies. Results: [F-18]FEAnGA-Me was obtained in 5%-10% overall radiochemical yield. It is 10-fold less hydrophilic than [F-18]FEAnGA and it is stable in PBS and in the presence of beta-GUS for 1 h. However, in the presence of esterase or plasma [F-18]FEAnGA-Me is converted to [F-18]FEAnGA, and subsequently converted to [F-18]FEA by beta-GUS. MicroPET studies in Wistar rats bearing a C6 glioma and a sterile inflammation showed similar uptake in tumors after injection of either [F-18]FEAnGA-Me or [F-18]FEAnGA. Both tracers had a rapid two-phase clearance of total plasma radioactivity with a half-life of 1 and 8 min. The [F-18]FEAnGA fraction generated from [F-18]FEAnGA-Me by in vivo hydrolysis had a circulation half-life of 1 and 11 min in plasma. Similar distribution volume in the viable part of the tumor was found after injection of either [F-18]FEAnGA-Me or [F-18]FEAnGA. Conclusion: The imaging properties of [F-18]FEAnGA-Me were not significantly better than those of [F-18]FEAnGA. Therefore, other strategies should be applied in order to improve the kinetics of these tracers. (C) 2012 Elsevier Inc. All rights reserved

A human monoclonal antibody that specifically binds and inhibits the staphylococcal complement inhibitor protein SCIN

Staphylococcus aureus is a serious public health burden causing a wide variety of infections. Earlier detection of such infections could result in faster and more directed therapies that also prevent resistance development. Human monoclonal antibodies (humAbs) are promising tools for diagnosis and therapy owing to their relatively straightforward synthesis, long history of safe clinical use and high target specificity. Here we show that the humAb 6D4, which was obtained from a random screen of B-cells producing antibodies that bind to whole cells of S. aureus, targets the staphylococcal complement inhibitor (SCIN). The epitope recognized by 6D4 was localized to residues 26 to 36 in the N-terminus of SCIN, which overlap with the active site. Accordingly, 6D4 can inhibit SCIN activity as demonstrated through the analysis of C3b deposition on S. aureus cells and complement-induced lysis of rabbit erythrocytes. Importantly, while SCIN is generally regarded as a secreted virulence factor, 6D4 allowed detection of strongly increased SCIN binding to S. aureus cells upon exposure to human serum, relating to the known binding of SCIN to C3 convertases deposited on the staphylococcal cell surface. Lastly, we show that labeling of humAb 6D4 with a near-infrared fluorophore allows one-step detection of SCIN-producing S. aureus cells. Together, our findings show that the newly described humAb 6D4 specifically recognizes S. aureus SCIN, which can potentially be used for detection of human serum-incubated S. aureus strains expressing SCIN

Refraction Wiggles for Measuring Fluid Depth and Velocity from Video

We present principled algorithms for measuring the velocity and 3D location of refractive fluids, such as hot air or gas, from natural videos with textured backgrounds. Our main observation is that intensity variations related to movements of refractive fluid elements, as observed by one or more video cameras, are consistent over small space-time volumes. We call these intensity variations “refraction wiggles”, and use them as features for tracking and stereo fusion to recover the fluid motion and depth from video sequences. We give algorithms for 1) measuring the (2D, projected) motion of refractive fluids in monocular videos, and 2) recovering the 3D position of points on the fluid from stereo cameras. Unlike pixel intensities, wiggles can be extremely subtle and cannot be known with the same level of confidence for all pixels, depending on factors such as background texture and physical properties of the fluid. We thus carefully model uncertainty in our algorithms for robust estimation of fluid motion and depth. We show results on controlled sequences, synthetic simulations, and natural videos. Different from previous approaches for measuring refractive flow, our methods operate directly on videos captured with ordinary cameras, do not require auxiliary sensors, light sources or designed backgrounds, and can correctly detect the motion and location of refractive fluids even when they are invisible to the naked eye.Shell ResearchMotion Sensing Wi-Fi Sensor Networks Co. (Grant 6925133)National Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374)Microsoft Research (PhD Fellowship

PET imaging of the autonomic myocardial function: methods and interpretation.

Cardiac positron emission tomography (PET) is mainly applied in myocardial perfusion and viability detection. Noninvasive imaging of myocardial innervation using PET is a valuable additional methodology in cardiac imaging. Novel methods and different PET ligands have been developed to measure presynaptic and postsynaptic function of the cardiac neuronal system. Obtained PET data can be analysed quantitatively or interpreted qualitatively. Thus far, PET is not a widely used clinical application in autonomic heart imaging; however, due to its technical advantages, the excellent properties of the imaging agents, and the availability of tools for quantification, it deserves a better position in the clinic. From a historical point of view, the focus of PET software packages for image analysis was mainly oncology and neurology driven. Actually, commercially available software for cardiac PET image analysis is still only available for the quantification of myocardial blood flow. Thus far, no commercial software package is available for the interpretation and quantification of PET innervation scans. However, image data quantification and analysis of kinetic data can be performed using adjusted generic tools. This paper gives an overview of different neuronal PET ligands, interpretation and quantification of acquired PET data

Monitoring SARS-CoV-2 Circulation and Diversity through Community Wastewater Sequencing, the Netherlands and Belgium

Severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has rapidly become a major global health problem, and public health surveillance is crucial to monitor and prevent virus spread. Wastewater-based epidemiology has been proposed as an addition to disease-based surveillance because virus is shed in the feces of ≈40% of infected persons. We used next-generation sequencing of sewage samples to evaluate the diversity of SARS-CoV-2 at the community level in the Netherlands and Belgium. Phylogenetic analysis revealed the presence of the most prevalent clades (19A, 20A, and 20B) and clustering of sewage samples with clinical samples from the same region. We distinguished multiple clades within a single sewage sample by using low-frequency variant analysis. In addition, several novel mutations in the SARS-CoV-2 genome were detected. Our results illustrate how wastewater can be used to investigate the diversity of SARS-CoV-2 viruses circulating in a community and identify new outbreaks

Effects of proton therapy on regional [¹⁸F]FDG uptake in non-tumor brain regions of patients treated for head and neck cancer

Background and purpose: Previous pre-clinical research using [18F]FDG-PET has shown that whole-brain photon-based radiotherapy can affect brain glucose metabolism. This study, aimed to investigate how these findings translate into regional changes in brain [18F]FDG uptake in patients with head and neck cancer treated with intensity-modulated proton therapy (IMPT). Materials and methods: Twenty-three head and neck cancer patients treated with IMPT and available [18F]FDG scans before and at 3 months follow-up were retrospectively evaluated. Regional assessment of the [18F]FDG standardized uptake value (SUV) parameters and radiation dose in the left (L) and right (R) hippocampi, L and R occipital lobes, cerebellum, temporal lobe, L and R parietal lobes and frontal lobe were evaluated to understand the relationship between regional changes in SUV metrics and radiation dose. Results: Three months after IMPT, [18F]FDG brain uptake calculated using SUVmean and SUVmax, was significantly higher than that before IMPT. The absolute SUVmean after IMPT was significantly higher than before IMPT in seven regions of the brain (p ≤ 0.01), except for the R (p = 0.11) and L (p = 0.15) hippocampi. Absolute and relative changes were variably correlated with the regional maximum and mean doses received in most of the brain regions. Conclusion: Our findings suggest that 3 months after completion of IMPT for head and neck cancer, significant increases in the uptake of [18F]FDG (reflected by SUVmean and SUVmax) can be detected in several individual key brain regions, and when evaluated jointly, it shows a negative correlation with the mean dose. Future studies are needed to assess whether and how these results could be used for the early identification of patients at risk for adverse cognitive effects of radiation doses in non-tumor tissues.</p

The effects of molar activity on [F-18]FDOPA uptake in patients with neuroendocrine tumors

BACKGROUND: 6-[(18)F]fluoro-l-3,4-dihydroxyphenyl alanine ([(18)F]FDOPA) is a commonly used PET tracer for the detection and staging of neuroendocrine tumors. In neuroendocrine tumors, [(18)F]FDOPA is decarboxylated to [(18)F]dopamine via the enzyme amino acid decarboxylase (AADC), leading to increased uptake when there is increased AADC activity. Recently, in our hospital, a new GMP compliant multi-dose production of [(18)F]FDOPA has been developed, [(18)F]FDOPA-H, resulting in a higher activity yield, improved molar activity and a lower administered mass than the conventional method ([(18)F]FDOPA-L). AIMS: This study aimed to investigate whether the difference in molar activity affects the [(18)F]FDOPA uptake at physiological sites and in tumor lesions, in patients with NET. It was anticipated that the specific uptake of [(18)F]FDOPA-H would be equal to or higher than [(18)F]FDOPA-L. METHODS: We retrospectively analyzed 49 patients with pathologically confirmed NETs and stable disease who underwent PET scanning using both [(18)F]FDOPA-H and [(18)F]FDOPA-L within a time span of 5 years. A total of 98 [(18)F]FDOPA scans (49 [(18)F]FDOPA-L and 49 [(18)F]FDOPA-H with average molar activities of 8 and 107 GBq/mmol) were analyzed. The SUVmean was calculated for physiological organ uptake and SUVmax for tumor lesions in both groups for comparison, and separately in subjects with low tumor load (1–2 lesions) and higher tumor load (3–10 lesions). RESULTS: Comparable or slightly higher uptake was demonstrated in various physiological uptake sites in subjects scanned with [(18)F]FDOPA-H compared to [(18)F]FDOPA-L, with large overlap being present in the interquartile ranges. Tumor uptake was slightly higher in the [(18)F]FDOPA-H group with 3–10 lesion (SUVmax 6.83 vs. 5.19, p < 0.001). In the other groups, no significant differences were seen between H and L. CONCLUSION: [18F]FDOPA-H provides a higher activity yield, offering the possibility to scan more patients with one single production. Minor differences were observed in SUV’s, with slight increases in uptake of [(18)F]FDOPA-H in comparison to [(18)F]FDOPA-L. This finding is not a concern for clinical practice, but could be of importance when quantifying follow-up scans while introducing new production methods with a higher molar activity of [(18)F]FDOPA