Astatine-211 is a short-lived alpha-emitting radionuclide with high potential for cancer treatment by targeted alpha therapy (TAT). Reversed-phase high-performance liquid chromatography (RP-HPLC) is central to the development and quality control of 211At-labeled radiopharmaceuticals. However, accurate analysis remains challenging due to the ultra-trace levels of astatine and its complex, unpredictable chemical behaviour. In this study, we systematically evaluated the recovery of representative inorganic astatine formulations under different redox conditions using various chromatographic conditions, which is a prerequisite for reliable quantification. Examination of four different columns with distinct stationary phase chemistry demonstrated that significant discrepancies can arise when radiochemical conversion is assessed solely based on eluted activity, as is common standard for RP-HPLC analysis. Among the chromatographic conditions examined, the highest and most consistent astatine recoveries (88-98%) were achieved using a basic mobile phase containing 0.4% triethylamine in combination with a base-tolerant stationary phase, likely due to a shift in astatine speciation under alkaline conditions, reduced secondary interactions with the stationary phase, and/or potentially beneficial ion pairing effects. In contrast, widely used standard solvent systems based on acetonitrile/water with or without 0.1% trifluoroacetic acid resulted in unsatisfactory and highly variable recoveries (7-71% or 30-79%, respectively) across all columns investigated. These findings highlight the necessity of optimized chromatographic conditions and suggest that inadequate recovery of free astatine could lead to substantial misestimation of the radiochemical conversion and purity of radiopharmaceutical formulations if not explicitly accounted for by auxiliary quantification strategies.

Summary:This procedure guideline for SPECT examinations of striatal dopamine transporter availability is intended to support the planning, execution, quality control, interpretation and reporting of cerebral SPECT scans with [123I]ioflupane. It is an update and expansion built on the 2019 version of the procedure guideline. It was developed through an informal process as a consensus of the Neuroimaging Working Group of the German Society of Nuclear Medicine and in consultation with the German Neurological Society. It is intended for use by physicians and technical staff working in the field of nuclear medicine.

Sleep is essential for synaptic homeostasis, a proposed mechanism whereby wakefulness leads to synaptic potentiation and sleep facilitates synaptic down-selection. Synaptic vesicle glycoprotein 2A (SV2A), whose availability is quantifiable by [¹⁸F]SynVesT-1 positron emission tomography (PET), is commonly interpreted as a proxy for synaptic density. In this randomized study, we examined 40 healthy adults (mean age 27.5 ± 6.5 years) who underwent two [¹⁸F]SynVesT-1 PET scans on consecutive days. Half of the participants were assigned to the normal sleep (i.e., control) condition and half to the sleep deprivation condition. Scans were performed at the same circadian time point, approximately 4 h after awakening in the control group and during baseline in the sleep deprivation group or after ~28 h of continuous wakefulness in the sleep deprivation group after sleep deprivation. Sleep deprivation led to significant increases in synaptic vesicle glycoprotein 2A binding in multiple brain regions, including the thalamus (+4.6%), hippocampus (+5.6%), and parietal cortex (+3.2%), whereas no changes were observed in controls. The degree of increase in synaptic vesicle glycoprotein 2A positively correlated with elevated slow wave activity during recovery sleep, a physiological marker of sleep pressure. These findings provide in vivo support for the synaptic homeostasis hypothesis in humans and suggest that synaptic vesicle glycoprotein 2A PET imaging is sensitive to sleep-wake dependent synaptic plasticity.Trial registrationThe study was prospectively registered on 19.01.2022 here: German Clinical Trials Registry: DRKS # DRKS00027867, https://drks.de/search/en/trial/DRKS00027867.

Therapeutic resistance and limited brain penetration remain major challenges in high-grade gliomas. Protein-based nanocarriers, such as the heavy chain of human ferritin (FTH1), facilitate transferrin receptor-mediated transport across the blood-brain barrier. Here, we present multifunctional FTH1 nanocages as a unified nanoplatform for dual-drug chemotherapy and molecular imaging. The nanocages achieve > 98 % gallium-68 labeling efficiency and enable pH-responsive release of doxorubicin and paclitaxel. In isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant tumor models in ovo, FTH1 nanocages exhibit robust intracerebral distribution, tumor accumulation, and enhanced therapeutic efficacy. Dual-drug nanocages significantly reduce tumor growth (p < 0.001), with a stronger effect in the IDH-mutant model (p < 0.001), and improve embryo survival. Kinomic profiling reveals broad suppression of AGC and CMGC kinase families, consistent with attenuation of pro-survival and cell-cycle signaling, particularly in IDH-mutant models. These findings suggest treatment-associated kinase network adaptation linked to the IDH status of the models, consistent with increased therapeutic vulnerability, and support further evaluation of FTH1 nanocages as a platform for improved glioma treatment.

Preamble:This represents a substantial development of the guideline on the topic first published in 2016. The following notable points have been updated: the sections on background information; the clinical benefit of the method; the resulting differential diagnostic considerations; the outlook for possible future extensions of the indication spectrum; the quantitative analysis of the PET images; the embedding of the method in diagnostic pathways; and the relation to alternative biomarker methods such as amyloid measurement in CSF/blood.

STUDY OBJECTIVES:The cerebral adenosinergic system is involved in sleep-wake regulation and presumably represents a neuro-molecular correlate of homeostatic sleep pressure. For acute sleep deprivation, it has been shown that increased cerebral A1 adenosine receptor (A1AR) availability was related to impairments in cognitive performance. The present study examined A1AR availability in response to chronic sleep restriction and recovery. METHODS:To quantify A1AR availability we used 8-Cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine ([18F] CPFPX) positron emission tomography in 21 volunteers after 5 nights with 5-h sleep opportunities followed by 8 h recovery sleep. Data were compared to a control group of 15 volunteers who slept 8 h each night. In addition, polysomnography, cognitive performance, and alertness were recorded. RESULTS:Chronic sleep restriction did not increase the A1AR availability. Slow wave sleep (SWS) and EEG slow-wave-activity (SWA) in the first 5 h of sleep did not differ from baseline (BL), but SWA in the last 3 h of sleep was increased and cognitive performance and alertness were impaired. While SWA returned to BL in the last 3 h of recovery sleep, performance, and alertness remained impaired. CONCLUSION:The results indicate that chronic sleep loss likely induces parallel upregulations of extracellular adenosine and A1AR resulting in no net gain in receptor availability. The results contrast with findings from acute sleep deprivation in which we found impaired performance and increased A1AR availability that were restored to rested levels after recovery sleep. The findings reveal fundamental differences in the mechanisms through which acute and chronic sleep loss affect adenosinergic regulation and cognitive performance.

N-Aryl sulfamoyl fluorides (ArSAFs) are hydrolytically stable motifs widely used in drug design, yet their suitability for radiotracer development has not been explored. Here, we report the efficient radiosynthesis of [18F]ArSAFs by base-free sulfur(VI) fluoride exchange (SuFEx), affording high molar activities from nanomolar precursor amounts. The resulting compounds exhibited excellent in vitro stability across a wide pH range and in human plasma. In vivo studies in mice confirmed high metabolic stability for selected N-alkyl-N-aryl derivatives. Additionally, several Nin-[18F]SAF-substituted tryptophan analogues showed up to 2-3-fold higher cellular uptake than the current gold standard [18F]FET in U87 MG glioblastoma cells, and their accumulation was sensitive to inhibition of amino acid transporters. However, Nin-[18F]SAF-substituted indole derivatives exhibited rapid in vivo defluorination, independent of substitution pattern. In contrast, [18F]SAF-substituted dihydrotryptophan and 4-(MeNH)Phe derivatives showed high in vivo stability. These findings establish N-alkyl-N-aryl sulfamoyl [18F]fluorides as robust and accessible scaffolds for radiotracer development.

Targeting microglia to modulate neuroinflammation after acute brain injuries (ABIs) is promising but limited by poor blood-brain barrier (BBB) penetration and systemic toxicity of candidate agents. In addition, multifunctional platforms combining targeted therapy with real-time traceability remain limited. We developed and characterized a multifunctional theranostic, folate-functionalized, polydopamine (PDA)-coated mesoporous silica nanoparticle (FA-NP) system for microglia-selective delivery and intracellular release of cytoskeleton inhibitor Cytochalasin D (CytoD). FA-NPs exhibited ideal physicochemical properties for parenchymal brain accumulation and pH-sensitive PDA shells enabled intracellular retention and gradual degradation. Using radiolabeled and fluorescein-isothiocyanate-functionalized FA-NPs, SPECT/CT imaging, γ-counting, autoradiography, and immunohistochemistry confirmed parenchymal brain accumulation with cellular uptake following systemic administration. Activated microglia upregulated folate receptors (FOLR1/2) and internalized FA-NPs via FOLR-mediated, dynamin-dependent endocytosis. CytoD-loaded FA-NPs (FA-NP[CytoD]) significantly reduced microglial migration, phagocytosis, ROS production, and proinflammatory cytokines, outperforming molecular CytoD while exhibiting notably lower toxicity compared to both CytoD and unfunctionalized particles. In organotypic brain slice models of hypoxia-reoxygenation and traumatic injury, FA-NP[CytoD] reduced inflammation at 24 and 96 h. Systemic administration enabled brain accumulation with clearance over time. Together, this multifunctional theranostic platform integrates selective microglial targeting, controlled drug release, and multimodal imaging, offering translational potential for ABIs.

Sleep is proposed to regulate synaptic strength; yet, the underlying mechanisms remain debated under the synaptic homeostasis hypothesis (SHY). We examined synaptic vesicle glycoprotein 2A (SV2A) and dendritic spine density in mouse brain across conditions of physiological sleep and sleep deprivation. Spine density decreased during sleep and increased following sleep deprivation, consistent with the SHY. In contrast, [18F]SynVesT-1 positron emission tomography (PET) imaging and [3H]UCB-J autoradiography revealed reduced SV2A following sleep deprivation. Layer-specific analyses in somatosensory and visual cortices further supported coordinated regulation between SV2A and dendritic spines. Developmentally, adolescent mice exhibited higher baseline SV2A and spine density than adults, with greater SV2A sensitivity to sleep deprivation, whereas adults were more responsive to physiological sleep. Together, these findings reveal bidirectional regulation of pre- and postsynaptic compartments and highlight developmental differences in sleep-dependent synaptic organization.

With the increasing significance of positron emission tomography in medicine, the need for development of novel positron emitters is increasing. A prerequisite for their use is a precise knowledge of the positron emission intensity in their decay. The literature data are generally based on standardisation of older decay schemes and therefore often lack accuracy. We have developed a new approach of directly measuring the positron emission component through high-resolution γ-ray spectroscopy, beta counting and γγ-coincidence counting, and the electron capture component via high-resolution X-ray spectroscopy. This article provides an overview of the seven radionuclides investigated, namely 45Ti, 64Cu, 72As, 76Br, 86gY, 120gI and 124I. Our results agree with the literature values derived from the extensively investigated decay schemes in recent years, but not with those obtained from poorly characterised older decay schemes. The potentially useful positron emitters that require such studies are briefly outlined.

103 Pd is a possible candidate for radiation therapy using Auger-Meitner electrons. The cross-sections of the 99 Tc( 7 Li,3n) 103 Pd nuclear reaction were measured for the first time in the energy range from 20 MeV to 34 MeV using the 10 MV FN-Tandem Accelerator at the Institute of Nuclear Physics, University of Cologne. The 99 Tc target was prepared by electrodeposition of ammonium pertechnetate onto gold foil. The thickness of the technetium layer was determined by Rutherford backscattering (RBS). The number of produced 103 Pd nuclei was quantified with the HORUS setup by measuring prompt γ-rays emitted from excited 103 Pd nuclei in parallel to irradiation (in-beam γ-ray spectroscopy). The maximum of the excitation function was found at an energy of 30 MeV. At higher projectile energies, contributions from the competing 99 Tc( 7 Li,4n) 102 Pd reaction channel are likely to affect the observed cross-sections.

Abstract:This procedure guideline for brain perfusion SPECT is intended to support the planning, execution, quality control, evaluation and reporting of brain perfusion SPECT studies using the 99 mTc-labelled radiopharmaceuticals [99 mTc]Tc-HMPAO and [99 mTc]Tc-ECD. It is an update and expansion built on the 2019 version of the procedure guideline. It was developed through an informal process as a consensus of the Neuroimaging Working Group of the German Society of Nuclear Medicine. It is intended for use by physicians and physical-technical staff (technologists, physicists) working in nuclear medicine.

Summary This procedure guideline for SPECT examinations of striatal dopamine transporter availability is intended to support the planning, execution, quality control, interpretation and reporting of cerebral SPECT scans with [123I]ioflupane. It is an update and expansion built on the 2019 version of the procedure guideline. It was developed through an informal process as a consensus of the Neuroimaging Working Group of the German Society of Nuclear Medicine and in consultation with the German Neurological Society. It is intended for use by physicians and technical staff working in the field of nuclear medicine.

The nuclear reaction cross-sections of the 93 Nb(p,n) 93m Mo process were measured in three experiments up to 17 MeV proton energy by using the stacked target foil technique. The target stacks were irradiated at the cyclotron JSW BC 1710 at the Forschungszentrum Jülich, INM-5. The nat Cu(p,x) 62/63 Zn reactions were used as monitor reactions to determine the proton particle flux and the incident proton energy. The experimental results were compared with literature data and with theoretical nuclear model calculations based on the TALYS-1.96 code and the data from TENDL-2023. Furthermore, it could be shown that the 93 Nb(p,n) 93m Mo reaction delivers sufficient amounts of activity for the later application of 93m Mo as a tracer to optimize the radiochemical separation of low specific activity 99 Mo and 99m Tc.

Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity. Outside the conventional housekeeping role, autophagy is also involved in the ATG5-mediated regulation of glucose transporter 2 (GLUT2) levels during cerebellar maturation. Autophagy-deficient PCs exhibit GLUT2 accumulation on the plasma membrane, along with increased glucose uptake and alterations in glycolysis. We identify lysophosphatidic acid and serine as glycolytic intermediates that trigger PC death and demonstrate that the deletion of GLUT2 in ATG5-deficient mice mitigates PC neurodegeneration and rescues their ataxic gait. Taken together, this work reveals a mechanism for regulating GLUT2 levels in neurons and provides insights into the neuroprotective role of autophagy by controlling glucose homeostasis in the brain.

Background: The radiotracer [18F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an 18F-labeled active ester as a prosthetic group, which had to be isolated and purified before it could be linked to the pharmacologically active Lys-urea-Glu motif. Although this procedure could be automated on two-reactor modules like the GE TRACERLab FX2N (FXN) to afford the tracer in modest radiochemical yields (RCY) of 18–25%, it is unsuitable for cassette-based systems with a single reactor. Methods: To simplify implementation on an automated synthesis module, the radiosynthesis of [18F]JK-PSMA-7 was devised as a one-pot, two-step reaction. The new method is based on direct (“late-stage”) radiofluorination of an appropriate onium triflate precursor and subsequent deprotection with ortho-phosphoric acid. It was successfully established on the cassette-based Trasis AllInOne (AIO) module. Results: Overall, the new protocol enabled the production of [18F]JK-PSMA-7 in activity yields of 39 ± 4% (RCY = 58%) with an overall synthesis time of about 1 h. In a single production run with an initial activity of 36-43 GBq, 13-19 GBq of [18F]JK-PSMA-7 with a radiochemical purity of >99% was obtained. Conclusions: We have established a highly reliable, GMP-compliant process for the automated radiosynthesis of [18F]JK-PSMA-7 on the Trasis AllinOne (AIO) synthesizer, ensuring consistent and efficient production of this radioligand.