Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas that can develop either de novo or as a result of malignant transformation of neurofibromas. Diagnostic modalities of choice, such as MRI or 18F-FDG PET/CT, show high sensitivity for the detection of MPNSTs but moderate specificity, as MPNSTs and benign peripheral nerve sheath tumors (BPNSTs) can initially present similar clinical and radiologic pictures. PET/CT with 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) showed specific uptake in sarcomas and enabled differentiation of benign and malignant lesions in other entities. Here, we analyzed the ability of 68Ga-FAPI PET/CT to differentiate between MPNSTs and BPNSTs. Methods: Twenty-six patients with suspected or histologically confirmed peripheral nerve sheath tumors who were scheduled to have surgical resection/biopsy underwent 68Ga-FAPI-46 PET/CT with static and dynamic acquisition. SUVmax, SUVmean, maximum and mean tumor-to-background ratios, and time-activity curves were evaluated using volume-of-interest-based analysis (isocontour 50%). Time to peak was derived from time-activity curves. Statistical analyses were performed, and receiver-operating-characteristic curves were calculated. Exemplary target validation by fibroblast activation protein immunohistochemistry was performed in 13 cases. Results: Eighteen patients (4 with MPNSTs, 5 with neurofibromas, 9 with schwannomas) were included in the final analysis. MPNSTs showed significantly higher 68Ga-FAPI uptake compared with BPNSTs. Neurofibromas showed higher 68Ga-FAPI uptake compared with schwannomas. In dynamic imaging, time to peak of MPNSTs and neurofibromas was prolonged compared with schwannomas. Analysis of receiver-operating-characteristic curves displayed high sensitivity (100%) and specificity (92.86%) of 68Ga-FAPI PET/CT for discrimination of MPNSTs and BPNSTs, for an exploratory SUVmax cutoff value of 7.53. Fibroblast activation protein expression was strong in MPNSTs and moderate in BPNSTs. Conclusion: 68Ga-FAPI PET/CT may aid in differentiating between MPNSTs and BPNSTs, thereby improving lesion characterization in indeterminate MRI or 18F-FDG PET/CT scenarios.

The pathologies pancreatic ductal adenocarcinomas, inflammatory lesions of the pancreas, postpancreatectomy reactive tissue, and recurrent pancreatic ductal adenocarcinomas all express fibroblast activation protein and are hardly distinguishable by static PET using [68Ga]Ga-labeled fibroblast activation protein inhibitors (FAPIs) combined with CT. Dynamic imaging allows full [68Ga]-Ga-FAPI kinetic profile analysis, highlighting differences among these pathologies. Here, we applied a voxel-level digital biopsy approach combined with network analysis and clustering to characterize healthy, nonmalignant pathologic, and malignant pathologic kinetic signatures. Methods: This monocentric, retrospective study included 47 patients (>18 y) with morphologically unclear pancreatic lesions on CT or MRI and supplemental [68Ga]Ga-FAPI-46 PET/CT in a primary (31 patients) or recurrent (16 patients) setting. Lesions were classified according to biopsy results (primary cases) or CT appearance and clinical course (recurrent cases). Digital biopsy samples (300 voxels) of pancreatic lesions and control organs (muscle, fat, kidneys, liver, and blood) were taken and then masked and imported into an open source visual analytics application. Voxel networks were created with multiple digital biopsy samples from a single scan or digital biopsy samples combined from multiple scans, with a minimum Pearson correlation value of 0.7. A k-nearest-neighbor edge reduction was applied before Markov clustering. Datasets were then unmasked for interpretation. Static PET parameters (SUVmax and SUVmean) and time to peak of pancreatic lesions and control tissues were extracted from isotropic volumes and analyzed by a t test (threshold for significance, P = 0.05). Results: This work created 47 individual networks and 2 combined networks. Within individual networks, voxels tended to arrange and cluster within the sampled volume of interest (VOI; left and right kidneys strongly coclustered). Networks typically arranged into healthy controls, elimination organs, and pathologic (malignant and nonmalignant) regions. Pathologies tended to cluster with high purity (>95% from the same VOI), with multiple clusters per VOI, indicating intralesional heterogeneity. Our analysis approach could differentiate between malignant and nonmalignant pathologies in the primary and recurrence settings. This differentiation was driven by slower FAPI clearance within malignant voxels. Conclusion: The kinetics of [68Ga]Ga-FAPI-46 across the different tissues, coupled with this sampling and analysis approach, allowed the separation and identification of healthy, nonmalignant pathologic, and malignant pathologic clusters and kinetic features that may facilitate diagnosis and warrant further investigation.

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.

Oncological treatment in a substantial portion of patients with cancer of unknown primary (CUP) remains challenging due to limitations of conventional imaging and positron emission tomography/computed tomography with 18Fluor-fluorodeoxyglucose (18F-FDG-PET/CT). In head and neck-like CUP (HNCUP), several studies found significantly higher tracer-uptake and detection rates of primary tumors in 68Gallium-labeled fibroblast activation protein inhibitor-PET/CT (68Ga-FAPI-PET/CT). Here, we address a gap in CUP literature by retrospectively evaluating the diagnostic accuracy of both tracer in a head-to-head comparison of patients with single-site and oligometastatic extra-cervical CUP. 13 patients with extra-cervical CUP underwent both 18F-FDG- and 68Ga-FAPI-PET/CT. Suspicious PET-positive lesions were delineated using the volume of interest-technique (50

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.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attentional deficits, hyperactivity and impulsivity that often persists into adulthood. While dysfunction of dopaminergic neurotransmitter systems has been observed, underlying mechanisms remain incompletely understood. Current treatments with methylphenidate and amphetamines show limited long-term effectiveness and do not address broader clinical needs. The endocannabinoid system represents a promising therapeutic target. Cannabinoid type 1 (CB1) receptors are highly concentrated in the prefrontal cortex and striatum, brain regions central to ADHD pathophysiology. The "dual pathway model of ADHD" describes deficits in inhibition-related executive functions and reward-related functions, both mediated by fronto-striatal networks. Striatal CB1 receptor availability correlates negatively with impulsivity. Given the interaction between dopaminergic and endocannabinoid systems, CB1 receptors may play a key role in ADHD pathogenesis. This controlled study will investigate CB1 receptor availability in ADHD using positron emission tomography (PET) with the CB1-selective radiotracer [ 18 F]MK-9470. The primary outcome is the CB1 receptor distribution volume (V T ) in the striatum. Secondary outcomes include CB1 receptor availability in prefrontal cortex and other ADHD-relevant brain regions, plasma concentrations of endocannabinoids (anandamide, 2-arachidonoylglycerol), and validated neuropsychological assessments of attention and impulsivity. We will compare three groups (n=34 each): medication-naïve participants with ADHD, methylphenidate-treated participants with ADHD, and healthy controls. Statistical analysis will employ ANOVA with post-hoc comparisons and correlation analyses between neuroimaging and behavioral measures. This first investigation of the endocannabinoid system in ADHD will provide crucial insights into disease mechanisms and identify potential therapeutic targets. Results may inform development of novel cannabinoid-based treatments and improve evidence-based therapeutic strategies for ADHD management. Trial registration : German Clinical Trials Register (DRKS-ID: DRKS00037526, Registration date: 25 September 2025)

Inflammatory Bowel Diseases (IBD) comprise ulcerative colitis (UC) and Crohn’s disease (CD). Management of IBD requires assessment of disease activity, severity, extent and complications. Here, we describe the signal behavior of both CD and UC in 68Gallium- fibroblast activation protein inhibitor-based radiopharmaceuticals-46-positron emission tomography (68Ga-FAPI-46-PET) and evaluate the potential of 68Ga-FAPI-46-PET for activity assessment in IBD. This analysis includes data of 43 IBD patients and 43 control patients examined by 68Ga-FAPI-46-PET/computed tomography (CT). Disease activity of IBD patients was assessed by colonoscopy. FAPI-positive gastrointestinal tract (GIT)-findings and healthy appearing GI structures were contoured. Non-IBD related FAPI-positive GIT-findings were ruled out by interdisciplinary consensus. Static and dynamic PET-parameters of FAPI-positive IBD lesions and healthy appearing GI structures were extracted and PET signalling was analyzed with respect to IBD subtype and disease activity. We examined 20 CD patients and 23 UC patients (29 with active, 14 with inactive disease). FAPI-uptake in most healthy appearing GI structures of IBD patients was significantly increased compared to controls. Of 80 FAPI-positive GIT-findings, 14 were ruled out as non-IBD related and 66 FAPI-positive IBD lesions were analyzed. We observed equally high lesional FAPI-uptake in CD and UC. All patients with active disease showed at least one intensively FAPI-positive IBD lesion, while only 4/14 patients with inactive disease showed any FAPI-positive IBD lesion. Lesional and patientwise FAPI-uptake was significantly higher in active than in inactive disease. FAPI-positive IBD lesions showed a characteristic kinetic behaviour with two types of uptake patterns – one showing a continuous increase and the other an early peak followed by a plateau. 68Ga-FAPI-46-PET/CT appears promising for assessing disease activity in terms of fibroblast activation in both CD and UC.

Several studies have compared validated tracers, such as the radioactive tracer technetium-99m nanocolloid (99mTc-nanocolloid) and superparamagnetic iron oxide (SPIO), for sentinel node biopsy (SNB) in early-stage breast cancer (eBC). These studies mostly investigated the differences in detection rate and SNB-related adverse events. The aim of our study was to determine whether there are any crucial differences between the two procedures, including the duration of surgery and the number of detected sentinel lymph nodes (SN), which may affect patient treatment and the standard of care in eBC. All patients were treated at the University Medical Centre Mainz by certified breast surgeons. Two consecutive groups of patients were identified based on the injected tracer: Technetium Group (N=517), patients treated from January 1 2017 to December 31 2019, with 99mTc-nanocolloid as tracer and SPIO Group (N=456), patients treated from January 1 2020 to December 31 2022, with superparamagnetic iron oxide particles as ferromagnetic tracer. To avoid potential bias, we performed propensity score matching. After performing propensity score matching, the total surgery time was significantly shorter in the Technetium Group compared to the SPIO Group [64 (48 - 84) vs. 71.5 (58 - 98) minutes; p<0.001]. Both groups did not differ regarding detection rates, or complications (p>0.05). The median number of removed SN was 1.0 in the 99mTc-nanocolloid Group and 2.0 in the SPIO Group. In conclusion, our analysis showed that the use of 99mTc- nanocolloid for SNB resulted in shorter operation time and removal of less SN compared to the SPIO intervention.

Abstract Purpose Differential diagnoses of primary pancreatic lesions include pancreatic ductal adenocarcinomas (PDAC) and inflammatory lesions of the pancreas (ILP). Post-pancreatic surgery, differentiation of postoperative reactive tissue (PRT) and PDAC-recurrence challenges oncological imaging. Static 68Ga-FAPI-PET/CT uptake is increased in all of these lesions with marked overlap in signal intensity, hampering their FAPI-PET-based assessment. Here, we evaluated static and parametric imaging parameters for discrimination of pancreatic lesions in primary and post-pancreatic surgery scenarios. Methods 55 Patients with pancreatic lesions (36 primary, 19 post-pancreatic surgery) underwent static and dynamic 68Ga-FAPI-46-PET/CT. Primary lesions were classified either by histology following PET/CT or follow-up (> 6 months). Post-surgery, PRT and PDAC-recurrence were classified by CT- and clinical course (> 18 months). Parametric maps (1 tissue compartment (1TC), 2TC and Logan plot (LP)) from dynamic PET-data were generated via image-based aortic input function using PMOD-software. Pancreatic lesions (PDAC, ILP, PRT, PDAC-recurrence) were then delineated using VOI-technique (30–70% isocontour) and signal intensities were analyzed. SPSS was used to detect outliers, unpaired t-tests was applied for comparison of static and parametric imaging parameters. Receiver-operating-characteristic curves for differentiating PDAC/ILP or recurrent PDAC/PRT were generated. Results 42 patients were included in the final analysis: in primary setting, 16 PDAC and 10 ILP; in post-surgery setting 9 PDAC-recurrences and 7 PRT. In the primary setting, although PDAC showed higher SUVmax/mean than ILP, no significant differences in maximum/mean signal values neither in static imaging nor in parametric maps were detected. With regard to the differentiation of PDAC-recurrences versus postoperative tissue, LPmax were significantly higher in PDAC-recurrences compared to PRT (4.74 vs. 2.40, p-value 0.020) with AUC 82.5% (95-CI 0.62-1.0) and a possible diagnostic threshold at > 3,49 (LR + 5.44), while differences in static imaging or other parametric maps were not statistically significant. Conclusion Differentiating pancreatic lesions remains challenging. While LPmax significantly distinguished PDAC-recurrence from PRT, other parametric mapping parameters yielded no significant results. Larger studies and additional dynamic data analysis methods should be explored.

Acidic pH values of the tumor microenvironment (TME) have crucial effects on metastatic behavior, host defense, immune regulation and cellular metabolism. Several studies have shown that the acidity of the interstitial space in the TME influences the functions of cancer and stromal cells, particularly regarding immune effects. Changing intratumoral pH might therefore be a potential target for therapy, and pH imaging might guide further developments. We describe radiopharmaceutical probes for positron emission tomography (PET) that exploit the concept of pH-dependent intratumoral hydrolysis of glycosylamine bonds of PET-tracers ([18F]FDG-4-methoxybenzylamine ([18F]FDG-4MBA) and [18F]FDG-benzylamine ([18F]FDG-BA)) to release [18F]FDG as functional moiety with the aim to non-invasively image pH changes. Nuclear magnetic resonance (NMR) spectroscopy demonstrated hydrolysis at pseudo first order and showed pH dependent hydrolysis time, at which 50

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 advent of disease-modifying therapies for neurodegenerative diseases may result in a growing demand for nuclear neuroimaging procedures presenting opportunities but also challenges to the nuclear medicine community. Whether capacity and expertise in Germany are sufficient to meet an increasing demand for nuclear neuroimaging is under discussion. Against this background, the Neuroimaging Working Group of the German Society of Nuclear Medicine initiated the first survey on the status of nuclear neuroimaging in Germany in 2023. 82 institutions participated in the survey: 33 practices, 15 community hospitals, 34 university hospitals. Primary findings were the following. In practices, brain scans are less frequently performed than in hospitals and are often limited to dopamine transporter SPECT. Brain PET is mainly performed in hospitals, and in community hospitals it is often restricted to FDG PET. Nevertheless, availability of amyloid PET with well-certified quality can be taken for granted. Thus, access to amyloid PET will not be a major bottleneck for new treatments of Alzheimer's disease. Adequate reimbursement and clear anchoring in clinical guidelines have the greatest potential to advance nuclear neuroimaging in Germany. Clinical dopamine transporter SPECT is largely in agreement with procedure guidelines. An area for improvement is the limited availability of MR images to avoid misinterpretation of structural/vascular lesions as nigrostriatal degeneration. The survey provides the first systematic assessment of the status of nuclear neuroimaging in Germany. It underscores the capacity of the German nuclear medicine community to meet an increasing demand for neuroimaging procedures, its adherence to procedure guidelines and identifies topics for improvement.

BACKGROUND:Adrenal tumours are frequently detected by conventional imaging. However, computed tomography and magnet resonance imaging have limited specificity in classifying the most prevalent tumour type, adrenocortical adenoma (ACA), which typically does not require surgery. We proposed that combined molecular imaging with [18F]Fluorodeoxyglucose-positron emission tomography (FDG PET) and [123I]Iodometomidate-single photon emission tomography (IMTO SPECT) improves non-invasive classification of ACA. METHODS:This cross-sectional, multicentre diagnostic study included patients (≥30 years) with non-functioning indeterminate adrenal masses (>3 cm or increase >1 cm, Hounsfield units [HU] ≥10 on unenhanced computed tomography [CT]) scheduled for surgery. Using histopathology as the reference, we assessed the accuracy of FDG/IMTO imaging as an ACA-test, assuming that low FDG with high IMTO uptake is indicative of ACA, with a focus on high specificity and moderate to high sensitivity. We also investigated its accuracy in detecting or excluding adrenocortical carcinoma (ACC) and evaluated FDG and unenhanced CT in assessing malignancy. TRIAL-REGISTRATION:EudraCT 2012-003604-13; ClinicalTrials.gov-identifier NCT02010957. FINDINGS:From July 2015 to December 2020, 85 patients were enrolled, with 77 included in the final analysis (53 benign, 30 ACA, 9 ACC). FDG/IMTO-imaging classified ACA with high specificity (95·7% [95% CI 85·2%-99·47%]), high positive predictive value (87·5% [95% CI 61·7%-98·4%]) and high positive likelihood ratio (11·1 [95% CI 3·2-122]). However, sensitivity was low (48·3% [95% CI 29·4%-67·5%]) due to moderate/high FDG uptake in 14 of 30 ACA. Malignant masses were classified with high sensitivity but low-to-moderate specificity by both unenhanced CT (cut-off HU ≥20 sensitivity 100% [95% CI 85·8%-100%], specificity 26·4% [95% CI 15·3%-40·3%]) and FDG (visual analysis sensitivity 95·8% [95% CI 78·9%-99·9%], specificity 62·3% [95% CI 47·9%-75·2%]). All four study-related AEs were grade 1, the seven serious AEs were not study-related. INTERPRETATION:Combined FDG/IMTO-imaging classifies ACA with high specificity, potentially reducing unnecessary surgery. A sub-group of FDG-positive ACA lowers sensitivity. FUNDING:German Research Foundation and EU-FP7.

Ziel/Aim: With static 68Ga-FAPI-PET/CT, distinguishing pathologies like pancreatic ductal adenocarcinomas (PDAC), inflammatory lesions of the pancreas (ILP), post- pancreatectomy reactive tissue (PRT) and recurrent-PDAC (RPDAC) is a challenge due to their marked increase in signal intensity. Dynamic imaging allows 68Ga-FAPI kinetic profile analysis, highlighting differences between these pathologies. Heretofore, analysis of such dynamic PET data is challenging. The use of a voxel-level "digital biopsy" approach combined with network analysis and clustering could overcome this challenge. We hypothesise this approach will allow the identification of healthy, non- malignant pathological and malignant pathological kinetic signatures which could aid diagnosis.

Neuroendocrine tumors have increased in prevalence and diversity in recent years and are often diagnosed at metastatic stages. Compared with nonradioactive systemic treatment with somatostatin analogs, peptide receptor radionuclide therapy (PRRT) has shown superior overall survival benefits for well-differentiated neuroendocrine tumor patients. This study aimed to identify biomarkers from 68Ga‒DOTATOC PET/CT scans to predict survival in patients treated with PRRT in the clinic. This retrospective study analyzed 68Ga-DOTATOC PET/CT data from 67 NET patients undergoing PRRT. Tumor volumes and SUV metrics were segmented using standardized protocols. Radiomics features from liver metastases were extracted and preprocessed for analysis. Data were analysed via Kaplan-Meier, Cox regression, and PCA to evaluate the prognostic value of volumetric-, radiomics-, and clinicopathological parameters. This study included scans from 67 patients with an average age of 67 years. The mean survival time was 46.5 months, with 43

The Auger emitter 161Tb is an increasingly discussed radionuclide for targeted radionuclide therapy. The aim of this study was to assess the feasibility of scintigraphic imaging with 161Tb in terms of image quality and quantitative capabilities by phantom measurements and to evaluate the suitability of this radionuclide for clinical use. Phantom measurements were conducted using a standardized NEMA IEC body phantom filled with activity concentrations ranging from 2.5 GBq to 100 MBq. Both visual and quantitative analyses were performed, including assessment of the image calibration factor (CF), as well as the recovery coefficient (RC) and the contrast-to-noise ratio (CNR) of the individual spheres. The results observed in this study demonstrate that quantitative SPECT/CT imaging with 161Tb is feasible over a wide range of activity making this radionuclide suitable for clinical applications. Acquiring a total of at least 5 million photopeak counts enables visual detectability of lesions of diameter lower than 20 mm and quantitative calibration for dosimetry purposes.

Ziel/Aim: Ziel ist es zu untersuchen, inwiefern 68Ga-FAPI-46-PET-Texturparameter bei der Differenzierung zwischen Bronchialkarzinomen und benignen pulmonalen Läsionen helfen können.