Aim:[⁸⁹Zr]Zr-DFO-trastuzumab has emerged as a powerful tool to visualise non-invasively HER2 expression across metastatic lesions, complementing conventional pathological HER2 evaluation and helping to identify patients unlikely to benefit from therapy with trastuzumab-based therapies. This paper outlines the roadmap of the manufacturing implementation of [89Zr]Zr-DFO-trastuzumab at our centre in Germany. Methods:In this paper, we describe the key questions encountered during implementation of the manufacturing process for [89Zr]Zr-DFO-trastuzumab and how these were addressed through discussions between academia, hospital departments, teams experienced in the radiolabelling of antibodies and regulatory authorities. Results:Discussions with multiple institutions were essential for the implementation of the GMP-compliant radiosynthesis of [⁸⁹Zr]Zr-DFO-trastuzumab at our manufacturing site. Example decisions included shortening the shelf-life of [⁸⁹Zr]Zr-DFO-trastuzumab to 24 hours to mitigate container-closure integrity concerns and adoption of a bead-based method to determine the immunoreactive fraction. Conclusion:This work presents a practical overview of operational considerations relevant to the clinical implementation of [⁸⁹Zr]Zr-DFO-trastuzumab, with potential applicability to other ⁸⁹Zr-labelled high-molecular-weight radiotracers in Germany. By sharing these practical insights, we aim to support broader patient access to established radiopharmaceuticals and encourage dialogue around open regulatory and practical questions, particularly in anticipation of future clinical trials.
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.
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.
Aim The aim of this study was to assess the impact of [ 18 F]FDG PET/CT in predicting EGFR gene mutation status in patients with lung adenocarcinoma using recovery coefficient-based (RC-based) correction of semi-quantitative and volume-based PET metrics. Methods A retrospective multi-center study included 63 patients diagnosed with lung adenocarcinoma who underwent [ 18 F]FDG PET/CT. Acquisition was performed according to the EANM guidelines using two EARL-accredited PET/CT-systems. All patients were divided into an EGFR-mutant (n=30) and a wild-type (n=33) groups based on the results of molecular testing. Maximal diameter and CT volume of each primary tumor lesion were measured. [ 18 F]FDG uptake was evaluated by measurement of semi-quantitative and volume-based PET metrics such as SUVmax, SUVpeak, MTV, and TLG. TLG was measured using PET segmentation method by 3D-Isocontour tool with a 41% of SUVmax threshold (TLG 41% ) and a threshold adapted to the CT volume (TLG CT ). Additionally, TLR was calculated as the ratio of tumor SUVpeak to liver SUVmean. Acquisition data of the NEMA IEC Body Phantom Set NU2-2018 were applied for plotting the RC curves which were used for following RC-based correction of PET metrics. Results No significant difference in tumor lesion maximal diameter, CT volume, evaluated values of PET metrics before and after RC-based correction was found between the EGFR-mutant and wild-type groups (p > 0.05). Conclusion Observed semi-quantitative and volume-based PET metrics obtained from [ 18 F]FDG PET/CT have no significant value for predicting EGFR gene mutation status in patients with lung adenocarcinoma, regardless of whether RC-based correction is applied.
Abstract:AIM: To present the updated S1 guideline recommendations on bone scintigraphy, including SPECT and SPECT/CT, in children and adolescents, with a particular focus on its positioning relative to alternative imaging modalities and on optimization of radiation protection. Abstract:METHODS: Narrative literature review and evaluation of interdisciplinary national and international guidelines, combined with expert consensus within the German Society of Nuclear Medicine. Indications, dosimetry and CT protocols were revised based on EANM recommendations, ICRP Publication 128 and newly established diagnostic reference levels. Abstract:RESULTS: Compared with the 2015 version, the clinical indications were comprehensively re-evaluated and restructured, with explicit consideration particularly of MRI and FDG-PET/CT or PET/MRI. Potential drug interactions relevant to image interpretation are listed systematically. Radiation exposure data were updated according to ICRP 128. For SPECT/CT, detailed age- and diameter-adapted recommendations for low-dose CT dose reduction were formulated. In addition, the role of [18F]NaF PET as a potential alternative to conventional bone scintigraphy in childhood is described. Abstract:CONCLUSIONS: The updated guideline refines and sharpens the indications for bone scintigraphy in the context of MRI and PET techniques and reinforces the use of radiation dose-optimized protocols. It supports nuclear medicine teams in evidence- and guideline-based imaging of paediatric skeletal disorders.
To estimate (i) the rate of difficult-to-interpret cases in dopamine transporter (DAT)-SPECT with [123I]ioflupane and (ii) the diagnostic accuracy of binary visual categorization in difficult-to-interpret DAT-SPECT.The study included 178 control subjects (49% females, 63.7±11.7y) and 178 sex- and age-matched patients with pre-screening clinical diagnosis of Parkinson's disease (PD) from the Parkinson's Progression Markers Initiative (PPMI). SPECT images reconstructed by the PPMI and a local method were visually interpreted twice by 2 independent readers with respect to Parkinson-like reduction of the striatal signal using the following 6-score: -3 = clearly reduced, -2 = probably reduced, -1 = more likely reduced than normal, 1 = more likely normal than reduced, 2 = probably normal, 3 = clearly normal. Cases with 6-score of -1 or 1 were considered "difficult-to-interpret", all other cases were considered "conclusive". To assess diagnostic accuracy relative to the clinical group label (control, PD), the 6-score was binarized using 0 as cutoff.The proportion of difficult-to-interpret cases ranged between 3.4% (95%-CI 1.5-5.2%) and 7.6% (4.8-10.3%) across readers and reconstruction methods. The proportion of cases misclassified by the binarized score ranged between 17.4% (1.9-32.9%) and 50.0% (25.5-74.5%) among the difficult-to-interpret cases, and between 5.1% (2.7-7.4%) and 6.4% (3.8-9.0%) among the conclusive cases.(i) the proportion of difficult-to-interpret cases in DAT-SPECT for the diagnosis of parkinsonism is not larger than 10%, (ii) the diagnostic accuracy of binary decisions is severely reduced in these cases. We therefore recommend reporting difficult-to-interpret cases as "inconclusive", unless in special situations.
This updated position paper from the German Society of Nuclear Medicine (DGN) and the German Cardiac Society (DGK) replaces the original statement from 2018. It gives an overview of the fields of application and the current value of nuclear cardiological imaging. The topics covered include chronic coronary syndrome, including viability diagnostics and the special value of positron emission tomography (PET), cardiomyopathies, cardiac sarcoidosis, amyloidosis, infectious endocarditis and inflammation of cardiac implants.
Aim:This review aims to explore the evolving field of theranostics in oncology, focusing on its potential application to head and neck squamous cell carcinoma (HNSCC). Specifically, it examines the integration of molecular imaging and radionuclide therapy in the context of theranostics. Methods:A comprehensive review of current literature was conducted to evaluate the state-of-the-art theranostic approaches in HNSCC. The review includes an analysis of established and emerging molecular targets relevant to HNSCC, as well as the potential for future theranostic developments. Results:The integration of theranostic principles into head and neck oncology is gaining momentum, with increasing interest in novel targets in the context of theranostics. Although [18F]FDG PET/CT still remains the dominant imaging modality in HNSCC, the application of novel radiotracers for imaging and radionuclide therapy holds considerable promise. Conclusion:Theranostics represents a promising future for head and neck oncology, offering the potential for personalized, biology-driven diagnostic and therapeutic strategies. While many emerging approaches are still under investigation, the combination of molecular imaging and targeted radionuclide therapy may significantly enhance the treatment of HNSCC, providing more precise and effective patient care in the future.1.
The study investigated routinely used radiopharmaceuticals containing lutetium-177 (177Lu), providing reference values for their effective half-life (T1/2,eff). So far, no guidelines regarding discharging this patients exist, are essential to ensure radiation protection of the public. This study contributes to the development of binding discharge criteria regarding 177Lu therapies. This retrospective multicenter study comprised eight nuclear medicine departments. Two commercially available products and two in-house preparations were considered. Radiation measurement methods, in terms of measuring device, setup, and time points were reported, as well as dose rate measurements for T1/2,eff calculation. The study includes 210 dose rate measurement sets with a mean administered activity of (7149 ± 522) MBq. When only measurements up to 48 h p.i. were taken into account the T1/2, eff were shorter (Pluvicto 1.30 d, Lutathera 1.40 d, ihPSMA 1.45 d, ihRRT 1.97 d) compared to 168 h (1.60 d, 1.89 d, 2.10 d, and 2.85 d, respectively). Differences were statistically significant for all compounds except Lutathera. The 90th percentile of the T1/2,eff observed in late measurements (Pluvicto 2.0 d, Lutathera 3.0 d, ihPSMA 3.5 d, ihRRT 4.0 d) can be considered conservative values for discharge calculations. The T1/2,eff of 177Lu is considerably shorter than its T1/2,phy, owing to the pharmacokinetics of the entire molecule. This highlights the need of considering biological clearance mechanisms into calculations of discharge times for patients treated with 177Lu. If direct measurements are not feasible in clinical routine, reference values support inpatient planning while ensuring radiation protection.
This retrospective study aimed to investigate whether the differing biology of right-sided primary tumors (RSP) and left-sided primary tumors (LSP) in metastatic colorectal cancer (mCRC) affects survival outcomes following selective internal radiation therapy (SIRT).A cohort of 140 mCRC patients with liver metastases treated with SIRT between 2009 and 2016 was analyzed. Patients were stratified by tumor localization (RSP: proximal colon; LSP: distal colon and rectum), clinical, histopathological, and molecular data, were collected. Survival outcomes (OS and PFS) were evaluated using Kaplan-Meier analysis. Cox regression analysis identified independent predictors of survival, and subgroup analyses examined differences between RSP and LSP patients.Of the patients, 80.7% had LSP, and 19.3% had RSP. RSP patients demonstrated more aggressive tumor biology, with a higher frequency of poorly differentiated tumors (G3), extrahepatic metastases and K-RAS mutations. Median OS was significantly longer for LSP patients (7.0 months) compared to RSP patients (4.0 months, p<0.005). Similarly, PFS was longer for LSP patients (3.0 months) than for RSP patients (1.6 months, p<0.032). Multivariable Cox regression analysis revealed that K-RAS mutation (HR 3.345, p=0.017), N2 lymph node involvement (HR 2.458, p=0.015), and RSP localization (HR 0.338, p=0.001) were independently associated with poor survival.This study demonstrates that right-sided tumor localization, K-RAS mutation, and N2 lymph node involvement are key predictors of poor survival following SIRT in mCRC patients. RSP tumors, with distinct molecular and clinical profiles, exhibit shorter median OS and PFS after SIRT compared to LSP tumors.
Alveolar echinococcosis (AE) is a rare, potentially fatal zoonosis with highly heterogeneous morphology. This study compares AE lesions in B-scan ultrasound, categorized according to the Echinococcus multilocularis Ulm Classification – Ultrasound (EMUC-US), with the maximum standardized uptake value (SUVmax) in 18F-Fluorodeoxyglucose Positron-Emission-Tomography (18F-FDG-PET/CT). 18F-FDG-PET/CT is the gold standard for evaluating disease activity, with SUVmax as the key parameter indirectly reflecting AE lesion activity. Retrospective analysis of data from the German National Echinococcosis Database. A total of 121 patients with 18F-FDG-PET/CT and B-scan ultrasound (US) between 2018–2019 were included. Based on EMUC-US, AE liver lesions were compared with the corresponding SUVmax in PET/CT. Additionally, SUV ratios (SUVTLR=tumor SUVmax/liver SUVmean) were calculated. The mean SUVmax, regardless of the EMUC-US subtype, was 6.0 ± 3.3 (range: 2.4–18.0). SUVmax comparison between subtypes shows significant differences (p<0.001). The highest SUVmax and SUVTLR were measured for the pseudocystic pattern with a mean of 9.2 ± 3.5 (range: 4.1–18.0). In contrast, the metastasis-like pattern yielded 3.7 ± 0.9 (range: 2.4–5.8) and the lowest SUVTLR. An SUVmax of 6.1 ± 3.3 (range: 2.6–16.8) was measured for the hailstorm pattern and 5.8 ± 2.2 (range: 3.6–10.4) for the hemangioma-like pattern. The results show significant differences between specific US patterns and the corresponding SUVmax. Lesions with very high or low SUV correlate with characteristic morphological patterns. Hence, in clinical practice B-scan can be a valuable bedside tool for assessing certain lesions. For evaluating inflammatory activity, 18F-FDG-PET/CT remains the method of choice.
Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies characterized by variable immune microenvironment. This study aimed to analyze the infiltration of NETs by CD68+ tumor-associated macrophages (TAMs) and FoxP3+ regulatory T cells (Tregs) using Qupath software for semi-automated histopathological quantificationThirty-two patients with resected NETs were included. CD68 and FoxP3 expression were assessed by immunohistochemistry followed by automated cell detection and spatial analysis.The mean percentage of CD68+ cells was 0.35%, with no significant differences between pancreatic and gastrointestinal NETs. FoxP3+ cells were less frequent (mean: 0.06%), with higher levels in gastrointestinal NETs compared to pancreatic NETs (p < 0.05). Kaplan-Meier analysis revealed that CD68+ cells showed a trend to positive correlation with progression-free survival (PFS) and overall survival (OS). Thereby, patients exceeding a 0.1% CD68+ cell threshold exhibited longer survival (PFS: not reached vs. 106 months). In contrast, FoxP3+ cells showed a trend to inverse correlation with survival; patients with >0.05% FoxP3+ cells had shorter PFS (36 months vs. 147 months) and OS (180 months vs. not reached). Multivariate Cox regression identified N-stage as the sole predictor of OS. CD68+ TAM density was not associated with other clinical parameters, while FoxP3+ cell infiltration correlated significantly with venous invasion and advanced N- and M-stages.These findings highlight the potential prognostic relevance of immune cell infiltration in NETs and underscore the utility of Qupath for quantifying immune markers in histopathological analyses. The contrasting roles of CD68+ TAMs and FoxP3+ Tregs in the NET microenvironment warrant further exploration to inform immunotherapeutic strategies.
Nuclear medicine landscape has been changing over the past decade due to the rise of radioligand therapies. However, patients receiving radioiodine therapy for benign thyroid disease still account for approx. one third of the patients on a regular nuclear medicine ward. A substantial part of these patients are hospitalized for radiation protection only and do not require nursing staff. This report aims at describing the implementation of a "no-care" nuclear medicine ward with medical students as staff. We report on the training process, patient and student satisfaction as well as the impact and strengths of this concept.A separated nuclear medicine ward (10 beds) was established at a university hospital in Germany. After specific training, two students were assigned per working shift in a regular three-shift-system. Patients were evaluated according to predefined inclusion and exclusion criteria. Patients and students answered two separate surveys, assessing the satisfaction with the concept.172/319 (53.9%) of the patients met the inclusion criteria. The "no-care" ward was opened six times between April 2024 and June 2025 and the duration was between 10 and 20 days. 101 patients were treated using I-131 sodium iodine, achieving 68.5 DRG relative units. Patient satisfaction survey revealed very high positive response rates. 27 medical students were assigned to the "no-care" ward. The majority of students stated a positive effect on overall medical knowledge and workflow understanding in a hospital.Using medical students as staff on a "no-care" nuclear medicine ward is feasible and safe. In view of nursing staff shortage, this concept might contribute to adaptive caring in nuclear medicine therapies after careful patient selection.
This paper presents the results of the 10th survey of myocardial perfusion SPECT (MPS) from the year 2024. A total of 198 questionnaires were evaluated, comprising 115 practices (PR), 57 hospitals (HO) and 26 university hospitals (UH). The results of the previous survey 2021 are shown in squared brackets. MPS data from 128.707 [133.057] patients (–3.3%) with 125.175 [131.868] stress and 102.903 [106.546] rest MPS were analysed. A comparison with official data revealed that 53% of all MPS were recorded. From 2018 to 2024, official data showed an increase in MPS every year. In 2024, on average, 650 [610] MPS patients (+7%) were examined in each department. Of the participating departments, 69% [74%] reported an increase or no changes in their patient numbers. As always ambulatory care cardiologists represented the major referral group (68% [69%]). Pharmacological stress was performed more frequently than ergometry (43% [42%]). Regadenoson was mostly used. The use of the different protocols remained almost unchanged. Two-day protocols were predominantly applied (49% [49%]). Multi-head cameras were used in (56% [58%] of the departments and SPECT-CT systems in (31% [28%]). Attenuation correction was performed in 35% [33%] of all MPS. 95% [89%] of all stress, 93% [88%] of all rest and 92% [87%] of all stress and rest scan were acquired as gated SPECT. 84% [72%] of the departments performed scoring by default. The proportion of departments not scoring decreased to 4% [13%]. The MPS 2024 survey indicates that the long-term positive development of MPS imaging is continuing. The procedural and technical details of MPS imaging demonstrate a high level of conformity with guidelines, with a slight improvement observed from 2021 to 2024.
To develop a site-specifically radiolabeled version of IMMU-132 (sacituzumab govitecan) using zirconium-89 (⁸⁹Zr) with the chelator 3,4,3-LI(1,2-HOPO) and evaluate its stability, specificity, and quantitative targeting ability in TROP-2–positive prostate cancer models. IMMU-132 was conjugated to 3,4,3-LI(1,2-HOPO)-maleimide and its integrity was confirmed by SDS-PAGE, SE-HPLC and mass spectrometry. Radiolabeling with ⁸⁹Zr was performed, and radiochemical yield and purity were measured. In vitro stability was assessed in human serum at 37 °C for 120 h. Binding affinity and specificity were evaluated using PC3 (TROP-2⁺) and A549 (TROP-2⁻) cells. Immunoreactivity was determined by Lindmo assay. In vivo PET imaging and ex vivo biodistribution were conducted in PC3-TROP-2⁺ xenograft-bearing mice. Radiolabeling with ⁸⁹Zr yielded 71.88 ± 0.21% with a radiochemical purity of 98.70 ± 0.55%. The radioconjugate maintained >90% stability in serum over 120 h. High-specific binding was observed in PC3 cells (Bmax ≈ 4750 CPM; Kd = 0.4 × 10⁶ cells/mL), with minimal uptake in A549 cells. The immunoreactive fraction was 88.10%. PET imaging revealed tumor-specific accumulation with a peak SUV mean of 5.8 ± 0.7 at 72 h post-injection. Biodistribution confirmed high tumor uptake (19.4 ± 2.1 %ID/g) and significantly reduced bone uptake (3.2 ± 0.5 %ID/g) compared to conventional ⁸⁹Zr-DFO tracers (p < 0.01). ⁸⁹Zr–IMMU-132–HOPO exhibits excellent in vivo stability, specificity, and selective accumulation in TROP-2–positive prostate tumors, while minimizing off-target bone uptake. These findings support its potential as a next-generation immuno-radiopharmaceutical for quantitative TROP-2 imaging and future theranostic applications in prostate cancer.
This study aimed to determine the optimized scan time and injected activity regimen for clinical 68Ga DOTATATE PET/CT in neuroendocrine tumor imaging through an experimental approach without using machine learning techniques. A NEMA PET body phantom was used with Ga-68 to simulate a 9:1 sphere-to-background ratio. PET data were acquired on a high-sensitivity scanner at various scan times (15–300 s/bed). For each scan time, coefficient of variation (COV) and contrast-to-noise ratio (CNR) were calculated. The minimum scan time (Tmin) needed to meet the Rose Criterion (CNR > 5) for the smallest sphere was identified. This Tmin was then applied to patient scans with neuroendocrine tumors (originally acquired at 120 s/bed) to evaluate image quality and determine an optimized activity regimen for clinical 68Ga-DOTATATE PET imaging. Phantom experiments showed that a COVmax of 20% is the highest acceptable noise level for detecting the smallest lesions, corresponding to a minimum scan time of about 1 minute per bed position. Patient image analysis confirmed that all tumors visible at routine scan times were still detectable at this minimum duration. This supports the use of a lower activity regimen (~1 MBq/kg), which can reduce patient radiation exposure compared to the standard 1.85 MBq/kg protocol. This work demonstrated that scan time and activity for 68Ga-DOTATATE NET imaging can be significantly minimized without compromising image interpretation and quantification.
Aim Digitalization in the healthcare sector is becoming increasingly widespread. Yet, the degree of digitalization in nuclear medicine has not been systematically investigated. The "Digitalization and AI" working group of the German Society of Nuclear Medicine conducted a survey to assess the status quo of digitalization of the nuclear medicine health infrastructure in Germany. Methods 100 questions were defined on eleven topics covering the main work processes in nuclear medicine. The survey primarily included single-select multiple-choice questions, yes-no questions on the availability of specific digital structures and processes, and questions assessing the degree of digitalization of certain processes and current satisfaction. The level of satisfaction was measured with an ordinal scale (1, very good to 5, poor). Results In most subject areas, processes relied on a combination of paper-based and electronic procedures for the topics analyzed. Differences in satisfaction regarding the different types of processes for any of the questions were not observed, and the overall level of satisfaction among responding sites was quite high. Conclusion The survey did not reveal a clear need of the responding sites for complete digitalization of clinical processes. Yet, the participants highlighted the lack of proper Wi-Fi (60%) and the desire for a platform for communication between hospitals, registered doctors and patients (74%). Nevertheless, it is important to take a focused and unbiased look at the daily clinical procedures in every institution and place it in the frame of the existing tools or solutions of peer institutions to discover aspects of digitalization that can create added value in terms of time efficiency, integrity and sustainability.
