Publikationen

The emerging PET tracer [Ga]Ga-PSMA-11 has been established for staging in prostate cancer (PCa). Aim was to determine the value of early static imaging in two-phase PET/CT. 100 men with newly diagnosed histopathologically confirmed untreated PCa who underwent [Ga]Ga-PSMA-11 PET/CT from January 2017 to October 2019 were included. The two-phase imaging protocol consisted of an early static scan of the pelvis (6 min p.i.) and a late total-body scan (60 min p.i). Associations of semi-quantitative parameters derived via volumes of interest (VOI) with Gleason grade group and PSA were investigated. In 94/100 patients (94%) the primary tumor was detected in both phases. In 29/100 patients (29%) metastases were detected at a median PSA level of 32.2 ng/ml (0.41-503 ng/ml). In 71/100 patients (71%) without metastasis a median PSA level of 10.1 ng/ml (0.57-103 ng/ml) was observed (p = < 0.001). Primary tumors demonstrated a median standard uptake value maximum (SUVmax) of 8.2 (3.1-45.3) in early phase versus 12.2 (3.1-73.4) in late phase and a median standard uptake value mean (SUVmean) of 4.2 (1.6-24.1) in early phase versus 5.8 (1.6-39.9) in late phase, significantly increasing over time (p = < 0.001). Higher SUVmax and SUVmean were associated with higher Gleason grade group (p = 0.004 and p = 0.003, respectively) and higher PSA levels (p = < 0.001). In 13/100 patients the semi-quantitative parameters including SUVmax were declining in the late phase compared to early phase. Two-phase [Ga]Ga-PSMA-11 PET/CT demonstrates a high detection rate for primary tumor of untreated PCa of 94% and improves diagnostic accuracy. Higher PSA levels and Gleason grade group are associated with higher semi-quantitative parameters in the primary tumor. Early imaging provides additional information in a small sub-group with declining semi-quantitative parameters in the late phase.

External tasks evoke characteristic fMRI BOLD signal deactivations in the default mode network (DMN). However, for the corresponding metabolic glucose demands both decreases and increases have been reported. To resolve this discrepancy, functional PET/MRI data from 50 healthy subjects performing Tetris were combined with previously published data sets of working memory, visual and motor stimulation. We show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive networks. Specifically, the dorsal attention and frontoparietal network shape the glucose metabolism of the posteromedial DMN in opposing directions. While tasks that mainly require an external focus of attention lead to a consistent downregulation of both metabolism and the BOLD signal in the posteromedial DMN, cognitive control during working memory requires a metabolically expensive BOLD suppression. This indicates that two types of BOLD deactivations with different oxygen-to-glucose index may occur in this region. We further speculate that consistent downregulation of the two signals is mediated by decreased glutamate signaling, while divergence may be subject to active GABAergic inhibition. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation.

To assess 18F-Fluoroethylcholine (18F-FEC) as a PET/MRI tracer in the evaluation of breast lesions, breast cancer aggressiveness, and prediction of lymph node status.

This study aims to determine the diagnostic accuracy of staging PET/CT and neck MRI in patients with laryngeal carcinoma and to assess the value of PET/CT in predicting progression-free survival (PFS) and overall survival (OS). Sixty-eight patients who had both modalities performed before treatment between 2014 and 2021 were included in this study. The sensitivity and specificity of PET/CT and MRI were evaluated. PET/CT had 93.8% sensitivity, 58.3% specificity, and 75% accuracy for nodal metastasis, whereas MRI had 68.8%, 61.1%, and 64.7% accuracy, respectively. At a median follow-up of 51 months, 23 patients had developed disease progression and 17 patients had died. Univariate-survival analysis revealed all utilized PET parameters as significant prognostic factors for OS and PFS (-value < 0.03 each). In multivariate analysis, metabolic-tumor volume (MTV) and total lesion glycolysis (TLG) predicted better PFS (-value < 0.05 each). In conclusion, PET/CT improves the accuracy of nodal staging in laryngeal carcinoma over neck MRI and adds to the prognostication of survival outcomes through the use of several PET metrics.

Imaging modalities are increasingly being used to evaluate the underlying pathophysiology of heart failure. Positron emission tomography (PET) is a non-invasive imaging technique that uses radioactive tracers to visualize and measure biological processes in vivo. PET imaging of the heart uses different radiopharmaceuticals to provide information on myocardial metabolism, perfusion, inflammation, fibrosis, and sympathetic nervous system activity, which are all important contributors to the development and progression of heart failure. This narrative review provides an overview of the use of PET imaging in heart failure, highlighting the different PET tracers and modalities, and discussing fields of present and future clinical application.

Total-body PET scanners with axial field of views (FOVs) longer than 1 m enable new applications to study multiple organs (e.g., the brain-gut-axis) simultaneously. As the spatial resolution and the associated partial volume effect (PVE) can vary significantly along the FOV, detailed knowledge of the contrast recovery coefficients (CRCs) is a prerequisite for image analysis and interpretation of quantitative results. The aim of this study was to determine the CRCs, as well as voxel noise, for multiple isotopes throughout the 1.06 m axial FOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers).

Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum.

Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [Lu]Lu-PSMA-617 and [Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

The optimal first-line treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) diagnosed in early stages is largely undefined. We therefore analyzed 100 NLPHL patients (early-stage favorable: 85 patients; early-stage unfavorable: 15 patients) treated within the randomized HD16 (early-stage favorable) and HD17 (early-stage unfavorable) studies. These studies investigated the omission of consolidation radiotherapy (RT) in patients with a negative interim positron emission tomography (iPET) (defined as a Deauville score < 3) at the end of chemotherapy (HD16: 2xABVD; HD17: 2xBEACOPPescalated plus 2xABVD). Patients with NLPHL treated within the HD16 and HD17 studies had 5-year progression-free survival (PFS) rates of 90.3% (95%-CI: 83.8%-96.7%) and 92.9% (95%-CI: 79.4%-100%), respectively. Thus, the 5-year PFS did not differ significantly from patients with classical Hodgkin lymphoma treated within the same studies (p=0.88 for HD16; p=0.50 for HD17). Patients with early-stage favorable NLPHL who had a negative iPET after 2xABVD and did not undergo consolidation RT (n=25) tended to have a worse PFS than iPET-negative patients who received consolidation RT (n=21) (5-year PFS: 83% (95%-CI: 67.8%-98.2%) vs 100%; p=0.05). Overall, there were 10 cases of NLPHL recurrence (HD16: 9 patients; HD17: 1 patient). However, no NLPHL patient died during follow-up. Hence, the 5-year overall survival rate was 100%. Taken together, contemporary HL-directed treatment approaches result in excellent outcomes for patients with newly diagnosed early-stage NLPHL and thus represent valid treatment options. In patients with early-stage favorable NLPHL, consolidation RT appears necessary after 2xABVD to achieve the optimal disease control irrespective of the iPET result.

[This corrects the article DOI: 10.3389/fnins.2023.1144248.].

To support acquisition of accurate, reproducible and high-quality preclinical imaging data, various standardisation resources have been developed over the years. However, it is unclear the impact of those efforts in current preclinical imaging practices. To better understand the status quo in the field of preclinical imaging standardisation, the STANDARD group of the European Society of Molecular Imaging (ESMI) put together a community survey and a forum for discussion at the European Molecular Imaging Meeting (EMIM) 2022. This paper reports on the results from the STANDARD survey and the forum discussions that took place at EMIM2022.

Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT.

Ictal single photon emission computed tomography (SPECT) can be used as an advanced diagnostic modality to detect the seizure onset zone in the presurgical evaluation of people with epilepsy. In addition to visual assessment (VSA) of ictal and interictal SPECT images, postprocessing methods such as ictal-interictal SPECT analysis using SPM (ISAS) can visualize regional ictal blood flow differences. We aimed to evaluate and differentiate the diagnostic value of VSA and ISAS in the Bonn cohort.

Tafamidis treatment positively affects left ventricular (LV) structure and function and improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). We aimed to investigate the relationship between treatment response and cardiac amyloid burden identified by serial quantitative 99mTc-DPD SPECT/CT. We furthermore aimed to identify nuclear imaging biomarkers that could be used to quantify and monitor response to tafamidis therapy.

Broad availability and cost-effectiveness of Mo/Tc generators worldwide support the use, and thus the development, of novel Tc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST) antagonists, mainly due to their superiority in SST-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a Tc-labelled SST antagonist, [Tc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [Tc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [Tc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial.

Novel molecular imaging opportunities to preoperatively diagnose renal cell carcinoma is under development and will add more value in limiting the postoperative renal function loss and morbidity. We aimed to comprehensively review the research on single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography computed tomography (PET-CT) molecular imaging and to enhance the urologists' and radiologists' knowledge of the current research pattern. We identified an increase in prospective and also retrospective studies that researched to distinguish between benign and malignant lesions and between different clear cell renal cell carcinoma subtypes, with small numbers of patients studied, nonetheless with excellent results on specificity, sensitivity and accuracy, especially for Tc-sestamibi SPECT/CT that delivers quick results compared to a long acquisition time for girentuximab PET-CT, which instead gives better image quality. Nuclear medicine has helped clinicians in evaluating primary and secondary lesions, and has lately returned with new and exciting insights with novel radiotracers to reinforce its diagnostic potential in renal carcinoma. To further limit the renal function loss and post-surgery morbidity, future research is mandatory to validate the results and to clinically implement the diagnostic techniques in the context of precision medicine.

Bone scintigraphy plays an important role in the diagnosis of cardiac Transthyretin-Related Amyloidosis (ATTR). The mechanism of myocardial tracer accumulation and its dependence over time are not fully understood. Recently, a scintigraphic quantification of the cardiac amyloid deposition has been discussed. Nevertheless, little is known regarding the right time of quantitative imaging.

Percutaneous coronary intervention of chronic total occlusion (CTO PCI) is a challenging procedure with high complication rates and, as not yet fully understood long-term clinical benefits. Ischemic symptom relief in patients with high ischemic burden is to date the only established clinical indication to undergo CTO PCI, supported by randomized controlled trials. In this context, current guidelines suggest attempting CTO PCI only in non-invasively assessed viable CTO correspondent myocardial territories, with large ischemic areas. Hence, besides a comprehensive coronary angiography lesion evaluation, the information derived from non-invasive cardiac imaging techniques is crucial to selecting candidates who may benefit from the revascularization of the occluded vessel. Currently, there are no clear recommendations for a non-invasive myocardial evaluation or choice of imaging modality pre-CTO PCI. Therefore, selecting among available options is left to the physician's discretion. As CTO PCI is strongly recommended to be carried out explicitly in experienced centers, full access to non-invasive imaging for risk-benefit assessment as well as a systematic institutional evaluation process has to be encouraged. In this framework, we opted to review the current myocardial imaging tools and their use for indicating a CTO PCI. Furthermore, based on our experience, we propose a cost-effective systematic approach for myocardial assessment to help guide clinical decision-making for patients presenting with chronic total occlusions.

The brain coordinates the heart through the autonomic nervous system (ANS). Numerous mediator signals along the brain-heart axis interact with the neuronal-metabolic system in heart failure (HF). Disturbances in cardio-neural interactions influence the disease progression in patients with HF.

Cardiac amyloidosis (CA) is a heterogeneous group of diseases in which extracellular insoluble amyloid proteins are deposited in specific organs and tissues locally or systemically, thereby interfering with physiological function. Transthyretin protein (TTR) and light chain (AL) amyloidosis are the most common types of cardiac amyloidosis. Radionuclide bone scintigraphy has recently become the most common non-invasive test for the diagnosis of TTR-CA but is of limited value for the diagnosis of AL-CA. PET has proved promising for the diagnosis of CA and its applications are expected to expand in the future. This review summarizes the current bone scintigraphy and amyloid-targeting Positron emission tomography (PET) imaging, the binding imaging properties of radiotracers, and the values of diagnosis, prognosis, and monitoring therapy response in CA.

Partial volume effect (PVE) is a consequence of the limited spatial resolution of PET scanners. PVE can cause the intensity values of a particular voxel to be underestimated or overestimated due to the effect of surrounding tracer uptake. We propose a novel partial volume correction (PVC) technique to overcome the adverse effects of PVE on PET images.

Merkel cell carcinoma is a rare, aggressive skin malignancy, also known as neuroendocrine carcinoma of the skin, with high rates of recurrence and distant metastasis. In refractory metastatic Merkel cell carcinoma (mMCC), besides immunotherapy, chemotherapy, and radiation, peptide receptor radionuclide therapy (PRRT) may be a viable option since this type of tumor can express somatostatin receptors. We performed a comprehensive review of the literature to evaluate the efficacy of PRRT in mMCC patients. Thirty-seven patients with mMCC received PRRT (1-5 cycles) with Lu- or Y-labeled somatostatin analogs (cumulative activity, 1.5-30 GBq). Radiographic response was available for 19 of 28 patients who received PRRT alone. Six (31.6%) of 19 patients showed objective responses, from partial to complete, and no severe adverse events were reported. Our analysis supports the use of PRRT in mMCC with sufficient somatostatin receptor uptake, although the quality of the available evidence is low. Prospective clinical trials are already in development and have started accruing in some parts of the world.

Targeted radionuclide therapy with [Lu]Lu-PSMA I&T (zadavotide guraxetan) has proven high efficacy and safety in treating patients with advanced prostate cancer worldwide. Several methods to determine the radiochemical purity have been reported but also limitations in the HPLC analysis due to retention of the sample and tailing effects when using standard gradients containing trifluoroacetic acid (TFA). We here report on the validation of a method for quality control of [Lu]Lu-PSMA I&T including determination of radiochemical purity, identity testing and limit test for PSMA I&T by HPLC using a Phosphate buffer /Acetonitrile gradient system, complemented with a TLC system with 0.1N Citrate buffer pH 5 as mobile phase including validation of the methods, batch and stability data as well as identification of the main radiochemical impurity by mass spectrometry.

The therapeutic potential of minigastrin (MG) analogs for the treatment of cholecystokinin-2 receptor (CCK2R)-expressing cancers is limited by poor in vivo stability or unfavorable accumulation in non-target tissues. Increased stability against metabolic degradation was achieved by modifying the C-terminal receptor-specific region. This modification led to significantly improved tumor targeting properties. In this study, further -terminal peptide modifications were investigated. Two novel MG analogs were designed starting from the amino acid sequence of DOTA-MGS5 (DOTA-DGlu-Ala-Tyr-Gly-Trp-(-Me)Nle-Asp-1Nal-NH). Introduction of a penta-DGlu moiety and replacement of the four -terminal amino acids by a non-charged hydrophilic linker was investigated. Retained receptor binding was confirmed using two CCK2R-expressing cell lines. The effect on metabolic degradation of the new Lu-labeled peptides was studied in human serum in vitro, as well as in BALB/c mice in vivo. The tumor targeting properties of the radiolabeled peptides were assessed using BALB/c nude mice bearing receptor-positive and receptor-negative tumor xenografts. Both novel MG analogs were found to have strong receptor binding, enhanced stability, and high tumor uptake. Replacement of the four -terminal amino acids by a non-charged hydrophilic linker lowered the absorption in the dose-limiting organs, whereas introduction of the penta-DGlu moiety increased uptake in renal tissue.

Different attempts have been made in the past two decades to develop radiolabeled peptide conjugates with enhanced pharmacokinetic properties in order to improve the application for tumor imaging and peptide receptor radionuclide therapy (PRRT), which targets the cholecystokinin-2 receptor (CCK2R). In this paper, the influence of different side chain and peptide bond modifications has been explored for the minigastrin analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(-Me)Nle-Asp-1Nal-NH (DOTA-MGS5). Based on this lead structure, five new derivatives were synthesized for radiolabeling with trivalent radiometals. Different chemical and biological properties of the new derivatives were analyzed. Receptor interaction of the peptide derivatives and cell internalization of the radiolabeled peptides were studied in A431-CCK2R cells. The stability of the radiolabeled peptides in vivo was investigated using BALB/c mice. Tumor targeting of all In-labeled peptide conjugates, and of a selected compound radiolabeled with gallium-68 and lutetium-177, was evaluated in BALB/c nude mice xenografted with A431-CCK2R and A431-mock cells. All In-labeled conjugates, except [In]In-DOTA-[Phe]MGS5, showed a high resistance against enzymatic degradation. A high receptor affinity with IC values in the low nanomolar range was confirmed for most of the peptide derivatives. The specific cell internalization over time was 35.3-47.3% for all radiopeptides 4 h after incubation. Only [In]In-DOTA-MGS5[NHCH] exhibited a lower cell internalization of 6.6 ± 2.8%. An overall improved resistance against enzymatic degradation was confirmed in vivo. Of the radiopeptides studied, [In]In-DOTA-[(-Me)1Nal]MGS5 showed the most promising targeting properties, with significantly increased accumulation of radioactivity in A431-CCK2R xenografts (48.1 ± 9.2% IA/g) and reduced accumulation of radioactivity in stomach (4.2 ± 0.5% IA/g). However, in comparison with DOTA-MGS5, a higher influence on the targeting properties was observed for the change of radiometal, resulting in a tumor uptake of 15.67 ± 2.21% IA/g for [Ga]Ga-DOTA-[(-Me)1Nal]MGS5 and 35.13 ± 6.32% IA/g for [Lu]Lu-DOTA-[(-Me)1Nal]MGS5.

Therapy options for advanced pancreatic neuroendocrine tumors (pNETs) include the mTOR inhibitor everolimus and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE, however further optimization in the therapeutic landscape is required as response rates are still low. In this study, we investigated the synergistic and potentially enhanced efficacy of a combined treatment with everolimus and [177Lu]Lu-DOTA-TATE in a mouse model. Baseline [68Ga]Ga-DOTA-TATE PET scans were obtained five days after athymic CD1 mice were inoculated with AR42J tumor cells, before separating the animals into four groups. Group 1 received a placebo, group 2 everolimus, group 3 a placebo and PRRT, and group 4 everolimus and PRRT. The treatment response was monitored by manually measuring the tumor volumes (manual tumor volume, MTV) and conducting sequential [68Ga]Ga-DOTA-TATE PET scans at one, two, and four weeks after treatment induction. The biological tumor volume (BTV) was derived from PET scans using threshold-based volume of interest (VOI) measurements. Tracer uptake was measured semi-quantitatively as a tumor to background ratio (TBR). Mice were euthanized due to excessive tumor growth according to the ethics protocol; blood samples were drawn for the preparation of full blood counts and kidneys were obtained for histological analysis. For the histological assessment, a standardized score (renal damage score, RDS) was used. Full blood counts showed significantly increased numbers of neutrophils and lymphocytes in the groups receiving PRRT. All other parameters did not differ relevantly. In the histological analysis, groups receiving PRRT had a significantly higher RDS, whereas everolimus only tended to cause an increase in the RDS. Mice in groups 1 and 2 had to be euthanized due to excessive tumor growth two weeks after the start of the therapy, whereas follow-up in groups 3 and 4 comprised four weeks. PRRT significantly inhibited tumor growth; the administration of everolimus did not induce an additional effect. A good correlation existed between MTV and BTV. PRRT significantly reduced the TBR. [68Ga]Ga-DOTA-TATE PET is suitable for monitoring tumor growth in the applied model. The high efficacy of [177Lu]Lu-DOTA-TATE is not enhanced by the combination with everolimus.

The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression.

Different oncological therapies have been approved for small intestinal neuroendocrine tumors (SI-NETs), but relatively little is known about efficacy and long-term outcome outside of phase III trials.