Publikationen

Presence of lymph node metastases (LNM) is an important prognostic factor for cancer-specific survival (CSS) in patients with upper tract urothelial carcinoma (UTUC). In various neoplasms, F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) is an established modality for preoperative lymph node (LN) staging. In UTUC, the diagnostic value of FDG-PET/CT for LN staging is unknown.

Previous evidence indicates that transcranial direct stimulation (tDCS) is a neuromodulatory brain stimulation technique. Easy applicability, low side-effects and negligible costs facilitated its wide-spread application in efforts to modulate brain function, however neuronal mechanisms of tDCS are insufficiently understood. Hence, we investigated the immediate impact of tDCS on the brain's glucose consumption in a continuous infusion protocol with the radioligand 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG) and positron emission tomography (PET). This novel functional PET (fPET) method is capable to reliably detect area-specific and dynamic absolute glucose demand related to neuronal activity in a single molecular imaging session. Fifteen healthy subjects underwent tDCS at 0.5, 1 and 2 mA (mA) at the bilateral dorsolateral prefrontal cortex (dlPFC, cathodal right) for 10 min during functional [F]FDG-PET lasting 70 min. Active stimulation compared to sham did not yield significant changes in glucose consumption at any tested stimulation intensity in this paradigm. Exploratory investigation of aftereffects provided hints for increased glucose consumption with a delay of 5 min at 1 mA in the right posterior temporal cortex. This is the first study investigating changes of glucose consumption in the brain during tDCS. The lack of immediately increased glucose consumption indicates that energy demanding processes in the brain such as glutamatergic signaling might not be immediately increased by tDCS. However, our results implicate the need of fPET investigations for medium-term and long-term effects.

We aimed to assess the value of C-choline positron emission tomography (PET) in patients with primary hyperparathyroidism (pHPT) with negative or discordant results in methoxyisobutylisonitrile (MIBI) imaging and neck ultrasound. Eighty-seven patients with pHPT and negative or discordant neck ultrasound and MIBI single photon emission computed tomography/computed tomography (SPECT/CT) were assessed using C-choline PET/CT and subsequently received a parathyroidectomy. PET/CT image data were analysed semi-quantitatively using maximum standardised uptake value (SUV) and ratios (target to the contralateral thyroid gland and carotid artery). A positive PET/CT was defined as a focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered to be positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT was considered be negative. When dichotomizing the C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, 84 of 92 lesions (91.3%) were found to have true-positive uptake versus 8 lesions (8.7%) with false-positive uptake. One lesion showed a false-negative uptake; sensitivity was 98.8%. The corresponding lesioned positive predictive value was 91.3%. The mean SUV was 6.15±4.92 in 72 lesions with positive uptake (70 patients); and mean SUV was 2.96±2.32 in 20 lesions with inconclusive uptake (18 patients). These results in a large group of patients indicate thatC-choline PET/CT is a promising tool for PTA localisation, in cases in which ultrasound and MIBI imaging yield negative or discordant results.

To critically review the potential clinical applications of prostate-specific membrane antigen (PSMA) radioactive ligands in renal cell carcinoma (RCC).

To assess which parameters of [ Ga]Ga-PSMA-11 positron emission tomography (PSMA-PET) predict response to systemic therapies in metastatic (m) castration-resistant prostate cancer (CRPC). In addition, to investigate which of these factors are associated with overall survival (OS).

The costimulatory molecule CD80 is an early marker for immune activation. It is upregulated on activated antigen-presenting cells. We aimed at developing a tracer for imaging CD80 by positron emission tomography (PET). Novel CD80 ligands were synthesized and tested by SPR for affinity to human CD80 (hCD80) and displacement of endogenous ligands. Several compounds bound with one-digit nanomolar affinity to hCD80 and displaced CTLA-4 and CD28 at nanomolar concentrations. A structure-affinity relationship study revealed relevant moieties for strong affinity to hCD80 and positions for further modifications. Lead compound MT107 () was radiolabeled with carbon-11. In vitro, [C]MT107 showed specific binding to hCD80-positive tissue and high plasma protein binding. In vivo, [C]MT107 accumulated in liver, gall bladder, and intestines but only scarcely in hCD80-positive xenografts. The unfavorable in vivo performance may result from high plasma protein binding and extensive biliary excretion.

Hybrid PET/MR offers new opportunities in radiation oncology for tissue/tumour characterisation and response assessment. Attenuation correction (AC) is an important issue especially in the presence of immobilization devices and flat table tops (FTT). The goal of this study was to compare two methods of AC using CT- and Ge/Ga transmission scan-based attenuation maps (μ-maps) for a custom-designed FTT. Measurements were performed in the mMR PET/MR and TrueV PET/CT Biograph Siemens scanners with three different phantoms, namely the Siemens MR-QA, a cubic canister and the NEMA IEC body phantom. The study revealed that the MR image quality is not hampered by the presence of the FTT. For cubic canister applying the scanner's inherent AC alone resulted in inaccuracies in PET images, with up to -4.0% underestimation of the activity. The mean NEMA sphere activity measurements without FTT, agreed within 3.5% with the respective inserted activity. Placing the FTT in the PET/MR scanner resulted in a difference to the injected activity of 4.5% when the table was not corrected for. By introducing the μ-maps the discrepancy between the used activity and the measurements decreased down to 2.6%. To improve the AC of the FTT the creation of a dedicated μ-map was necessary while the CT-based μ-map performed equally good as the source transmission scan-based one.

Combined-modality treatment (CMT) with 2× ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and small-field radiotherapy is standard of care for patients with early-stage favorable Hodgkin lymphoma (HL). However, the role of radiotherapy has been challenged. Positron emission tomography (PET) after 2× ABVD (PET-2) might help to predict individual outcomes and guide treatment.

PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI.

We aimed to assess the value of C-choline positron emission tomography (PET) in patients with primary hyperparathyroidism (pHPT) with negative or discordant results in methoxyisobutylisonitrile (MIBI) imaging and neck ultrasound. Eighty-seven patients with pHPT and negative or discordant neck ultrasound and MIBI single photon emission computed tomography/computed tomography (SPECT/CT) were assessed using C-choline PET/CT and subsequently received a parathyroidectomy. PET/CT image data were analysed semi-quantitatively using maximum standardised uptake value (SUV) and ratios (target to the contralateral thyroid gland and carotid artery). A positive PET/CT was defined as a focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered to be positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT was considered be negative. When dichotomizing the C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, 84 of 92 lesions (91.3%) were found to have true-positive uptake versus 8 lesions (8.7%) with false-positive uptake. One lesion showed a false-negative uptake; sensitivity was 98.8%. The corresponding lesioned positive predictive value was 91.3%. The mean SUV was 6.15±4.92 in 72 lesions with positive uptake (70 patients); and mean SUV was 2.96±2.32 in 20 lesions with inconclusive uptake (18 patients). These results in a large group of patients indicate thatC-choline PET/CT is a promising tool for PTA localisation, in cases in which ultrasound and MIBI imaging yield negative or discordant results.

Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results.

Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) was introduced as a hybrid SPECT/CT imaging modality two decades ago. The main advantage of SPECT/CT is the increased specificity achieved through a more precise localization and characterization of functional findings. The improved diagnostic accuracy is also associated with greater diagnostic confidence and better inter-specialty communication.

Left ventricular diastolic dyssynchrony (LVDD) can be assessed by gated myocardial perfusion single-photon emission computed tomography (GMP-SPECT). LVDD is an area of interest in subjects who underwent cardiac resynchronization therapy (CRT). The aim of this post hoc analysis was to assess the role of LVDD in subjects with CRT who were followed up at 6-month period.

Bone metastasis is a disastrous manifestation of most malignancies, especially in breast, prostate and lung cancers. Since asymptomatic bone metastases are not uncommon, early detection, precise assessment, and localization of them are very important. Various imaging modalities have been employed in the setting of diagnosis of bone metastasis, from plain radiography and bone scintigraphy to SPECT, SPECT/CT, PET/CT, MRI. However, each modality showed its own limitation providing accurate diagnostic performance. In this regard, various tumor-targeted radiotracers have been introduced for molecular imaging of bone metastases using modern hybrid modalities. In this article we review the strength of different cancer-specific radiopharmaceuticals in the detection of bone metastases. As shown in the literature, among various tumor-targeted tracers, 68Ga DOTA-conjugated-peptides, 68Ga PSMA, 18F DOPA, 18F galacto-RGD integrin, 18F FDG, 11C/18F acetate, 11C/18F choline, 111In octreotide, 123/131I MIBG, 99mTc MIBI, and 201Tl have acceptable capabilities in detecting bone metastases depending on the cancer type. However, different study designs and gold standards among reviewed articles should be taken into consideration.

Combined PET/MR imaging (PET/MRI) was proposed for patient management in 2006 with first commercial versions of integrated whole-body systems becoming available as of 2010. PET/MRI followed the prior evolution of hybrid imaging as attested by the successful adoption of combined PET/CT and SPECT/CT since the early 2000 s. Today, around 150 whole-body PET/MRI systems have become operational worldwide. One of the main application fields of PET/MRI is oncologic imaging. Despite the increasing use of PET/MRI, little governance regarding standardized PET/MRI protocols has been provided to date. Standardization and harmonization of imaging protocols is, however, mandatory for efficient on-site patient management and multi-center studies. This document summarizes consensus recommendations on key aspects of patient referral and preparation, PET/MRI workflow and imaging protocols, as well as reporting strategies for whole-body [18F]-FDG-PET/MRI. These recommendations were created by early adopters and key experts in the field of PET, MRI and PET/MRI. This document is intended to provide guidance for the harmonization and standardization of PET/MRI today and to support wider clinical adoption of this imaging modality for the benefit of patients. CITATION FORMAT: · Umutlu L, Beyer T, Grueneisen JS et al. Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation. Fortschr Röntgenstr 2019; 191: 289 - 297.

We evaluated the effect of cardiac resynchronization therapy (CRT) on septal perfusion and thickening at 6 months post implantation assessed on Tc99m-MIBI Gated myocardial perfusion SPECT (GMPS).We also studied the association of change in septal perfusion and thickening with primary outcome defined as at least one [improvement in ≥1NYHA class, left ventricular ejection fraction (LVEF) by ≥ 5%, reduction of end-systolic volume (ESV) by ≥ 15%, and improvement ≥ 5 points in Minnesota living with heart failure questionnaire (MLHFQ)].

F-Fluoro-L-dihydroxyphenylalanine (F-DOPA) PET offers high sensitivity and specificity in the imaging of non-malignant head and neck paraganglioma (HNPGL) but lower sensitivity in metastatic disease of these neuroendocrine tumours (NET). In contrast to the radiotracer F-DOPA, both I-meta-iodo-benzylguanidine (I-MIBG) and Ga-DOTA-Tyr3-octreotide (Ga-DOTA-TOC) offer valuable clinical information on norepinephrine and somatostatin (SST) receptor status for planning I-MIBG and radionuclide peptide therapy (PRRT), respectively. Therefore, we compared Ga-DOTA-TOC and F-DOPA PET/CT with I-MIBG planar and SPECT/CT imaging, for the detection of HNPGL. Combined cross-sectional imaging was the reference standard.

Placing the left ventricular (LV) lead in a viable segment with the latest mechanical activation (vSOLA) may be associated with optimal cardiac resynchronization therapy (CRT) response. We assessed the role of gated SPECT myocardial perfusion imaging (gSPECT MPI) in predicting clinical outcomes at 6 months in patients submitted to CRT.

Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results.

Prostate-specific membrane antigen (PSMA) is expressed in most prostate cancers and can be identified by PSMA-ligand imaging, which has already become clinically accepted in several countries in- and outside Europe. PSMA-directed radioligand therapy (PSMA-RLT) with Lutetium-177 (Lu-PSMA) is currently undergoing clinical validation. Retrospective observational data have documented favourable safety and striking clinical responses. Recent results from a prospective clinical trial (phase II) have been published confirming high response rates, low toxicity and reduction of pain in metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed after conventional treatments. Such patients typically survive for periods less than 1.5 years. This has led some facilities to adopt compassionate or unproven use of this therapy, even in the absence of validation within a randomised-controlled trial. As a result, a consistent body of evidence exists to support efficacy and safety data of this treatment. The purpose of this guideline is to assist nuclear medicine specialists to deliver PSMA-RLT as an "unproven intervention in clinical practice", in accordance with the best currently available knowledge.

Peptide receptor radionuclide therapy (PRRT) has been used for more than 20 y as a systemic treatment approach in inoperable or metastatic somatostatin receptor-positive tumors. The purpose of this study was to analyze the long-term outcome of PRRT with regard to the most commonly used radiopharmaceuticals, Y-DOTATOC and Lu-DOTATATE. This retrospective clinical study included a total of 44 consecutive patients (27 men) with advanced tumors and enhanced somatostatin receptor expression. Mean age at initial diagnosis was 60 y (SD, 11.3 y; range, 40-84 y). Median follow-up was 80 mo. For Lu-PRRT, the mean number of cycles administered was 5.3 ± 2.5 and the mean activity was 27.2 ± 14.9 GBq per patient. For Y-PRRT, the mean number of cycles administered was 5.5 ± 2.6 and the mean activity was 14.7 ± 7.3 GBq per patient. Overall, 378 cycles were administered (mean, 8.6 ± 3.4 cycles per patient), with an overall cumulative activity of 1,514.1 GBq. Median overall survival was 79 mo. Twenty-one (77.8%) of the 27 men and 9 (52.9%) of the 17 women had died 12 y after commencement of PRRT. The shortest duration of illness was 8 mo and the longest 155 mo. Severe side effects (World Health Organization grades III and IV) were seen in 9 of the 14 patients still alive. Chronic kidney disease in combination with anemia was the most common finding in the 9 patients with severe side effects. A poor prognosis was found for those patients who showed progressive disease, in comparison with patients with cumulative disease control after initial PRRT (log rank, < 0.001), whereas women and patients with no more than 2 tumor sites seemed to especially benefit from PRRT (not reaching significance levels). PRRT is encouraging in terms of long-term outcome. Thirty-two percent (14/44 patients) of the patients with metastatic or inoperable disease were still alive more than 12 y after the beginning of radionuclide therapy. Possible predictors for favorable outcome are having an initial response to PRRT, having a low number of affected sites, and being female.

F-Fluoro-L-dihydroxyphenylalanine (F-DOPA) PET offers high sensitivity and specificity in the imaging of non-malignant head and neck paraganglioma (HNPGL) but lower sensitivity in metastatic disease of these neuroendocrine tumours (NET). In contrast to the radiotracer F-DOPA, both I-meta-iodo-benzylguanidine (I-MIBG) and Ga-DOTA-Tyr3-octreotide (Ga-DOTA-TOC) offer valuable clinical information on norepinephrine and somatostatin (SST) receptor status for planning I-MIBG and radionuclide peptide therapy (PRRT), respectively. Therefore, we compared Ga-DOTA-TOC and F-DOPA PET/CT with I-MIBG planar and SPECT/CT imaging, for the detection of HNPGL. Combined cross-sectional imaging was the reference standard.

Defining an optimal therapeutic approach in metastatic castration-resistance prostate cancer (mCRPC) patients in advanced stages is still challenging in routine clinical practice. Prostate-specific membrane antigen (PSMA) targeted radionuclide therapy with β- or α-emitters such as 177-Lutethium (177Lu) or 225-Actinium (225A) has been a main focus at multiple academic research centers in the last few years. This review article provides an overview of PSMA characteristics, clinical performance, safety and toxicity of PSMA targeted β- or α-radiation therapy.

Lu-PSMA radioligand therapy (LuPRLT) is mainly used for patients with metastatic castration-resistant prostate cancer who are resistant to established drugs. This study describes LuPRLT, either LuPSMA I&T or LuPSMA RLT-617, for 45 patients with predominant lymph node metastatic prostate cancer (LNM PC). Thirty-five patients had LNM and ten patients had LNM and one or two bone metastases. Before LuPRLT, the patients had prostate specific antigen (PSA) of median 18 µg/l (interquartile range (IQR): 3.3-39). LuPRLT was given with a cumulative injected Lu activity of median 14.5 GBq (IQR: 12.2-20.4). Maximum percentage decline of PSA was median 92% (IQR: 70-99). Thirty-five patients with only LNM had a better overall survival (OS) than ten patients with LNM and one or two bone metastases. Thirty-three docetaxel-naïve patients had a longer PSMA PET/CT progression-free survival than twelve patients who were resistant to docetaxel. Twenty-two patients who received LuPRLT with a cumulative injected Lu activity ≥ 14.8 GBq had a better PSMA PET/CT progression-free survival than 23 patients who received LuPRLT with a lower cumulative injected Lu activity. Seventeen patients with relapse after LuPRLT who received rechallenge LuPRLT or ActPRLT had a better OS than five patients who received other forms for relapse treatment. LuPRLT gave mild and transitory adverse effects. The findings of the present study suggest that LuPRLT of patients with LNM may be effective and safe. The promising results motivate randomized phase II trials to further quantify the impact of LuPRLT as treatment of patients with LNM.

The article "Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy," was originally published electronically on the publisher's internet portal without open access.

In patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs), we evaluated health-related quality of life (HRQoL) from the first peptide receptor radionuclide therapy (PRRT) to the first restaging and compared the scores with general-population (GP) norms. The data were from routine HRQoL monitoring using the core quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30). Patients received 4-6 cycles of Lu-DOTATATE or Y-DOTATOC. To be eligible for analysis, patients had to have at least one HRQoL assessment before PRRT and at least one HRQoL assessment at the end of or after treatment completion. Linear mixed models were used to consider HRQoL changes over time. In total, 61 gastroenteropancreatic NET patients (small-intestine NETs, = 37; pancreatic NETs, = 24) were eligible for analysis. Clear improvements from baseline to the first restaging were found for diarrhea in small-intestine NET patients, showing a decrease of 16 points, which represents a moderately large change. We observed a clinically relevant decrease in appetite loss (17 points), but for female small-intestine NET patients only. Other HRQoL changes were also restricted to sociodemographic or clinical subgroups and mainly reflected improvements, except for physical and social functioning, which showed decreasing scores in older small-intestine NET patients. Compared with HRQoL GP norms, patients had impairments consisting of diarrhea; fatigue; appetite loss; reduced physical, social, and role functioning; and reduced global HRQoL. Except for diarrhea and appetite loss, patient scores at the first restaging did not reach GP levels. Our analyses support previous findings of overall stable HRQoL under PRRT. Yet, significant HRQoL impairments compared with the GP and potentially specific subgroup patterns need to be considered.

Prostate cancer is most common tumor in men causing significant patient mortality and morbidity. In newer diagnostic/therapeutic agents PSMA linked ones are specifically important. Analysis of textural heterogeneity parameters is associated with determination of innately aggressive and therapy resistant cell lines thus emphasizing their importance in therapy planning. The objective of current study was to assess predictive ability of tumor textural heterogeneity parameters from baseline Ga-PSMA PET prior to Lu-PSMA therapy.