Publikationen

With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer.

Inhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI.

It is challenging to differentiate unilateral aldosterone-producing adenoma (APA) from bilateral idiopathic adrenal hyperplasia (IAH) and nonfunctional adrenal adenoma (NFA) in primary aldosteronism (PA). In a first primarily ex vivo study detection, CXC chemokine receptor type 4 (CXCR4) expression has been shown to be a valuable tool for the detection of APA. In this study, we aimed to clinically evaluate CXCR4 imaging with Ga-pentixafor PET/CT for detecting APA.

This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE).

The aim of the study was to evaluate the clinical impact of pre-ablation rhTSH-stimulated fluorine-18 fluorodeoxyglucose (F-18 FDG) PET/CT in addition to post-therapeutic whole body radioiodine scanning in patients with intermediate to high risk differentiated thyroid carcinoma (DTC). This was a retrospective single center study including 73 patients with thyroid cancer (44 females, mean age 43.2±16.2 years, 62% papillary, 31% follicular, 7% poorly differentiated). All patients underwent ablative radioiodine treatment (mean activity: 3661±673 MBq I-131) using rhTSH after thyroidectomy and lymph node (LN) dissection (01/2013-10/2016) and TSH-stimulated F-18 FDG PET/CT (4 MBq/kg body weight, low dose CT). Post-treatment I-131 whole body scan (I-131 WBS) was obtained 9 days afterwards in planar technique and in case of equivocal or abnormal findings using SPECT/CT. Thirty-one patients (42%) showed F-18 FDG avid lesions, 14 patients showed more FDG than iodine positive lesions and 5 patients more iodine positive lesions in I-131 WBS, respectively. Fifty-three patients showed identical F-18 FDG PET/CT and I-131 WBS. The initial treatment plan was changed from follow-up to therapy (surgery, systemic therapy using tyrosine-kinase inhibition) in 11 patients (15%) on the basis of F-18 FDG PET/CT imaging. Six of these 11 patients had papillary thyroid cancer. Three patients with histologically proven LN metastases had stimulated thyroglobulin-levels<2.0 ng/ml. Our study demonstrated a clinical benefit of pre-ablation rhTSH-stimulated F-18 FDG PET/CT imaging in about 20% of patients with intermediate to high risk DTC, leading to change in patient management in 15%.

When increasing the PET acquisition time to match the longer MRI protocol in simultaneous PET/MR, the injected PET tracer dose can possibly be lowered to reduce radiation exposure. Moreover, applying new commercially available time-of-flight (TOF) block sequential regularized expectation maximization (BSREM)-based reconstruction algorithms could allow for further dose reductions. The purpose of this study was to find the minimal dose of the tracer targeting the prostate specific membrane antigen (Ga-PSMA-11) for a dedicated 15-min pelvic PET/MR scan that still matches the image quality of a reference 3-min scan at 100% (150 MBq) dose.

This study assesses the value of image fusion using 18F-fluoro-L-DOPA (18F-DOPA) positron emission tomography (PET) and magnetic resonance imaging (MRI) for examining patients with neuroendocrine tumors (NETs) and a suspicion of metastasis of the liver.

Unilateral onset of parkinsonism due to nigrostriatal damage of the contralateral hemisphere is frequent in Parkinson disease (PD). There is evidence for a left-hemispheric bias of motor asymmetry in right-handed patients with PD indicating a hemispheric dominance. Isolated REM sleep behavior disorder (IRBD) constitutes the prodromal stage of PD and other synucleinopathies. To test the hypothesis that right-handed patients with IRBD exhibit left-hemispheric predominance of subclinical nigrostriatal dysfunction, we evaluated this aspect using neuroimaging instruments.

Impaired myocardial sympathetic innervation assessed by Iodine-Metaiodobenzylguanidine (I-MIBG) scintigraphy is associated with cardiac events. Since regional disparities of structural abnormalities are common in inherited arrhythmia syndromes (iAS), a chamber-specific innervation assessment of the right (RV) and left ventricle (LV) could provide important insights for a patient-individual therapy. Aim of this study was to evaluate chamber-specific patterns of autonomic innervation by Single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with iAS with respect to clinical outcome regarding cardiac events.

The aim of the study was to evaluate the clinical impact of pre-ablation rhTSH-stimulated fluorine-18 fluorodeoxyglucose (F-18 FDG) PET/CT in addition to post-therapeutic whole body radioiodine scanning in patients with intermediate to high risk differentiated thyroid carcinoma (DTC). This was a retrospective single center study including 73 patients with thyroid cancer (44 females, mean age 43.2±16.2 years, 62% papillary, 31% follicular, 7% poorly differentiated). All patients underwent ablative radioiodine treatment (mean activity: 3661±673 MBq I-131) using rhTSH after thyroidectomy and lymph node (LN) dissection (01/2013-10/2016) and TSH-stimulated F-18 FDG PET/CT (4 MBq/kg body weight, low dose CT). Post-treatment I-131 whole body scan (I-131 WBS) was obtained 9 days afterwards in planar technique and in case of equivocal or abnormal findings using SPECT/CT. Thirty-one patients (42%) showed F-18 FDG avid lesions, 14 patients showed more FDG than iodine positive lesions and 5 patients more iodine positive lesions in I-131 WBS, respectively. Fifty-three patients showed identical F-18 FDG PET/CT and I-131 WBS. The initial treatment plan was changed from follow-up to therapy (surgery, systemic therapy using tyrosine-kinase inhibition) in 11 patients (15%) on the basis of F-18 FDG PET/CT imaging. Six of these 11 patients had papillary thyroid cancer. Three patients with histologically proven LN metastases had stimulated thyroglobulin-levels<2.0 ng/ml. Our study demonstrated a clinical benefit of pre-ablation rhTSH-stimulated F-18 FDG PET/CT imaging in about 20% of patients with intermediate to high risk DTC, leading to change in patient management in 15%.

: Membrane transporters of the SLC and ABC families are abundantly expressed in the liver, where they control the transfer of drugs/drug metabolites across the sinusoidal and canalicular hepatocyte membranes and play a pivotal role in hepatic drug clearance. Noninvasive imaging methods, such as PET, SPECT or MRI, allow for measuring the activity of hepatic transporters , provided that suitable transporter imaging probes are available.: We give an overview of the working principles of imaging-based assessment of hepatic transporter activity. We discuss different currently available PET/SPECT radiotracers and MRI contrast agents and their applications to measure hepatic transporter activity in health and disease. We cover mathematical modeling approaches to obtain quantitative parameters of transporter activity and provide a critical assessment of methodological limitations and challenges associated with this approach.: PET in combination with pharmacokinetic modeling can be potentially applied in drug development to study the distribution of new drug candidates to the liver and their clearance mechanisms. This approach bears potential to mechanistically assess transporter-mediated drug-drug interactions, to assess the influence of disease on hepatic drug disposition and to validate and refine currently available extrapolation methods to predict hepatic clearance of drugs.

Radiomics is a rapidly evolving field of research concerned with the extraction and quantification of patterns - the so-called radiomic features - within medical images. Radiomic features capture tissue and lesion characteristics such as heterogeneity and shape, and may, alone or in combination with demographic, histological, genomic or proteomic data, be used for clinical problem-solving. The goal of this CE article is to provide an introduction to the field, covering the basic radiomics workflow:feature calculation and selection, dimensionality reduction, and data processing using tools such as machine learning. Potential clinical applications in nuclear medicine that include prediction of treatment response and survival based on PET radiomic features will be discussed. Current limitations of radiomics, including its sensitivity to image acquisition parameter variations, and common pitfalls such as "overfitting", will also be covered.

Tumor targeting using agents with slow pharmacokinetics represents a major challenge in nuclear imaging and targeted radionuclide therapy as they most often result in low imaging contrast and high radiation dose to healthy tissue. To address this challenge, we developed a polymer-based targeting agent that can be used for pretargeted imaging and thus separates tumor accumulation from the imaging step in time. The developed targeting agent is based on polypeptide--polypeptoid polymers (PeptoBrushes) functionalized with -cyclooctene (TCO). The complementary In-labeled imaging agent is a 1,2,4,5-tetrazine derivative, which can react with aforementioned TCO-modified PeptoBrushes in a rapid bioorthogonal ligation. A high degree of TCO loading (up to 30%) was achieved, without altering the physicochemical properties of the polymeric nanoparticle. The highest degree of TCO loading resulted in significantly increased reaction rates (77-fold enhancement) compared to those with small molecule TCO moieties when using lipophilic tetrazines. Based on computer simulations, we hypothesize that this increase is a result of hydrophobic effects and significant rearrangements within the polymer framework, in which hydrophobic patches of TCO moieties are formed. These patches attract lipophilic tetrazines, leading to increased reaction rates in the bioorthogonal ligation. The most reactive system was evaluated as a targeting agent for pretargeted imaging in tumor-bearing mice. After the setup was optimized, sufficient tumor-to-background ratios were achieved as early as 2 h after administration of the tetrazine imaging agent, which further improved at 22 h, enabling clear visualization of CT-26 tumors. These findings show the potential of PeptoBrushes to be used as a pretargeting agent when an optimized dose of polymer is used.

The development of so-called Proticles opens attractive possibilities for new drug delivery systems. Proticles are nanoparticles (NPs), which are formed by self-assembly of negatively charged oligonucleotides in combination with the positively charged peptide protamine. Polyethylene glycol (PEG) is a widely known pharmaceutical agent to stop particle growth and prolong circulation half-life of drug delivery systems. Therefore, two different NP formulations - one PEGylated and one non-PEGylated - were used in this work to gain information about the biological stability and half-life in circulation of Proticles. Thus, this study presents data of in vitro stability and in vivo pharmacokinetics of both, non-PEGylated and PEGylated Proticles radiolabeled with InCl. The study demonstrated that successful radiolabeling of both Proticle-formulations was performed resulting in high radiochemical yields (> 85 %). Furthermore, the influence of PEGylation on the in vitro stability of In-radiolabeled NPs was investigated. No significant difference due to PEGylation was found. Unlike in vitro results, non-PEGylated In-Proticles seemed to degrade faster in vivo than PEGylated In-proticles, resulting in significantly higher blood values (In-PEG-proticles: 0.23 ± 0.01 % ID/g 1 h p.i.; In-proticles: 0.06 ± 0.01 % ID/g 1 h p.i.; p < 0.05). Visualized by SPECT imaging urinary excretion represented the major pathway of elimination for both NP-formulations. In conclusion, this study provides data indicating a positive influence of PEG-derivatization on the biodistribution and pharmacokinetics of Proticles. These results form the basis for further developments as drug delivery and active drug targeting devices.

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.

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.

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.

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

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.

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.

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.