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We present a novel tool designed for the semiautomatic detection and assessment of prostate cancer during recurrence diagnostics using PET-CT with prostate-specific membrane antigen (PSMA). The tool automatically generates a structured report, which is enhanced by 3D images and ensures the reproducibility of the findings. Moreover, the area of the findings is automatically determined and can be corrected manually. Image data from 50 patients following radical prostatectomy was used. Our approach and its user interface were qualitatively evaluated by a nuclear medicine specialist. The segmentation analysis revealed a requirement for further automation. The resulting report was deemed highly beneficial, particularly in terms of the resulting reproducibility and the presentation of 3D images depicting the findings. The presented tool has great potential for much-needed support in everyday clinical practice, as it facilitates the communication of the diagnostic results to colleagues and patients and thus prevents misunderstandings.

Aims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan).Methods: We retrospectively identified 47 patients (17 Alzheimer’s dementia, 10 idiopathic Parkinson’s disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores.Results: DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right p < 0.01, putamen right p < 0.05, left p < 0.05) and between pNfH and putamen (right p < 0.05; left p < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results.Conclusion: We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases.

AimPurpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP[In]) and an intra-therapeutic [177Lu]-SPECT/CT (ASP[Lu]).Materials and methodsData from first therapy cycle [177Lu-DOTA0-Tyr3]octreotate ([177Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46-88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman's rank correlation coefficient (ρ) and Bland-Altman plots.ResultsA total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5-15.5; SD, median: 3.4, IQR: 2.1-4.5; PR, median 1.7, IQR: 0.9-2.8; CR, median: 0.5, IQR: 0.0-1.3); Kruskal-Wallis, p5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p ConclusionPre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.

Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS. Methods: this retrospective bicentric cohort study included 30 patients (f = 13, median age, 66.5 (48–81) years) with pretherapeutic [111In-DTPA0]octreotide scintigraphy (Octreoscan®). ASP of functional volumes of up to three leading lesions per patient (n = 74) was calculated after semiautomatic, background-adapted segmentation. Uni- and multivariable Cox regression regarding PFS for clinical factors and the maximum ASP per patient was obtained. Results: all 30 patients showed metachronous or progressive liver metastases. ASP, primary tumor site, metastases pattern, and prior peptide receptor radionuclide therapy (PRRT) were significantly associated with PFS in univariable Cox regression. Only ASP > 12.9% (hazard ratio (HR), 3.33; p = 0.024) and prior PRRT (HR, 0.35; p = 0.043) remained significant in multivariable Cox. Median PFS was 6.7 months for ASP > 12.9% (95% confidence interval (CI), 2.1–11.4 months) versus 14.4 (12.5–16.3) months for ASP ≤ 12.9% (log-rank, p = 0.028). Conclusion: pretherapeutic ASP of SSR positive lesions independently predicted PFS for treatment with everolimus in GEP-NET. ASP may supplement risk-benefit assessment before patient inclusion to treatment.

Purpose: Pre-operative assessment of thoracic lymphonodal (LN) involvement in patients with lung cancer (LC) is crucial when choosing the treatment modality. Visual assessment of F-18-FDG-PET/CT (PET/CT) is well established, however, there is still a need for prospective quantitative data to differentiate benign from malignant lesions which would simplify staging and guide the further implementation of computer-aided diagnosis (CAD). Methods: In this prospective study, 37 patients with confirmed lung cancer (m/f = 24/13; age: 70 [52–83] years) were analyzed. All patients underwent PET/CT and quantitative data (standardized uptake values) were obtained. Histological results were available for 101 thoracic lymph nodes. Quantitative data were matched to determine cut-off values for delineation between benign vs. malignant lymph nodes. Furthermore, a scoring system derived from these cut-off values was established. Statistical analyses were performed through ROC analysis. Results: Quantitative analysis revealed the optimal cut-off values (p < 0.01) for the differentiation between benign and malignant thoracic lymph nodes in patients suffering from lung cancer. The respective areas under the curve (AUC) ranged from 0.86 to 0.94. The highest AUC for a ratio of lymph node to healthy lung tissue was 0.94. The resulting accuracy ranged from 78.2% to 89.1%. A dedicated scoring system led to an AUC of 0.93 with a negative predictive value of 95.4%. Conclusion: Quantitative analysis of F-18-FDG-PET/CT data provides reliable results for delineation between benign and malignant thoracic lymph nodes. Thus, quantitative parameters can improve diagnostic accuracy and reliability and can also facilitate the handling of the steadily increasing number of clinical examinations.

Purpose: Pre-operative assessment of thoracic lymphonodal (LN) involvement in patients with lung cancer (LC) is crucial when choosing the treatment modality. Visual assessment of F-18-FDG-PET/CT (PET/CT) is well established, however, there is still a need for prospective quantitative data to differentiate benign from malignant lesions which would simplify staging and guide the further implementation of computer-aided diagnosis (CAD)., Methods: In this prospective study, 37 patients with confirmed lung cancer (m/f = 24/13; age: 70 [52-83] years) were analyzed. All patients underwent PET/CT and quantitative data (standardized uptake values) were obtained. Histological results were available for 101 thoracic lymph nodes. Quantitative data were matched to determine cut-off values for delineation between benign vs. malignant lymph nodes. Furthermore, a scoring system derived from these cut-off values was established. Statistical analyses were performed through ROC analysis., Results: Quantitative analysis revealed the optimal cut-off values ( p < 0.01) for the differentiation between benign and malignant thoracic lymph nodes in patients suffering from lung cancer. The respective areas under the curve (AUC) ranged from 0.86 to 0.94. The highest AUC for a ratio of lymph node to healthy lung tissue was 0.94. The resulting accuracy ranged from 78.2% to 89.1%. A dedicated scoring system led to an AUC of 0.93 with a negative predictive value of 95.4%., Conclusion: Quantitative analysis of F-18-FDG-PET/CT data provides reliable results for delineation between benign and malignant thoracic lymph nodes. Thus, quantitative parameters can improve diagnostic accuracy and reliability and can also facilitate the handling of the steadily increasing number of clinical examinations.

Aims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan). Methods: We retrospectively identified 47 patients (17 Alzheimer's dementia, 10 idiopathic Parkinson's disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores. Results: DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right p < 0.01, putamen right p < 0.05, left p < 0.05) and between pNfH and putamen (right p < 0.05; left p < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results. Conclusion: We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Diekämper, Brix, Stöcker, Vielhaber, Galazky, Kreissl, Genseke, Düzel and Körtvelyessy.)

Background:  The blockade of immune escape mechanisms (e. g. PD1 /PD-L1) using immune checkpoint inhibition (ICI) can significantly prolong survival and induce remission in patients with advanced non-small cell lung cancer (NSCLC). Less is known about neoadjuvant ICI in patients with resectable (UICC stage III) or oligometastatic (UICC stage IVa) NSCLC., Methods:  Tissue biopsies from patients with advanced or oligometastatic NSCLC were screened for PD-L1 expression. In case of PD-L1-expression > 50 %, ECOG status of 0 or 1 and expected operability, patients received ICI. After about four weeks, patients underwent thoracic surgical resection. In all patients, a complete staging, including PET-CT, cMRI, and endobronchial ultrasound, was performed. The tolerability, the radiological and the histopathological tumor response as well as the surgical and oncological outcomes were analyzed., Findings:  Four patients (2 male, 2 female, age 56 - 78 years, n = 3 adenocarcinoma, n = 1 squamous cell carcinoma) with local advanced tumors received ICI before surgical resection. In three cases the mediastinal lymph nodes were positive. One patient had a single cerebral metastasis which was treated with radiotherapy. All four patients underwent therapy with two to six cycles of ICI (3 × pembrolizumab, 1 × atezolizumab) without any complication, and ICI did not delay the time of surgical resection. According to iRECIST, three patients showed partial response (PR), one patient had stable disease (SD). All tumors were completely resected. The thoracic surgical procedures proved to be technically unproblematic despite inflammatory changes. There were neither treatment-related deaths nor perioperative complications. In the resectates, complete pathological response (CPR, regression grade III ) and regression grade IIb were detected twice. The average time of follow-up was 12 (1 - 24) months. Patients with PPR developed distant metastasis after six months or a local recurrence after four months. The CPR patient is relapse free to date., Conclusion:  In selected patients, neoadjuvant therapy with ICI is well tolerated and can induce a complete remission of the tumor. Treatment with ICI has no negative impact on the surgical procedure. Prognosis seems to be promising in CPR and limited in PPR., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS., Methods: this retrospective bicentric cohort study included 30 patients (f = 13, median age, 66.5 (48-81) years) with pretherapeutic [ 111 In-DTPA 0 ]octreotide scintigraphy (Octreoscan ® ). ASP of functional volumes of up to three leading lesions per patient ( n = 74) was calculated after semiautomatic, background-adapted segmentation. Uni- and multivariable Cox regression regarding PFS for clinical factors and the maximum ASP per patient was obtained., Results: all 30 patients showed metachronous or progressive liver metastases. ASP, primary tumor site, metastases pattern, and prior peptide receptor radionuclide therapy (PRRT) were significantly associated with PFS in univariable Cox regression. Only ASP > 12.9% (hazard ratio (HR), 3.33; p = 0.024) and prior PRRT (HR, 0.35; p = 0.043) remained significant in multivariable Cox. Median PFS was 6.7 months for ASP > 12.9% (95% confidence interval (CI), 2.1-11.4 months) versus 14.4 (12.5-16.3) months for ASP ≤ 12.9% (log-rank, p = 0.028)., Conclusion: pretherapeutic ASP of SSR positive lesions independently predicted PFS for treatment with everolimus in GEP-NET. ASP may supplement risk-benefit assessment before patient inclusion to treatment.

The bone scan index (BSI), initially introduced for metastatic prostate cancer, quantifies the osseous tumor load from planar bone scans. Following the basic idea of radiomics, this method incorporates specific deep-learning techniques (artificial neural network) in its development to provide automatic calculation, feature extraction, and diagnostic support. As its performance in tumor entities, not including prostate cancer, remains unclear, our aim was to obtain more data about this aspect. The results of BSI evaluation of bone scans from 951 consecutive patients with different tumors were retrospectively compared to clinical reports (bone metastases, yes/no). Statistical analysis included entity-specific receiver operating characteristics to determine optimized BSI cut-off values. In addition to prostate cancer (cut-off = 0.27%, sensitivity (SN) = 87%, specificity (SP) = 99%), the algorithm used provided comparable results for breast cancer (cut-off 0.18%, SN = 83%, SP = 87%) and colorectal cancer (cut-off = 0.10%, SN = 100%, SP = 90%). Worse performance was observed for lung cancer (cut-off = 0.06%, SN = 63%, SP = 70%) and renal cell carcinoma (cut-off = 0.30%, SN = 75%, SP = 84%). The algorithm did not perform satisfactorily in melanoma (SN = 60%). For most entities, a high negative predictive value (NPV ≥ 87.5%, melanoma 80%) was determined, whereas positive predictive value (PPV) was clinically not applicable. Automatically determined BSI showed good sensitivity and specificity in prostate cancer and various other entities. Particularly, the high NPV encourages applying BSI as a tool for computer-aided diagnostic in various tumor entities.

Aim: Purpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP[In]) and an intra-therapeutic [177Lu]-SPECT/CT (ASP[Lu])., Materials and Methods: Data from first therapy cycle [177Lu-DOTA0-Tyr3]octreotate ([177Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46-88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman's rank correlation coefficient (ρ) and Bland-Altman plots., Results: A total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5-15.5; SD, median: 3.4, IQR: 2.1-4.5; PR, median 1.7, IQR: 0.9-2.8; CR, median: 0.5, IQR: 0.0-1.3); Kruskal-Wallis, p<0.001). ROC analyses revealed a significant separation between RL and NRL for ASP after 4 months (AUC 0.85, p<0.001) and after 12 months (AUC 0.94, p<0.001). The optimal threshold for ASP was >5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p <0.01). The mean absolute difference between ASP[In] and ASP[Lu] was -0.04 (95% Limits of Agreement, -6.1-6.0)., Conclusion: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Pre-operative lobar function is estimated by scintigraphy in patients with pulmonary malignancies and compromised function. This study compared the lobar perfusion determined by scintigraphy (PS) with data from SPECT/low-dose-CT (SPECT/ldCT) analyzed manually and semi-automatic., Methods: Retrospective analysis on 39 patients (m/f = 25/14; age: 72.5 [22-89] years) with indication for pulmonary perfusion scintigraphy. Imaging was performed using SPECT/ldCT. Data was analyzed manually and by semi-automatic software. Readers' confidence in 3D-segmentation was scored by two independent readers. Interrater agreement was calculated. In addition, Spearman's rank correlation and Wilcoxon's test were used., Results: Results from PS differed significantly from SPECT/ldCT processed manually or semi-automatically in 4/5 lobes (total difference ≤21.6%; rho ≥0.44) and in 3/5 (total difference 21.6%; rho ≥0.37), respectively. Readers' confidence in 3D-segmentation showed a perfect interrater agreement (κ = 0.98)., Conclusion: Quantification of lobar perfusion by SPECT/ldCT differs significantly from planar scintigraphy (e.g., with potential influence on therapy). The semi-automatic software analysis provides an applicable methodology., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: 223 Radium-dichloride ( 223 Ra) administration is an upcoming therapeutic option in patients with castration-resistant metastatic prostate cancer (mCRPC), whose renal and faecal excretion of 223 Ra has been primarily estimated from data of a phase-I clinical trial in patients with normal renal function. In the rare case of concomitant renal insufficiency requiring haemodialysis (HD), an estimation of the contamination of dialysate would be beneficial., Methods: The excretion of 223 Ra and its concentration in the dialysate in a patient with mCRPC and end-stage renal disease was examined for six consecutive treatment cycles. Dialysate samples were measured using a commercial system with NaI-scintillation detector., Results: HD showed a residual activity level in the remaining dialysate. The excreted activity was a median of 46.1 kBq (range = 42.0- 83.4 kBq) and 11.2 kBq (range = 8.4- 19.9 kBq) for the first (24 h post injection p.i.) and second HD (96 h p.i.), respectively. The activity concentration decreased significantly from a median of 4.18 kBq/l (range = 2.98-5.14 kBq/l) to 0.85 kBq/l (range = 0.69- 1.31 kBq/l, p < 0.0001). For all consecutive time points, the activity concentration further decreased significantly (p < 0.0001). The activity concentration of dialysate from HD performed 125.4 h p.i. [95 % confidence interval = 120.5-130.4 h p.i.] reached the threshold for unrestricted waste disposal., Conclusion: The observed extraction of 223 Ra by HD exceeded the data determined from the phase-I study. The activity concentration in the dialysate observed for the first HD's p.i. was above the threshold for unrestricted disposal of radioactive waste in Germany. Therefore, the specific requirement for waste handling has to be followed to fulfil the radiation protection regulations.

Objectives: Routine visual assessment of positron emission tomography (PET) for thoracic lymph node (LN) staging in patients with non-small cell lung cancer (NSCLC) is limited by a lack of reliable assessment criteria. This study evaluates the accuracy and inter-rater agreement of a standardized approach with unified windowing and a PET-based visual score., Materials and Methods: This retrospective analysis included pretherapeutic FDG-PET data of 86 patients with NSCLC. After standardized windowing (threshold: 2×liver SUVmean) the LN uptake was assessed visually by three independent readers with varying levels of experience using a 4-step score (1, LN uptake≤mediastinal blood pool structures (MBPS); 2, MBPS3). The inexperienced (n=1), advanced (n=1), and expert readers (n=1) achieved similar accuracies of 93.5%, 91.4% and 92.1%, respectively (P>0.05 each). Cohen's κ ranged from 0.92 to 0.96 and Fleiss' κ was 0.93. ROC-analyses showed no significant differences between attendant readers within any subgroup (AUC, 0.92-0.96)., Conclusion: Applying unified windowing, the introduced PET-score achieved highly accurate and robust LN assessment. This approach may shorten learning curves of inexperienced readers, facilitate multicenter trials, and improve comparability of future studies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Perfusion scintigraphy using (99m)Tc-labeled albumin aggregates is mandatory before hepatic radioembolization with (90)Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, (99m)Tc-MAA (macroaggregated serum albumin [MAA]) and (99m)Tc-HSA (human serum albumin [HSA]), was assessed., Methods: In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver-lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection)., Results: Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation., Conclusion: Compared with (99m)Tc-MAA-microspheres, (99m)Tc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)