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Background: 68 Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68 Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC., Methods: Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68 Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUV mean ) and SUV max measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually., Results: Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUV max of 4.35 and SUV mean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUV max 9.05 (4.86-29.16)), followed by bone metastases (SUV max 5.56 (0.97-15.85)), and lymph node metastases (SUV max 3.90 (2.13-6.28)) and visceral metastases (SUV max 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68 Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines., Conclusion: Targeting c-MET expression, 68 Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68 Ga-EMP-100 as a biomarker in mRCC patients., (© 2021. The Author(s).)

The 18 kDa translocator protein (TSPO) is increasingly recognized as an interesting target for the imaging of glioblastoma (GBM). Here, we investigated TSPO PET imaging and autoradiography in the frequently used GL261 glioblastoma mouse model and aimed to generate insights into the temporal evolution of TSPO radioligand uptake in glioblastoma in a preclinical setting. We performed a longitudinal [18F]GE-180 PET imaging study from day 4 to 14 post inoculation in the orthotopic syngeneic GL261 GBM mouse model (n = 21 GBM mice, n = 3 sham mice). Contrast-enhanced computed tomography (CT) was performed at the day of the final PET scan (±1 day). [18F]GE-180 autoradiography was performed on day 7, 11 and 14 (ex vivo: n = 13 GBM mice, n = 1 sham mouse; in vitro: n = 21 GBM mice; n = 2 sham mice). Brain sections were also used for hematoxylin and eosin (H&E) staining and TSPO immunohistochemistry. [18F]GE-180 uptake in PET was elevated at the site of inoculation in GBM mice as compared to sham mice at day 11 and later (at day 14, TBRmax +27% compared to sham mice, p = 0.001). In GBM mice, [18F]GE-180 uptake continuously increased over time, e.g., at day 11, mean TBRmax +16% compared to day 4, p = 0.011. [18F]GE-180 uptake as depicted by PET was in all mice co-localized with contrast-enhancement in CT and tissue-based findings. [18F]GE-180 ex vivo and in vitro autoradiography showed highly congruent tracer distribution (r = 0.99, n = 13, p < 0.001). In conclusion, [18F]GE-180 PET imaging facilitates non-invasive in vivo monitoring of TSPO expression in the GL261 GBM mouse model. [18F]GE-180 in vitro autoradiography is a convenient surrogate for ex vivo autoradiography, allowing for straightforward identification of suitable models and scan time-points on previously generated tissue sections.

Background: The PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI)., Methods: Fifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18 F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18 F-FDG PET/CT using a standard threshold (liver SUV mean  + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS)., Results: Overall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses., Conclusion: In stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load., (© 2021. The Author(s).)

Purpose: Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence., Methods: A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method and uni- and multivariate analysis was performed., Results: Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1-40.1) in patients with bcP and 1.4 ng/ml (range 0.3-5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD2 1.5 Gy of 66 Gy (60-70 Gy) was delivered to the prostatic fossa, 70 Gy (66-72 Gy) to the local recurrence, if present, 65.1 Gy (56-66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4-50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes., Conclusions: Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome., (© 2021. The Author(s).)

Background: Red blood cells (RBC) scintigraphy can be used not only for detection of bleeding sites, but also of spleen tissue. However, there is no established quantitative readout. Therefore, we investigated uptake in suspected splenic lesions in direct quantitative correlation to sites of physiologic uptake in order to objectify the readout., Methods: 20 patients with Tc-99m-labelled RBC scintigraphy and SPECT/low-dose CT for assessment of suspected splenic tissue were included. Lesions were rated as vital splenic or non-splenic tissue, and uptake and physiologic uptake of bone marrow, pancreas, and spleen were then quantified using a volume-of-interest based approach. Hepatic uptake served as a reference., Results: The median uptake ratio was significantly higher in splenic (2.82 (range, 0.58-24.10), n = 47) compared to other lesions (0.49 (0.01-0.83), n = 7), p < 0.001, and 5 lesions were newly discovered. The median pancreatic uptake was 0.09 (range 0.03-0.67), bone marrow 0.17 (0.03-0.45), and orthotopic spleen 14.45 (3.04-29.82). Compared to orthotopic spleens, the pancreas showed lowest uptake (0.09 vs. 14.45, p = 0.004). Based on pancreatic uptake we defined a cutoff (0.75) to distinguish splenic from other tissues., Conclusion: As the uptake in extra-splenic regions is invariably low compared to splenules, it can be used as comparator for evaluating suspected splenic tissues.

Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [ 18 F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [ 18 F]GE-180 PET. The cortical and subcortical regions were delineated by deep nuclei parcellation (DNP) of a 3D-T1 MRI. Region-specific subcortical volumes and standardized uptake values and ratios (SUV and SUVr) were extracted before and after region-based voxel-wise PVEC. Regional volumes were compared between patients with CBS and controls. The % group differences and effect sizes (CBS vs. controls) of uncorrected and PVE-corrected SUVr data were compared. Single-region positivity in patients with CBS was assessed by a >2 SD threshold vs. controls and compared between uncorrected and PVE-corrected data. Smaller regional volumes were detected in patients with CBS compared to controls in the right ventral striatum ( p = 0.041), the left putamen ( p = 0.005), the right putamen ( p = 0.038) and the left pallidum ( p = 0.015). After applying PVEC, the % group differences were distinctly higher, but the effect sizes of TSPO uptake were only slightly stronger due to the higher variance after PVEC. The single-region positivity of TSPO PET increased in patients with CBS after PVEC (100 vs. 83 regions). PVEC in the cortical and subcortical regions is valuable for TSPO imaging of patients with CBS, leading to the improved detection of elevated [ 18 F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly.

In this study, dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [ 18 F]GE180 and the amino acid [ 18 F]FET were acquired and normalized to healthy background (tumor-to-background ratio, TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

Background: O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ( 18 F-FET) is a highly sensitive PET tracer for glioma imaging, and its uptake is suggested to be driven by an overexpression of the L-type amino-acid transporter 1 (LAT1). However, 30% of low- and 5% of high-grade gliomas do not present enhanced 18 F-FET uptake at primary diagnosis (" 18 F-FET-negative gliomas") and the pathophysiologic basis for this phenomenon remains unclear. The aim of this study was to determine the expression of LAT1 in a homogeneous group of newly diagnosed 18 F-FET-negative gliomas and to compare them to a matched group of 18 F-FET-positive gliomas. Forty newly diagnosed IDH-mutant astrocytomas without 1p/19q codeletion were evaluated (n = 20 18 F-FET-negative (tumour-to-background ratio (TBR) < 1.6), n = 20 18 F-FET-positive gliomas (TBR > 1.6)). LAT1 immunohistochemistry (IHC) was performed using SLC7A5/LAT1 antibody. The percentage of LAT1-positive tumour cells (%) and the staining intensity (range 0-2) were multiplied to an overall score (H-score; range 0-200) and correlated to PET findings as well as progression-free survival (PFS)., Results: IHC staining of LAT1 expression was positive in both, 18 F-FET-positive as well as 18 F-FET-negative gliomas. No differences were found between the 18 F-FET-negative and 18 F-FET-positive group with regard to percentage of LAT1-positive tumour cells, staining intensity or H-score. Interestingly, the LAT1 expression showed a significant negative correlation with the PFS (p = 0.031), whereas no significant correlation was found for TBR max , neither in the overall group nor in the 18 F-FET-positive group only (p = 0.651 and p = 0.140)., Conclusion: Although LAT1 is reported to mediate the uptake of 18 F-FET into tumour cells, the levels of LAT1 expression do not correlate with the levels of 18 F-FET uptake in IDH-mutant astrocytomas. In particular, the lack of tracer uptake in 18 F-FET-negative gliomas cannot be explained by a reduced LAT1 expression. A higher LAT1 expression in IDH-mutant astrocytomas seems to be associated with a short PFS. Further studies regarding mechanisms influencing the uptake of 18 F-FET are necessary., (© 2021. The Author(s).)

Purpose: To evaluate radiomic features extracted from standard static images (20-40 min p.i.), early summation images (5-15 min p.i.), and dynamic [ 18 F]FET PET images for the prediction of TERTp-mutation status in patients with IDH-wildtype high-grade glioma., Methods: A total of 159 patients (median age 60.2 years, range 19-82 years) with newly diagnosed IDH-wildtype diffuse astrocytic glioma (WHO grade III or IV) and dynamic [ 18 F]FET PET prior to surgical intervention were enrolled and divided into a training (n = 112) and a testing cohort (n = 47) randomly. First-order, shape, and texture radiomic features were extracted from standard static (20-40 min summation images; TBR 20-40 ), early static (5-15 min summation images; TBR 5-15 ), and dynamic (time-to-peak; TTP) images, respectively. Recursive feature elimination was used for feature selection by 10-fold cross-validation in the training cohort after normalization, and logistic regression models were generated using the radiomic features extracted from each image to differentiate TERTp-mutation status. The areas under the ROC curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive value were calculated to illustrate diagnostic power in both the training and testing cohort., Results: The TTP model comprised nine selected features and achieved highest predictability of TERTp-mutation with an AUC of 0.82 (95% confidence interval 0.71-0.92) and sensitivity of 92.1% in the independent testing cohort. Weak predictive capability was obtained in the TBR 5-15 model, with an AUC of 0.61 (95% CI 0.42-0.80) in the testing cohort, while no predictive power was observed in the TBR 20-40 model., Conclusions: Radiomics based on TTP images extracted from dynamic [ 18 F]FET PET can predict the TERTp-mutation status of IDH-wildtype diffuse astrocytic high-grade gliomas with high accuracy preoperatively., (© 2021. The Author(s).)

Background: Prostate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential of PSMA PET imaging in the syngeneic GL261 GBM model and to give an outlook regarding the potential of PMSA radioligand therapy in this model., Methods: We performed an 18 F-PSMA-1007 PET study in the orthotopic GL261 model (n=14 GBM, n=7 sham-operated mice) with imaging at day 4, 8, 11, 15, 18 and 22 post implantation. Time-activity-curves (TAC) were extracted from dynamic PET scans (0-120 min p. i.) in a subset of mice (n=4 GBM, n=3 sham-operated mice) to identify the optimal time frame for image analysis, and standardized-uptake-values (SUV) as well as tumor-to-background ratios (TBR) using contralateral normal brain as background were calculated in all mice. Additionally, computed tomography (CT), ex vivo and in vitro 18 F-PSMA-1007 autoradiographies (ARG) were performed., Results: TAC analysis of GBM mice revealed a plateau of TBR values after 40 min p. i. Therefore, a 30 min time frame between 40-70 min p. i. was chosen for PET quantification. At day 15 and later, GBM mice showed a discernible PSMA PET signal on the inoculation site, with highest TBR mean in GBM mice at day 18 (7.3 ± 1.3 vs . 1.6 ± 0.3 in shams; p =0.024). Ex vivo ARG confirmed high tracer signal in GBM compared to healthy background (TBR mean 26.9 ± 10.5 vs . 1.6 ± 0.7 in shams at day 18/22 post implantation; p =0.002). However, absolute uptake values in the GL261 tumor remained low (e.g., SUV mean 0.21 ± 0.04 g/ml at day 18) resulting in low ratios compared to dose-relevant organs (e.g., mean tumor-to-kidney ratio 1.5E -2 ± 0.5E -2 )., Conclusions: Although 18 F-PSMA-1007 PET imaging of GL261 tumor-bearing mice is feasible and resulted in high TBRs, absolute tumoral uptake values remained low and hint to limited applicability of the GL261 model for PSMA-directed therapy studies. Further investigations are warranted to identify suitable models for preclinical evaluation of PSMA-targeted theranostic approaches in GBM., 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 Kirchner, Holzgreve, Brendel, Orth, Ruf, Steiger, Pötter, Gold, Unterrainer, Mittlmeier, Barci, Kälin, Glass, Lindner, Kaiser, Maas, von Baumgarten, Ilhan, Belka, Notni, Bartenstein, Lauber and Albert.)

Importance: The presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy., Objective: To assess the accuracy of prostate-specific membrane antigen (PSMA) 68Ga-PSMA-11 positron emission tomographic (PET) imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection., Design, Setting, and Participants: This investigator-initiated prospective multicenter single-arm open-label phase 3 imaging trial of diagnostic efficacy enrolled 764 patients with intermediate- to high-risk prostate cancer considered for prostatectomy at University of California, San Francisco and University of California, Los Angeles from December 2015 to December 2019. Data analysis took place from October 2018 to July 2021., Interventions: Imaging scan with 3 to 7 mCi of 68Ga-PSMA-11 PET., Main Outcomes and Measures: The primary end point was the sensitivity and specificity for the detection pelvic lymph nodes compared with histopathology on a per-patient basis using nodal region correlation. Each scan was read centrally by 3 blinded independent central readers, and a majority rule was used for analysis., Results: A total of 764 men (median [interquartile range] age, 69 [63-73] years) underwent 1 68Ga-PSMA-11 PET imaging scan for primary staging, and 277 of 764 (36%) subsequently underwent prostatectomy with lymph node dissection (efficacy analysis cohort). Based on pathology reports, 75 of 277 patients (27%) had pelvic nodal metastasis. Results of 68Ga-PSMA-11 PET were positive in 40 of 277 (14%), 2 of 277 (1%), and 7 of 277 (3%) of patients for pelvic nodal, extrapelvic nodal, and bone metastatic disease. Sensitivity, specificity, positive predictive value, and negative predictive value for pelvic nodal metastases were 0.40 (95% CI, 0.34-0.46), 0.95 (95% CI, 0.92-0.97), 0.75 (95% CI, 0.70-0.80), and 0.81 (95% CI, 0.76-0.85), respectively. Of the 764 patients, 487 (64%) did not undergo prostatectomy, of which 108 were lost to follow-up. Patients with follow-up instead underwent radiotherapy (262 of 379 [69%]), systemic therapy (82 of 379 [22%]), surveillance (16 of 379 [4%]), or other treatments (19 of 379 [5%])., Conclusions and Relevance: This phase 3 diagnostic efficacy trial found that in men with intermediate- to high-risk prostate cancer who underwent radical prostatectomy and lymph node dissection, the sensitivity and specificity of 68Ga-PSMA-11 PET were 0.40 and 0.95, respectively. This academic collaboration is the largest known to date and formed the foundation of a New Drug Application for 68Ga-PSMA-11., Trial Registration: ClinicalTrials.gov Identifiers: NCT03368547, NCT02611882, and NCT02919111.

Purpose: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, leading to a string of approvals in recent years. Herein, a narrative review on the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the ever-evolving treatment landscape of advanced NSCLC is presented., Methods: This comprehensive review will begin with an introduction into current treatment paradigms incorporating ICIs; the evolution of CT-based criteria; moving onto novel phenomena observed with ICIs and the current state of hybrid imaging for diagnosis, treatment planning, evaluation of treatment efficacy and toxicity in advanced NSCLC, also taking into consideration its limitations and future directions., Conclusions: The advent of ICIs marks the dawn of a new era bringing forth new challenges particularly vis-à-vis treatment response assessment and observation of novel phenomena accompanied by novel systemic side effects. While FDG PET/CT is widely adopted for tumor volume delineation in locally advanced disease, response assessment to immunotherapy based on current criteria is of high clinical value but has its inherent limitations. In recent years, modifications of established (PET)/CT criteria have been proposed to provide more refined approaches towards response evaluation. Not only a comprehensive inclusion of PET-based response criteria in prospective randomized controlled trials, but also a general harmonization within the variety of PET-based response criteria is pertinent to strengthen clinical implementation and widespread use of hybrid imaging for response assessment in NSCLC., (© 2021. The Author(s).)

Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether translocator protein (TSPO) PET imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from multiple sclerosis lesions. For this monocentre pilot study we followed eight patients with natalizumab-associated PML with PET imaging using the TSPO radioligand 18F-GE-180 combined with frequent 3 T MRI. In addition we compared TSPO PET signals in PML lesions with the signal pattern of multiple sclerosis lesions from 17 independent multiple sclerosis patients. We evaluated the standardized uptake value ratio as well as the morphometry of the TSPO uptake for putative PML and multiple sclerosis lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore, TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/multiple sclerosis). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogeneous distribution in putative multiple sclerosis lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52 months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3D diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated >96% of PML and multiple sclerosis lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active multiple sclerosis lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent multiple sclerosis activity from PML progression., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). [ 18 F]SiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68 Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis., Methods: Eight NET patients received a [ 18 F]SiTATE-PET/CT (250 ± 66 MBq) with repeated emission scans (10, 30, 60, 120, 180 min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18 F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times., Results: After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004 mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120 min images., Conclusion: [ 18 F]SiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180 min after injection and an effective dose comparable to 68 Ga-labelled alternatives. For clinical use of [ 18 F]SiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120 min, followed by 60 min after injection., (© 2021. The Author(s).)

Abstract: PET using 68Ga-labeled somatostatin receptor (SSTR) ligands adds significant information in meningioma patients. 18F-SiTATE is a novel, 18F-labeled SSTR-targeting peptide with remarkable imaging properties. Here, we present a 72-year-old woman with falx meningioma and transosseous extension. 18F-SiTATE PET/CT was performed 12 months after the previous 68Ga-DOTATOC PET/CT with comparable quantitative uptake and very good spatial resolution. So far, the widespread use of SSTR ligands for NET and meningioma imaging is hampered by cost-intensive 68Ge/68Ga generators, low activity amounts, lower spatial resolution, and short half-life. 18F-SiTATE might foster widespread use of SSTR ligands, overcoming the shortcomings of 68Ga-labeled ligands., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Benign so-called "brown tumors" secondary to hyperparathyroidism are a rare diagnostic pitfall due to their impressively malignant-like character in various imaging modalities. We present the case of a 65-year-old male patient with multiple unclear osteolytic lesions on prior imaging suspicious for metastatic malignant disease. Eventually, findings of 18 F-FDG PET/CT staging and 99m Tc-MIBI scintigraphy resulted in revision of the initially suspected malignant diagnosis. This case illustrates how molecular imaging findings non-invasively corroborate the correct diagnosis of osteitis fibrosa cystica generalisata with the formation of multiple benign brown tumors.

Background: IDHwt diffuse gliomas represent the tumor entity with one of the worst clinical outcomes. Only rare cases present with a long-term survival of several years. Here we aimed at comparing the uptake characteristics on dynamic 18 F-FET PET, clinical and molecular genetic parameters of long-term survivors (LTS) versus short-term survivors (STS): Methods: Patients with de-novo IDHwt glioma (WHO grade III/IV) and 18 F-FET PET prior to any therapy were stratified into LTS (≥36 months survival) and STS (≤15 months survival). Static and dynamic 18 F-FET PET parameters (mean/maximal tumor-to-background ratio (TBR mean/max ), biological tumor volume (BTV), minimal time-to-peak (TTP min )), diameter and volume of contrast-enhancement on MRI, clinical parameters (age, sex, Karnofksy-performance-score), mode of surgery; initial treatment and molecular genetics were assessed and compared between LTS and STS., Results: Overall, 75 IDHwt glioma patients were included (26 LTS, 49 STS). LTS were significantly younger ( p < 0.001), had a higher rate of WHO grade III glioma ( p = 0.032), of O(6)-Methylguanine-DNA methyltransferase ( MGMT ) promoter methylation ( p < 0.001) and missing Telomerase reverse transcriptase promoter (TERTp) mutations ( p = 0.004) compared to STS. On imaging, LTS showed a smaller median BTV ( p = 0.017) and a significantly longer TTP min ( p = 0.008) on 18 F-FET PET than STS, while uptake intensity (TBR mean/max ) did not differ. In contrast to the tumor-volume on PET, MRI-derived parameters such as tumor size as well as all other above-mentioned parameters did not differ between LTS and STS ( p > 0.05 each)., Conclusion: Besides molecular genetic prognosticators, a long survival time in IDHwt glioma patients is associated with a longer TTP min as well as a smaller BTV on 18 F-FET PET at initial diagnosis. 18 F-FET uptake intensity as well as the MRI-derived tumor size (volume and maximal diameter) do not differ in patients with long-term survival.

Background: In certain malignancies, patients with oligometastatic disease benefit from radical ablative or surgical treatment. The SABR-COMET trial demonstrated a survival benefit for oligometastatic patients randomized to local stereotactic ablative radiation (SABR) compared to patients receiving standard care (SC) alone. Our aim was to determine the cost-effectiveness of SABR., Materials and Methods: A decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY) associated with both strategies in a United States setting from a health care perspective. Analyses were performed over the trial duration of six years as well as a long-term horizon of 16 years. Model input parameters were based on the SABR-COMET trial data as well as best available and most recent data provided in the published literature. An annual discount of 3% for costs was implemented in the analysis. All costs were adjusted to 2019 US Dollars according to the United States Consumer Price Index. SABR costs were reported with an average of $11,700 per treatment. Deterministic and probabilistic sensitivity analyses were performed. Incremental costs, effectiveness, and cost-effectiveness ratios (ICER) were calculated. The willingness-to-pay (WTP) threshold was set to $100,000/QALY., Results: Based on increased overall and progression-free survival, the SABR group showed 0.78 incremental QALYs over the trial duration and 1.34 incremental QALYs over the long-term analysis. Treatment with SABR led to a marginal increase in costs compared to SC alone (SABR: $304,656; SC: $303,523 for 6 years; ICER $1,446/QALY and SABR: $402,888; SC: $350,708 for long-term analysis; ICER $38,874/QALY). Therapy with SABR remained cost-effective until treatment costs of $88,969 over the trial duration (i.e. 7.6 times the average cost). Sensitivity analysis identified a strong model impact for ongoing annual costs of oligo- and polymetastatic disease states., Conclusion: Our analysis suggests that local treatment with SABR adds QALYs for patients with certain oligometastatic cancers and represents an intermediate- and long-term cost-effective treatment strategy., 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 Mehrens, Unterrainer, Corradini, Niyazi, Manapov, Westphalen, Froelich, Wildgruber, Seidensticker, Ricke, Rübenthaler and Kunz.)

The sarcoid-like reaction represents an autoinflammatory cause of mediastinal and hilar lymphadenopathy but may also involve other lymph node regions and organs. This rare phenomenon has mainly been reported in patients with Hodgkin's lymphoma (HL) or solid tumors (particularly melanoma) undergoing immunotherapy and chemotherapy. Cases in non-Hodgkin's lymphoma (NHL) are very uncommon. We present an uncommon case of a patient with primarily mediastinal diffuse large B-cell lymphoma (DLBCL) who showed a CT-based partial response in interim staging, whereas at end-of-treatment multiple newly enlarged and hypermetabolic mediastinal and bilateral hilar lymph nodes were detected by 18 F-FDG PET/CT imaging. A subsequent histological workup determined a sarcoid-like reaction without any lymphomatous tissue. Therefore, sarcoid-like reactions should be considered as a potential pitfall in Deauville staging with 18 F-FDG PET/CT imaging for patients with NHL.

TSPO-PET tracers are sensitive to a single-nucleotide polymorphism (rs6971-SNP), resulting in low-, medium- and high-affinity binders (LABs, MABs and HABS), but the clinical relevance of [ 18 F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [ 18 F]GE-180 binding in a healthy brain and in pseudo-reference tissue in neuro-oncological and neurodegenerative diseases. Standardized uptake values (SUVs) of [ 18 F]GE-180-PET were assessed using a manually drawn region of interest in the frontoparietal and cerebellar hemispheres. The SUVs were compared between the LABs, MABs and HABs in control, glioma, four-repeat tauopathy (4RT) and Alzheimer's disease (AD) subjects. Second, the SUVs were compared between the patients and controls within their rs6971-subgroups. After excluding patients with prior therapy, 24 LABs (7 control, 5 glioma, 6 4RT and 6 AD) were analyzed. Age- and sex-matched MABs (n = 38) and HABs (n = 50) were selected. The LABs had lower frontoparietal and cerebellar SUVs when compared with the MABs and HABs, but no significant difference was observed between the MABs and HABs. Within each rs6971 group, no SUV difference between the patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [ 18 F]GE-180 quantification, revealing lower binding in the LABs when compared to the MABs and HABs. The frontoparietal and cerebellar ROIs were successfully validated as pseudo-reference regions.

Background: Delineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68 Ga-labeled ligands; nonetheless, 18 F-labeled PET ligands are gaining increasing importance due to advantages over 68 Ga-labeled compounds. However, standardized tumor delineation methods for 18 F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18 F-PSMA-1007 PET., Methods: Fifty patients with metastatic prostate cancer, 18 F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUV max (SUV%), and thresholds relative to III) liver (SUV liver ), IV) parotis (SUV parotis ) and V) spleen (SUV spleen )., Results: A fixed SUV of 4.0 (r=0.807, r 2 = 0.651, p<0.001) showed the best overall association with the volumetric reference. 55% SUV max (r=0.627, r 2 = 0.393, p<0.001) showed highest association using an isocontour-based threshold. Best background-based approaches were 60% SUV liver (r=0.715, r 2 = 0.511, p<0.001), 80% SUV parotis (r=0.762, r 2 = 0.581, p<0.001) and 60% SUV spleen (r=0.645, r 2 = 0.416, p<0.001). Background tissues SUV liver, SUV parotis & SUV spleen did not correlate (p>0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUV max , 42% SUV max and 20% SUV max ) revealed inferior association for LNM delineation., Conclusions: A threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated., 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 Mittlmeier, Brendel, Beyer, Albert, Todica, Zacherl, Wenter, Herlemann, Kretschmer, Ledderose, Schmidt-Hegemann, Kunz, Ricke, Bartenstein, Ilhan and Unterrainer.)

Objectives: In recent years several 18 F-labeled amyloid PET (Aβ-PET) tracers have been developed and have obtained clinical approval. There is evidence that Aβ-PET perfusion can provide surrogate information about neuronal injury in neurodegenerative diseases when compared to conventional blood flow and glucose metabolism assessment. However, this paradigm has not yet been tested in neurodegenerative disorders with cortical and subcortical affection. Therefore, we investigated the performance of early acquisition 18 F-flutemetamol Aβ-PET in comparison to 18 F-fluorodeoxyglucose (FDG)-PET in corticobasal syndrome (CBS). Methods: Subjects with clinically possible or probable CBS were recruited within the prospective Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease (ActiGliA) observational study and all CBS cases with an available FDG-PET prior to Aβ-PET were selected. Aβ-PET was acquired 0-10 min p.i. (early-phase) and 90-110 min p.i. (late-phase) whereas FDG-PET was recorded statically from 30 to 50 min p.i. Semiquantitative regional values and asymmetry indices (AI) were compared between early-phase Aβ-PET and FDG-PET. Visual assessments of hypoperfusion and hypometabolism were compared between both methods. Late-phase Aβ-PET was evaluated visually for assessment of Aβ-positivity. Results: Among 20 evaluated patients with CBS, 5 were Aβ-positive. Early-phase Aβ-PET and FDG-PET SUVr correlated highly in cortical (mean R = 0.86, range 0.77-0.92) and subcortical brain regions (mean R = 0.84, range 0.79-0.90). Strong asymmetry was observed in FDG-PET for the motor cortex (mean |AI| = 2.9%), the parietal cortex (mean |AI| = 2.9%), and the thalamus (mean |AI| = 5.5%), correlating well with AI of early-phase Aβ-PET (mean R = 0.87, range 0.62-0.98). Visual assessments of hypoperfusion and hypometabolism were highly congruent. Conclusion: Early-phase Aβ-PET facilitates assessment of neuronal injury in CBS for cortical and subcortical areas. Known asymmetries in CBS are captured by this method, enabling assessment of Aβ-status and neuronal injury with a single radiation exposure at a single visit., Competing Interests: MB received speaker honoraria from GE healthcare and LMI and is an advisor of LMI. GH has ongoing research collaborations with Prothena; serves as a consultant for AbbVie, AlzProtect, Asceneuron, Biogen, Biohaven, Lundbeck, Novartis, Roche, Sanofi, UCB; received honoraria for scientific presentations from AbbVie, Bial, Biogen, Bristol Myers Squibb, Roche, Teva, UCB, and Zambon; and holds a patent on PERK Activation for the Treatment of Neurodegenerative Diseases (PCT/EP2015/068734). CH is chief scientific advisor of ISAR biosciences and collaborates with DENALI therapeutics. RP is on the advisory board for Biogen, has consulted for Eli Lilly and Roche, is a grant recipient from Janssen Pharmaceutica and Boehringer Ingelheim, and has received speaker honoraria from Janssen-Cilag, Pfizer and Biogen. JL reports speaker fees from Bayer Vital, consulting fees from Axon Neuroscience, author fees from Thieme medical publishers and W. Kohlhammer GmbH medical publishers, non-financial support from Abbvie and compensation for duty as part-time CMO from MODAG GmbH, all outside the submitted work. The remaining 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 Schmitt, Palleis, Sauerbeck, Unterrainer, Harris, Prix, Weidinger, Katzdobler, Wagemann, Danek, Beyer, Rauchmann, Rominger, Simons, Bartenstein, Perneczky, Haass, Levin, Höglinger, Brendel and the German Imaging Initiative for Tauopathies.)

Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA)-targeting β- and α-emitters have been introduced, with promising response rates. Here, we present the first-to our knowledge-clinical data for PSMA-targeted α-therapy (TAT) using 225 Ac-PSMA imaging and therapy (I&T). Methods: Fourteen patients receiving 225 Ac-PSMA-I&T were included in this retrospective analysis. Eleven of the 14 had prior second-line antiandrogen treatment with abiraterone or enzalutamide, prior chemotherapy, and prior 177 Lu-PSMA treatment. Patients were treated at bimonthly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) was measured for response assessment. Hematologic and nonhematologic side effects were recorded according to the Common Terminology Criteria for Adverse Events, version 5.0. Results: Thirty-four cycles of 225 Ac-PSMA-I&T were applied (median dose, 7.8 MBq; range, 6.0-8.5), with 1 cycle in 3 patients, 2 cycles in 7 patients, 4 cycles in 3 patients, and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 112 ng/mL (range, 20.5-818 ng/mL). The best PSA response after TAT (a PSA decline ≥ 50%) was observed in 7 patients, and a PSA decline of any amount was observed in 11 patients. Three patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior 177 Lu-PSMA treatment showed any PSA decline in 8 patients and a decline of at least 50% in 5 patients. After TAT, grade 3 anemia was observed in 3 of the 14 patients, with 2 of them presenting with grade 2 anemia already at baseline. Grade 3 leukopenia was observed in 1 patient. Eight patients with preexisting xerostomia after 177 Lu-PSMA showed no worsening after TAT. Newly diagnosed grade 1 or 2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Conclusion: Our first clinical data for TAT using 225 Ac-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer. These results are highly comparable to data on 225 Ac-PSMA-617 TAT., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: The mutation of the 'telomerase reverse transcriptase gene promoter' (TERTp) has been identified as an important factor for individual prognostication and tumorigenesis and will be implemented in upcoming glioma classifications. Uptake characteristics on dynamic 18 F-FET PET have been shown to serve as additional imaging biomarker for prognosis. However, data on the correlation of TERTp-mutational status and amino acid uptake on dynamic 18 F-FET PET are missing. Therefore, we aimed to analyze whether static and dynamic 18 F-FET PET parameters are associated with the TERTp-mutational status in de-novo IDH -wildtype glioblastoma and whether a TERTp-mutation can be predicted by dynamic 18 F-FET PET., Methods: Patients with de-novo IDH -wildtype glioblastoma, WHO grade IV, available TERTp-mutational status and dynamic 18 F-FET PET scan prior to any therapy were included. Here, established clinical parameters maximal and mean tumor-to-background-ratios (TBR max /TBR mean ), the biological-tumor-volume (BTV) and minimal-time-to-peak (TTP min ) on dynamic PET were analyzed and correlated with the TERTp-mutational status., Results: One hundred IDH -wildtype glioblastoma patients were evaluated; 85/100 of the analyzed tumors showed a TERTp-mutation (C228T or C250T), 15/100 were classified as TERTp-wildtype. None of the static PET parameters was associated with the TERTp-mutational status (median TBR max 3.41 vs. 3.32 (p=0.362), TBR mean 2.09 vs. 2.02 (p=0.349) and BTV 26.1 vs. 22.4 ml (p=0.377)). Also, the dynamic PET parameter TTP min did not differ in both groups (12.5 vs. 12.5 min, p=0.411). Within the TERTp-mutant subgroups (i.e., C228T (n=23) & C250T (n=62)), the median TBR max (3.33 vs. 3.69, p=0.095), TBR mean (2.08 vs. 2.09, p=0.352), BTV (25.4 vs. 30.0 ml, p=0.130) and TTP min (12.5 vs. 12.5 min, p=0.190) were comparable, too., Conclusion: Uptake characteristics on dynamic 18 F-FET PET are not associated with the TERTp-mutational status in glioblastoma However, as both, dynamic 18 F-FET PET parameters as well as the TERTp-mutation status are well-known prognostic biomarkers, future studies should investigate the complementary and independent prognostic value of both factors in order to further stratify patients into risk groups., Competing Interests: NA is a member of the Neuroimaging Committee of the EANM. The remaining 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 Unterrainer, Ruf, von Rohr, Suchorska, Mittlmeier, Beyer, Brendel, Wenter, Kunz, Bartenstein, Herms, Niyazi, Tonn and Albert.)

Background: Neuroinflammation has received growing interest as a therapeutic target in neurodegenerative disorders, including 4-repeat tauopathies., Objectives: The aim of this cross-sectional study was to investigate 18 kDa translocator protein positron emission tomography (PET) as a biomarker for microglial activation in the 4-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy., Methods: Specific binding of the 18 kDa translocator protein tracer 18 F-GE-180 was determined by serial PET during pharmacological depletion of microglia in a 4-repeat tau mouse model. The 18 kDa translocator protein PET was performed in 30 patients with corticobasal syndrome (68 ± 9 years, 16 women) and 14 patients with progressive supranuclear palsy (69 ± 9 years, 8 women), and 13 control subjects (70 ± 7 years, 7 women). Group comparisons and associations with parameters of disease progression were assessed by region-based and voxel-wise analyses., Results: Tracer binding was significantly reduced after pharmacological depletion of microglia in 4-repeat tau mice. Elevated 18 kDa translocator protein labeling was observed in the subcortical brain areas of patients with corticobasal syndrome and progressive supranuclear palsy when compared with controls and was most pronounced in the globus pallidus internus, whereas only patients with corticobasal syndrome showed additionally elevated tracer binding in motor and supplemental motor areas. The 18 kDa translocator protein labeling was not correlated with parameters of disease progression in corticobasal syndrome and progressive supranuclear palsy but allowed sensitive detection in patients with 4-repeat tauopathies by a multiregion classifier., Conclusions: Our data indicate that 18 F-GE-180 PET detects microglial activation in the brain of patients with 4-repeat tauopathy, fitting to predilection sites of the phenotype. The 18 kDa translocator protein PET has a potential for monitoring neuroinflammation in 4-repeat tauopathies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Aim: The aim of the current study was to enlighten the evolution of prostate-specific membrane antigen (PSMA) expression in glioblastoma between initial diagnosis and recurrence in order to provide preliminary insight for further clinical investigations into innovative PSMA-directed treatment concepts in neuro-oncology., Methods: Patients who underwent resection for de-novo glioblastoma (GBM) and had a re-resection in case of a recurrent tumor following radiochemotherapy and subsequent chemotherapy were included (n = 16). Histological and immunohistochemical stainings were performed at initial diagnosis and at recurrence (n = 96 tissue specimens). Levels of PSMA expression both in endothelial and non-endothelial cells as well as vascular density (CD34) were quantified via immunohistochemistry and changes between initial diagnosis and recurrence were determined. Immunohistochemical findings were correlated with survival and established clinical parameters., Results: PSMA expression was found to be present in all GBM tissue samples at initial diagnosis as well as in all but one case of recurrent tumor samples. The level of PSMA expression in glioblastoma varied inter-individually both in endothelial and non-endothelial cells. Likewise, the temporal evolution of PSMA expression highly varied in between patients. The level of vascular PSMA expression at recurrence and its change between initial diagnosis and recurrence was associated with post recurrence survival time: Patients with high vascular PSMA expression at recurrence as well as patients with increasing PSMA expression throughout the disease course survived shorter than patients with low vascular PSMA expression or decreasing vascular PSMA expression. There was no significant correlation of PSMA expression with MGMT promoter methylation status or Ki-67 labelling index., Conclusion: PSMA is expressed in glioblastoma both at initial diagnosis and at recurrence. High vascular PSMA expression at recurrence seems to be a negative prognostic marker. Thus, PSMA expression in GBM might present a promising target for theranostic approaches in recurrent glioblastoma. Especially PSMA PET imaging and PSMA-directed radioligand therapy warrant further studies in brain tumor patients., 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 Holzgreve, Biczok, Ruf, Liesche-Starnecker, Steiger, Kirchner, Unterrainer, Mittlmeier, Herms, Schlegel, Bartenstein, Tonn, Albert and Suchorska.)

Background: Colorectal cancer is among the most prevalent cancer entities worldwide, with every second patient developing liver metastases during their illness. For local treatment of liver metastases, a surgical approach as well as ablative treatment options, such as microwave ablation (MWA) and radiofrequency ablation (RFA), are available. The aim of this study is to evaluate the cost-effectiveness of RFA, MWA and surgery in the treatment of liver metastases of oligometastatic colorectal cancer (omCRC) that are amenable for all investigated treatment modalities., Methods: A decision analysis based on a Markov model assessed lifetime costs and quality-adjusted life years (QALY) related to the treatment strategies RFA, MWA and surgical resection. Input parameters were based on the best available and most recent evidence. Probabilistic sensitivity analyses (PSA) were performed with Monte Carlo simulations to evaluate model robustness. The percentage of cost-effective iterations was determined for different willingness-to-pay (WTP) thresholds., Results: The base-case analysis showed that surgery led to higher long-term costs compared to RFA and MWA (USD 41,848 vs. USD 36,937 vs. USD 35,234), while providing better long-term outcomes than RFA, yet slightly lower than MWA (6.80 vs. 6.30 vs. 6.95 QALYs for surgery, RFA and MWA, respectively). In PSA, MWA was the most cost-effective strategy for all WTP thresholds below USD 80,000 per QALY., Conclusions: In omCRC patients with liver metastases, MWA and surgery are estimated to provide comparable efficacy. MWA was identified as the most cost-effective strategy in intermediate resource settings and should be considered as an alternative to surgery in high resource settings.

We present a 71-year-old female patient who underwent 18 F-PSMA-1007 PET/CT for suspected metastatic renal cell carcinoma (RCC), as RCC also shows high PSMA-expression in tumor neovascularization. 18 F-PSMA-1007 PET/CT showed a high PSMA-avidity in the renal tumor, enlarged intra-abdominal and mediastinal lymph nodes. Moreover, PSMA-positive pleural, pulmonal and osseous lesions were found. However, histopathology revealed an immature plasma cell myeloma with an endothelial PSMA-expression of the neovasculature. This case illustrates the increased PSMA-avidity in multiple myeloma and highlights PSMA as a potential theragnostic target in multiple myeloma. For clinical routine, lymphatic diseases such as extramedullary myeloma should be considered as differential diagnosis in PSMA-avid renal masses on PET/CT.

Background: Sarcoid lesions may mimic metastatic disease or recurrence in thyroid cancer (TC) patients as both diseases may affect the lungs and lymph nodes. We present the first study to systematically evaluate the clinical course of patients with (TC) after adjuvant radioactive iodine therapy (RIT) and concomitant sarcoidosis of the lung or the lymph nodes., Methods: We screened 3285 patients and retrospectively identified 16 patients with TC (11 papillary thyroid cancer (PTC), 3 follicular thyroid cancer (FTC), 1 oncocytic PTC, 1 oncocytic FTC) and coexisting sarcoidosis of the lung and/or the lymph nodes treated at our institute. All patients had undergone thyroidectomy and initial adjuvant RIT. Challenges in diagnosing and the management of these patients were evaluated during long term follow-up (median 4.9 years (0.8-15.0 years))., Results: Median age at first diagnosis of TC was 50.1 years (33.0-71.5 years) and of sarcoidosis 39.4 years (18.0-63.9 years). During follow-up, physicians were able to differentiate between SA and persistent or recurrent TC in 10 of 16 patients (63%). Diagnosis was complicated by initial negative thyroglobulin (Tg), positive Tg antibodies and non-specific imaging findings. Histopathology can reliably distinguish between SA and TC in patients with one suspicious lesion., Conclusion: Physicians should be aware of the rare coexistence of sarcoidosis and TC. Lymphadenopathy and pulmonary lesions could be metastases, sarcoidosis or even a mix of both. Therefore, this rare patient group should receive a thorough work up including histopathological clarification and, if necessary, separately for each lesion.

Objectives : Asymmetric disease characteristics on neuroimaging are common in structural and functional imaging of neurodegenerative diseases, particularly in Alzheimer's disease (AD). However, a standardized clinical evaluation of asymmetric neuronal degeneration and its impact on clinical findings has only sporadically been investigated for F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG-PET). This study aimed to evaluate the impact of lateralized neuronal degeneration on the detection of AD by detailed clinical testing. Furthermore, we compared associations between clinical evaluation and lateralized neuronal degeneration between FDG-PET hypometabolism and hippocampal atrophy. Finally, we investigated if specific subtests show associations with lateralized neuronal degeneration. Methods : One-hundred and forty-six patients with a clinical diagnosis of AD (age 71 ± 8) were investigated by FDG-PET and the "Consortium to Establish a Registry for Alzheimer's disease" (CERAD) test battery. For assessment of neuronal degeneration, FDG-PET hypometabolism in brain regions typically affected in AD were graded by visual (3D-surface projections) and semiquantitative analysis. Asymmetry of the hippocampus (left-right) in magnetic resonance tomography (MRI) was rated visually by the Scheltens scale. Measures of asymmetry were calculated to quantify lateralized neuronal degeneration and asymmetry scores were subsequently correlated with CERAD. Results : Asymmetry with left-dominant neuronal degeneration to FDG-PET was an independent predictor of cognitive impairment (visual: β = -0.288, p < 0.001; semiquantitative: β = -0.451, p < 0.001) when controlled for age, gender, years of education and total burden of neuronal degeneration, whereas hippocampal asymmetry to MRI was not ( β = -0.034; p = 0.731). Direct comparison of CERAD-PET associations in cases with right- and left-lateralized neuronal degeneration estimated a detection gap of 2.7 years for right-lateralized cases. Left-hemispheric neuronal degeneration was significantly associated with the total CERAD score and multiple subscores, whereas only MMSE (semiquantitative: β = 0.429, p < 0.001) and constructional praxis (semiquantitative: β = 0.292, p = 0.008) showed significant associations with right-hemispheric neuronal degeneration. Conclusions : Asymmetry of deteriorated cerebral glucose metabolism has a significant impact on the coupling between neuronal degeneration and cognitive function. Right dominant neuronal degeneration shows a delayed detection by global CERAD testing and requires evaluation of specific subdomains of cognitive testing., Competing Interests: RP is on the advisory board for Biogen, has consulted for Eli Lilly, is a grant recipient from Janssen Pharmaceutica and Boehringer Ingelheim, and has received speaker honoraria from Janssen-Cilag, Pfizer, and Biogen. PB declares a research collaboration with GE. AR received speaker honoraria from Piramal Imaging and GE Healthcare. MB received speaker honoraria from GE healthcare and LMI and is an advisor of LMI. The remaining 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 Kreuzer, Sauerbeck, Scheifele, Stockbauer, Schönecker, Prix, Wlasich, Loosli, Kazmierczak, Unterrainer, Catak, Janowitz, Pogarell, Palleis, Perneczky, Albert, Bartenstein, Danek, Buerger, Levin, Zwergal, Rominger, Brendel and Beyer.)

Purpose: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT)., Methods: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival., Results: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0-19.8) vs. 20.1 years (95% CI 19.0-21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309-0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years)., Conclusions: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.

Background and Objective: Reserve is defined as the ability to maintain cognitive functions relatively well at a given level of pathology. Early life experiences such as education are associated with lower dementia risk in general. However, whether more years of education guards against the impact of brain alterations also in frontotemporal dementia (FTD) has not been shown in a large patient collective. Therefore, we assessed whether education is associated with relatively high cognitive performance despite the presence of [ 18 F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET) hypometabolism in FTD., Methods: Sixty-six FTD subjects (age 67 ± 8 years) and twenty-four cognitively healthy controls (HC) were evaluated. Brain regions with FTD-related glucose hypometabolism in the contrast against HC and brain regions that correlate with the cognitive function were defined by a voxel-based analysis and individual FDG-PET values were extracted from all frontotemporal brain areas. Linear regression analysis served to test if education is associated with residualized cognitive performance and regional FDG-PET hypometabolism after controlling for global cognition., Results: Compared to healthy controls, patients with FTD showed glucose hypometabolism in bilateral frontal and temporal brain areas whereas cognition was only associated with deteriorated glucose metabolism in the left temporal lobe. The education level was significantly correlated with the residualized cognitive performance (residuals from regression analysis between hypometabolism and cognitive function as a quantitative index of reserve) and also negatively correlated with left temporal FDG-PET hypometabolism after controlling for cognition., Conclusions: In patients with FTD, the education level predicts the existing left temporal FDG-PET hypometabolism at the same cognition level, supporting the cognitive reserve hypothesis in FTD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Surgeon's intraoperative estimation of meningioma extent of resection (Simpson Grade, SG) is widely used as a prognostic factor for recurrence. However, the validity of SG is still a matter of debate. In preoperative imaging, 68Ga-DOTATATE/PET-CT has been shown to detect meningioma tissue even more sensitively than magnetic resonance imaging (MRI)., Objective: To evaluate the Simpson grading within the framework of modern postoperative imaging techniques (MRI; PET-CT)., Methods: At first, patients with WHO grade I meningioma, surgical resection, and postoperative 68Ga-DOTATATE/PET-CT within 6 mo after surgery were retrospectively analyzed. Second, an analogous prospective cohort of patients with WHO grade I meningioma was investigated by comparing SG after meningioma removal with postoperative MRI and 68Ga-DOTATATE/PET-CT within 6 mo after surgery., Results: A total of 37 patients were retrospectively analyzed. In total, 5/8 patients with SG-I and II resections showed tumor remnants according to postoperative PET-CT (SG 62.5% false negative). In the prospective cohort of 52 tumors, PET-CT displayed tracer uptake in 15/37 SG-I or II resections indicating unexpected tumor remnants (SG 40.5% false negative). MRI was false negative in 7 of these 15 cases (MRI 18.9% false negative) (P = .037). Discordant results according to PET-CT were more often found in convexity (40%) and falcine (46.7%) meningiomas than in skull base meningiomas (18.2%)., Conclusion: Intraoperative Simpson grading is at risk to underestimate tumor remnants, predominantly in grade I and II resections. Postoperative PET-CT improves detection rates compared to MRI. Prognostic impact of postoperative meningioma remnants according to PET-CT needs to be investigated prospectively., (Copyright © 2020 by the Congress of Neurological Surgeons.)

A 25-year-old man presented with headache and intracranial pressure symptoms. On MRI, an intracranial lesion was detected in the right thalamus with exophytic growth into the third ventricle and inhomogeneous contrast enhancement without necrosis. Dual amino acid (F-FET) and TSPO (F-GE-180) PET imaging showed high tumor-to-background ratios in both scans and a short time-to-peak in F-FET uptake dynamics. Biopsy revealed a diffuse midline glioma, H3K27M-mutant (WHO grade IV), a novel entity in the 2016 WHO classification with poor clinical outcome. Our case shows that the highly aggressive features of this tumor entity can be visualized in vivo by both PET modalities.

Recent immunotherapeutic approaches have evolved as powerful treatment options with high anti-tumour responses involving the patient's own immune system. Passive immunotherapy applies agents that enhance existing anti-tumour responses, such as antibodies against immune checkpoints. Active immunotherapy uses agents that direct the immune system to attack tumour cells by targeting tumour antigens. Active cellular-based therapies are on the rise, most notably chimeric antigen receptor T cell therapy, which redirects patient-derived T cells against tumour antigens. Approved treatments are available for a variety of solid malignancies including melanoma, lung cancer and haematologic diseases. These novel immune-related therapeutic approaches can be accompanied by new patterns of response and progression and immune-related side-effects that challenge established imaging-based response assessment criteria, such as Response Evaluation Criteria in Solid tumours (RECIST) 1.1. Hence, new criteria have been developed. Beyond morphological information of computed tomography (CT) and magnetic resonance imaging, positron emission tomography (PET) emerges as a comprehensive imaging modality by assessing (patho-)physiological processes such as glucose metabolism, which enables more comprehensive response assessment in oncological patients. We review the current concepts of response assessment to immunotherapy with particular emphasis on hybrid imaging with 18 F-FDG-PET/CT and aims at describing future trends of immunotherapy and additional aspects of molecular imaging within the field of immunotherapy.

Background: Extrathyroidal extension of differentiated thyroid cancer is a poor outcome factor but seems to be less significant in minimal extrathyroidal extension (mETE). However, the impact of mETE on response rate after (adjuvant) initial radioactive iodine (RAI) therapy remains unclear. We therefore compared response rates of patients with classical and follicular variants of papillary thyroid cancer (PTC) according to the updated eighth tumor-node-metastasis (TNM) classification to a control group., Methods: 455 patients with T3 (primary tumor > 4 cm) PTC according to the seventh classification who underwent total thyroidectomy followed by RAI therapy were screened. Patients formerly classified as T3 PTC solely due to mETE were reclassified into patients with T1 (primary tumor ≤ 2 cm) or T2 (primary tumor > 2 cm but ≤ 4 cm) +mETE and compared to a control group of T1/T2 -mETE PTC patients., Results: 138/455 patients were reclassified as T1/2 +mETE and compared to 317/455 T1/T2 -mETE control patients. At initial presentation, +mETE patients showed significantly higher rates of cervical lymph node metastases ( p -value 0.001). Response rates were comparable in both groups ( p -value n.s.). N1a/N1b-stage (Hazard ratio, HR 0.716; 95% CI 0.536-0.956, p -value 0.024) was identified as an independent prognostic factor for lower response rates., Conclusion: Response rates after RAI therapy were comparable in PTC patients irrespective of mETE but with higher rates of lymph node metastases.

A 16-year-old male patient underwent 18 F-FDG PET/CT staging after multiple surgical resections and radiotherapy of an uncommon metastatic pediatric sebaceous carcinoma of the parotid gland. Initial PET/CT imaging exhibited a recurrent paravertebral metastasis (C4) as well as a metabolically active tumor tissue at the primary site. Follow-up PET/CT after radiotherapy of the cervical spine (C4) and four cycles of chemotherapy with cisplatin and palbociclib revealed complete functional remission in the cervical spine and partial remission at the primary site. This case illustrates the 18 F-FDG-uptake behavior and the disease course of a very rare malignant epithelial tumor of the salivary glands.

Purpose: Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [ 18 F]PI-2620 as a potential substitute for [ 18 F]fluorodeoxyglucose ([ 18 F]FDG)., Methods: Twenty-six subjects were referred with suspected tauopathies or overlapping parkinsonian syndromes (Alzheimer's disease, progressive supranuclear palsy, corticobasal syndrome, multi-system atrophy, Parkinson's disease, multi-system atrophy, Parkinson's disease, frontotemporal dementia) and received a dynamic [ 18 F]PI-2620 tau-PET (0-60 min p.i.) and static [ 18 F]FDG-PET (30-50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R 1 ) of [ 18 F]PI-2620-PET were correlated with corresponding quantification of [ 18 F]FDG-PET (global mean/cerebellar normalization). Reduced tracer uptake in cortical target regions was also interpreted visually using 3-dimensional stereotactic surface projections by three more and three less experienced readers. Spearman rank correlation coefficients were calculated between early-phase [ 18 F]PI-2620 tau-PET and [ 18 F]FDG-PET images for all cortical regions and frequencies of disagreement between images were compared for both more and less experienced readers., Results: Highest agreement with [ 18 F]FDG-PET quantification was reached for [ 18 F]PI-2620-PET acquisition from 0.5 to 2.5 min p.i. for global mean (lowest R = 0.69) and cerebellar scaling (lowest R = 0.63). Correlation coefficients (summed 0.5-2.5 min SUVr & R 1 ) displayed strong agreement in all cortical target regions for global mean (R SUVr 0.76, R R1  = 0.77) and cerebellar normalization (R SUVr 0.68, R R1  = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and [ 18 F]FDG-PET. There were no relevant differences between more and less experienced readers., Conclusion: Early-phase imaging of [ 18 F]PI-2620 can serve as a surrogate biomarker for neuronal injury. Dynamic imaging or a dual time-point protocol for tau-PET imaging could supersede additional [ 18 F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.

PET targeting the translocator protein (TSPO) expression is an interesting approach to detect neuroinflammation, as TSPO is upregulated in activated macrophages and microglia. Considering the variable pathophysiology of multiple sclerosis (MS) variants, we compare TSPO PET using F-GE-180 in 3 different demyelinating diseases of the central nervous system: relapsing-remitting MS, tumefactive MS, and Baló's concentric sclerosis. Visualization of neuroinflammation and its PET patterns in addition to MRI may contribute to accurate distinction and monitoring of central nervous system demyelination.

Background: Systemic infiltration of the brain by tumor cells is a hallmark of glioma pathogenesis which may cause disturbances in functional connectivity. We hypothesized that aggressive high-grade tumors cause more damage to functional connectivity than low-grade tumors., Methods: We designed an imaging tool based on resting-state functional (f)MRI to individually quantify abnormality of functional connectivity and tested it in a prospective cohort of patients with newly diagnosed glioma., Results: Thirty-four patients were analyzed (World Health Organization [WHO] grade II, n = 13; grade III, n = 6; grade IV, n = 15; mean age, 48.7 y). Connectivity abnormality could be observed not only in the lesioned brain area but also in the contralateral hemisphere with a close correlation between connectivity abnormality and aggressiveness of the tumor as indicated by WHO grade. Isocitrate dehydrogenase 1 (IDH1) mutation status was also associated with abnormal connectivity, with more alterations in IDH1 wildtype tumors independent of tumor size. Finally, deficits in neuropsychological performance were correlated with connectivity abnormality., Conclusion: Here, we suggested an individually applicable resting-state fMRI marker in glioma patients. Analysis of the functional connectome using this marker revealed that abnormalities of functional connectivity could be detected not only adjacent to the visible lesion but also in distant brain tissue, even in the contralesional hemisphere. These changes were associated with tumor biology and cognitive function. The ability of our novel method to capture tumor effects in nonlesional brain suggests a potential clinical value for both individualizing and monitoring glioma therapy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: P301S tau transgenic mice show age-dependent accumulation of neurofibrillary tangles in the brainstem, hippocampus, and neocortex, leading to neuronal loss and cognitive deterioration. However, there is hitherto only sparse documentation of the role of neuroinflammation in tau mouse models. Thus, we analyzed longitudinal microglial activation by small animal 18 kDa translocator protein positron-emission-tomography (TSPO μPET) imaging in vivo, in conjunction with terminal assessment of tau pathology, spatial learning, and cerebral glucose metabolism., Methods: Transgenic P301S (n = 33) and wild-type (n = 18) female mice were imaged by 18 F-GE-180 TSPO μPET at the ages of 1.9, 3.9, and 6.4 months. We conducted behavioral testing in the Morris water maze, 18 F-fluordesoxyglucose ( 18 F-FDG) μPET, and AT8 tau immunohistochemistry at 6.3-6.7 months. Terminal microglial immunohistochemistry served for validation of TSPO μPET results in vivo, applying target regions in the brainstem, cortex, cerebellum, and hippocampus. We compared the results with our historical data in amyloid-β mouse models., Results: TSPO expression in all target regions of P301S mice increased exponentially from 1.9 to 6.4 months, leading to significant differences in the contrasts with wild-type mice at 6.4 months (+ 11-23%, all p < 0.001), but the apparent microgliosis proceeded more slowly than in our experience in amyloid-β mouse models. Spatial learning and glucose metabolism of AT8-positive P301S mice were significantly impaired at 6.3-6.5 months compared to the wild-type group. Longitudinal increases in TSPO expression predicted greater tau accumulation and lesser spatial learning performance at 6.3-6.7 months., Conclusions: Monitoring of TSPO expression as a surrogate of microglial activation in P301S tau transgenic mice by μPET indicates a delayed time course when compared to amyloid-β mouse models. Detrimental associations of microglial activation with outcome parameters are opposite to earlier data in amyloid-β mouse models. The contribution of microglial response to pathology accompanying amyloid-β and tau over-expression merits further investigation.

Background: We aimed to investigate the clinical value of a 3D-T1w turbo-spin-echo (TSE) sequence and [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) for the diagnosis of active large vessel vasculitis (LVV) and single-organ vasculitis (SOV) of the aorta., Methods: Twenty-four patients with suspected vasculitis who underwent MRI and PET/CT were retrospectively evaluated. MRI was analyzed for concentric contrast enhancement and wall thickening, and flow artifact intensity (4-point-scales). PET/CT analysis comprised qualitative, quantitative and semiquantitative methods. Imaging findings were correlated with final diagnosis derived from the clinical follow-up data., Results: Fifteen of 24 patients had a clinically confirmed active vasculitis, two had inactive vasculitis and 7 no vasculitis. [18F]FDG-PET/CT and 3D-T1w TSE-MRI revealed both a high diagnostic accuracy of 88% and 83%, respectively. In patients in whom both PET/CT and MRI showed concordant findings (19 patients), the accuracy increased to 95% with a high positive predictive value (92%) and negative predictive value (100%); thus, a correct diagnosis was obtained in 18 of 19 patients. Among the five patients with discordant findings PET/CT correctly identified the two patients without active vasculitis while rated false positive on MRI. Of the three remaining patients with active vasculitis, two were correctly identified by MRI and one by PET/CT., Conclusions: 3D-T1w TSE-MRI and [18F]FDG-PET/CT are both useful in the diagnosis of active vasculitis with high diagnostic accuracies. The diagnostic accuracy was even optimized by combining the two analysis methods. Therefore, there might be substantial potential for the application of whole-body hybrid PET/MRI in the evaluation of vasculitis in future studies.

Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.

Introduction: PET/CT using 68 Ga-labeled somatostatin analogs (SSA) targeting somatostatin receptors (SSR) on the cell surface of well-differentiated neuroendocrine tumors (NET) represents the clinical reference standard for imaging. However, economic and logistic challenges of the 68 Ge/ 68 Ga generator-based approach have disadvantages over 18 F-labeled compounds. Here, we present the first in-human data of 18 F-SiFAlin-TATE, a novel 18 F-labeled, SSR-targeting peptide. The aim was to compare the intra-individual biodistribution, tumor uptake, and image quality of 18 F-SiFAlin-TATE to the clinical reference standard 68 Ga-DOTA-TOC., Methods: Thirteen patients with NET staged with both 68 Ga-DOTA-TOC and 18 F-SiFAlin-TATE PET/CT have been included in this retrospective analysis. We compared the biodistribution in normal organs and tumor uptake of NET lesions by SUVmean and SUVmax measurement for tracers. Additionally mean and max tumor-to-liver (TLR) and tumor-to-spleen ratios (TSR) have been calculated by division of SUVmean and SUVmax of tumor lesions by the SUVmean of the liver and spleen, respectively. Additionally, image quality was visually rated by 5 blinded readers and an intra-class correlation (ICC) analysis on inter-observer agreement has been performed., Results: Compared with 68 Ga-DOTA-TOC, the biodistribution of 18 F-SiFAlin-TATE showed somewhat higher, however, statistically not significant higher uptake in the liver, spleen, and adrenal glands. Significantly higher uptake was observed in the kidneys. Tumor uptake was higher in most tumor lesions with significantly higher uptake in common metastatic sites of NET including the liver (SUVmax 18.8 ± 8.4 vs. 12.8 ± 5.6; p < 0.001), lymph nodes (SUVmax 23.8 ± 20.7 vs. 17.4 ± 16.1; p < 0.001) and bone (SUVmax 16.0 ± 10.1 vs. 10.3 ± 5.7; p < 0.01) for 18 F-SiFAlin-TATE. The high tumor uptake resulted in favorable TLR and TSR, comparable with that of 68 Ga-DOTA-TOC. The ICC analysis on the inter-observer agreement on image quality was substantial and almost perfect. Image quality was rated as excellent in most cases in both 68 Ga-DOTA-TOC and 18 F-SiFAlin-TATE PET., Conclusion: The favorable characteristics of 18 F-SiFAlin-TATE with a high image quality, the kit-like labeling procedure, and the promising clinical performance enable improved logistics and diagnostic possibilities for PET imaging of NET. Our first clinical results warrant further systematic studies investigating the clinical use of 18 F-SiFAlin-TATE in NET patients.

Background: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood., Objective: We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies., Methods: We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls., Results: There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism., Conclusions: Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

Background and Purpose: 18 F-fluoroethyltyrosine ( 18 F-FET) PET is increasingly used in radiation treatment planning for the primary treatment of glioblastoma (GBM) patients additionally to contrast-enhanced MRI. To answer the question, whether a margin reduction in the primary treatment setting could be achieved through 18 F-FET PET imaging, a recurrence pattern analysis was performed., Patients and Methods: GBM patients undergoing 18 F-FET PET examination before primary radiochemotherapy from 05/2009 to 11/2014 were included into the recurrence pattern analysis. Biological tumour volumes were semi-automatically created and fused with MR-based gross tumour volumes ( MR GTVs). The pattern of recurrence was examined for MR GTVs and for PET-MR GTVs. The minimal margin including all recurrent tumour sites was assessed by gradual expansion of the PET-MR GTVs and MR GTVs until inclusion of all contrast-enhancing areas at recurrence., Results: 36 GBM patients were included to the analysis. The minimal margin including all contrast enhancing tumour at recurrence was significantly smaller for the PET-MR GTVs compared to the MR GTVs (median 12.5 mm vs. 16.5 mm; p < 0.001, Wilcoxon-Test). PET-MR GTVs with 15 mm CTV margins were significantly smaller than MR GTVs with 20 mm CTV margins (median volume 255.92 vs. 258.35 cm 3 ; p = 0.020, Wilcoxon-Test; excluding 3 cases with large non-contrast enhancing tumours). The pattern of recurrence of PET-MR GTVs with 15 mm CTV margins was comparable to MR GTVs with 20 mm CTV margins (32 vs. 30 central, 2 vs. 4 in-field, 2 vs. 2 ex-field and no marginal recurrences)., Conclusion: Target volume delineation of GBM patients can be improved through 18 F-FET PET imaging prior to primary radiation treatment, since vital tumour can be detected more accurately. Furthermore, the results suggest that CTV margins could be reduced through 18 F-FET PET imaging prior to primary RT of GBM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A 66-year-old man with colorectal carcinoma and liver-only metastases underwent radioembolization using Y-loaded, resin-based microspheres. One day after radioembolization, the patient experienced severe hypertension and multiple seizures. On MRI, symmetric edematous areas in the cerebellum and the parietal and occipital lobe were observed, a typical finding for posterior reversible encephalopathy syndrome (PRES). The PRES is associated with, for example, renal failure or blood pressure fluctuations leading to cerebral endothelial dysfunction. Antihypertensive and antiepileptic therapies led to normotensive blood pressure and neurological remission. Therefore, newly developed neurological symptoms accompanied by high blood pressure fluctuations after radioembolization should lead to PRES as differential diagnosis.