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Simple Summary: Amino acid positron emission tomography (PET) complements standard magnetic resonance imaging (MRI) since it directly visualizes the increased amino acid transport into tumor cells. Amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) has proven to be relevant, for example, for glioma classification, identification of tumor progression or recurrence, or for the delineation of tumor extent. Nevertheless, a relevant proportion of low-grade gliomas (30%) and few high-grade gliomas (5%) were found to show no or even decreased amino acid uptake by conventional visual analysis of PET images. Advanced image analysis with the extraction of radiomic features is known to provide more detailed information on tumor characteristics than conventional analyses. Hence, this study aimed to investigate whether radiomic features derived from dynamic [18F]FET PET data differ between [18F]FET-negative glioma and healthy background and thus provide information that cannot be extracted by visual read. The purpose of this study was to evaluate the possibility of extracting relevant information from radiomic features even in apparently [18F]FET-negative gliomas. A total of 46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [18F]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [18F]FET PET data, i.e., early and late tumor-to-background (TBR5–15, TBR20–40) and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume of interest mirrored in the contralateral hemisphere. The ability to distinguish tumors from healthy tissue was assessed using the Wilcoxon test and logistic regression. A total of 5, 15, and 69% of features derived from TBR20–40, TBR5–15, and TTP images, respectively, were significantly different. A high number of significantly different TTP features was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [18F]FET uptake in static images. However, the differences did not reach satisfactory predictability for machine-learning-based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [18F]FET PET data may extract additional information even in [18F]FET-negative gliomas, which should be investigated in larger cohorts and correlated with histological and outcome features in future studies. [ABSTRACT FROM AUTHOR]

Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing role in mCRPC patients. Hence, we aimed to assess TTV and its changes during 225Ac-PSMA-I&T RLT. Methods: mCRPC patients undergoing RLT with 225Ac-PSMA-I&T with available 18F-PSMA-1007 PET/CT prior to therapy initiation were included. TTV was assessed in all patients using established cut-off values. Image derived, clinical and biochemistry parameters (PSA, LDH, AP, pain score) were analyzed prior to and after two cycles of 225Ac-PSMA. Changes in TTV and further parameters were directly compared and then correlated with established response criteria, such as RECIST 1.1 or mPERCIST. Results: 13 mCRPC patients were included. The median overall survival (OS) was 10 months. Prior to 225Ac-PSMA RLT, there was no significant correlation between TTV with other clinical parameters (p > 0.05 each). Between short-term survivors (STS, <10 months OS) and long-term survivors (LTS, ≥10 months OS), TTV and PSA were comparable (p = 0.592 & p = 0.286, respectively), whereas AP was significantly lower in the LTS (p = 0.029). A total of 7/13 patients completed two cycles and underwent a follow-up 18F-PSMA-1007 PET/CT. Among these patients, there was a significant decrease in TTV (median 835 vs. 201 mL, p = 0.028) and PSA (median 687 ng/dL vs. 178 ng/dL, p = 0.018) after two cycles of 225Ac-PSMA RLT. Here, percentage changes of TTV after two cycles showed no direct correlation to all other clinical parameters (p > 0.05 each). In two patients, new PET-avid lesions were detected on 18F-PSMA-1007 PET/CT. However, TTV and PSA were decreasing or stable. Conclusion: PET-derived assessment of TTV is an easily applicable imaging biomarker independent of other established parameters prior to 225Ac-PSMA RLT in these preliminary follow-up data. Even after the failure of 177Lu-PSMA, patients with extensive TTV seem to profit from RLT. All but one patient who was eligible for ≥2 cycles of 225Ac-PSMA-RLT demonstrated drastic TTV decreases without direct correlation to other biomarkers, such as serum PSA changes. Changes in TTV might hence improve the response assessment compared to standard classifiers by reflecting the current tumor load independent of the occurrence of new lesions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [18F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [18F]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 [18F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study retrospectively analyzed the performance of artificial neural networks (ANN) to predict overall survival (OS) or locoregional failure (LRF) in HNSCC patients undergoing radiotherapy, based on 2-[18F]FDG PET/CT and clinical covariates. We compared predictions relying on three different sets of features, extracted from 230 patients. Specifically, (i) an automated feature selection method independent of expert rating was compared with (ii) clinical variables with proven influence on OS or LRF and (iii) clinical data plus expert-selected SUV metrics. The three sets were given as input to an artificial neural network for outcome prediction, evaluated by Harrell's concordance index (HCI) and by testing stratification capability. For OS and LRF, the best performance was achieved with expert-based PET-features (0.71 HCI) and clinical variables (0.70 HCI), respectively. For OS stratification, all three feature sets were significant, whereas for LRF only expert-based PET-features successfully classified low vs. high-risk patients. Based on 2-[18F]FDG PET/CT features, stratification into risk groups using ANN for OS and LRF is possible. Differences in the results for different feature sets confirm the relevance of feature selection, and the key importance of expert knowledge vs. automated selection. [ABSTRACT FROM AUTHOR]

Simple Summary: IDH-wildtype (IDHwt) gliomas represent a tumor entity with poor overall survival. Only rare cases have an overall survival over several years. Dynamic and static 18F-FET PET is recommended as valuable complementary tool for glioma imaging in gliomas. This study shows that, besides molecular genetic prognosticators, long survival (≥36 months survival) in IDHwt gliomas is associated with a longer time-to-peak and smaller volume on 18F-FET PET at initial diagnosis compared to glioma patients with a short-term survival (≤15 months survival). 18F-FET uptake intensity and MRI-derived tumor size do not differ in patients with long-term survival compared to patient with a short-term survival. 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 18F-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 18F-FET PET prior to any therapy were stratified into LTS (≥36 months survival) and STS (≤15 months survival). Static and dynamic 18F-FET PET parameters (mean/maximal tumor-to-background ratio (TBRmean/max), biological tumor volume (BTV), minimal time-to-peak (TTPmin)), 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 TTPmin (p = 0.008) on 18F-FET PET than STS, while uptake intensity (TBRmean/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 TTPmin as well as a smaller BTV on 18F-FET PET at initial diagnosis. 18F-FET uptake intensity as well as the MRI-derived tumor size (volume and maximal diameter) do not differ in patients with long-term survival. [ABSTRACT FROM AUTHOR]

A 16-year-old male patient underwent 18F-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 18F-FDG-uptake behavior and the disease course of a very rare malignant epithelial tumor of the salivary glands. [ABSTRACT FROM AUTHOR]

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.

This review provides an overview of current applications and perspectives of PET imaging in neuro-oncological surgery. The past and future of PET imaging in the management of patients with glioma and brain metastases are elucidated with an emphasis on amino acid tracers, such as O -(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET). The thematic scope includes surgical resection planning, prognostication, non-invasive prediction of molecular tumor characteristics, depiction of intratumoral heterogeneity, response assessment, differentiation between tumor progression and treatment-related changes, and emerging new tracers. Furthermore, the role of PET using specific somatostatin receptor ligands for the management of patients with meningioma is discussed. Further advances in neuro-oncological imaging can be expected from promising new techniques, such as hybrid PET/MR scanners and the implementation of artificial intelligence methods, such as radiomics.