68Ga-EMP-100 PET/CT-a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma-first in-human biodistribution and imaging results.

BACKGROUND: 68Ga-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 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. METHODS: Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax 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 SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 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 68Ga-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, 68Ga-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 68Ga-EMP-100 as a biomarker in mRCC patients.

Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic 18F-FET PET.

PURPOSE: According to the updated WHO classification of gliomas with its emphasis on molecular parameters, tumours with an IDH-wildtype status have a dismal prognosis. To ensure timely adjustment of treatment, demand for non-invasive prediction methods is high. 18F-FET PET has been shown to be an important diagnostic tool for glioma management. The aim of this study was to assess the value of dynamic 18F-FET PET for the non-invasive prediction of the IDH-mutation status. METHODS: Newly diagnosed WHO grade II-IV glioma patients with MRI and dynamic 18F-FET PET were included. The 18F-FET PET parameters mean and maximal tumour-to-background ratio (TBRmean, TBRmax) and minimal time-to-peak (TTPmin) were evaluated. The diagnostic power for the prediction of the IDH genotype (positive/negative predictive value) was tested in the overall study group and in the subgroup of non-contrast enhancing gliomas. RESULTS: Three hundred forty-one patients were evaluated. Molecular analyses revealed 178 IDH-mutant and 163 IDH-wildtype tumours. Overall, 270/341 gliomas were classified as 18F-FET-positive (TBRmax > 1.6), 90.2% of the IDH-wildtype and 69.1% of IDH-mutant gliomas. Median TBRmax was significantly higher in IDH-wildtype compared with IDH-mutant gliomas (2.9 vs. 2.3, p < 0.001); however, ROC-analyses revealed no reliable cutoff due to a high overlap (range 1.0-7.1 vs. 1.1-7.9). Dynamic analysis revealed a significantly shorter TTPmin in IDH-wildtype gliomas; using TTPmin ≤ 12.5 min as indicator for IDH-wildtype gliomas, a positive predictive value of 87% was reached (negative predictive value 72%, AUC = 0.796, p ≤ 0.001). A total of 161/341 gliomas did not show contrast enhancement on MRI; even within this subgroup, TTPmin ≤ 12.5 min remained a good predictor of IDH-wildtype glioma (positive predictive value 83%, negative predictive value 90%; AUC = 0.868, p < 0.001). CONCLUSION: A short TTPmin in dynamic 18F-FET PET serves as good predictor of highly aggressive IDH-wildtype status in gliomas. In particular, a high diagnostic power was observed in the subgroup of non-contrast enhancing gliomas, which helps to identify patients with worse prognosis.

Noradrenaline transporter availability on [11C]MRB PET predicts weight loss success in highly obese adults.

PURPOSE: Although the mechanisms by which the central noradrenaline (NA) system influences appetite and controls energy balance are quite well understood, its relationship to changes in body weight remains largely unknown. The main goal of this study was to further clarify whether the brain NA system is a stable trait or whether it can be altered by dietary intervention. METHODS: We aimed to compare central NA transporter (NAT) availability in ten obese, otherwise healthy individuals with a body mass index (BMI) of 42.4 ± 3.7 kg/m2 (age 34 ± 9 years, four women) and ten matched non-obese, healthy controls (BMI 23.9 ± 2.5 kg/m2, age 33 ± 10 years, four women) who underwent PET with the NAT-selective radiotracer (S,S)-[11C]O-methylreboxetine (MRB) before and 6 months after dietary intervention. RESULTS: MRI-based individual volume-of-interest analyses revealed an increase in binding potential (BPND) in the insula and the hippocampus of obese individuals, which correlated well with changes in BMI (-3.3 ± 5.3%; p = 0.03) following completion of the dietary intervention. Furthermore, voxel-wise regression analyses showed that lower BPND in these regions, but also in the midbrain and the prefrontal cortex, at baseline was associated with higher achieved weight loss (e.g., hippocampal area R2 = 0.80; p < 0.0001). No changes were observed in non-obese controls. CONCLUSION: These first longitudinal interventional data on NAT availability in highly obese individuals indicate that the central NA system is modifiable. Our findings suggest that NAT availability before intervention could help predict the amount and success of weight loss in obese individuals and help adjust treatment options individually by allowing prediction of the benefit of a dietary intervention.

L-type amino acid transporter (LAT) 1 expression in 18F-FET-negative gliomas.

BACKGROUND: O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-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 18F-FET uptake at primary diagnosis ("18F-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 18F-FET-negative gliomas and to compare them to a matched group of 18F-FET-positive gliomas. Forty newly diagnosed IDH-mutant astrocytomas without 1p/19q codeletion were evaluated (n = 20 18F-FET-negative (tumour-to-background ratio (TBR) < 1.6), n = 20 18F-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, 18F-FET-positive as well as 18F-FET-negative gliomas. No differences were found between the 18F-FET-negative and 18F-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 TBRmax, neither in the overall group nor in the 18F-FET-positive group only (p = 0.651 and p = 0.140). CONCLUSION: Although LAT1 is reported to mediate the uptake of 18F-FET into tumour cells, the levels of LAT1 expression do not correlate with the levels of 18F-FET uptake in IDH-mutant astrocytomas. In particular, the lack of tracer uptake in 18F-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 18F-FET are necessary.

Impact of TSPO Receptor Polymorphism on [18F]GE-180 Binding in Healthy Brain and Pseudo-Reference Regions of Neurooncological and Neurodegenerative Disorders.

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 [18F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [18F]GE-180 binding in a healthy brain and in pseudo-reference tissue in neuro-oncological and neurodegenerative diseases. Standardized uptake values (SUVs) of [18F]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 [18F]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.

Simpson Grade Revisited - Intraoperative Estimation of the Extent of Resection in Meningiomas Versus Postoperative Somatostatin Receptor Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging.

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.

Dual PET Imaging of an H3K27M-Mutant Glioma With 18F-GE-180 and 18F-FET PET.

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.

Whole-Body Staging of Metastatic Atypical Meningioma Using 68Ga-DOTATATE PET/CT.

A 43-year-old woman with suspected recurrence of atypical meningioma World Health Organization grade II presented extensive intracranial lesions with high Ga-DOTATATE uptake. Moreover, numerous Ga-DOTATATE-positive bone, lung, and liver lesions were seen. For final diagnosis, biopsies taken from a lung lesion revealed distant metastases of the atypical meningioma. This case underlines the high diagnostic power of Ga-DOTATATE PET/CT for the staging of meningioma even beyond cerebral or spinal lesions; in case of distant lesions in patients with known meningioma, differential diagnosis should also contain metastases despite their rare occurrence. Moreover, this case emphasizes radioligand therapy especially in metastatic meningioma.

68Ga-DOTATOC PET/CT Differentiates Meningioma From Dural Metastases.

A 77-year-old woman with history of breast cancer presented with 2 unclear dural contrast-enhancing lesions on MRI; differential diagnoses were breast cancer metastases and meningiomas. On Ga-DOTATOC PET/CT, the temporal lesion showed high uptake and was classified as meningioma, whereas the lesion at the falx showed barely any Ga-DOTATOC uptake uncharacteristic for meningioma and suggestive for a brain metastasis. After resection, histological specimens from the temporal lesion showed meningioma tissue with distinct SSTR2A expression, whereas the falx lesion revealed a breast cancer metastasis without significant SSTR2A expression. Therefore, Ga-DOTATOC PET represents a powerful imaging modality for the evaluation of unclear dural lesions.

Photopenic defects on O-(2-[18F]-fluoroethyl)-L-tyrosine PET: clinical relevance in glioma patients.

BACKGROUND: O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET has a sensitivity of more than 90% to detect gliomas. In the remaining small fraction of gliomas without increased tracer uptake, some tumors even show photopenic defects whose clinical significance is unclear. METHODS: Glioma patients with a negative FET PET scan prior to neuropathological confirmation were identified retrospectively. Gliomas were rated visually as (i) having indifferent FET uptake or (ii) photopenic, if FET uptake was below background activity. FET uptake in the area of signal hyperintensity on the T2/fluid attenuated inversion recovery-weighted MRI was evaluated by mean standardized uptake value (SUV) and mean tumor-to-brain ratio (TBR). The progression-free survival (PFS) of photopenic gliomas was compared with that of gliomas with indifferent FET uptake. RESULTS: Of 100 FET-negative gliomas, 40 cases with photopenic defects were identified. Fifteen of these 40 cases (38%) had World Health Organization (WHO) grades III and IV gliomas. FET uptake in photopenic gliomas was significantly decreased compared with both the healthy-appearing brain tissue (SUV, 0.89 ± 0.26 vs 1.08 ± 0.23; P < 0.001) and gliomas with indifferent FET uptake (TBR, 0.82 ± 0.09 vs 0.96 ± 0.13; P < 0.001). Irrespective of the applied treatment, isocitrate dehydrogenase (IDH)-mutated WHO grade II diffuse astrocytoma patients with indifferent FET uptake (n = 25) had a significantly longer PFS than patients with IDH-mutated diffuse astrocytomas (WHO grade II) with photopenic defects (n = 11) (51 vs 24 mo; P = 0.027). The multivariate survival analysis indicated that photopenic defects predict an unfavorable PFS (P = 0.009). CONCLUSION: Photopenic gliomas in negative FET PET scans should be managed more actively, as they seem to have a higher risk of harboring a higher-grade glioma and an unfavorable outcome.

Neurosarcoidosis Mimics High-Grade Glioma in Dynamic 18F-FET PET Due to LAT Expression.

We present a 45-year-old man with newly generalized tonic-clonic seizures due to a contrast-enhancing frontal lesion with perifocal edema suggestive for high-grade glioma (HGG). For further evaluation, a dynamic F-FET PET scan was performed, which showed high F-FET-uptake with early peak and constantly decreasing time-activity curves, a characteristic feature of HGG. Stereotactic biopsy and histological evaluation excluded a neoplastic lesion but confirmed a manifestation of neurosarcoidosis with strong expression of the L-amino-acid-transporter considered responsible for F-FET-uptake. Therefore, unknown manifestations of neurosarcoidosis represent a clinical pitfall in F-FET PET and can mimic HGG.

Relationship Between Body Mass Index, ApoE4 Status, and PET-Based Amyloid and Neurodegeneration Markers in Amyloid-Positive Subjects with Normal Cognition or Mild Cognitive Impairment.

Body weight loss in late-life is known to occur at a very early stage of Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-ß (Aß) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 Aß-positive cognitively healthy or mild cognitive impaired subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations. Composite cortical [18F]-AV45 uptake and [18F]-FDG uptake in posterior cingulate cortex were calculated as surrogates of cortical Aß load and glucose metabolism, respectively. Multiple linear regressions were performed to assess the relationships between these PET biomarkers with BMI, present cognitive performance, and cognitive changes over time. Multivariate analysis of covariance was conducted to test for statistical differences between ApoE4/BMI categories on the PET markers and cognitive scores. In carriers of the ApoE4 allele only, BMI was inversely associated with cortical amlyoid load (ß= -0.193, p < 0.005) and recent cognitive decline (ß= -0.209, p < 0.05), and positively associated with cortical glucose metabolism in an AD-vulnerable region (ß= 0.145, p < 0.05). ApoE4/BMI category analyses demonstrated lower Aß load, higher posterior cingulate glucose metabolism, improved cognitive performance, and lower progression of cognitive decline in obese ApoE4 carriers. The effect of ApoE4 in promoting the accumulation of cortical amyoid, which may itself be a driver for weight loss, may be moderated by altering leptin signaling in the hypothalamus.

Characterization of Diffuse Gliomas With Histone H3-G34 Mutation by MRI and Dynamic 18F-FET PET.

BACKGROUND: Recent data suggest that diffuse gliomas carrying mutations in codon 34 of the H3 histone family 3A protein represent a very rare, distinct subgroup of IDH-wild type malignant astrocytic gliomas. However, characteristics detectable by MRI and F-FET PET in H3-G34-mutant gliomas are unknown. METHODS: We report on MRI and F-FET PET findings in 8 patients from 4 German centers with H3-G34-mutant diffuse gliomas. MRI analyses included multifocality, contrast enhancement, necrosis, cysts, hemorrhages, calcification, and edema. F-FET PET characteristics were evaluated on the basis of static F-FET PET parameters, such as maximal tumor-to-background ratio (TBRmax) and biological tumor volume (BTV), as well as the minimal time-to-peak (TTPmin) obtained from dynamic F-FET PET data. RESULTS: MRI showed multifocal lesions in 2 of 8, contrast enhancement in 6 of 8, necrosis in 3 of 8, cysts in 3 of 8, hemorrhage in 1 of 8, and calcifications in 1 of 8 patients. None of the tumors showed marked peritumoral edema. However, all 8 H3-G34-mutant gliomas were characterized by a high uptake intensity on F-FET PET with a median TBRmax of 3.4 (range, 2.5-11.7) and a relatively diffuse uptake pattern leading to a large BTV (median, 41.9 mL; range, 7.5-115.6). Dynamic PET data revealed a short median TTPmin of 12.5 minutes. CONCLUSIONS: MRI features of diffuse gliomas with H3-G34 mutation may present very heterogeneously with some cases not even fulfilling the imaging criteria of high-grade glioma. In contrast, in F-FET PET, these tumors show an extensive and diffuse tracer uptake resulting in large BTV with a high TBRmax and a short TTPmin, thus resembling PET characteristics of aggressive high-grade gliomas, namely, glioblastomas.

Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment?

BACKGROUND: PET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18F-FET PET reading. The background activity of 20 18F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans. RESULTS: Compared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more. CONCLUSIONS: The commonly applied methods for background activity assessment show different variability which might hamper 18F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.

Improved Detection of Transosseous Meningiomas Using 68Ga-DOTATATE PET/CT Compared with Contrast-Enhanced MRI.

68Ga-DOTATATE PET/CT enables detection of meningioma tissue based on somatostatin receptor 2 expression. Transosseous extension of intracranial meningiomas is known to be an important risk factor for tumor recurrence and patient mortality. We analyzed the diagnostic performance of 68Ga-DOTATATE PET/CT and contrast-enhanced MRI (CE-MRI) for the detection of osseous infiltration using qualitative and quantitative imaging parameters. Methods: In this institutional review board-approved retrospective study, subjects were selected from 327 consecutive 68Ga-DOTATATE PET/CT examinations for evaluation of confirmed or suspected meningioma. Inclusion criteria were CE-MRI within 30 d and pathology-confirmed meningioma diagnosis with inclusion or exclusion of transosseous extension as the standard of reference. Imaging was analyzed by two readers. Tracer uptake values and meningioma volumes were determined. χ2, Mann-Whitney U, Wilcoxon signed rank, and McNemar tests, as well as receiver-operating-characteristic analyses, were performed to compare variables and diagnostic performance. Results: Eighty-two patients fulfilled the inclusion criteria. Patients with transosseous extension of meningioma (n = 67) showed significantly larger lesions (median, 12.8 vs. 3.3 mL; P < 0.001) and significantly higher tracer uptake values (median SUVmax, 14.2 vs. 7.6; P = 0.011) than patients with extraosseous meningiomas (n = 15). 68Ga-DOTATATE PET/CT in comparison to CE-MRI performed at a higher sensitivity (98.5% vs. 53.7%) while maintaining high specificity (86.7% vs. 93.3%) in the detection of osseous involvement (P < 0.001). In receiver-operating-characteristic analysis, PET/CT assessment performed better than CE-MRI (area under the curve, 0.932 vs. 0.773). PET/CT- and CE-MRI-based volume estimation yielded comparable results for extraosseous meningiomas (P = 0.132) and the extraosseous part of transosseous meningiomas (P = 0.636), whereas the volume of the intraosseous part was assessed as significantly larger by PET/CT (P < 0.001). Conclusion:68Ga-DOTATATE PET/CT enables improved detection of the transosseous extension of intracranial meningiomas compared with CE-MRI.

[18F]-THK5351 PET Correlates with Topology and Symptom Severity in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder characterized by deposition of fibrillar aggregates of 4R tau-protein in neurons and glial cells of the brain. These deposits are a key neuropathological finding, allowing a diagnosis of "definite PSP," which is usually established post mortem. To date criteria for clinical diagnosis of PSP in vivo do not include biomarkers of tau pathology. For intervention trials, it is increasingly important to (i) establish biomarkers for an early diagnosis and (ii) to develop biomarkers that correlate with disease progression of PSP. [18F]-THK5351 is a novel PET-ligand that may afford in vivo visualization and quantification of tau-related alterations. We investigated binding characteristics of [18F]-THK5351 in patients with clinically diagnosed PSP and correlate tracer uptake with clinical findings. Eleven patients (68.4 ± 7.4 year; N = 6 female) with probable PSP according to current clinical criteria and nine healthy controls (71.7 ± 7.2 year; N = 4 female) underwent [18F]-THK5351 PET scanning. Voxel-wise statistical parametric comparison and volume-of-interest based quantification of standardized-uptake-values (SUV) were conducted using the cerebellar cortex as reference region. We correlated disease severity as measured with the help of the PSP Rating Scale (PSPRS) as well as several other clinical parameters with the individual PET findings. By voxel-wise mapping of [18F]-THK5351 uptake in the patient group we delineated typical distribution patterns that fit to known tau topology for PSP post mortem. Quantitative analysis indicated the strongest discrimination between PSP patients and healthy controls based on tracer uptake in the midbrain (+35%; p = 3.01E-7; Cohen's d: 4.0), followed by the globus pallidus, frontal cortex, and medulla oblongata. Midbrain [18F]-THK5351 uptake correlated well with clinical severity as measured by PSPRS (R = 0.66; p = 0.026). OCT and MRI delineated PSP patients from healthy controls by use of established discrimination thresholds but only OCT did as well correlate with clinical severity (R = 0.79; p = 0.024). Regional [18F]-THK5351 binding patterns correlated well with the established post mortem distribution of lesions in PSP and with clinical severity. The contribution of possible MAO-B binding to the [18F]-THK5351 signal needs to be further evaluated, but nevertheless [18F]-THK5351 PET may still serve as valuable biomarker for diagnosis of PSP.