Preoperative Imaging with [F-18]-Fluorocholine PET/CT in Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. F-18-Fluorocholine positron emission tomography/computed tomography (F-18-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received F-18-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes F-18-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of F-18-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of F-18-FCH PET/CT for successful surgical guidance

Lymphoma tumor burden before chimeric antigen receptor T-Cell treatment: RECIL vs. Lugano vs. metabolic tumor assessment

Purpose: High tumor burden has emerged as a negative predictor of efficacy in chimeric antigen receptor T-cell therapy (CART) in patients with refractory or relapsed large B-cell lymphoma. This study analyzed the deviation among imaging-based tumor burden (TB) metrics and their association with progression-free (PFS) and overall survival (OS). Materials and methods: In this single-center observational study, we included all consecutively treated patients receiving CD19 CART with available baseline PET-CT imaging. Imaging-based TB was determined based on response evaluation criteria in lymphoma (RECIL), the Lugano criteria, and metabolic tumor volume. Total, nodal and extranodal TB were represented, according to the respective criteria, by sum of longest diameters (TBRECIL), sum of product of perpendicular diameters (TBLugano), and metabolic tumor volume (TBMTV). Correlation statistics were used for comparison. Proportional Cox regression analysis studied the association of TB metrics with PFS and OS. Results: 34 consecutive patients were included (median age: 67 years, 41% female) with total median baseline TBRECIL of 12.5 cm, TBLugano of 4,030 mm2 and TBMTV of 330 mL. The correlation of TBRECIL and TBLugano with TBMTV was strong (ρ=0.744, p50% (HR=2.915, p=0.042), whereas total TBRECIL>50% and total TBLugano>50% were not significant (both p>0.05). None of the total TB metrics were associated with OS (all p>0.05). Conclusion: Pre-CART TB metrics vary significantly based on the assessment method, impacting their association with survival outcomes. The correlation between TBRECIL, TBLugano and TBMTV was influenced by disease phenotype and prior bridging therapy. TB method of assessment must be considered when interpreting the impact of TB on outcomes in clinical trials. Considering the heterogeneity, our results argue for standardization and harmonization across centers

Impact of Partial Volume Correction on [18F]GE-180 PET Quantification in Subcortical Brain Regions of Patients with Corticobasal Syndrome.

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

Staging of lymphoma under chimeric antigen receptor T-cell therapy: reasons for discordance among imaging response criteria

Abstract Background Chimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with refractory or relapsed lymphoma. Discrepancies among different response criteria for lymphoma under CART were recently shown. Our objective was to evaluate reasons for discordance among different response criteria and their relation to overall survival. Methods Consecutive patients with baseline and follow-up imaging at 30 (FU1) and 90 days (FU2) after CART were included. Overall response was determined based on Lugano, Cheson, response evaluation criteria in lymphoma (RECIL) and lymphoma response to immunomodulatory therapy criteria (LYRIC). Overall response rate (ORR) and rates of progressive disease (PD) were determined. For each criterion reasons for PD were analyzed in detail. Results 41 patients were included. ORR was 68%, 68%, 63%, and 68% at FU2 by Lugano, Cheson, RECIL, and LYRIC, respectively. PD rates differed among criteria with 32% by Lugano, 27% by Cheson, 17% by RECIL, and 17% by LYRIC. Dominant reasons for PD according to Lugano were target lesion (TL) progression (84.6%), new appearing lesions (NL; 53.8%), non-TL progression (27.3%), and progressive metabolic disease (PMD; 15.4%). Deviations among the criteria for defining PD were largely explained by PMD of preexisting lesions that are defined as PD only by Lugano and non-TL progression, which is not defined as PD by RECIL and in some cases classified as indeterminate response by LYRIC. Conclusions Following CART, lymphoma response criteria show differences in imaging endpoints, especially in defining PD. The response criteria must be considered when interpreting imaging endpoints and outcomes from clinical trials

Modification of Lugano criteria by pre-infusion tumor kinetics improves early survival prediction for patients with lymphoma under chimeric antigen receptor T-cell therapy

Background Chimeric antigen receptor T-cell therapy (CART) is effective for patients with refractory or relapsed lymphoma with prolongation of survival. We aimed to improve the prediction of Lugano criteria for overall survival (OS) at 30-day follow-up (FU1) by including the pre-infusion tumor growth rate (TGRpre-BL) and its early change to 30-day FU1 imaging (TGRpost-BL).Methods Consecutive patients with pre-baseline (pre-BL), baseline (BL) and FU1 imaging with CT or positron emission tomography/CT before CART were included. TGR was defined as change of Lugano criteria-based tumor burden between pre-BL, BL and FU1 examinations in relation to days between imaging examinations. Overall response and progression-free survival were determined based on Lugano criteria. Proportional Cox regression analysis studied association of TGR with OS. For survival analysis, OS was analyzed using Kaplan-Meier survival curves.Results Fifty-nine out of 81 patients met the inclusion criteria. At 30-day FU1 8 patients (13.6%) had a complete response (CR), 25 patients (42.4%) a partial response (PR), 15 patients (25.4%) a stable disease (SD), and 11 patients (18.6%) a progressive disease (PD) according to CT-based Lugano criteria. The median TGRpre-BL was −0.6 mm2/day, 24.4 mm2/day, −5.1 mm2/day, and 18.6 mm2/day and the median TGRpost-BL was −16.7 mm2/day, −102.0 mm2/day, −19.8 mm2/day and 8.5 mm2/day in CR, PR, SD, and PD patients, respectively. PD patients could be subclassified into a cohort with an increase in TGR (7 of 11 patients (64%), PD TGRpre-to-post-BL INCR) and a cohort with a decrease in TGR (4 of 11 patients (36%), PD TGRpre-to-post-BL DECR) from pre-BL to post-BL. PD TGRpre-to-post-BL DECR patients exhibited similar OS to patients classified as SD, while PD TGRpre-to-post-BL INCR patients had significantly shorter OS (65 days vs 471 days, p<0.001).Conclusion In the context of CART, the additional use of TGRpre-BL and its change to TGRpost-BL determined at 30-day FU1 showed better OS prognostication for patients with overall PD according to Lugano criteria. Therefore, this modification of the Lugano classification should be explored as a potential novel imaging biomarker of early response and should be validated prospectively in future studies

Central Serotonin/Noradrenaline Transporter Availability and Treatment Success in Patients with Obesity

Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [11C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [11C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m2) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes

Differential Spatial Distribution of TSPO or Amino Acid PET Signal and MRI Contrast Enhancement in Gliomas

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 [18F]GE180 and the amino acid [18F]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

TSPO PET signal using [F-18]GE180 is associated with survival in recurrent gliomas

Purpose Glioma patients, especially recurrent glioma, suffer from a poor prognosis. While advances to classify glioma on a molecular level improved prognostication at initial diagnosis, markers to prognosticate survival in the recurrent situation are still needed. As 18 kDa translocator protein (TSPO) was previously reported to be associated with aggressive histopathological glioma features, we correlated the TSPO positron emission tomography (PET) signal using [F-18]GE180 in a large cohort of recurrent glioma patients with their clinical outcome. Methods In patients with [F-18]GE180 PET at glioma recurrence, [F-18]GE180 PET parameters (e.g., SUVmax) as well as other imaging features (e.g., MRI volume, [F-18]FET PET parameters when available) were evaluated together with patient characteristics (age, sex, Karnofsky-Performance score) and neuropathological features (e.g. WHO 2021 grade, IDH-mutation status). Uni- and multivariate Cox regression and Kaplan-Meier survival analyses were performed to identify prognostic factors for post-recurrence survival (PRS) and time to treatment failure (TTF). Results Eighty-eight consecutive patients were evaluated. TSPO tracer uptake correlated with tumor grade at recurrence (p < 0.05), with no significant differences in IDH-wild-type versus IDH-mutant tumors. Within the subgroup of IDH-mutant glioma (n = 46), patients with low SUVmax (median split, <= 1.60) had a significantly longer PRS (median 41.6 vs. 25.3 months, p = 0.031) and TTF (32.2 vs 8.7 months, p = 0.001). Also among IDH-wild-type glioblastoma (n = 42), patients with low SUVmax (<= 1.89) had a significantly longer PRS (median not reached vs 8.2 months, p = 0.002). SUVmax remained an independent prognostic factor for PRS in the multivariate analysis including CNS WHO 2021 grade, IDH status, and age. Tumor volume defined by [F-18]FET PET or contrast-enhanced MRI correlated weakly with TSPO tracer uptake. Treatment regimen did not differ among the median split subgroups. Conclusion Our data suggest that TSPO PET using [F-18]GE180 can help to prognosticate recurrent glioma patients even among homogeneous molecular subgroups and may therefore serve as valuable non-invasive biomarker for individualized patient management