The role of [18F]F-DOPA PET/CT in diagnostic and prognostic assessment of medullary thyroid cancer: a 15-year experience with 109 patients.

Objective: Correct diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial to treat patients. The purpose of this study was to evaluate the diagnostic and prognostic value of [18F]F-DOPA PET/CT in patients with MTC. Methods: We reviewed MTC patients who underwent [18F]F-DOPA PET/CT from June 2008 to November 2023. Clinical characteristics, follow-up data, and the following [18F]F-DOPA PET/CT parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and SUVmean of multiple organs. The diagnostic value of PET/CT for the detection of tumor lesions was calculated. Serum basal calcitonin (bCt) and stimulated calcitonin (sCt) were determined. Receiver operating characteristics, Kaplan-Meier, and Cox regression analyses were performed. Results: In total, 109 patients (50 women, 59 men; average age, 55 ± 14 years) were included in the analysis. The patient-related sensitivity, specificity, and accuracy of [18F]F-DOPA PET/CT were 95%, 93%, and 94%, respectively. The lesion-related sensitivity, specificity, and accuracy were 65%, 99%, and 72%, respectively. The optimal cutoff values of bCt, sCt, and CEA to obtain positive [18F]F-DOPA PET/CT results were 64 pg/mL, 1808 pg/mL, and 4 µg/L, respectively. Patients with negative [18F]F-DOPA PET/CT had longer overall survival than patients with positive [18F]F-DOPA PET/CT results (P = 0.017). Significant positive correlations were found between bCt, sCt, and CEA with SUVmax, SUVmean, and MTV of [18F]F-DOPA PET/CT (P < 0.001). [18F]F-DOPA PET/CT results and MTV may be useful for the evaluation of the prognosis of patients with recurrent MTC, while age and MTV were independent prognostic factors in patients with primary MTC. For all patients, SUVmean of the left kidney, liver, aorta, and pancreas might be used to independently predict OS. Conclusion: [18F]F-DOPA PET/CT had great value for diagnosis and prognostic assessment in patients with MTC. The DOPA PET/CT parameter SUVmean and MTV showed significant association with OS.

In vivo assessment of safety, biodistribution, and radiation dosimetry of the [18F]Me4FDG PET-radiotracer in adults.

BACKGROUND: Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [18F] labeled alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside ([18F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.4 ± 0.1) MBq/kg (range: 2.3-2.5 MBq/kg) administered activity. The PET/CT scans were conducted in 5 separate sessions, blood pressure and temperature were measured, and blood and urine samples were collected before the scans and one hour after injection to assess toxicity. Measurements of [18F]Me4FDG radioactivity in organs of interest were determined from the PET/CT scans at 5 time points. Internal dosimetry was performed on voxel level using a fast Monte Carlo approach. RESULTS: All studied volunteers could well tolerate the [18F]Me4FDG and no adverse event was reported. The calculated effective dose was (0.013 ± 0.003) mSv/MBq. The organs with the highest absorbed dose were the kidneys with 0.05 mSv/MBq per kidney. The brain showed almost no uptake. After 60 min, (12 ± 15) % of the administered dose was excreted into the bladder. CONCLUSION: Featuring an effective dose of only 0.013 ± 0.003 mSv/MBq and no occurrence of side effects, the glucose analogue [18F]Me4FDG seems to be a safe radio-tracer with a favorable biodistribution for PET imaging and also within several consecutive scans. TRIAL REGISTRATION NUMBER: NCT03557138, Registered 22 February 2017, https://ichgcp.net/clinical-trials-registry/NCT03557138 .

FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study.

Background: Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using 68Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT). Methods: In this prospective observational pilot study, consecutive patients with IIM and participants without rheumatic conditions or ILD serving as a control group were recruited at the Medical University of Vienna, Austria, and underwent FAPi PET/CT imaging. Standard-of-care procedures including clinical examination, assessment of severity of dyspnoea, high-resolution computed tomography (HR-CT), and pulmonary function testing (PFT) were performed on all patients with IIM at baseline and for patients with IIM-ILD at follow-up of 12 months. Baseline pulmonary FAPi-uptake was assessed by the maximum (SUVmax) and mean (SUVmean) standardized uptake values (SUV) over the whole lung (wl). SUV was corrected for blood pool background activity and target-to-background ratios (TBR) were calculated. We compared pulmonary FAPi-uptake between patients with IIM-ILD and those without ILD, as well as controls, and correlated baseline FAP-uptake with standard diagnostic tools such as HR-CT and PFT. For predictive implications, we investigated whether patients with IIM and progressive ILD exhibited higher baseline FAPi-uptake compared to those with stable ILD. Metrics are reported as mean with standard deviation (±SD). Findings: Between November 16, 2021 and October 10, 2022, a total of 32 patients were enrolled in the study. Three participants from the control group were excluded due to cardiopulmonary disease. In individuals with IIM-ILD (n = 14), wlTBRmax and wlTBRmean were significantly increased as compared with both non-ILD-IIM patients (n = 5) and the control group (n = 16): wlTBRmax: 2.06 ± 1.04 vs. 1.04 ± 0.22 (p = 0.019) and 1.08 ± 0.19 (p = 0.0012) and wlTBRmean: 0.45 ± 0.19 vs. 0.26 ± 0.06 (p = 0.025) and 0.27 ± 0.07 (p = 0.0024). Similar values were observed in wlTBRmax or wlTBRmean between non-ILD IIM patients and the control group. Patients with progressive ILD displayed significantly enhanced wlTBRmax and wlTBRmean values at baseline compared to patients with stable ILD: wlTBRmax: 1.30 ± 0.31 vs. 2.63 ± 1.04 (p = 0.0084) and wlTBRmean: 0.32 ± 0.08 vs. 0.55 ± 0.19 (p = 0.021). Strong correlations were found between FAPi-uptake and disease extent on HR-CT (wlTBRmax: R = 0.42, p = 0.07; wlTBRmean: R = 0.56, p = 0.013) and severity of respiratory symptoms determined by the New York Heart Association (NYHA) classification tool (wlTBRmax: R = 0.52, p = 0.022; wlTBRmean: R = 0.59, p = 0.0073). Further, pulmonary FAPi-uptake showed inverse correlation with forced vital capacity (FVC) (wlTBRmax: R = -0.56, p = 0.012; wlTBRmean: R = -0.64, p = 0.0033) and diffusing capacity of the lungs for carbon monoxide (DLCO) (wlTBRmax: R = -0.52, p = 0.028; wlTBRmean: R = -0.68, p = 0.0017). Interpretation: Our study demonstrates higher fibroblast activation in patients with IIM-ILD compared to non-ILD patients and controls. Intensity of pulmonary FAPi accumulation was associated with progression of ILD. Considering that this study was carried out on a small population, FAPi PET/CT may serve as a useful non-invasive tool for risk stratification of lung disease in IIM. Funding: The Austrian Research Fund.

Assessment of PSMA Expression of Healthy Organs in Different Stages of Prostate Cancer Using [68Ga]Ga-PSMA-11-PET Examinations.

The efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is currently being investigated for its application in patients with early-stage prostate cancer (PCa). However, little is known about PSMA expression in healthy organs in this cohort. Collectively, 202 [68Ga]Ga-PSMA-11 positron emission tomography (PET) scans from 152 patients were studied. Of these, 102 PET scans were from patients with primary PCa and hormone-sensitive biochemically recurrent PCa and 50 PET scans were from patients with metastatic castration-resistant PCa (mCRPC) before and after three cycles of [177Lu]Lu-PSMA-RLT. PSMA-standardized uptake values (SUV) were measured in multiple organs and PSMA-total tumor volume (PSMA-TTV) was determined in all cohorts. The measured PET parameters of the different cohorts were normalized to the bloodpool and compared using t- or Mann-Whitney U tests. Patients with early-stage PCa had lower PSMA-TTVs (10.39 mL vs. 462.42 mL, p < 0.001) and showed different SUVs in the thyroid, submandibular glands, heart, liver, kidneys, intestine, testes and bone marrow compared to patients with advanced CRPC, with all tests showing p < 0.05. Despite the differences in the PSMA-TTV of patients with mCRPC before and after [177Lu]Lu-PSMA-RLT (462.42 mL vs. 276.29 mL, p = 0.023), no significant organ differences in PET parameters were detected. These suggest different degrees of PSMA-ligand binding among patients with different stages of PCa that could influence radiotoxicity during earlier stages of disease in different organs when PSMA-RLT is administered.

Non-invasive assessment of stimulation-specific changes in cerebral glucose metabolism with functional PET.

PURPOSE: Functional positron emission tomography (fPET) with [18F]FDG allows quantification of stimulation-induced changes in glucose metabolism independent of neurovascular coupling. However, the gold standard for quantification requires invasive arterial blood sampling, limiting its widespread use. Here, we introduce a novel fPET method without the need for an input function. METHODS: We validated the approach using two datasets (DS). For DS1, 52 volunteers (23.2 ± 3.3 years, 24 females) performed Tetris® during a [18F]FDG fPET scan (bolus + constant infusion). For DS2, 18 participants (24.2 ± 4.3 years, 8 females) performed an eyes-open/finger tapping task (constant infusion). Task-specific changes in metabolism were assessed with the general linear model (GLM) and cerebral metabolic rate of glucose (CMRGlu) was quantified with the Patlak plot as reference. We then estimated simplified outcome parameters, including GLM beta values and percent signal change (%SC), and compared them, region and whole-brain-wise. RESULTS: We observed higher agreement with the reference for DS1 than DS2. Both DS resulted in strong correlations between regional task-specific beta estimates and CMRGlu (r = 0.763…0.912). %SC of beta values exhibited strong agreement with %SC of CMRGlu (r = 0.909…0.999). Average activation maps showed a high spatial similarity between CMRGlu and beta estimates (Dice = 0.870…0.979) as well as %SC (Dice = 0.932…0.997), respectively. CONCLUSION: The non-invasive method reliably estimates task-specific changes in glucose metabolism without blood sampling. This streamlines fPET, albeit with the trade-off of being unable to quantify baseline metabolism. The simplification enhances its applicability in research and clinical settings.

Radiobiological Assessment of Targeted Radionuclide Therapy with [177Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models.

In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [177Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others.

Novel approach using [18F]FTHA-PET and de novo synthesized VLDL for assessment of FFA metabolism in a rat model of diet induced NAFLD.

BACKGROUND AND AIMS: The worldwide prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) raises concerns about associated risk factors, such as obesity and type 2 Diabetes Mellitus, for leading causes of disability and death. Besides Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS), functional imaging with Positron Emission Tomography (PET) could contribute to a deeper understanding of the pathophysiology of NAFLD. Here we describe a novel approach using the PET tracer [18F]FTHA, which is an analog of long-chain free fatty acids (FFA) and is taken up by tissues to enter mitochondria or to be incorporated into complex lipids for further export as very-low-density lipoprotein (VLDL). METHODS: Male Sprague Dawley rats, after 6 weeks on a high-fat diet (HFD), were used as a model of diet induced NAFLD, while a standard diet (SD) served as a control group. Liver fat was estimated by MR spectroscopy at a 9.4 T system for phenotyping. To measure hepatic FFA uptake, rats underwent 60 min dynamic [18F]FTHA-PET scans after unrestricted access to food (HFD: n = 6; SD: n = 6) or overnight (≤16h) fasting (HFD: n = 6; SD: n = 5). FFA removal was assessed from incorporated 18F-residual in de novo synthesized VLDL out of plasma. RESULTS: MRS of the liver confirmed the presence of NAFLD (>5.6% fat). Under non-fasting conditions, hepatic [18F]FTHA uptake was significantly increased in NAFLD: SUVmean (p = 0.03) within [0; 60] min interval, SUVmean (p = 0.01) and SUVmax (p = 0.03) within [30; 60] min interval. SUVs for hepatic uptake under fasting conditions were not significantly different between the groups. Analysis of FFA removal demonstrated elevated values of 18F-residue in the VLDL plasma fraction of the healthy group compared to the NAFLD (p = 0.0569). CONCLUSION: Our novel approach for assessing FFA metabolism using [18F]FTHA demonstrated differences in the hepatic FFA uptake and FFA incorporation into VLDL between healthy and NAFLD rats. [18F]FTHA-PET could be used to study metabolic disturbances involved in the progression of NAFLD.

68Ga-Pentixafor PET/MRI for Treatment Response Assessment in Mantle Cell Lymphoma: Comparison Between Changes in Lesion CXCR4 Expression on PET and Lesion Size and Diffusivity on MRI.

PURPOSE: The aim of this study was to compare CXCR4 imaging with 68Ga-pentixafor PET to MRI for treatment response assessment in patients with mantle cell lymphoma (MCL). PATIENTS AND METHODS: Twenty-two posttreatment 68Ga-pentixafor PET/MRI scans of 16 patients (7 women and 9 men; mean age, 69.9 ± 7.9) with a total of 67 target lesions on baseline PET/MRI were analyzed. Rates of complete remission per lesion and per scan, according to MRI (based on lesion size) and 68Ga-pentixafor PET (based on SUV decrease to lower than liver and blood pool uptake), were compared using McNemar tests. The t tests and Pearson correlation coefficients (r) were used to compare rates of change in lesion diameter products (DPs) on MRI, and standardized uptake values (SUVmax, SUVmean) on PET, relative to baseline. RESULTS: At interim PET/MRI, 18/32 (56.3%) target lesions met CR criteria on 68Ga-pentixafor PET, and 16/32 (50.0%) lesions met size-based MRI criteria for CR (P = 0.63). At end-of-treatment PET/MRI, 40/57 (70.2%) target lesions met 68Ga-pentixafor PET criteria for CR, and 27/57 (47.4%) lesions met size-based MRI criteria for CR (P = 0.021). Complete remission after treatment was observed more frequently on 68Ga-pentixafor PET (11/22 scans, 54.5%) than on MRI (6/22 scans, 27.3%) (P = 0.031). Rates of change did not differ significantly between lesion DP (-69.20% ± 34.62%) and SUVmax (-64.59% ± 50.78%, P = 0.22), or DP and SUVmean (-60.15 ± 64.58, P = 0.064). Correlations were strong between DP and SUVmax (r = 0.71, P < 0.001) and DP and SUVmean (r = 0.73, P < 0.001). CONCLUSIONS: In MCL patients, 68Ga-pentixafor PET may be superior for assessment of complete remission status than anatomic MRI using lesion size criteria, especially at the end of treatment.

Assessment of cerebral glucose metabolism in patients with heart failure by 18F-FDG PET/CT imaging.

BACKGROUND: To evaluate the cerebral metabolism in patients with heart failure (HF). METHODS: One hundred and two HF patients were prospectively enrolled, who underwent gated 99mTc-sestamibi single photon emission computed tomography (SPECT)/CT, cardiac and cerebral 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Fifteen healthy volunteers served as controls. Patients were stratified by extent of hibernating myocardium (HM) and left ventricular ejection fraction (LVEF) into 4 groups where Group1: HM < 10% (n = 33); Group2: HM ≥ 10%, LVEF < 25% (n = 34); Group3: HM ≥ 10%, 25% ≤ LVEF ≤ 40% (n = 16) and Group 4: LVEF > 40% (n = 19). The standardized uptake value (SUV) in the whole brain (SUVwhole-brain) and the SUV ratios (SUVR) in 24 cognition-related brain regions were determined. SUVwhole-brain and SUVRs were compared between the 4 patient groups and the healthy controls. RESULTS: SUVwhole-brain (r = 0.245, P = 0.013) and SUVRs in frontal areas, hippocampus, and para-hippocampus (r: 0.213 to 0.308, all P < 0.05) were correlated with HM. SUVwhole-brain differed between four patient groups and the healthy volunteers (P = 0.016) and SUVwhole-brain in Group 1 was lower than that in healthy volunteers (P < 0.05). SUVRs of Group 3 in frontal areas were the highest among four patient subgroups (P < 0.05). CONCLUSIONS: Cerebral metabolism in the whole brain was reduced but maintained in cognition-related frontal areas in HF patients with HM and moderately impaired global left ventricular function.

Assessment of left and right ventricular functional parameters using dynamic dual-tracer [13N]NH3 and [18F]FDG PET/MRI.

BACKGROUND: Cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) can assess various cardiovascular diseases. In this study, we intra-individually compared right (RV) and left ventricular (LV) parameters obtained from dual-tracer PET/MRI scan. METHODS: In 22 patients with coronary heart disease (69 ± 9 years) dynamic [13N]NH3 (NH3) and [18F]FDG (FDG) PET scans were acquired. The first 2 minutes were used to calculate LV and RV first-pass ejection fraction (FPEF). Additionally, LV end-systolic (LVESV) and end-diastolic (LVEDV) volume and ejection fraction (LVEF) were calculated from the early (EP) and late-myocardial phases (LP). MRI served as a reference. RESULTS: RVFPEF and LVFPEF from FDG and NH3 as well as RVEF and LVEF from MRI were (28 ± 11%, 32 ± 15%), (32 ± 11%, 41 ± 14%) and (42 ± 16%, 45 ± 19%), respectively. LVESV, LVEDV and LVEF from EP FDG and NH3 in 8 and 16 gates were [71 (15 to 213 mL), 98 (16 to 241 mL), 32 ± 17%] and [50 (17 to 206 mL), 93 (13 to 219 mL), 36 ± 17%] as well as [60 (19 to 360 mL), 109 (56 to 384 mL), 41 ± 22%] and [54 (16 to 371 mL), 116 (57 to 431 mL), 46 ± 24%], respectively. Moreover, LVESV, LVEDV and LVEF acquired from LP FDG and NH3 were (85 ± 63 mL, 138 ± 63 mL, 47 ± 19%) and (79 ± 56 mL, 137 ± 63 mL, 47 ± 20%), respectively. The LVESV, LVEDV from MRI were 93 ± 66 mL and 153 ± 71 mL, respectively. Significant correlations were observed for RVFPEF and LVFPEF between FDG and MRI (R = .51, P = .01; R = .64, P = .001), respectively. LVESV, LVEDV, and LVEF revealed moderate to strong correlations to MRI when they acquired from EP FDG and NH3 in 16 gates (all R > .7, P = .000). Similarly, all LV parameters from LP FDG and NH3 correlated good to strongly positive with MRI (all R > .7, and P < .001), except EDV from NH3 weakly correlated to EDV of MRI (R = .54, P < .05). Generally, Bland-Altman plots showed good agreements between PET and MRI. CONCLUSIONS: Deriving LV and RV functional values from various phases of dynamic NH3 and FDG PET is feasible. These results could open a new perspective for further clinical applications of the PET examinations.

Assessment of cardiac tumors by 18F-FDG PET/CT imaging: Histological correlation and clinical outcomes.

BACKGROUND: To evaluate the diagnostic value of 18F-FDG PET/CT in distinguishing benign versus malignant cardiac tumors as well as to assess its prognostic value. METHODS: We analyzed 38 patients with cardiac tumors who underwent 18F-FDG PET/CT and followed for median 8.5 ± 12.5 months. SUVmax and TBRmax (maximum tumor-to-background ratio) by receiver-operating characteristic (ROC) curve analysis were used to obtain threshold for the diagnosis of malignancy as defined by histology (n = 38). Survival was assessed and correlated with the dignity of the lesions and PET parameters. RESULTS: Optimal cut-off values indicating malignancy were as follows: SUVmax = 3.44, with 100% sensitivity and 92.9% specificity, and TBRmax = 1.55, with 95.8% sensitivity and 92.9% specificity. A significant difference of 18F-FDG uptake was observed between primary benign (n = 14, SUVmax = 2.35 ± 1.31, TBRmax = 1.05 ± 0.50) compared to primary malignant cardiac tumors (n = 11, SUVmax = 8.90 ± 4.23, TBRmax = 3.82 ± 1.44) as well as cardiac metastases and lymphoma (n = 13, SUVmax = 14.37 ± 8.05, TBRmax = 6.19 ±  3.38) (all P < .001). Survival rate was significantly lower in patients with malignant as compared to benign cardiac tumors (P < .05). Regression analysis revealed that the lesion dignity determined by the cut-off value of SUVmax was an independent predictor for death in patients with cardiac tumors (P < .05). CONCLUSION: 18F-FDG uptake in cardiac tumors can differentiate between benign and malignant cardiac tumors and predicts survival.

Assessment of Central Nervous System Lymphoma Based on CXCR4 Expression In Vivo Using 68Ga-Pentixafor PET/MRI.

PURPOSE OF THE REPORT: F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL. MATERIALS AND METHODS: Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests. RESULTS: Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI). CONCLUSIONS: Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.

Differential impact of radiation therapy after radical prostatectomy on recurrence patterns: an assessment using [68Ga]Ga-PSMA ligand PET/CT(MRI).

PURPOSE: To evaluate the differential impact of postoperative radiotherapy (RT) on recurrence patterns in patients treated with radical prostatectomy (RP) using [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA 11-PET). METHODS: We assessed 162 consecutive patients who experienced biochemical recurrence (BCR) after RP for nonmetastatic prostate cancer (PC). All had at least one positive lesion on imaging. No patient was on androgen deprivation therapy (ADT). Patients were categorized into those who had received adjuvant/salvage RT ± ADT and those who did not (RP only). Lesion- and patient-based analyses were performed. The impact of the radiation field was assessed. RESULTS: Overall, 57 BCR patients underwent RP only, 105 received postoperative RT. Median PSA was 1.01 ng/ml (IQR 0.58-2). In the lesion-based analysis, compared to the RP only patients, those who had received postoperative RT, had less lymph node (LN) recurrences distal to the common iliac bifurcation (35.2 vs. 57.9%, p = 0.05), but were more likely to harbor positive LNs proximal to the iliac bifurcation and in the presacral (34.2 vs. 12.3%, p = 0.002) areas as well as bone metastases (25.7 vs. 8.8%, p = 0.01). In the patient-based analysis, the patients with postoperative RT after RP had less recurrence in the pelvis only (pelvic LNs and/or prostate bed) (52.4 vs. 79%, p = 0.002), but were more likely to harbor extrapelvic recurrence (41.9 vs. 15.8%, p = 0.001). Patients who received RT to the prostate bed only had more recurrence to the pelvic LN only (54.2% vs. 23.4%, p = 0.002), but less extrapelvic recurrence (31.3 vs. 53.2%, p = 0.03) and less bone recurrence (16.7 vs. 36.2%, p = 0.031) compared to those patients, who received RT to the prostate bed and pelvic nodes. CONCLUSIONS: Postoperative radiation treatment alters the recurrence pattern in BCR patients after RP. Further prospective studies are needed to establish a decision tree for optimal imaging/management according to previous treatments.

Reconfiguration of functional brain networks and metabolic cost converge during task performance.

The ability to solve cognitive tasks depends upon adaptive changes in the organization of whole-brain functional networks. However, the link between task-induced network reconfigurations and their underlying energy demands is poorly understood. We address this by multimodal network analyses integrating functional and molecular neuroimaging acquired concurrently during a complex cognitive task. Task engagement elicited a marked increase in the association between glucose consumption and functional brain network reorganization. This convergence between metabolic and neural processes was specific to feedforward connections linking the visual and dorsal attention networks, in accordance with task requirements of visuo-spatial reasoning. Further increases in cognitive load above initial task engagement did not affect the relationship between metabolism and network reorganization but only modulated existing interactions. Our findings show how the upregulation of key computational mechanisms to support cognitive performance unveils the complex, interdependent changes in neural metabolism and neuro-vascular responses.

Assessment of right ventricular sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy: An 123I-metaiodobenzylguanidine SPECT/CT study.

PURPOSE: The purpose of the study was to evaluate a novel approach for the quantification of right ventricular sympathetic dysfunction in patients diagnosed with ARVC/D through state-of-the-art functional SPECT/CT hybrid imaging. METHODS: Sympathetic innervation of the heart was assessed using 123I-MIBG-SPECT/CT in 17 patients diagnosed with ARVC according to the modified task force criteria, and in 10 patients diagnosed with idiopathic ventricular fibrillation (IVF). The 123I-MIBG-uptake in the left (LV) and right ventricle (RV) was evaluated separately based on anatomic information derived from the CT scan, and compared to the uptake in the mediastinum (M). RESULTS: There was a significant difference in the LV/M ratio between the ARVC/D and the IVF groups (3.2 ± 0.5 vs. 3.9 ± 0.8, P = 0.014), with a cut-off value of 3.41 (77% sensitivity, 80% specificity, AUC 0.78). There was a highly significant difference in the mean RV/M ratios between both groups (1.6 ± 0.3 vs. 2.0 ± 0.2, P = 0.001), with optimal cut-off for discrimination at 1.86 (88% sensitivity, 90% specificity, AUC 0.93). CONCLUSION: Employing state-of-the-art functional SPECT/CT hybrid imaging, we could reliably assess and quantify right and left ventricular sympathetic innervation. The RV/M ratio was significantly lower in patients diagnosed with ARVC/D and provided sensitive and specific discrimination between patients with ARVC/D and IVF patients.

Response assessment using [68 Ga]Ga-PSMA ligand PET in patients undergoing systemic therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: To assess which parameters of [68 Ga]Ga-PSMA-11 positron emission tomography (PSMA-PET) predict response to systemic therapies in metastatic (m) castration-resistant prostate cancer (CRPC). In addition, to investigate which of these factors are associated with overall survival (OS). METHODS: We retrospectively assessed the following PSMA-PET parameters in 43 patients before and after systemic therapies for mCRPC: PSMA total tumor volume (TTV), mean standardized uptake value (SUVmean), SUVmax, and SUVpeak. prostate-specific antigen (PSA) levels and PSMA-PET/CT(magnetic resonance imaging [MRI]) imaging were both performed within 8 weeks before and 6 weeks after systemic therapy. PSMA-PET and CT (MRI) images were reviewed according to the modified PET Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results were compared to PSA response. Univariable survival analyses were performed. RESULTS: Overall, 43 patients undergoing 67 systemic therapies were included (9 patients radium-223, 12 cabazitaxel, 22 docetaxel, 6 abiraterone, and 18 enzalutamide). Median serum PSA level before any therapy was 11.3 ng/mL (interquartile range [IQR] = 3.3, 30.1). Delta (d) PSA after systemic therapies was -41%, dTTV 10.5%, dSUVmean -7.5%, dSUVmax -13.3%, dSUVpeak -12%, and dRECIST -13.3%. Overall, 31 patients had dPSA response (46.3%), 12 stable disease (17.9%), and 24 progressive disease (35.8%). All observed PET parameters, as well as the RECIST evaluation, were significantly associated with PSA response (dTTV P = .003, dSUVmean P = .003, dSUVmax P = .011, dSUVpeak P < 0001, dRECIST P = .012), while RECIST assessment was applicable in 37 out of 67 patients (55.2%). Within a median follow-up of 33 months (IQR = 26, 38), 10 patients (23.3%) died of PC. On univariable survival analyses, neither the investigated PET parameters nor PSA level or RECIST criteria were associated with OS. CONCLUSION: PSMA-PET provides reliable parameters for prediction of response to systemic therapies for mCRPC. These parameters, if confirmed, could enhance RECIST criteria, specifically concerning its limitations for sclerotic bone lesions.

Assessment of Myocardial Viability in Ischemic Heart Disease by PET/MRI: Comparison of Left Ventricular Perfusion, Hibernation, and Scar Burden.

RATIONALE AND OBJECTIVES: Hybrid positron emission tomography-magnetic resonance (PET-MR) is a novel imaging technology that enables a comprehensive assessment of myocardial viability. The aim of this study was to intra-individually compare simultaneously acquired viability parameters from MRI and PET to determine complementary and redundant information. MATERIALS AND METHODS: Thirty-nine patients with ischemic heart disease (IHD) underwent cardiac PET-MR for myocardial viability assessment. Cardiac magnetic resonance (CMR), including late gadolinium enhancement (LGE), and PET, including a dynamic dual-tracer acquisition of [13N]ammonia ([13N]NH3)/[18F]fluorodeoxyglucose ([18F]FDG), were performed simultaneously. Allocation, extent, and transmural degree of left ventricular (LV) scars were measured from LGE. Perfusion, viability, and hibernation were assessed by PET. RESULTS: A comparison of scar location revealed six more areas of infarction on MR than on PET. Mean LV scarring by CMR was 14% (range, 2% to 42%) and 14% (range, 1% to 46%) by PET (CMR vs. PET: p = 0.9). An intra-individual comparison of scarring showed a good inter-method correlation (r = 0.7), which was also evident in the subgroup with low ejection fraction (EF) (r = 0.6). Hibernation and transmural degree of scars showed a moderate to weak correlation (r = 0.4), which was even worse in the low EF group (r = 0.1). CONCLUSIONS: In patients with IHD, there was a good correlation between PET and CMR for the LV scar extent using hybrid cardiac PET-MR. The degree of transmural scarring by CMR showed no correlation to PET hibernation. Therefore, cardiac PET-MR might be a suitable tool for a comprehensive assessment of myocardial viability if used to predict response to cardiac reperfusion strategies.

Assessment of brain delivery of a model ABCB1/ABCG2 substrate in patients with non-contrast-enhancing brain tumors with positron emission tomography.

BACKGROUND: P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters expressed at the blood-brain barrier which effectively restrict the brain distribution of the majority of currently known anticancer drugs. High-grade brain tumors often possess a disrupted blood-brain tumor barrier (BBTB) leading to enhanced accumulation of magnetic resonance imaging contrast agents, and possibly anticancer drugs, as compared to normal brain. In contrast to high-grade brain tumors, considerably less information is available with respect to BBTB integrity in lower grade brain tumors. MATERIALS AND METHODS: We performed positron emission tomography imaging with the radiolabeled ABCB1 inhibitor [11C]tariquidar, a prototypical ABCB1/ABCG2 substrate, in seven patients with non-contrast -enhancing brain tumors (WHO grades I-III). In addition, ABCB1 and ABCG2 levels were determined in surgically resected tumor tissue of four patients using quantitative targeted absolute proteomics. RESULTS: Brain distribution of [11C]tariquidar was found to be very low across the whole brain and not significantly different between tumor and tumor-free brain tissue. Only one patient showed a small area of enhanced [11C]tariquidar uptake within the brain tumor. ABCG2/ABCB1 ratios in surgically resected tumor tissue (1.4 ± 0.2) were comparable to previously reported ABCG2/ABCB1 ratios in isolated human micro-vessels (1.3), which suggested that no overexpression of ABCB1 or ABCG2 occurred in the investigated tumors. CONCLUSIONS: Our data suggest that the investigated brain tumors had an intact BBTB, which is impermeable to anticancer drugs, which are dual ABCB1/ABCG2 substrates. Therefore, effective drugs for antitumor treatment should have high passive permeability and lack ABCB1/ABCG2 substrate affinity. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT), 2011-004189-13. Registered on 23 February 2012, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-004189-13.

Assessment of sympathetic reinnervation after cardiac transplantation using hybrid cardiac PET/MRI: A pilot study.

BACKGROUND: Sympathetic reinnervation after heart transplantation (HTX) is a known phenomenon, which has an impact on patient heart rate variability and exercise capacity. The impact of reinnervation on myocardial structure has not been evaluated yet. PROPOSE: To evaluate the feasibility of simultaneous imaging of cardiac reinnervation and cardiac structure using a hybrid PET/MRI system. STUDY TYPE: Prospective / pilot study. SUBJECTS: Ten patients, 4-21 years after cardiac transplantation. FIELD STRENGTH/SEQUENCE: 3 T hybrid PET/MRI system. Cine SSFP, T1 mapping (modified Look-Locker inversion recovery sequence) pre/postcontrast as well as dynamic [11 C]meta-hydroxyephedrine ([11 C]mHED) PET. ASSESSMENT: All MRI and PET parameters were evaluated by experienced readers using dedicated postprocessing software packages for cardiac MRI and PET. For all parameters a 16-segment model for the left ventricle was applied. STATISTICAL TESTS: Mann-Whitney U-test; Spearman correlations. RESULTS: Thirty-six of 160 myocardial segments showed evidence of reinnervation by PET. On a segment-based analysis, mean native T1 relaxation times were nonsignificantly altered in segments with evidence of reinnervation (1305 ± 151 msec vs. 1270 ± 112 msec; P = 0.1), whereas mean extracellular volume (ECV) was significantly higher in segments with evidence of reinnervation (35.8 ± 11% vs. 30.9 ± 7%; P = 0.019). There were no significant differences in wall motion (WM) and wall thickening (WT) between segments with or without reinnervation (mean WM: 7.6 ± 4 mm vs. group B: 9.3 ± 7 mm [P = 0.13]; WT: 79 ± 63% vs. 94 ± 74% [P = 0.27]) under resting conditions. DATA CONCLUSION: The assessment of cardiac reinnervation using a hybrid PET/MRI system is feasible. Segments with evidence of reinnervation by PET showed nonsignificantly higher T1 relaxation times and a significantly higher ECV, suggesting a higher percentage of diffuse fibrosis in these segments, without impairment of rest WM and WT. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1326-1335.

Assessment of attenuation correction for myocardial PET imaging using combined PET/MRI.

OBJECTIVE: To evaluate the frequency of artifacts in MR-based attenuation correction (AC) maps and their impact on the quantitative accuracy of PET-based flow and metabolism measurements in a cohort of consecutive heart failure patients undergoing combined PET/MR imaging. METHODS: Myocardial viability studies were performed in 20 patients following a dual-tracer protocol involving the assessment of myocardial perfusion (13N-NH3: 813 ± 86 MBq) and metabolism (18F-FDG: 335 ± 38 MBq). All acquisitions were performed using a fully-integrated PET/MR system, with standard DIXON-attenuation correction (DIXON-AC) mapping for each PET scan. All AC maps were examined for spatial misalignment with the emission data, total lung volume, susceptibility artifacts, and tissue inversion (TI). Misalignment and susceptibility artifacts were corrected using rigid co-registration and retrospective filling of the susceptibility-induced gaps, respectively. The effects of the AC artifacts were evaluated by relative difference measures and perceived changes in clinical interpretations. RESULTS: Average respiratory misalignment of (7 ± 4) mm of the PET-emission data and the AC maps was observed in 18 (90%) patients. Substantial changes in the lung volumes of the AC maps were observed in the test-retest analysis (ratio: 1.0 ± 0.2, range: 0.8-1.4). Susceptibility artifacts were observed in 10 (50%) patients, while six (30%) patients had TI artifacts. Average differences of 14 ± 10% were observed for PET images reconstructed with the artifactual AC maps. The combined artifact effects caused false-positive findings in three (15%) patients. CONCLUSION: Standard DIXON-AC maps must be examined carefully for artifacts and misalignment effects prior to AC correction of cardiac PET/MRI studies in order to avoid misinterpretation of biased perfusion and metabolism readings from the PET data.