Diagnostic Potential of Supplemental Static and Dynamic 68Ga-FAPI-46 PET for Primary 18F-FDG-Negative Pulmonary Lesions.

PET using 68Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, 18F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently 18F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic 68Ga-FAPI-46 PET in the 18F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Methods: Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic 68Ga-FAPI-46 PET in addition to 18F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUVmax, SUVmean, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (68Ga-FAPI-46 in relation to18F-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, k 1, k 2, k 3, and k 4) were extracted from dynamic 68Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. Results: FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated 68Ga-FAPI-46 uptake, higher TBRs, and higher 68Ga-FAPI-46-to-18F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative 68Ga-FAPI-46-to-18F-FDG ratios regarding SUVmax and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Conclusion: 68Ga-FAPI-46 PET is a powerful new tool for the assessment of single 18F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.

Detection Efficacy of 68Ga-PSMA-11 PET/CT in Biochemical Recurrence of Prostate Cancer with Very Low PSA Levels: A 7-Year, Two-Center "Real-World" Experience.

In biochemical recurrence of prostate cancer (BCR), prompt tumor localization guides early treatment, potentially improving patient outcomes. Gallium-68 prostate-specific membrane antigen-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) detection rates of lesions suspicious for prostate cancer are well known to rise along with prostate-specific antigen (PSA) concentration. However, published data are limited regarding very low values (≤0.2 ng/mL). We retrospectively analyzed ~7-year "real-world" experience in this setting in a large post-prostatectomy cohort (N = 115) from two academic clinics. Altogether 44 lesions were detected in 29/115 men (25.2%) (median [minimum-maximum] 1 [1-4]/positive scan). The apparent oligometastatic disease was found in nine patients (7.8%) at PSA as low as 0.03 ng/mL. Scan positivity rates were highest when PSA was >0.15 ng/mL, PSA doubling time was ≤12 months, or the Gleason score was ≥7b (in 83 and 107 patients, respectively, with available data); these findings were statistically significant (p ≤ 0.04), except regarding PSA level (p = 0.07). Given the benefits of promptly localizing recurrence, our observations suggest the potential value of 68Ga-PSMA-11 PET/CT in the very low PSA BCR setting, especially in cases with more rapid PSA doubling time or with high-risk histology.

Hypermetabolic Ipsilateral Supraclavicular and Axillary Lymphadenopathy: Optimal Time Point for Performing an 18F-FDG PET/CT after COVID-19 Vaccination.

Background: We aimed to evaluate the incidence of severe acute respiratory syndrome coronavirus type-2 (SARS-CoV2) vaccine-related hypermetabolic lymphadenopathy (HLA) and evaluate which time point produces the least number of false-positive findings in an 18F-2-Fluor-2-desoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods: For this retrospective, multi-center imaging study, patients with any form of SARS-CoV2 vaccination prior to an 18F-FDG-PET/CT were included between January 2021 and December 2021. Patients were divided into six groups according to the time point of vaccination prior to their 18F-FDG-PET/CT imaging, e.g., group one (0−6 days) and group six (35−80 days). As the reference standards, the SUVmax of the mediastinal blood pool (MBP) and the SUVmax contralateral reference lymph node (RL) were determined. (A) The absolute SUVmax of HLA, (B) the ratio of SUVmaxHLA/SUVmax mediastinal blood pool (rHLA/MBP), (C) the ratio SUVmax HLA vs. SUVmax contralateral reference lymph node (rHLA/RL), (D) and the incidence of HLA defined as rHLA/MBP > 1.5 were assessed. Results: Group one (days 0−6) showed the highest incidence of HLA 16/23 (70%) and rHLA/MBP (2.58 ± 2.1). All three parameters for HLA reduced statistically significantly in the comparison of Groups 1−3 (days 0−20) versus Groups 4−6 (days 21−80) (p-values < 0.001). Conclusions: If feasible, an FDG PET should be postponed by at least 3 weeks after SARS-CoV2 vaccination, especially if an accurate evaluation of axillary status is required.

Primary Staging of Prostate Cancer Patients with [18F]PSMA-1007 PET/CT Compared with [68Ga]Ga-PSMA-11 PET/CT.

BACKGROUND: Hybrid imaging with prostate-specific membrane antigen (PSMA) is gaining importance as an increasingly meaningful tool for prostate cancer (PC) diagnostics and as a guide for therapy decisions. This study aims to investigate and compare the performance of [18F]PSMA-1007 (18F-PSMA) and [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (68Ga-PSMA) in the initial staging of PC patients. METHODS: The data of 88 biopsy-proven patients were retrospectively evaluated. PSMA-avid lesions were compared with the histopathologic Gleason Score (GS) for prostate biopsies, and the results were plotted by receiver operating characteristic (ROC)-curve. Optimal maximum standardized uptake value (SUVmax) cut-off values were rated using the Youden index. RESULTS: 18F-PSMA was able to distinguish GS ≤ 7a from ≥7b with a sensitivity of 62%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 67% for a SUVmax of 8.95, whereas sensitivity was 54%, specificity 91%, PPV 93%, and accuracy 66% for 68Ga-PSMA (SUVmax 8.7). CONCLUSIONS: Both methods demonstrated a high concordance of detected PSMA-avid lesions with histopathologically proven PC. 18F-PSMA and 68Ga-PSMA are both suitable for the characterization of primary PC with a comparable correlation of PSMA-avid lesions with GS. Neither method showed a superior advantage. Our calculated SUVmax thresholds may represent valuable parameters in clinical use to distinguish clinically significant PC (csPC) from non-csPC.

Comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 PET/CT in Restaging of Prostate Cancer Patients with PSA Relapse.

This study aimed to compare the diagnostic performance of [18F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (18F-PSMA) and [68Ga]Ga-PSMA-11 PET/CT (68Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and to compare both methods. Retrospectively, the study included 264 patients. The performances of 18F-PSMA and 68Ga-PSMA in relation to the pre-scan PSA were assessed by receiver operating characteristic (ROC) curve. 18F-PSMA showed PC-lesions in 87.5% (112/128 patients), while 68Ga-PSMA identified them in 88.9% (121/136). For 18F-PSMA biochemical recurrent (BCR) patients treated with radical prostatectomy (78/128, patient group: F-RP), a PSA of 1.08 ng/mL was found to be the optimal cut-off level for predicting positive and negative scans (AUC = 0.821; 95%, CI: 0.710−0.932), while for prostatectomized 68Ga-PSMA BCR-patients (89/136, patient group: Ga-RP), the cut-off was 1.84 ng/mL (AUC = 0.588; 95%, CI: 0.410−0.766). In patients with PSA < 1.08 ng/mL (F-RP) 76.3% and <1.84 ng/mL (Ga-RP) 78.6% scans were positive, whereas patients with PSA ≥ 1.08 ng/mL (F-RP) or 1.84 ng/mL (Ga-RP) had positive scan results in 100% and 91.5% (p < 0.001/p = 0.085). The identified PSA thresholds for PSMA-mappable PC lesions in BCR-patients (RP) showed a better separation for 18F-PSMA with regard to the distinguishing of positive and negative PC-lesions compared to 68Ga-PSMA. However, the two PSMA PET/CT tracers gave similar overall findings.

Prefrontal and striatal dopamine D2/D3 receptors correlate with fMRI BOLD activation during stopping.

D2-like dopamine receptors in animals and humans have been shown to be linked to impulsive behaviors that are highly relevant for several psychiatric disorders. Here, we investigate the relationship between the fronto-striatal D2/D3 dopamine receptor availability and response inhibition in a selected population of healthy OPRM1 G-allele carriers. Twenty-two participants successively underwent blood-oxygen level dependent functional magnetic resonance imaging (fMRI) while performing a stop-signal task and a separate positron emission tomography (PET) scan. Striatal and extrastriatal D2/D3 dopamine receptor availability was measured using the radiotracer [18F]fallypride. Caudate D2/D3 dopamine receptor availability positively correlated with stopping-related fronto-striatal fMRI activation. In addition, right prefrontal D2/D3 dopamine receptor availability correlated positively with stopping-related striatal fMRI BOLD signal. Our study partially replicates previous findings on correlations between striatal D2/D3 dopamine receptor availability and response inhibition in a population selected for its genetic determination of dopamine response to alcohol and as a modulator of impulse control via the endogenous opioid system. We confirm the important role of D2/D3 dopamine receptor availability in the fronto-striatal neural circuit for response inhibition. Moreover, we extend previous findings suggesting that dopamine receptor availability in the right inferior frontal cortex, a crucial region of the stopping network, is also strongly associated with stopping-related striatal fMRI activity in healthy OPRM1 G-allele carriers.

Age- and Sex-Graded Data Evaluation of Vaccination Reactions after Initial Injection of the BNT162b2 mRNA Vaccine in a Local Vaccination Center in Germany.

A high vaccination rate of older and particularly chronically ill people against coronavirus disease-2019 (COVID-19) is likely one of the most important factors in containing the pandemic. When Germany's vaccination campaign started on December 2020, vaccination prioritization was initially carried out starting with older population groups. Side effect rates in 1065 individuals who had received the first dose of the messenger ribonucleic acid (mRNA) vaccine BNT162b2 Tozinameran from BioNTech/Pfizer three weeks earlier were examined retrospectively. An age- and gender-graded data analysis showed clear age and gender differences with regard to vaccine-related adverse effects. In 77% of all individuals over 80 years of age, no local or systemic side effects were reported after the first vaccination, whereas in the age group up to 80 years, only 37% showed no side effects. In the whole study population, 64% of females and 73% of males reported no adverse effects. The initial vaccination with mRNA vaccine BNT162b2 shows an overall low profile of side effects. Particularly in those over 80 years, an extraordinarily good tolerance with equally good effectiveness is evident. The sex comparison showed that women suffer more often from adverse vaccination reactions. In order to achieve sufficient herd immunity, both age- and gender-dependent vaccination reactions and any difference in the maintenance of immunity should be considered in future vaccination strategies.

Impact of prompt gamma emission of 44Sc on quantification in preclinical and clinical PET systems.

44Sc is an increasingly investigated positron emitter for use in positron emission tomography (PET) imaging. However, 44Sc is a non-pure positron emitter, since prompt photons are co-emitted during the decay process. This study investigates coincidence energy spectra of 44Sc and its impact on PET quantification on a preclinical and clinical PET system in comparison with 18F. The raw data of the coincidence events revealed characteristic differences comparing the photon energy distribution of 44Sc and 18F. Due to prompt gamma emission of 44Sc, activity recovery is underestimated on PET systems. However, clinical PET imaging of 44Sc with acceptable quantitative accuracy appears feasible by using a single, constant correction factor.

Dual-Time Point [68Ga]Ga-PSMA-11 PET/CT Hybrid Imaging for Staging and Restaging of Prostate Cancer.

Routine [68Ga]Ga-PSMA-11 PET/CT (one hour post-injection) has been shown to accurately detect prostate cancer (PCa) lesions. The goal of this study is to evaluate the benefit of a dual-time point imaging modality for the staging and restaging of PCa patients. Biphasic [68Ga]Ga-PSMA-11 PET/CT of 233 patients, who underwent early and late scans (one/three hours post-injection), were retrospectively studied. Tumor uptake and biphasic lesion detection for 215 biochemically recurrent patients previously treated for localized PCa (prostatectomized patients (P-P)/irradiated patients (P-I) and 18 patients suspected of having primary PCa (P-T) were separately evaluated. Late [68Ga]Ga-PSMA-11 PET/CT imaging detected 554 PCa lesions in 114 P-P patients, 187 PCa lesions in 33 P-I patients, and 47 PCa lesions in 13 P-T patients. Most patients (106+32 P-P/P-I, 13 P-T) showed no additional PCa lesions. However, 11 PSMA-avid lesions were only detected in delayed images, and 33 lesions were confirmed as malignant by a SUVmax increase. The mean SUVmax of pelvic lymph node metastases was 25% higher (p < 0.001) comparing early and late PET/CT. High positivity rates from routine [68Ga]Ga-PSMA-11 PET/CT for the staging and restaging of PCa patients were demonstrated. There was no decisive influence of additional late imaging with PCa lesion detection on therapeutic decisions. However, in a few individual cases, additional delayed scans provided an information advantage in PCa lesion detection due to higher tracer uptake and improved contrast.

Modeling Vestibular Compensation: Neural Plasticity Upon Thalamic Lesion.

The present study in rats was conducted to identify brain regions affected by the interruption of vestibular transmission and to explore selected aspects of their functional connections. We analyzed, by positron emission tomography (PET), the regional cerebral glucose metabolism (rCGM) of cortical, and subcortical cerebral regions processing vestibular signals after an experimental lesion of the left laterodorsal thalamic nucleus, a relay station for vestibular input en route to the cortical circuitry. PET scans upon galvanic vestibular stimulation (GVS) were conducted in each animal prior to lesion and at post-lesion days (PLD) 1, 3, 7, and 20, and voxel-wise statistical analysis of rCGM at each PLD compared to pre-lesion status were performed. After lesion, augmented metabolic activation by GVS was detected in cerebellum, mainly contralateral, and in contralateral subcortical structures such as superior colliculus, while diminished activation was observed in ipsilateral visual, entorhinal, and somatosensory cortices, indicating compensatory processes in the non-affected sensory systems of the unlesioned side. The changes in rCGM observed after lesion resembled alterations observed in patients suffering from unilateral thalamic infarction and may be interpreted as brain plasticity mechanisms associated with vestibular compensation and substitution. The second set of experiments aimed at the connections between cortical and subcortical vestibular regions and their neurotransmitter systems. Neuronal tracers were injected in regions processing vestibular and somatosensory information. Injections into the anterior cingulate cortex (ACC) or the primary somatosensory cortex (S1) retrogradely labeled neuronal somata in ventral posteromedial (VPM), posterolateral (VPL), ventrolateral (VL), posterior (Po), and laterodorsal nucleus, dorsomedial part (LDDM), locus coeruleus, and contralateral S1 area. Injections into the parafascicular nucleus (PaF), VPM/VPL, or LDDM anterogradely labeled terminal fields in S1, ACC, insular cortex, hippocampal CA1 region, and amygdala. Immunohistochemistry showed tracer-labeled terminal fields contacting cortical neurons expressing the µ-opioid receptor. Antibodies to tyrosine hydroxylase, serotonin, substance P, or neuronal nitric oxide-synthase did not label any of the traced structures. These findings provide evidence for opioidergic transmission in thalamo-cortical transduction.

Cortical Binding Potential of Opioid Receptors in Patients With Fibromyalgia Syndrome and Reduced Systemic Interleukin-4 Levels - A Pilot Study.

Objective: We investigated cerebral opioid receptor binding potential in patients with fibromyalgia syndrome (FMS) using positron-emission-tomography (PET) and correlated our results with patients' systemic interleukin-4 (IL-4) gene expression. Methods: In this pilot study, seven FMS patients (1 man, 6 women) agreed to participate in experimental PET scans. All patients underwent neurological examination, were investigated with questionnaires for pain, depression, and FMS symptoms. Additionally, blood for IL-4 gene expression analysis was withdrawn at two time points with a median latency of 1.3 years. Patients were investigated in a PET scanner using the opioid receptor ligand F-18-fluoro-ethyl-diprenorphine ([18F]FEDPN) and results were compared with laboratory normative values. Results: Neurological examination was normal in all FMS patients. Reduced opioid receptor binding was found in mid cingulate cortex compared to healthy controls (p < 0.005). Interestingly, three patients with high systemic IL-4 gene expression had increased opioid receptor binding in the fronto-basal cortex compared to those with low IL-4 gene expression (p < 0.005). Conclusion: Our data give further evidence for a reduction in cortical opioid receptor availability in FMS patients as another potential central nervous system contributor to pain in FMS.

Diagnostic Performance of 68Ga-PSMA-11 Positron-emission-tomography/Computed-tomography in a Large Cohort of Patients with Biochemical Recurrence of Prostate Carcinoma.

Gallium-68 (Ga) prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography is a highly promising method for imaging primary and recurrent prostate cancer. These dual-modality imaging technologies enable whole-body functional and anatomical evaluation in a single session. This study investigated the performance of Ga-prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography for detecting prostate carcinoma in patients with rising prostate-specific-antigen after primary therapy. Six hundred sixty (660) patients with biochemical recurrence referred for positron-emission-tomography/computed-tomography with Ga-prostate-specific-membrane-antigen-11 were evaluated retrospectively. Prostate-specific-antigen-stratified cohorts of pathological scan results were analyzed, and relationships between prostate-specific-antigen kinetics and PSMA-positive tumor lesions were correlated. Gallium-68 prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography showed a pathological prostate-specific-membrane-antigen uptake in 76% (500 of 660 patients). Positive scans were positively associated with prostate-specific-antigen (p<0.001). For patients with prostate-specific-antigen <0.2 ng mL, the PSMA-positive tumor lesions rate was 41%. Patients with prostate-specific-antigen of 0.2-<0.5 ng mL, 0.5-<1.0 ng mL, 1.0-<2.0 ng mL, and 2.0-<5.0 ng mL showed rates of 44.7%, 61.7%, 72.3%, 85.2%, respectively, and for prostate-specific-antigen of ≥5.0 ng mL it increased to 94%. Prostate-specific-antigen velocity was also correlated with PSMA-positive tumor lesions (p<0.001). In contrast, no association was found for prostate-specific-antigen doubling time (p=0.74). PSMA-positive tumor lesions were significantly increased in patients with primary intermediate- (Gleason Score7) and high-risk (Gleason Score>7) vs. low-risk prostate cancer (Gleason Score<7) (p<0.001). Our data confirm the high performance of Ga-prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography for the detection of recurrent prostate cancer. This may alter treatment planning and has been documented in other studies as well.

Image quality analysis of 44Sc on two preclinical PET scanners: a comparison to 68Ga.

BACKGROUND: 44Sc has been increasingly investigated as a potential alternative to 68Ga in the development of tracers for positron emission tomography (PET). The lower mean positron energy of 44Sc (0.63 MeV) compared to 68Ga (0.83 MeV) can result in better spatial image resolutions. However, high-energy γ-rays (1157 keV) are emitted at high rates (99.9%) during 44Sc decay, which can reduce image quality. Therefore, we investigated the impact of these physical properties and performed an unbiased performance evaluation of 44Sc and 68Ga with different imaging phantoms (image quality phantom, Derenzo phantom, and three-rod phantom) on two preclinical PET scanners (Mediso nanoScan PET/MRI, Siemens microPET Focus 120). RESULTS: Despite the presence of high-energy γ-rays in 44Sc decay, a higher image resolution of small structures was observed with 44Sc when compared to 68Ga. Structures as small as 1.3 mm using the Mediso system, and as small as 1.0 mm using the Siemens system, could be visualized and analyzed by calculating full width at half maximum. Full widths at half maxima were similar for both isotopes. For image quality comparison, we calculated recovery coefficients in 1-5 mm rods and spillover ratios in either air, water, or bone-equivalent material (Teflon). Recovery coefficients for 44Sc were significantly higher than those for 68Ga. Despite the lower positron energy, 44Sc-derived spillover ratio (SOR) values were similar or slightly higher to 68Ga-derived SOR values. This may be attributed to the higher background caused by the additional γ-rays. On the Siemens system, an overestimation of scatter correction in the central part of the phantom was observed causing a virtual disappearance of spillover inside the three-rod phantom. CONCLUSION: Based on these findings, 44Sc appears to be a suitable alternative to 68Ga. The superior image resolution makes it an especially strong competitor in preclinical settings. The additional γ-emissions have a small impact on the imaging resolution but cause higher background noises and can effect an overestimation of scatter correction, depending on the PET system and phantom.

PSA and PSA Kinetics Thresholds for the Presence of 68Ga-PSMA-11 PET/CT-Detectable Lesions in Patients With Biochemical Recurrent Prostate Cancer.

68Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT) is commonly used for restaging recurrent prostate cancer (PC) in European clinical practice. The goal of this study is to determine the optimum time for performing these PET/CT scans in a large cohort of patients by identifying the prostate-specific-antigen (PSA) and PSA kinetics thresholds for detecting and localizing recurrent PC. This retrospective analysis includes 581 patients with biochemical recurrence (BC) by definition. The performance of 68Ga-PSMA-11 PET/CT in relation to the PSA value at the scan time as well as PSA kinetics was assessed by the receiver-operating-characteristic-curve (ROC) generated by plotting sensitivity versus 1-specificity. Malignant prostatic lesions were identified in 77%. For patients that were treated with radical prostatectomy (RP) a PSA value of 1.24 ng/mL was found to be the optimal cutoff level for predicting positive and negative scans, while for patients previously treated with radiotherapy (RT) it was 5.75 ng/mL. In RP-patients with PSA value <1.24 ng/mL, 52% scans were positive, whereas patients with PSA ≥1.24 ng/mL had positive scan results in 87%. RT-patients with PSA <5.75 ng/mL had positive scans in 86% and and for those with PSA ≥5.75 ng/mL 94% had positive scans. This study identifies the PSA and PSA kinetics threshold levels for the presence of 68Ga-PSMA-11 PET/CT-detectable PC-lesions in BC patients.

The positivity rate of 68Gallium-PSMA-11 ligand PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.

Background: The aim of the present study is to analyze the efficacy of 68Gallium (Ga)-PSMA-11 PET/CT for detecting and localizing recurrent prostate carcinoma (PC) in patients with different prostate-specific antigen (PSA), PSA velocity (PSAvel) and doubling time (PSAdt). Results: The PR of 68Ga-PSMA-11 PET/CT showed a positive relationship with PSA levels. Even at restaging PSA-values (PSAV) of lower than 0.2 ng/ml, PR was 41%. For PSAV of 0.2-<0.5 ng/ml the PR was 45%, 62% for PSAV of 0.5-<1.0 and 72% for PSAV of 1.0-<2.0 ng/ml. The PR increased to 85% for PSAV of 2.0-<5.0 and reached 94% at PSAV of ≥5.0 ng/ml. At PSA of <1 ng/ml/y the PR of PSAvel was 50% and increased to 98% at PSA >5 ng/ml/y. No significant association was found for PSAdt. Methods: PET/CT scans of 660 patients with biochemical recurrence (BCR) after primary therapy of PC were included in the analysis. We correlated serum PSA levels, measured at the time of imaging with PSMA PET/CT-positivity rates (PR) as well as PSAvel (in 225 patients) and PSAdt (660 patients). Additionally we compared the incidence of localized disease to metastases as related to these PSA-biomarkers. Conclusion: We have shown, in a large cohort of patients, that 68Ga-PSMA-11 PET/CT is a sensitive tool for restaging PC and has a high detection efficacy, even in patients with very low PSA levels (<0.2 ng/ml). Thus 68Ga-PSMA-11 PET/CT both identify and localize recurrent disease with implications for a more direct treatment approach (localized vs. systemic therapy).

18F-FDG PET/CT: an unexpected case of Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a rare, genetic neurodegenerative disorder often presenting with emotional, cognitive and behavioral abnormalities before manifestation of disease defining motor symptoms. Cognitive impairment is a frequent clinical feature caused by different dementia subtypes. Imaging cortical and subcortical glucose metabolism via 18F-FDG PET/CT can help to discriminate the underlying disease. CASE PRESENTATION: The patient is a 54-year old man presenting with progressive cognitive impairment and mild orofacial dyskinesia. 18F-FDG PET/CT of the brain revealed a severe bilateral hypometabolism in the striatum. Following imaging Huntington's disease was suspected and a molecular genetic testing confirmed the diagnosis. CONCLUSIONS: Huntington's disease is a rare but important differential diagnosis of cognitive impairment, especially before motor symptoms are manifest. 18F-FDG PET is capable to show early striatal dysfunction in HD even when structural imaging is normal. We conclude that, in cases with negative family history the HD characteristic metabolic pattern can lead to the diagnosis when no other dementia-suspected changes are present.

Pharmacokinetics of the cannabinoid receptor ligand [18 F]MK-9470 in the rat brain - Evaluation of models using microPET.

PURPOSE: The positron emission tomography ligand [18 F]MK-9470 is an inverse agonist that binds reversibly and with high affinity to the cannabinoid type 1 receptor. Due to its slow brain kinetics, care is required in the definition of its dissociation rates from the receptor. The goal of this study was to investigate pharmacokinetic analysis methods using an arterial input function. METHODS: Five Sprague-Dawley rats received injections of 13 to 25 MBq of [18 F]MK-9470 and were scanned over a period of 90 min. Arterial blood samples were collected throughout the scan. Data were analyzed using four different compartmental models: a reversible one-tissue model, reversible two tissue models with and without parameter constraints and an irreversible two-tissue model. The outcome values were goodness of fit measures (Akaike information criterion; standard error), pharmacokinetic modeling parameters (volume of distribution; irreversible uptake constant) and intersubject variability. RESULTS: Goodness of fit measures indicated that the experimental data are more adequately described by a two-tissue model than a one-tissue model. Differences in mean Akaike information criterion values between all two-tissue models were < 5%. Mean standard errors of model parameters were lowest for the irreversible model (range: 1% to 6%). The irreversible model delivered plausible results for all animals that were less variable compared to results of the other two-tissue models. CONCLUSIONS: A reversible two-tissue model may not deliver stable results for all animals and regions within a 90-min microPET study protocol. Stable parameters for all animals and regions are obtained when an irreversible model is used. If the acquisition time of the experiment is limited, an irreversible model provides a consistent distribution of composite outcome parameters, suggesting its suitability for use in future studies.

Resting Brain Activity Related to Dispositional Mindfulness: a PET Study.

Mindfulness denotes a state of consciousness characterized by receptive attention to and awareness of present events and experiences. As a personality trait, it constitutes the ability to become aware of mental activities such as sensations, images, feelings, and thoughts, and to disengage from judgment, conditioned emotions, and their cognitive processing or automatic inhibition. Default brain activity reflects the stream of consciousness and sense of self at rest. Analysis of brain activity at rest in persons with mindfulness propensity may help to elucidate the neurophysiological basis of this important mental trait. The sample consisted of 32 persons-23 with mental disorders and 9 healthy controls. Dispositional mindfulness (DM) was operationalized by Mindful Attention Awareness Scale (MAAS). Brain activity at rest with eyes closed was assessed by fluorodeoxyglucose positron emission tomography (F-18-FDG PET). After adjustment for depression, anxiety, age and years of education, resting glucose metabolism in superior parietal lobule and left precuneus/Brodmann area (BA) 7 was positively associated with DM. Activity of the left inferior frontal orbital gyrus (BA 47) and bilateral anterior thalamus were inversely associated with DM. DM appears to be associated with increased metabolic activity in some core area of the default mode network (DMN) and areas connected to the DMN, such as BA 7, hosting sense of self functions. Hypometabolism on the other hand was found in some nodes connected to the DMN, such as left inferior frontal orbital gyrus and bilateral thalamus, commonly related to functions of memory retrieval, decision making, or outward attention.

Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2 /D3 binding potential. Twenty-four healthy male µ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BPND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BPND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BPND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D2 /D3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D2 /D3 receptors may hint at an addiction relevant trait.

Functional Plasticity after Unilateral Vestibular Midbrain Infarction in Human Positron Emission Tomography.

The aim of the study was to uncover mechanisms of central compensation of vestibular function at brainstem, cerebellar, and cortical levels in patients with acute unilateral midbrain infarctions presenting with an acute vestibular tone imbalance. Eight out of 17 patients with unilateral midbrain infarctions were selected on the basis of signs of a vestibular tone imbalance, e.g., graviceptive (tilts of perceived verticality) and oculomotor dysfunction (skew deviation, ocular torsion) in F18-fluordeoxyglucose (FDG)-PET at two time points: A) in the acute stage, and B) after recovery 6 months later. Lesion-behavior mapping analyses with MRI verified the exact structural lesion sites. Group subtraction analyses and comparisons with healthy controls were performed with Statistic Parametric Mapping for the PET data. A comparison of PET A of acute-stage patients with that of healthy controls showed increases in glucose metabolism in the cerebellum, motion-sensitive visual cortex areas, and inferior temporal lobe, but none in vestibular cortex areas. At the supratentorial level bilateral signal decreases dominated in the thalamus, frontal eye fields, and anterior cingulum. These decreases persisted after clinical recovery in contrast to the increases. The transient activations can be attributed to ocular motor and postural recovery (cerebellum) and sensory substitution of vestibular function for motion perception (visual cortex). The persisting deactivation in the thalamic nuclei and frontal eye fields allows alternative functional interpretations of the thalamic nuclei: either a disconnection of ascending sensory input occurs or there is a functional mismatch between expected and actual vestibular activity. Our data support the view that both thalami operate separately for each hemisphere but receive vestibular input from ipsilateral and contralateral midbrain integration centers. Normally they have gatekeeper functions for multisensory input to the cortex and automatic motor output to subserve balance and locomotion, as well as sensorimotor integration.