Search

Purpose: Despite its limitations, [123I]MIBG scintigraphy has been the standard for human norepinephrine transporter (hNET) imaging for several decades. Recently, [18F]MFBG has emerged as a promising PET alternative. This prospective trial aimed to evaluate safety, biodistribution, tumour lesion pharmacokinetics, and lesion targeting of [18F]MFBG and perform a head-to-head comparison with [123I]MIBG in neural crest tumour patients. Methods: Six neural crest tumour patients (4 phaeochromocytoma, 1 paraganglioma, 1 neuroblastoma) with a recent routine clinical [123I]MIBG scintigraphy (interval: − 37–75 days) were included. Adult patients (n = 5) underwent a 30-min dynamic PET, followed by 3 whole-body PET/CT scans at 60, 120, and 180 min after injection of 4 MBq/kg [18F]MFBG. One minor participant underwent a single whole-body PET/CT at 60 min after administration of 2 MBq/kg [18F]MFBG. Normal organ uptake (SUVmean) and lesion uptake (SUVmax; tumour-to-background ratio (TBR)) were measured. Regional distribution volumes (VT) were estimated using a Logan graphical analysis in up to 6 lesions per patient. A lesion-by-lesion analysis was performed to compare detection ratios (DR), i.e. fraction of detected lesions, between [18F]MFBG and [123I]MIBG. Results: [18F]MFBG was safe and well tolerated. Its biodistribution was overall similar to that of [123I]MIBG, with prominent uptake in the salivary glands, liver, left ventricle wall and adrenals, and mainly urinary excretion. In the phaeochromocytoma subgroup, the median VT was 37.4 mL/cm3 (range: 18.0–144.8) with an excellent correlation between VT and SUVmean at all 3 time points (R2: 0.92–0.94). Mean lesion SUVmax and TBR at 1 h after injection were 19.3 ± 10.7 and 23.6 ± 8.4, respectively. All lesions detected with [123I]MIBG were also observed with [18F]MFBG. The mean DR with [123I]MIBG was significantly lower than with [18F]MFBG (61.0% ± 26.7% vs. 99.8% ± 0.5% at 1 h; p = 0.043). Conclusion: [18F]MFBG is a promising hNET imaging agent with favourable imaging characteristics and improved lesion targeting compared with [123I]MIBG scintigraphy. Trial registration: Clinicaltrials.gov: NCT04258592 (Registered: 06 February 2020), EudraCT: 2019-003872-37A. [ABSTRACT FROM AUTHOR]

Purpose: Huntington's disease is caused by a trinucleotide expansion in the HTT gene, which leads to aggregation of mutant huntingtin (mHTT) protein in the brain and neurotoxicity. Direct in vivo measurement of mHTT aggregates in human brain parenchyma is not yet possible. In this first-in-human study, we investigated biodistribution and dosimetry in healthy volunteers of [11C]CHDI-00485180-R ([11C]CHDI-180R) and [11C]CHDI-00485626 ([11C]CHDI-626), two tracers designed for PET imaging of aggregated mHTT in the brain that have been validated in preclinical models. Methods: Biodistribution and radiation dosimetry studies were performed in 3 healthy volunteers (age 25.7 ± 0.5 years; 2 F) for [11C]CHDI-180R and in 3 healthy volunteers (age 35.3 ± 6.8 years; 2 F) for [11C]CHDI-626 using sequential whole-body PET-CT. Source organs were delineated in 3D using combined PET and CT data. Individual organ doses and effective doses were determined using OLINDA 2.1. Results: There were no clinically relevant adverse events. The mean effective dose (ED) for [11C]CHDI-180R was 4.58 ± 0.65 μSv/MBq, with highest absorbed doses for liver (16.9 μGy/MBq), heart wall (15.9 μGy/MBq) and small intestine (15.8 μGy/MBq). Mean ED for [11C]CHDI-626 was 5.09 ± 0.06 μSv/MBq with the highest absorbed doses for the gallbladder (26.5 μGy/MBq), small intestine (20.4 μGy/MBq) and liver (19.6 μGy/MBq). Decay-corrected brain uptake curves showed promising kinetics for [11C]CHDI-180R, but for [11C]CHDI-626 an increasing signal over time was found, probably due to accumulation of a brain-penetrant metabolite. Conclusion: [11C]CHDI-180R and [11C]CHDI-626 are safe for in vivo PET imaging in humans. The estimated radiation burden is in line with most 11C-ligands. While [11C]CHDI-180R has promising kinetic properties in the brain, [11C]CHDI-626 is not suitable for human in vivo mHTT PET due to the possibility of a radiometabolite accumulating in brain parenchyma. Trial registration : EudraCT number 2020-002129-27. Clinicaltrials.gov NCT05224115 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Purpose: Neurofibrillary tangles (NFTs) in Alzheimer's disease can be accurately quantified in vivo using [18F]MK-6240 PET. Short-term [18F]MK-6240 test-retest (TRT) is about 6%, but also long-term stability of cerebral uptake is of importance for longitudinal studies. Furthermore, although there is very little cerebral off-target binding, [18F]MK-6240 shows variable extracerebral uptake (ECU) assumed to represent off-target binding to leptomeningeal melanocytes. Here, we examined 6-month TRT of [18F]MK-6240 in healthy controls (HC) and investigated ECU in HC and patients with amnestic mild cognitive impairment (aMCI) with up to 2 years of follow-up. We also explored demographic factors that may be associated to ECU, including age, sex, education, smoking, and disease status. Methods: A total cohort of 40 HC (57 ± 19 years, 21F/19 M) and 24 aMCI (72 ± 8 years, 14F/10 M) underwent baseline [18F]MK-6240 PET-MR (GE Signa), 90–120 min post injection. [18F]MK-6240 was quantified by standardized uptake value ratios (SUVR) in predefined volumes-of-interest relative to the cerebellar cortex. Ten HC (56 ± 12 years, 8F/2 M) underwent a 6-month follow-up [18F]MK-6240 to assess TRT. Also, 10 aMCI (72 ± 6 years, 5F/5 M) underwent a 2-year follow-up [18F]MK-6240 PET-MR. Longitudinal changes in ECU were assessed in both cohorts. ECU was quantified as the mean SUVR of the skull parcel (FreeSurfer 6.0) that includes the meninges. Results: The mean gray matter [18F]MK-6240 SUVR TRT and absolute TRT in HC were 1.6 ± 3.4% and 2.4 ± 2.8%, respectively. We found no significant 6-month or 2-year differences in ECU in HC (4.4 ± 20%) and aMCI (7.9 ± 19%), respectively. In the total cohort, ECU was significantly correlated to age (rs = − 0.48; p < 0.0001), and a multivariate analysis also showed sex differences (higher ECU in women). Conclusion: [18F]MK-6240 shows excellent 6-month TRT, which confirms its suitability for quantification of longitudinal NFT changes. The ECU of [18F]MK-6240 is variable between subjects, influenced by age and sex, but remains stable within subjects over a 2-year time period. [ABSTRACT FROM AUTHOR]

Purpose: End-of-life studies have validated the binary visual reads of 18F-labeled amyloid PET tracers as an accurate tool for the presence or absence of increased neuritic amyloid plaque density. In this study, the performance of a support vector machine (SVM)-based classifier will be tested against pathological ground truths and its performance determined in cognitively healthy older adults. Methods: We applied SVM with a linear kernel to an 18F-Flutemetamol end-of-life dataset to determine the regions with the highest feature weights in a data-driven manner and to compare between two different pathological ground truths: based on neuritic amyloid plaque density or on amyloid phases, respectively. We also trained and tested classifiers based on the 10% voxels with the highest amplitudes of feature weights for each of the two neuropathological ground truths. Next, we tested the classifiers' diagnostic performance in the asymptomatic Alzheimer's disease (AD) phase, a phase of interest for future drug development, in an independent dataset of cognitively intact older adults, the Flemish Prevent AD Cohort-KU Leuven (F-PACK). A regression analysis was conducted between the Centiloid (CL) value in a composite volume of interest (VOI), as index for amyloid load, and the distance to the hyperplane for each of the two classifiers, based on the two pathological ground truths. A receiver operating characteristic analysis was also performed to determine the CL threshold that optimally discriminates between neuritic amyloid plaque positivity versus negativity, or amyloid phase positivity versus negativity, within F-PACK. Results: The classifiers yielded adequate specificity and sensitivity within the end-of-life dataset (neuritic amyloid plaque density classifier: specificity of 90.2% and sensitivity of 83.7%; amyloid phase classifier: specificity of 98.4% and sensitivity of 84.0%). The regions with the highest feature weights corresponded to precuneus, caudate, anteromedial prefrontal, and also posterior inferior temporal and inferior parietal cortex. In the cognitively normal cohort, the correlation coefficient between CL and distance to the hyperplane was −0.66 for the classifier trained with neuritic amyloid plaque density, and −0.88 for the classifier trained with amyloid phases. This difference was significant. The optimal CL cut-off for discriminating positive versus negative scans was CL = 48–51 for the different classifiers (area under the curve (AUC) = 99.9%), except for the classifier trained with amyloid phases and based on the 10% voxels with highest feature weights. There the cut-off was CL = 26 (AUC = 99.5%), which closely matched the CL threshold for discriminating phases 0–2 from 3–5 based on the end-of-life dataset and the neuropathological ground truth. Discussion: Among a set of neuropathologically validated classifiers trained with end-of-life cases, transfer to a cognitively normal population works best for a classifier trained with amyloid phases and using only voxels with the highest amplitudes of feature weights. [ABSTRACT FROM AUTHOR]

Purpose: Human ageing is associated with a regional reduction in cerebral neuronal activity as assessed by numerous studies on brain glucose metabolism and perfusion, grey matter (GM) density and white matter (WM) integrity. As glucose metabolism may impact energetics to maintain myelin integrity, but changes in functional connectivity may also alter regional metabolism, we conducted a cross-sectional simultaneous FDG PET/MR study in a large cohort of healthy volunteers with a wide age range, to directly assess the underlying associations between reduced glucose metabolism, GM atrophy and decreased WM integrity in a single ageing cohort. Methods: In 94 healthy subjects between 19.9 and 82.5 years (mean 50.1 ± 17.1; 47 M/47F, MMSE ≥ 28), simultaneous FDG-PET, structural MR and diffusion tensor imaging (DTI) were performed. Voxel-wise associations between age and grey matter (GM) density, RBV partial-volume corrected (PVC) glucose metabolism, white matter (WM) fractional anisotropy (FA) and mean diffusivity (MD), and age were assessed. Clusters representing changes in glucose metabolism correlating significantly with ageing were used as seed regions for tractography. Both linear and quadratic ageing models were investigated. Results: An expected age-related reduction in GM density was observed bilaterally in the frontal, lateral and medial temporal cortex, striatum and cerebellum. After PVC, relative FDG uptake was negatively correlated with age in the inferior and midfrontal, cingulate and parietal cortex and subcortical regions, bilaterally. FA decreased with age throughout the entire brain WM. Four white matter tracts were identified connecting brain regions with declining glucose metabolism with age. Within these, relative FDG uptake in both origin and target clusters correlated positively with FA (0.32 ≤ r ≤ 0.71) and negatively with MD (− 0.75 ≤ r ≤ − 0.41). Conclusion: After appropriate PVC, we demonstrated that regional cerebral glucose metabolic declines with age and that these changes are related to microstructural changes in the interconnecting WM tracts. The temporal course and potential causality between ageing effects on glucose metabolism and WM integrity should be further investigated in longitudinal cohort PET/MR studies. [ABSTRACT FROM AUTHOR]

Purpose: Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neuronal and behavioral responses to alcohol intake, little is known about the effects of alcohol exposure on in vivo PDE10A activity in relation to apparent risk factors for AUD such as decision-making and anxiety. Methods: We performed a longitudinal [18F]JNJ42259152 microPET study to evaluate PDE10A changes over a 9-week intermittent access to alcohol model, including 6 weeks of alcohol exposure, 2 weeks of abstinence followed by 1 week relapse. Parametric PDE10A-binding potential (BPND) images were generated using a Logan reference tissue model with cerebellum as reference region and were analyzed using both a volume-of-interest and voxel-based approach. Moreover, individual decision-making and anxiety levels were assessed with the rat Iowa Gambling Task and open-field test over the IAE model. Results: We observed an increased alcohol preference especially in those animals that exhibited poor initial decision-making. The first 2 weeks of alcohol exposure resulted in an increased striatal PDE10A binding (> 10%). Comparing PDE10A-binding potential after 2 versus 4 weeks of exposure showed a significant decreased PDE10A in the caudate-putamen and nucleus accumbens (pFWE-corrected < 0.05). This striatal PDE10A decrease was related to alcohol consumption and preference. Normalization of striatal PDE10A to initial levels was observed after 1 week of relapse, apart from the globus pallidus. Conclusion: This study shows that chronic voluntary alcohol consumption induces a reversible increased PDE10A enzymatic availability in the striatum, which is related to the amount of alcohol preference. Thus, PDE10A-mediated signaling plays an important role in modulating the reinforcing effects of alcohol, and the data suggest that PDE10A inhibition may have beneficial behavioral effects on alcohol intake. [ABSTRACT FROM AUTHOR]

Purpose: To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET). Methods: Three hundred ninety ALS cases with King's stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King's stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King's 1, King's 2, King's 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates. Results: Brain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3. Conclusions: Our findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions. [ABSTRACT FROM AUTHOR]

Purpose: Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme that modulates intracellular transport and protein quality control. Inhibition of HDAC6 deacetylase activity has shown beneficial effects in disease models, including Alzheimer's disease and amyotrophic lateral sclerosis. This first-in-human positron emission tomography (PET) study evaluated the brain binding of [18F]EKZ-001 ([18F]Bavarostat), a radiotracer selective for HDAC6, in healthy adult subjects. Methods: Biodistribution and radiation dosimetry studies were performed in four healthy subjects (2M/2F, 23.5 ± 2.4 years) using sequential whole-body PET/CT. The most appropriate kinetic model to quantify brain uptake was determined in 12 healthy subjects (6M/6F, 57.6 ± 3.7 years) from 120-min dynamic PET/MR scans using a radiometabolite-corrected arterial plasma input function. Four subjects underwent retest scans (2M/2F, 57.3 ± 5.6 years) with a 1-day interscan interval to determine test-retest variability (TRV). Regional volume of distribution (VT) was calculated using one-tissue and two-tissue compartment models (1-2TCM) and Logan graphical analysis (LGA), with time-stability assessed. VT differences between males and females were evaluated using volume of interest and whole-brain voxel-wise approaches. Results: The effective dose was 39.1 ± 7.0 μSv/MBq. Based on the Akaike information criterion, 2TCM was the preferred model compared to 1TCM. Regional LGA VT were in agreement with 2TCM VT, however demonstrated a lower absolute TRV of 7.7 ± 4.9%. Regional VT values were relatively homogeneous with highest values in the hippocampus and entorhinal cortex. Reduction of acquisition time was achieved with a 0 to 60-min scan followed by a 90 to 120-min scan. Males demonstrated significantly higher VT than females in the majority of cortical and subcortical brain regions. No relevant radiotracer related adverse events were reported. Conclusion: [18F]EKZ-001 is safe and appropriate for quantifying HDAC6 expression in the human brain with Logan graphical analysis as the preferred quantitative approach. Males showed higher HDAC6 expression across the brain compared to females. [ABSTRACT FROM AUTHOR]

Simultaneously acquired CT images of the [ SP 18 sp F]FDG PET/CT demonstrate wall thickening of the entire colon with mild infiltration of the paracolic fat tissue and some prominent mesenterial lymph nodes. [ SP 18 sp F]FDG PET/CT also demonstrates a liver lesion cranially in the liver and multiple lymph nodes with high [ SP 18 sp F]FDG-uptake. [Extracted from the article]

Purpose: The widespread use of gallium-68-labelled somatostatin analogue (SSA) PET, the current standard for somatostatin receptor (SSTR) imaging, is limited by practical and economic challenges that could be overcome by a fluorine-18-labelled alternative, such as the recently introduced [18F]AlF-NOTA-octreotide ([18F]AlF-OC). This prospective trial aimed to evaluate safety, dosimetry, biodistribution, pharmacokinetics and lesion targeting of [18F]AlF-OC and perform the first comparison with [68Ga]Ga-DOTATATE in neuroendocrine tumour (NET) patients. Methods: Six healthy volunteers and six NET patients with a previous clinical [68Ga]Ga-DOTATATE PET were injected with an IV bolus of 4 MBq/kg [18F]AlF-OC. Healthy volunteers underwent serial whole-body PET scans from time of tracer injection up to 90 min post-injection, with an additional PET/CT at 150 and 300 min post-injection. In patients, a 45-min dynamic PET was acquired and three whole-body PET scans at 60, 90 and 180 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake (SUVmean) and tumour lesion uptake (SUVmax and tumour-to-background ratio (TBR)) were measured. A lesion-by-lesion analysis was performed and the detection ratio (DR), defined as the fraction of detected lesions was determined for each tracer. Results: [18F]AlF-OC administration was safe and well tolerated. The highest dose was received by the spleen (0.159 ± 0.062 mGy/MBq), followed by the urinary bladder wall (0.135 ± 0.046 mGy/mBq) and the kidneys (0.070 ± 0.018 mGy/MBq), in accordance with the expected SSTR-specific uptake in the spleen and renal excretion of the tracer. The effective dose was 22.4 ± 4.4 μSv/MBq. The physiologic uptake pattern of [18F]AlF-OC was comparable to [68Ga]Ga-DOTATATE. Mean tumour SUVmax was lower for [18F]AlF-OC (12.3 ± 6.5 at 2 h post-injection vs. 18.3 ± 9.5; p = 0.03). However, no significant differences were found in TBR (9.8 ± 6.7 at 2 h post-injection vs. 13.6 ± 11.8; p = 0.35). DR was high and comparable for both tracers (86.0% for [68Ga]Ga-DOTATATE vs. 90.1% for [18F]AlF-OC at 2 h post-injection; p = 0.68). Conclusion: [18F]AlF-OC shows favourable kinetic and imaging characteristics in patients that warrant further head-to-head comparison to validate [18F]AlF-OC as a fluorine-18-labelled alternative for gallium-68-labelled SSA clinical PET. Trial registration: Clinicaltrials.gov: NCT03883776, EudraCT: 2018-002827-40 [ABSTRACT FROM AUTHOR]

Purpose: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with on average a 1-year delay between symptom onset and diagnosis. Studies have demonstrated the value of [18F]-FDG PET as a sensitive diagnostic biomarker, but the discriminatory potential to differentiate ALS from patients with symptoms mimicking ALS has not been investigated. We investigated the combination of brain and spine [18F]-FDG PET-CT for differential diagnosis between ALS and ALS mimics in a real-life clinical diagnostic setting. Methods: Patients with a suspected diagnosis of ALS (n = 98; 64.8 ± 11 years; 61 M) underwent brain and spine [18F]-FDG PET-CT scans. In 62 patients, ALS diagnosis was confirmed (67.8 ± 10 years; 35 M) after longitudinal follow-up (average 18.1 ± 8.4 months). In 23 patients, another disease was diagnosed (ALS mimics, 60.9 ± 12.9 years; 17 M) and 13 had a variant motor neuron disease, primary lateral sclerosis (PLS; n = 4; 53.6 ± 2.5 years; 2 M) and progressive muscular atrophy (PMA; n = 9; 58.4 ± 7.3 years; 7 M). Spine metabolism was determined after manual and automated segmentation. VOI- and voxel-based comparisons were performed. Moreover, a support vector machine (SVM) approach was applied to investigate the discriminative power of regional brain metabolism, spine metabolism and the combination of both. Results: Brain metabolism was very similar between ALS mimics and ALS, whereas cervical and thoracic spine metabolism was significantly different (in standardised uptake values; cervical: ALS 2.1 ± 0.5, ALS mimics 1.9 ± 0.4; thoracic: ALS 1.8 ± 0.3, ALS mimics 1.5 ± 0.3). As both brain and spine metabolisms were very similar between ALS mimics and PLS/PMA, groups were pooled for accuracy analyses. Mean discrimination accuracy was 65.4%, 80.0% and 81.5%, using only brain metabolism, using spine metabolism and using both, respectively. Conclusion: The combination of brain and spine FDG PET-CT with SVM classification is useful as discriminative biomarker between ALS and ALS mimics in a real-life clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: 18F-FDG PET is routinely used as an imaging marker in the early and differential diagnosis of dementing disorders and has incremental value over the clinical neurological and neuropsychological evaluation. Perfusion MR imaging by means of arterial spin labelling (ASL) is an alternative modality to indirectly measure neuronal functioning and could be used as complement measurement in a single MR session in the workup of dementia. Using simultaneous PET-MR, we performed a direct head-to-head comparison between enhanced multiplane tagging ASL (eASL) and 18F-FDG PET in a true clinical context of subjects referred for suspicion of neurodegenerative dementia. Methods: Twenty-seven patients underwent a 20-min 18F-FDG PET/MR and simultaneously acquired eASL on a GE Signa PET/MR. Data were compared with 30 screened age- and gender-matched healthy controls. Both integral eASL and 18F-FDG datasets were analysed visually by two readers unaware of the final clinical diagnosis, either in normal/abnormal classes, or full differential diagnosis (normal, Alzheimer type dementia [AD], dementia with Lewy Bodies [LBD], frontotemporal dementia [FTD] or other). Reader confidence was assessed with a rating scale (range 1–4). Data were also analysed semiquantitatively by VOI and voxel-based analyses. Results: The ground truth diagnosis for the patient group resulted in 14 patients with a neurodegenerative cognitive disorder (AD, FTD, LBD) and 13 patients with no arguments for an underlying neurodegenerative cause. Visual analysis resulted in equal specificity (0.70) for differentiating normal and abnormal cases between the two modalities, but in a higher sensitivity (0.93), confidence rating (0.64) and interobserver agreement for 18F-FDG PET compared with eASL. The same was true for assigning a specific differential diagnosis (sensitivity: and 0.39 for 18F-FDG PET and eASL, respectively). Semiquantitative analyses revealed prototypical patterns for AD and FTD, with both higher volumes of abnormality and intensity differences on 18F-FDG PET. Conclusion: In a direct head-to-head comparison on a simultaneous GE Signa PET/MR, 18F-FDG PET performed better compared with ASL in terms of sensitivity and reader confidence, as well as volume and intensity of abnormalities. However, using pure semiquantitative analysis, similar diagnostic accuracy between the two modalities was obtained. Therefore, ASL may still serve as complement to neuroreceptor or protein deposition PET studies when a single simultaneous investigation is warranted. [ABSTRACT FROM AUTHOR]

Purpose: In vivo tau-PET tracer retention in the anterior temporal lobe of patients with semantic variant primary progressive aphasia (SV PPA) has consistently been reported. This is unexpected as the majority of these patients have frontotemporal lobar degeneration TDP (FTLD-TDP). Methods: We conducted an in vitro [18F]AV1451 autoradiography binding study in five cases with a clinical diagnosis of SV PPA constituting the range of pathologies (i.e., three FTLD-TDP, one Alzheimer's disease (AD), and one Pick's disease (PiD)). Binding was compared with two controls without neurodegeneration, two typical AD, one corticobasal syndrome with underlying AD, and one frontotemporal dementia behavioral variant with FTLD-TDP. The effect of blocking with the authentic reference material and with the MAO-B inhibitor deprenyl was assessed. Immunohistochemistry was performed on adjacent cryosections. Results: Absence of specific [18F]AV1451 binding was observed for all three SV PPA FTLD-TDP cases. The absence of binding in controls as well as the successful blocking with authentic AV1451 in cases with tauopathy demonstrated specificity of the [18F]AV1451 signal for tau. The specific [18F]AV1451 binding was highest in AD, followed by PiD. This binding colocalized with the respective tau lesions and could not be blocked by deprenyl. Similar pilot findings were obtained with [18F]THK5351. Conclusion: In vitro autoradiography showed no [18F]AV1451 binding in SV PPA due to FTLD-TDP, while specific binding was present in SV PPA due to AD and PiD. The discrepancy between in vitro and in vivo findings remains to be explained. The discordance is not related to [18F]AV1451 idiosyncrasies as [18F]THK5351 findings were similar. [ABSTRACT FROM AUTHOR]

Rationale: Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism. 18F-FE-PE2I is a suitable PET radioligand for DAT quantification and imaging with good pharmacokinetics. The aim of this study was to determine a clinical optimal simplified reference tissue-based image acquisition protocol and to compare the discriminatory value and effect size for 18F-FE-PE2I to that for 123I-FP-CIT scan currently used in clinical practice. Methods: Nine patients with early Parkinson's disease (PD, 64.3 ± 6.8 years, 3M), who had previously undergone a 123I-FP-CIT scan as part of their diagnostic workup, and 34 healthy volunteers (HV, 47.7 ± 16.8 years, 13M) underwent a 60-min dynamic 18F-FE-PE2I PET-MR scan on a GE Signa 3T PET-MR. Based on dynamic data and MR-based VOI delineation, BPND, semi-quantitative uptake ratio and SUVR[t1–t2] images were calculated using either occipital cortex or cerebellum as reference region. For start-and-end time of the SUVR interval, three time frames [t1–t2] were investigated: [15–40] min, [40–60] min, and [50–60] min postinjection. Data for putamen (PUT) and caudate nucleus-putamen ratio (CPR) were compared in terms of quantification bias versus BPND and discriminative power. Results: Using occipital cortex as reference region resulted in smaller bias of SUVR with respect to BPND + 1 and higher correlation between SUVR and BPND + 1 compared with using cerebellum, irrespective of SUVR [t1–t2] interval. Smallest bias was observed with the [15–40]-min time window, in accordance with previous literature. The correlation between BPND + 1 and SUVR was slightly better for the late time windows. Discriminant analysis between PD and HV using both PUT and CPR SUVRs showed an accuracy of ≥ 90%, for both reference regions and all studied time windows. Semi-quantitative 123I-FP-CIT and 18F-FE-PE2I values and relative decrease in the striatum for patients were highly correlated, with a higher effect size for 18F-FE-PE2I for PUT and CPR SUVR. Conclusion: 18F-FE-PE2I is a suitable radioligand for in vivo DAT imaging with high discriminative power between early PD and healthy controls. Whereas a [15–40]-min window has lowest bias with respect to BPND, a [50–60]-min time window at pseudoequilibrium can be advocated in terms of clinical feasibility with optimal discriminative power. The occipital cortex may be slightly preferable as reference region because of the higher time stability, stronger correlation of SUVR with BPND + 1, and lower bias. Moreover, the data suggest that the diagnostic accuracy of a 10-min static 18F-FE-PE2I scan is non-inferior compared with 123I-FP-CIT scan used in standard clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The endocannabinoid system plays a regulatory role in a number of physiological functions, including motor control but also mood, emotion, and cognition. A number of preclinical studies in Parkinson's disease (PD) models demonstrated that modulating the type 1 cannabinoid receptor (CB1R) may improve motor symptoms and components of cognitive processing. However, the relation between CB1R, cognitive decline and behavioral symptoms has not been investigated in PD patients so far. The aim of this study was to examine whether CB1R availability is associated with measures of cognitive and behavioral function in PD patients. Methods: Thirty-eight PD patients and ten age- and gender-matched controls underwent a [18F]MK-9470 PET scan to assess CB1R availability, as well as volumetric MR imaging. Neuropsychological symptoms were evaluated using an extensive cognitive and behavioral battery covering the five cognitive domains, depression, anxiety, apathy, and psychiatric complications, and were correlated to CB1R availability using vowel-wise regression analysis (P < 0.05, corrected for familywise error). Results: PD patients with poorer performance in episodic memory, executive functioning, speed and mental flexibility (range P 0.003–0.03) showed lower CB1R availability in predominantly the midcingulate cortex and middle to superior frontal gyrus (Tpeak-level > 4.0). Also, PD patients with more severe visuospatial dysfunction showed decreased CB1R availability in the precuneus, midcingulate, supplementary motor cortex, inferior orbitofrontal gyrus and thalamus (Tpeak-level = 5.5). These correlations were not related to cortical gray matter atrophy. No relationship was found between CB1R availability and mood or behavioral symptom scores. Conclusions: Decreased CB1R availability in the prefrontal and midcingulate cortex in PD patients is strongly correlated with disturbances in executive functioning, episodic memory, and visuospatial functioning. Further investigation of regional CB1R expression in groups of PD patients with mild cognitive impairment or dementia is warranted in order to further investigate the role of CB1R expression in different levels of cognitive impairment in PD. [ABSTRACT FROM AUTHOR]

Purpose: The P2X7 receptor (P2X7R) is an ATP-gated ion channel predominantly expressed on activated microglia and is important in neurodegenerative diseases including Parkinson's disease (PD). In this first-in-human study, we investigated [11C]JNJ54173717 ([11C]JNJ717), a selective P2X7R tracer, in healthy volunteers (HV) and PD patients. Biodistribution, dosimetry, kinetic modelling and short-term test–retest variation (TRV), as well as possible genotype effects, were investigated. Methods: Biodistribution and radiation dosimetry studies were performed in three HV (mean age 30 ± 2 years, two women) using whole-body PET/CT. The most appropriate kinetic model was determined in 11 HV (mean age 62 ± 10 years, six women) and 10 PD patients (mean age 64 ± 8 years, three women; mean UPDRS motor score 21 ± 8) using 90-min dynamic simultaneous PET/MR scans. The total volume of distribution (VT) was calculated using a one-tissue and a two-tissue compartment model (1TCM, 2TCM) and Logan graphical analysis, and its time stability was assessed. Seven subjects underwent retest scans (mean age 60 ± 13 years, four HV, one woman). A group analysis was performed to compare PD patients and HV. Finally, 13 exons of P2X7R were genotyped in all subjects included in the second part of the study. Results: The mean effective dose was 4.47 ± 0.32 μSv/MBq, with the highest absorbed doses to the gallbladder, liver and small intestine. A reversible 2TCM was the most appropriate kinetic model with relatively homogeneous VT values in the grey and white matter. Average VT values were 3.4 ± 0.8 in HV and 3.3 ± 0.7 in PD patients, with no significant difference between the groups, but a possible genotype effect (rs3751143) was identified which can affect VT. Average TRV was 10–15%. The stability of VT over time allowed a reduction in scan time to 70 min. Conclusion: [11C]JNJ717 is safe and suitable for quantifying P2X7R expression in human brain. In this pilot study, no significant differences in P2X7R binding were found between HV and PD patients. The results also suggest that genotype effects need to be incorporated in future P2X7R PET analyses. [ABSTRACT FROM AUTHOR]

Purpose: A [11C]UCB-J blocking study was performed in healthy volunteers to validate simplified, non-invasive measures for quantifying presynaptic SV2A expression using subcortical white matter as reference tissue.Methods: Ninety minutes dynamic [11C]UCB-J PET scanning with arterial blood sampling was performed in 10 healthy volunteers (8 M/2F; age 27.6 ± 10.0 yrs), before and after administration of a novel chemical entity with selective affinity for SV2A. The centrum semi-ovale (SO) was validated as reference region by comparing baseline and post treatment distribution volume (VT). Using SO as reference tissue, Binding Potential (BPSO) using a Simplified Reference Tissue Model (SRTM, down to 60 min acquisition) and Standardized Uptake Value Ratios (60-90 min post injection - SUVRSO,60-90min) were compared with regional distribution volume ratios (DVR). Next, SV2A occupancy values based on SRTM BPSO and SUVRSO,60-90min were compared to occupancy estimates using regional VT values and a Lassen plot.Results: After pretreatment, regional VT values were reduced significantly except for SO. Highly significant correlations were found between DVR, SRTM BPSO and SUVRSO,60-90min. Compared to DVR, baseline SRTM BPSO showed a small bias (≤ 6.1%) with lower precision for shorter acquisition times, while SUVRSO,60-90min showed 3.5% bias with similar precision. Differences between SV2A occupancy values based on SUVRSO,60-90min and occupancy estimates using VT and a Lassen plot were small but significant, while negligible bias was found for SRTM based occupancy estimates (at least 70 min acquisition).Conclusion: This [11C]UCB-J blocking study validated SO as a suitable reference region for non-invasive quantification of SV2A availability and drug occupancy in the human brain. Accurate quantification can be achieved by using either SUVRSO,60-90min with a 60-90 min PET acquisition or SRTM BPSOwith at least 70 min dynamic PET acquisition. [ABSTRACT FROM AUTHOR]

Purpose: To assess the binding of the PET tracer [18F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respectively, while patients with the semantic variant (SV) have predominantly transactive response DNA binding protein 43-kDa pathology.Methods: The study included 20 PPA patients consecutively recruited through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All participants received an extensive neurolinguistic assessment, magnetic resonance imaging and amyloid biomarker tests. [18F]THK5351 binding patterns were assessed on standardized uptake value ratio (SUVR) images with the cerebellar grey matter as the reference using statistical parametric mapping. Whole-brain voxel-wise regression analysis was performed to evaluate the association between [18F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with and without partial volume correction.Results: Patients with NFV showed increased binding in the supplementary motor area, left premotor cortex, thalamus, basal ganglia and midbrain compared with controls and patients with SV. Patients with SV had increased binding in the temporal lobes bilaterally and in the right ventromedial frontal cortex compared with controls and patients with NFV. The whole-brain voxel-wise regression analysis revealed a correlation between agrammatism and motor speech impairment, and [18F]THK5351 binding in the left supplementary motor area and left postcentral gyrus. Analysis of [18F]THK5351 scans without partial volume correction revealed similar results.Conclusion: [18F]THK5351 imaging shows a topography closely matching the anatomical distribution of predicted underlying pathology characteristic of NFV and SV PPA. [18F]THK5351 binding correlates with the severity of clinical impairment. [ABSTRACT FROM AUTHOR]

Improved resolution and sensitivity of [18F]MFBG PET compared with [123I]MIBG SPECT in a patient with a norepinephrine transporter-expressing tumour Moreover, if neural crest tumour patients are considered for peptide receptor radionuclide therapy, addition of norepinephrine transporter imaging to the pre-therapeutic work-up allows evaluating whether [ SP 131 sp I]MIBG or a combination treatment may increase therapeutic efficacy. [ SP 18 sp F]MFBG is a promising clinical PET alternative for [ SP 123 sp I]MIBG, offering improved sensitivity, same-day imaging and the possibility of PET/MR imaging, as a one-stop-shop for patients with norepinephrine transporter-expressing tumours. [Extracted from the article]

Purpose: To review literature until November 2015 and reach a consensus on whether automatic semi-quantification of brain FDG-PET is useful in the clinical setting for neurodegenerative disorders.Methods: A literature search was conducted in Medline, Embase, and Google Scholar. Papers were selected with a lower limit of 30 patients (no limits with autopsy confirmation). Consensus recommendations were developed through a Delphi procedure, based on the expertise of panelists, who were also informed about the availability and quality of evidence, assessed by an independent methodology team.Results: Critical outcomes were available in nine among the 17 papers initially selected. Only three papers performed a direct comparison between visual and automated assessment and quantified the incremental value provided by the latter. Sensitivity between visual and automatic analysis is similar but automatic assessment generally improves specificity and marginally accuracy. Also, automated assessment increases diagnostic confidence. As expected, performance of visual analysis is reported to depend on the expertise of readers.Conclusions: Tools for semi-quantitative evaluation are recommended to assist the nuclear medicine physician in reporting brain FDG-PET pattern in neurodegenerative conditions. However, heterogeneity, complexity, and drawbacks of these tools should be known by users to avoid misinterpretation. Head-to-head comparisons and an effort to harmonize procedures are encouraged. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: F-flutemetamol and C-Pittsburgh compound B (PIB). Methods: In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on F-flutemetamol versus C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVR) and, alternatively, according to visual reads. We also determined the correlation between F-flutemetamol and C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. Results: Binary classification based on semiquantitative assessment was concordant between F-flutemetamol and C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between F-flutemetamol and C-PIB SUVR with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. Conclusion: For the definition of preclinical AD based on F-flutemetamol, concordance with C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region. [ABSTRACT FROM AUTHOR]

Purpose: Several lines of evidence strongly implicate a dysfunctional endocannabinoid system (ECS) in eating disorders. Using [F]MK-9470 and small animal positron emission tomography (PET), we investigated for the first time cerebral changes in type 1 cannabinoid (CB1) receptor binding in vivo in the activity-based rat model of anorexia (ABA), in comparison to distinct motor- and food-related control conditions and in relation to gender and behavioural variables. Methods: In total, experiments were conducted on 80 Wistar rats (23 male and 57 female). Male rats were assigned to the cross-sectional conditions: ABA ( n = 12) and CONTROL ( n = 11), whereas female rats were divided between two settings: (1) a cross-sectional design using ABA ( n = 13), CONTROL ( n = 9), and two extra control conditions for each of the variables manipulated in ABA, i.e. DIET ( n = 8) and WHEEL ( n = 9), and (2) a longitudinal one using ABA ( n = 10) and CONTROL ( n = 8) studied at baseline, during the model and upon recovery. The ABA group was subjected to food restriction in the presence of a running wheel, the DIET group to food restriction without wheel, the WHEEL group to a normal diet with wheel and CONTROL animals had a normal diet and no running wheel. Parametric CB1 receptor images of each group were spatially normalized to Paxinos space and analysed voxel-wise. Results: In the ABA model, absolute [F]MK-9470 binding was significantly increased in all cortical and subcortical brain areas as compared to control conditions (male +67 %; female >51 %, all p < 6.3×10) that normalized towards baseline values after weight gain. Additionally, relative [F]MK-9470 binding was increased in the hippocampus, inferior colliculus and entorhinal cortex of female ABA (+4.6 %; p < 1.3×10), whereas no regional differences were observed in male subjects. Again, relative [F]MK-9470 binding values normalized upon weight gain. Conclusion: These data point to a widespread transient disturbance of the endocannabinoid transmission, specifically for CB1 receptors in the ABA model. Our data also suggest (1) gender effects on regional CB1 receptor binding in the hippocampus and (2) add further proof to the validity of the ABA model to mimic aspects of human disease. [ABSTRACT FROM AUTHOR]

Purpose: Recent biochemical and post-mortem evidence suggests involvement of the endocannabinoid system in alcohol drinking behaviour and dependence. Using [F]MK-9470 small-animal PET imaging, our primary objective was to evaluate in vivo type 1 cannabinoid receptor (CB1R) binding changes in rats subjected to several ethanol conditions: (1) at baseline, (2) after acute intraperitoneal administration of ethanol (4 g/kg) or saline, (3) after 7 days of forced chronic ethanol consumption, and (4) after abstinence for 7 and 14 days. Secondly, levels of anandamide (AEA) in the nucleus accumbens (NAcc) were investigated in the same animals using in vivo microdialysis and correlated with the changes in CB1R binding. Methods: In total, 28 male Wistar rats were investigated. Small-animal PET was done on a FOCUS-220 tomograph with [F]MK-9470. Parametric images of [F]MK-9470 binding based on standard uptake values (SUV, as a measure of CB1R binding) were generated. Images were normalized to Paxinos space and analysed voxel-wise using SPM8 ( p = 0.005; k = 200). The AEA content was quantified using HPLC with tandem mass spectrometry detection. Results: Acute ethanol administration increased relative CB1R binding in the NAcc that was positively correlated with the change in AEA levels of that region. In contrast, compared to rats at baseline, AEA levels in the NAcc were not significantly different in rats after chronic ethanol consumption or after a 14-day abstinence period. Chronic ethanol consumption decreased relative CB1R binding in the hippocampus and caudate-putamen, whereas same regions showed increased relative CB1R binding after 7 and 14 days of abstinence compared to the baseline condition. After 7 and 14 days of abstinence, relative CB1R binding additionally decreased in the orbitofrontal cortex. The magnitude of the hippocampal and frontal changes was highly correlated with daily ethanol intake. Conclusion: This study provides in vivo evidence that acute ethanol consumption is associated with enhanced endocannabinoid signalling in the NAcc, indicated by an increased CB1R binding and AEA content. In addition, chronic ethanol exposure leads to regional dysfunctions in CB1R levels, involving the hippocampus and caudate-putamen that are reversible within 2 weeks in this animal model. [ABSTRACT FROM AUTHOR]

Purpose: [F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Methods: Dynamic small-animal PET scans with [F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume ( V) of [F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. Results: The percentage of intact [F]MK-9470 in arterial plasma samples was 80 ± 23 % at 10 min, 38 ± 30 % at 40 min and 13 ± 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability (≤10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [F]MK-9470 V, but was correlated. A correlation between [F]MK-9470 V and SUV in the brain was also found ( R = 0.26-0.33; p ≤ 0.03). Conclusion: While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. [ABSTRACT FROM AUTHOR]

Purpose: Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D receptor availability and amphetamine-induced turning behaviour. Methods: Twenty-one Wistar rats (11 QA and 10 shams) were investigated. Small animal PET acquisitions were conducted on a Focus 220 with approximately 18 MBq of [F]MK-9470, [F]FDG and [C]raclopride. Relative glucose metabolism and parametric CB receptor and D binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2). Results: In the QA model, [F]MK-9470 uptake, glucose metabolism and D receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p < 2.10), while an increase for these markers was observed on the contralateral side (>5%, all p < 7.10). [F]MK-9470 binding was also increased in the cerebellum ( p = 2.10), where it was inversely correlated to the number of ipsiversive turnings ( p = 7.10), suggesting that CB receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex ( p = 1.10). Conclusion: These data point to in vivo changes in endocannabinoid transmission, specifically for CB receptors in the QA model, with involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D and CB neurotransmission in the contralateral hemisphere. [ABSTRACT FROM AUTHOR]

Detection of hypometabolic areas on interictal FDG-PET images for assessing the epileptogenic zone is hampered by partial volume effects. We evaluated the performance of an anatomy-based maximum a-posteriori (A-MAP) reconstruction algorithm which combined noise suppression with correction for the partial volume effect in the detection of hypometabolic areas in patients with focal cortical dysplasia (FCD). FDG-PET images from 14 patients with refractory partial epilepsy were reconstructed using A-MAP and maximum likelihood (ML) reconstruction. In all patients, presurgical evaluation showed that FCD represented the epileptic lesion. Correspondence between the FCD location and regional metabolism on a predefined atlas was evaluated. An asymmetry index of FCD to normal cortex was calculated. Hypometabolism at the FCD location was detected in 9/14 patients (64%) using ML and in 10/14 patients (71%) using A-MAP reconstruction. Hypometabolic areas outside the FCD location were detected in 12/14 patients (86%) using ML and in 11/14 patients (79%) using A-MAP reconstruction. The asymmetry index was higher using A-MAP reconstruction (0.61, ML 0.49, p=0.03). The A-MAP reconstruction algorithm improved visual detection of epileptic FCD on brain FDG-PET images compared to ML reconstruction, due to higher contrast and better delineation of the lesion. This improvement failed to reach significance in our small sample. Hypometabolism outside the lesion is often present, consistent with the observation that the functional deficit zone tends to be larger than the epileptogenic zone. [ABSTRACT FROM AUTHOR]

Small animal PET can be applied to study molecular processes in animal models of a variety of human diseases. In order to keep the animals in a restricted position during imaging, anaesthesia is in many instances inevitable. Using small animal PET and ex vivo autoradiography, we examined the influence of pentobarbital and isoflurane anaesthesia on the rat brain uptake of [18F]MK-9470, a radioligand for the type 1 cannabinoid receptor. PET imaging was performed on adult Wistar rats under pentobarbital ( n = 6) and isoflurane anaesthesia ( n = 7), and under control conditions (free moving during tracer uptake, n = 8). Parametric PET images were generated, anatomically standardized and analysed by voxel-based Statistical Parametric Mapping and a predefined volume of interest approach. Immediately after in vivo PET, brains were processed for ex vivo autoradiography using manually placed regions of interest. An extra group ( n = 6) was included ex vivo, in which animals were intravenously injected without the use of anaesthetics. Using in vivo and ex vivo molecular imaging techniques, no significant changes in absolute [18F]MK-9470 uptake were present in the brain of pentobarbital and isoflurane rats as compared to control conditions. Relative [18F]MK-9470 uptake PET values obtained applying global scaling were, however, decreased in the cortex under both anaesthetics (pentobarbital: −13.3±1.4%; isoflurane −8.7 ± 3.1%), while an increase was seen in the cerebellum by 13.5 ± 4.0% and 13.9 ± 4.1% under pentobarbital and isoflurane, respectively. Ex vivo results were in agreement with in vivo findings. These findings suggest a similar, regionally specific interference of pentobarbital and isoflurane anaesthesia with in vivo CB1 receptor imaging using [18F]MK-9470. [ABSTRACT FROM AUTHOR]

Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [18F]MK-9470 in human brain. [18F]MK-9470 data were analysed using reversible models and the distribution volume VT and VND k3 ( VND k3 = K1 k2) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant Ki and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined. A reversible two-tissue compartment model using a global k4 value was necessary to describe brain kinetics. Both VT and VND k3 were estimated satisfactorily and their test–retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to Ki. The linear relationship between Ki and VND k3 demonstrated that Ki or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test–retest variability of Ki and FUR was <10% and estimates were independent of blood flow. Brain uptake can be used as a receptor availability index, albeit at the expense of potential bias due to between-subject differences in tracer plasma kinetics. [18F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [18F]MK-9470 plasma kinetics can be assessed using a few venous samples. [ABSTRACT FROM AUTHOR]

The guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2 receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, which will increase the impact of this technique in neurological practice. The present document is an update of the first guidelines for SPECT using D2 receptor ligands labelled with 123I [] and was guided by the views of the Society of Nuclear Medicine Brain Imaging Council [], and the individual experience of experts in European countries. The guidelines intend to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations. [ABSTRACT FROM AUTHOR]

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using 123I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [], a consensus statement of the imaging centres included in the “Kompetenznetz-Parkinson” sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine []. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations. [ABSTRACT FROM AUTHOR]

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose ([18F]FDG) PET imaging of the brain. The aim is to help achieve a high standard of FDG imaging, which will increase the diagnostic impact of this technique in neurological and psychiatric practice. The present document replaces a former version of the guidelines that were published in 2002 [] and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging. These guidelines are intended to present information specifically adapted for European practice. The information provided should be taken in the context of local conditions and regulations. [ABSTRACT FROM AUTHOR]

The unilateral 6-hydroxydopamine (6-OHDA) lesion rat model is a well-known acute model for Parkinson’s disease (PD). Its validity has been supported by invasive histology, behavioral studies and electrophysiology. Here, we have characterized this model in vivo by multitracer imaging [glucose metabolism and dopamine transporter (DAT)] in relation to behavioral and histological parameters. Eighteen female adult Wistar rats (eight 6-OHDA-lesioned, ten controls) were investigated using multitracer [18F]-fluoro-2-deoxy- D-glucose (FDG) and [18F]-FECT {2′-[18F]-fluoroethyl-(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)-8-azabicyclo(3.2.1)-octane-2-carboxylate} small animal positron emission tomography (PET). Relative glucose metabolism and parametric DAT binding images were anatomically standardized to Paxinos space and analyzed on a voxel-basis using SPM2, supplemented by a template-based predefined volumes-of-interest approach. Behavior was characterized by the limb-use asymmetry test; dopaminergic innervation was validated by in vitro tyrosine hydroxylase staining. In the 6-OHDA model, significant glucose hypometabolism is present in the ipsilateral sensory-motor cortex (−6.3%; p = 4 × 10−6). DAT binding was severely decreased in the ipsilateral caudate-putamen, nucleus accumbens and substantia nigra (all p < 5 × 10−9), as confirmed by the behavioral and histological outcomes. Correlation analysis revealed a positive relationship between the degree of DAT impairment and the change in glucose metabolism in the ipsilateral hippocampus ( p = 3 × 10−5), while cerebellar glucose metabolism was inversely correlated to the level of DAT impairment ( p < 3 × 10−4). In vivo cerebral mapping of 6-OHDA-lesioned rats using [18F]-FDG and [18F]-FECT small animal PET shows molecular–functional correspondence to the cortico-subcortical network impairments observed in PD patients. This provides a further molecular validation supporting the validity of the 6-OHDA lesion model to mimic multiple aspects of human PD. [ABSTRACT FROM AUTHOR]

Spatial covariance analysis has been used with FDG PET to identify a specific metabolic network associated with Parkinson’s disease (PD). In the current study, we utilized a new, fully automated voxel-based method to quantify network expression in ECD SPECT images from patients with classical PD, patients with multiple system atrophy (MSA), and healthy control subjects. We applied a previously validated voxel-based PD-related covariance pattern (PDRP) to quantify network expression in the ECD SPECT scans of 35 PD patients, 15 age- and disease severity-matched MSA patients, and 35 age-matched healthy control subjects. PDRP scores were compared across groups using analysis of variance. The sensitivity and specificity of the prospectively computed PDRP scores in the differential diagnosis of individual subjects were assessed by receiver operating characteristic (ROC) analysis. PDRP scores were significantly increased ( p < 0.001) in the PD group relative to the MSA and control groups. ROC analysis indicated that the overall diagnostic accuracy of the PDRP measures was 0.91 (AUC). The optimal cutoff value was consistent with a sensitivity of 0.97 and a specificity of 0.80 and 0.71 for discriminating PD patients from MSA and normal controls, respectively. Our findings suggest that fully automated voxel-based network assessment techniques can be used to quantify network expression in the ECD SPECT scans of parkinsonian patients. [ABSTRACT FROM AUTHOR]

The article describes the X-ray images of a 53-year-old male diagnosed with diffuse metastases of a rectal neuroendocrine tumor. Highlights include scans acquired on the same integrated Siemens Biograph 40 Truepoint PET/CT system, diffuse liver metastases and several bone and lymph node metastases, and evidence of in vivo defluorination.

The non-invasive assessment of postoperative spinal infections can pose a substantial diagnostic challenge, especially in the presence of orthopaedic devices. Whereas white blood cell scanning is of limited use in the spine, the low normal bone marrow uptake of technetium-99m ciprofloxacin combined with its claimed bacterial specificity makes it theoretically an ideal candidate for the evaluation of postoperative spinal infections. This study aimed to evaluate [sup 99m]Tc-ciprofloxacin planar and single-photon emission tomography (SPET) imaging in relation to microbiological and clinical diagnosis in the postoperative spine. Planar imaging was performed at 1, 3 and 24 h and SPET was performed at 3 h post injection of 370 MBq [sup 99m]Tc-ciprofloxacin. Images were scored by two independent certified nuclear medicine physicians, blinded to the final diagnosis. Within the 48 patients, there were 13 deep infections. Sensitivity, specificity and accuracy at visual scoring were respectively 54%, 71% and 67% (1 h), 62%, 77% and 73% (3 h), 42%, 91% and 77% (24 h) for planar imaging and 100%, 74% and 81% for SPET. When recently operated patients (<6 months) were excluded, the specificity of the SPET imaging rose to 81%. In conclusion, unlike white blood cell scanning, [sup 99m]Tc-ciprofloxacin SPET is sensitive in evaluating infections in the postoperative spine. Sensitivity is much higher for SPET than for planar imaging. However, the results presented prove that its specificity is limited, especially in recently operated patients. Taking this limitation into account, we advise planar and SPET imaging at 3 h post injection and an interval of at least 6 months after surgery to minimise the likelihood of false positives. [ABSTRACT FROM AUTHOR]

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders such as multiple system atrophy (MSA) is complicated by the presence of signs and symptoms common to both forms. The goal of this study was to re-evaluate the contribution of brain perfusion single-photon emission tomography (SPET) with anatomical standardisation and automated analysis in the differentiation of IPD and MSA. This was achieved by discriminant analysis in comparison with a large set of age- and gender-matched healthy volunteers. Technetium-99m ethyl cysteinate dimer SPET was performed on 140 subjects: 81 IPD patients (age 62.6±10.2 years; disease duration 11.0±6.4 years; 50 males/31 females), 15 MSA patients (61.5±9.2 years; disease duration 3.0±2.2 years; 9 males/6 females) and 44 age- and gender-matched healthy volunteers (age 59.2±11.9 years; 27 males/17 females). Patients were matched for severity (Hoehn and Yahr stage). Automated predefined volume of interest (VOI) analysis was carried out after anatomical standardisation. Stepwise discriminant analysis with cross-validation using the leave-one-out method was used to determine the subgroup of variables giving the highest accuracy for this differential diagnosis. Between MSA and IPD, the only regions with highly significant differences in uptake after Bonferroni correction were the putamen VOIs. Comparing MSA versus normals and IPD, with putamen VOI values as discriminating variables, cross-validated performance showed correct classification of MSA patients with a sensitivity of 73.3%, a specificity of 84% and an accuracy of 83.6%. Additional input from the right caudate head and the left prefrontal and left mesial temporal cortex allowed 100% discrimination even after cross-validation. Discrimination between the IPD group alone and healthy volunteers was accurate in 94% of the cases after cross-validation, with a sensitivity of 91.4% and a specificity... [ABSTRACT FROM AUTHOR]