Ultra-low foetal radiation exposure in 18F-FDG PET/CT imaging with a long axial field-of-view PET/CT system.

PURPOSE: Long axial field-of-view (LAFOV) PET/CT systems enable PET/CT scans with reduced injected activities because of improved sensitivity. With this study, we aimed to examine the foetal radiation dose from an 18F-FDG PET/CT scan on a LAFOV PET/CT system with reduced injected activity. METHODS: Two pregnant women were retrospectively included and received an 18F-FDG PET/CT scan on a LAFOV PET/CT system with an intravenous bolus injection of 0.30 MBq/kg. Foetal radiation exposure from the PET was estimated using dose conversion factors from three published papers. Radiation exposure from the CT scans was estimated using CT-Expo. RESULTS: Foetal radiation dose from the PET scan ranged between 0.11 and 0.44 mGy. Foetal radiation exposure from the CT scan ranged between < 0.10 - 0.90 mGy depending if the foetus was included in the field-of-view. CONCLUSION: Foetal radiation dose could be reduced to < 1.5 mGy when scanning pregnant patients on a LAFOV PET/CT system. The radiation dose to the foetus was reduced significantly in our study due to the increased sensitivity of the LAFOV PET/CT system.

Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers.

BACKGROUND: Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings. METHODS: Eight [18F]FDG and 10 [18F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system. PET images were reconstructed using various reconstruction settings. IDIFs were taken from ascending aorta (AA), descending aorta (DA), and left ventricular cavity (LV). The calibration factor (CF) extracted from the comparison between the IDIFs and the manual blood samples as reference was used for IDIFs accuracy and precision assessment. To illustrate the effect of various calibrated-IDIFs on Patlak linearization for [18F]FDG and Logan linearization for [18F]DPA-714, the same target time-activity curves were applied for each calibrated-IDIF. RESULTS: For [18F]FDG, the accuracy and precision of the IDIFs were high (mean CF ≥ 0.82, SD ≤ 0.06). Compared to the striatum influx (Ki) extracted using calibrated AA IDIF with the updated European Association of Nuclear Medicine Research Ltd. standard reconstruction (EARL2), Ki mean differences were < 2% using the other calibrated IDIFs. For [18F]DPA714, high accuracy of the IDIFs was observed (mean CF ≥ 0.86) except using absolute scatter correction, DA and LV (respectively mean CF = 0.68, 0.47 and 0.44). However, the precision of the AA IDIFs was low (SD ≥ 0.10). Compared to the distribution volume (VT) in a frontal region obtained using calibrated continuous arterial sampler input function as reference, VT mean differences were small using calibrated AA IDIFs (for example VT mean difference = -5.3% using EARL2), but higher using calibrated DA and LV IDIFs (respectively + 12.5% and + 19.1%). CONCLUSIONS: For [18F]FDG, IDIF do not need calibration against manual blood samples. For [18F]DPA-714, AA IDIF can replace continuous arterial sampling for simplified kinetic quantification but only with calibration against arterial blood samples. The accuracy and precision of IDIF from LAFOV PET/CT system depend on tracer, reconstruction settings and IDIF VOI locations, warranting careful optimization.

Endocannabinoid levels in plasma and neurotransmitters in the brain: a preliminary report on patients with a psychotic disorder and healthy individuals.

BACKGROUND: Interactions between the endocannabinoid system (ECS) and neurotransmitter systems might mediate the risk of developing a schizophrenia spectrum disorder (SSD). Consequently, we investigated in patients with SSD and healthy controls (HC) the relations between (1) plasma concentrations of two prototypical endocannabinoids (N-arachidonoylethanolamine [anandamide] and 2-arachidonoylglycerol [2-AG]) and (2) striatal dopamine synthesis capacity (DSC), and glutamate and y-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC). As anandamide and 2-AG might reduce the activity of these neurotransmitters, we hypothesized negative correlations between their plasma levels and the abovementioned neurotransmitters in both groups. METHODS: Blood samples were obtained from 18 patients and 16 HC to measure anandamide and 2-AG plasma concentrations. For all subjects, we acquired proton magnetic resonance spectroscopy scans to assess Glx (i.e. glutamate plus glutamine) and GABA + (i.e. GABA plus macromolecules) concentrations in the ACC. Ten patients and 14 HC also underwent [18F]F-DOPA positron emission tomography for assessment of striatal DSC. Multiple linear regression analyses were used to investigate the relations between the outcome measures. RESULTS: A negative association between 2-AG plasma concentration and ACC Glx concentration was found in patients (p = 0.008). We found no evidence of other significant relationships between 2-AG or anandamide plasma concentrations and dopaminergic, glutamatergic, or GABAergic measures in either group. CONCLUSIONS: Our preliminary results suggest an association between peripheral 2-AG and ACC Glx levels in patients.

Mitigating SUV uncertainties using total body PET imaging.

PURPOSE: Standardised uptake values (SUV) are commonly used to quantify 18F-FDG lesion uptake. However, SUVs may suffer from several uncertainties and errors. Long-axial field-of-view (LAFOV) PET/CT systems might enable image-based quality control (QC) by deriving 18F-FDG activity and weight from total body (TB) 18F-FDG PET images. In this study, we aimed to develop these image-based QC to reduce errors and mitigate SUV uncertainties. METHODS: Twenty-five out of 81 patient scans from a LAFOV PET/CT system were used to determine regression fits for deriving of image-derived activity and weight. Thereafter, the regression fits were applied to 56 independent 18F-FDG PET scans from the same scanner to determine if injected activity and weight could be obtained accurately from TB and half-body (HB) scans. Additionally, we studied the impact of image-based values on the precision of liver SUVmean and lesion SUVpeak. Finally, 20 scans were acquired from a short-axial field-of-view (SAFOV) PET/CT system to determine if the regression fits also applied to HB scans from a SAFOV system. RESULTS: Both TB and HB 18F-FDG activity and weight significantly predicted reported injected activity (r = 0.999; r = 0.984) and weight (r = 0.999; r = 0.987), respectively. After applying the regression fits, 18F-FDG activity and weight were accurately derived within 4.8% and 3.2% from TB scans and within 4.9% and 3.1% from HB, respectively. Image-derived values also mitigated liver and lesion SUV variability compared with reported values. Moreover, 18F-FDG activity and weight obtained from a SAFOV scanner were derived within 6.7% and 4.5%, respectively. CONCLUSION: 18F-FDG activity and weight can be derived accurately from TB and HB scans, and image-derived values improved SUV precision and corrected for lesion SUV errors. Therefore, image-derived values should be included as QC to generate a more reliable and reproducible quantitative uptake measurement.

PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is a group of aggressive hematological cancers with dismal outcomes that are in need of new therapeutic options. Polycomb repressor complex 2 (PRC2) loss-of-function alterations were reported in pediatric T-ALL, yet their clinical relevance and functional consequences remain elusive. Here, we extensively analyzed PRC2 alterations in a large series of 218 adult T-ALL patients. We found that PRC2 genetic lesions are frequent events in T-ALL and are not restricted to early thymic precursor ALL. PRC2 loss of function associates with activating mutations of the IL7R/JAK/STAT pathway. PRC2-altered T-ALL patients respond poorly to prednisone and have low bone marrow blast clearance and persistent minimal residual disease. Furthermore, we identified that PRC2 loss of function profoundly reshapes the genetic and epigenetic landscapes, leading to the reactivation of stem cell programs that cooperate with bromodomain and extraterminal (BET) proteins to sustain T-ALL. This study identifies BET proteins as key mediators of the PRC2 loss of function-induced remodeling. Our data have uncovered a targetable vulnerability to BET inhibition that can be exploited to treat PRC2-altered T-ALL patients.

Gelation enabled charge separation following visible light excitation using self-assembled perylene bisimides.

Perylene bisimides (PBIs) can be functionalised to enable controlled aggregation into complex supramolecular structures and are promising materials for photovoltaic and solar fuel applications. Amino acid appended PBIs such as PBI-alanine (PBI-A) have been found to form photoconductive films containing worm-like structures that enable charge transport. However, despite being strong chromophores in the visible region, when PBI-A films are prepared by drying down solutions, activity only occurs under UV illumination. This limits potential applications. The requirement for UV illumination has previously been suggested to be due to the large ion-pair energy in the low dielectric environment of the dried samples. Hydrogel films, rehydrated xerogels and dry xerogels of PBI-A can also be prepared offering an ideal sample set to examine the influence of hydration on charge-separation. Using transient absorption (TA) spectroscopy, we demonstrate a correlation between water content and efficiency of generation of long-lived charge separated states within the PBI-A materials, highlighting their potential, particularly for light-driven water splitting.

BET protein targeting suppresses the PD-1/PD-L1 pathway in triple-negative breast cancer and elicits anti-tumor immune response.

Therapeutic strategies aiming to leverage anti-tumor immunity are being intensively investigated as they show promising results in cancer therapy. The PD-1/PD-L1 pathway constitutes an important target to restore functional anti-tumor immune response. Here, we report that BET protein inhibition suppresses PD-1/PD-L1 in triple-negative breast cancer. BET proteins control PD-1 expression in T cells, and PD-L1 in breast cancer cell models. BET protein targeting reduces T cell-derived interferon-γ production and signaling, thereby suppressing PD-L1 induction in breast cancer cells. Moreover, BET protein inhibition improves tumor cell-specific T cell cytotoxic function. Overall, we demonstrate that BET protein targeting represents a promising strategy to overcome tumor-reactive T cell exhaustion and improve anti-tumor immune responses, by reducing the PD-1/PD-L1 axis in triple-negative breast cancer.

Photocatalytically active ladder polymers.

Conjugated ladder polymers (cLaPs) are introduced as organic semiconductors for photocatalytic hydrogen evolution from water under sacrificial conditions. Starting from a linear conjugated polymer (cLiP1), two ladder polymers are synthesized via post-polymerization annulation and oxidation techniques to generate rigidified, planarized materials bearing dibenzo[b,d]thiophene (cLaP1) and dibenzo[b,d]thiophene sulfone subunits (cLaP2). The high photocatalytic activity of cLaP1 (1307 µmol h-1 g-1) in comparison to that of cLaP2 (18 µmol h-1 g-1) under broadband illumination (λ > 295 nm) in the presence of a hole-scavenger is attributed to a higher yield of long-lived charges (µs to ms timescale), as evidenced by transient absorption spectroscopy. Additionally, cLaP1 has a larger overpotential for proton reduction and thus an increased driving force for the evolution of hydrogen under sacrificial conditions.

Directing the mechanism of CO2 reduction by a Mn catalyst through surface immobilization.

Immobilization of a Mn polypyridyl CO2 reduction electrocatalyst on nanocrystalline TiO2 electrodes yields an active heterogeneous system and also significantly triggers a change in voltammetric and catalytic behaviour, relative to in solution. A combination of spectroelectrochemical techniques are presented here to elucidate the mechanism of the immobilized catalyst in situ.

Improving the efficiency of electrochemical CO2 reduction using immobilized manganese complexes.

Immobilization of [Mn(bpy)(CO)3Br], (1) and [Mn(bpy((t)Bu)2)(CO)3Br] (2, where (bpy((t)Bu)2) = 4,4'-di-tert-butyl-2,2'-bipyridine) in Nafion/multi-walled carbon nanotubes (MWCNT) on glassy carbon yielded highly active electrodes for the reduction of CO2 to CO in aqueous solutions at pH 7. Films incorporating have significantly improved selectivity towards CO2, with CO : H2 ∼ 1 at -1.4 V vs. SCE, exceeding that for the previously reported /MWCNT/Nafion electrode. Furthermore, we report the synthesis and subsequent electrochemical characterization of two new substituted Mn(i) bipyridine complexes, [Mn(bpy(COOH)2)(CO)3Br] (3) and [Mn(bpy(OH)2)(CO)3Br] (4) (where (bpy(COOH)2) = 4,4'-di-carboxy-2,2'-bipyridine and (bpy(OH)2) = 4,4'-di-hydroxy-2,2'-bipyridine). Both 3 and 4 were found to have some activity towards CO2 in acetonitrile solutions; however once immobilized in Nafion membranes CO2 reduction was found to not occur at significant levels.

Electrocatalytic CO2 reduction with a membrane supported manganese catalyst in aqueous solution.

[Mn(bpy)(CO)3Br] cast in a Nafion membrane is an active heterogeneous electrocatalyst with good selectivity for CO2 reduction to CO in neutral aqueous electrolyte. Addition of multi-walled carbon nanotubes (MWCNT) leads to a ∼10 fold current enhancement and stable CO : H2 yields (1 : 2) at -1.4 V vs. Ag/AgCl at pH 7.