Unfavourable gender effect of high body mass index on brain metabolism and connectivity

The influence of Body Mass Index (BMI) on neurodegeneration in dementia has yet to be elucidated. We aimed at exploring the effects of BMI levels on cerebral resting-state metabolism and brain connectivity, as crucial measures of synaptic function and activity, in a large group of patients with Alzheimer\u2019s Dementia (AD) (n = 206), considering gender. We tested the correlation between BMI levels and brain metabolism, as assessed by18F-FDG-PET, and the modulation of the resting-state functional networks by BMI. At comparable dementia severity, females with high BMI can withstand a lower degree of brain metabolism dysfunction, as shown by a significant BMI-brain metabolism correlation in the temporal-parietal regions, which are typically vulnerable to AD pathology (R = 0.269, p = 0.009). Of note, high BMI was also associated with reduced connectivity in frontal and limbic brain networks, again only in AD females (p < 0.05 FDR-corrected, k = 100 voxels). This suggests a major vulnerability of neural systems known to be selectively involved in brain compensatory mechanisms in AD females. These findings indicate a strong gender effect of high BMI and obesity in AD, namely reducing the available reserve mechanisms in female patients. This brings to considerations for medical practice and health policy

Imaging biomarkers in prostate cancer: role of PET/CT and MRI

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed

Unveiling Sub-Pc supermassive black hole binary candidates in active galactic nuclei

The elusive supermassive black hole binaries (SMBHBs) are thought to be the penultimate stage of galaxy mergers, preceding a final coalescence phase. SMBHBs are sources of continuous gravitational waves, possibly detectable by pulsar timing arrays; the identification of candidates could help in performing targeted gravitational wave searches. Due to SMBHBs\u2019 origin in the innermost parts of active galactic nuclei (AGN), X-rays are a promising tool for unveiling their presence, by means of either double Fe K\u3b1 emission lines or periodicity in their light curve. Here we report on a new method for selecting SMBHBs by means of the presence of a periodic signal in their Swift Burst Alert Telescope (BAT) 105 month light curves. Our technique is based on Fisher\u2019s exact g-test and takes into account the possible presence of colored noise. Among the 553 AGN selected for our investigation, only the Seyfert 1.5 galaxy Mrk 915 emerges as a candidate SMBHB; from subsequent analysis of its light curve we find a period P0 = 35 \ub1 2 months, and the null hypothesis is rejected at the 3.7\u3c3 confidence level. We also present a detailed analysis of the BAT light curve of the only previously X-ray-selected binary candidate source in the literature, the Seyfert 2 galaxy MCG+11-11-032. We find P0 = 26.3 \ub1 0.6 months, consistent with the one inferred from previously reported double Fe K\u3b1 emission lines

Functionalized silica nanoparticles in the detection and treatment of Her2-positive breast cancer

Introduction: Nanobiotechnology can provide the development of nanoparticles for diagnosis/treatment of human cancer. Aim of this work was to validate a silica nanoparticles (SNP)-based system functionalized with anti-Her2 antibody fragment and loaded with radioactive/fluorescent probes for detection of aggressive breast cancer. Methods: SNPs carrying (ETZ-2) or not (ETZ-1, control) the Her2 antibody fragment were used in in vitro binding kinetic in Her2 positive (SKBR-3) and negative (MDA-MB-468) breast cancer cell lines. In parallel, the same SNPs were derivatized with nitril-triacetic acid and reacted with His-Tag, previously labelled with 99mTc-Tricarbonyl complex. Labelled SNPs were used for different experiments: in vitro uptake kinetic in SKBR-3 and MDA-MB-468 cells (20 min, 1h, 4h and 24h); ex vivo distribution in tumour and peripheral organs in animals implanted with MDA-MB-468 or SKBR-3 cells, at 4h from ETZ-2 injection. Afterwards, an additional experiment with ex vivo distribution and autoradiography at different time points (4h, 6h and 24h; n=4) were performed after the injection of labelled ETZ-1 and 2 SNPS on animals implanted with SKBR-3 cells. At the same times, in vitro uptake of both SNPs were measured by pre-treating SKBR-3 cells with 1 mg/ml of Trastuzumab. The uptake of labelled SNPs in cells was expressed as percentage of the total radioactivity counted, while in tumours and tissues was calculated as percentage of injected dose per gram of tissue (%ID/g). Tumour sample were also frozen in liquid N2 and sectioned for fluorescence microscopy. We have ongoing the evaluation of doxorubicin filled SNPs in comparison to liposomal doxorubicin (Caelix, 3 mg/kg in 40\ub5l) to assess the efficacy of nanoparticles to targeting chemotherapy. The effect will be assessed by measuring tumoral features as volume and [18F]FDG and [11C]Choline uptake. Results: ETZ-2 specifically binds SKBR-3 cells in vitro, reaching a maximum uptake ratio of 2,1 on MDA-MB-468 cells after 4h. The same result was confirmed in tumours, after the biodistribution study and observation in fluorescence. Caelix treatment particularly affected SKBR-3 lesions growth, in which we observed a 12,4% decrease of [18F]FDG and a 14.3% increase of [11C]Choline uptake, compared to control. Comparison with filled doxorubicin NPSs are in progress. Conclusion: Preliminary results showed that 99mTc-ETZ-2 SNPs could be a useful system for Her2 positive breast cancer detection and treatment

Functionalized silica nanoparticles in the detection and treatment of Her2-positive breast cancer

Introduction: Nanobiotechnology can provide the development of nanoparticles for diagnosis/treatment of human cancer. Aim of this work was to validate a silica nanoparticles (SNP)-based system functionalized with anti-Her2 antibody fragment and loaded with radioactive/fluorescent probes for detection of aggressive breast cancer. Methods: SNPs carrying (ETZ-2) or not (ETZ-1, control) the Her2 antibody fragment were used in in vitro binding kinetic in Her2 positive (SKBR-3) and negative (MDA-MB-468) breast cancer cell lines. In parallel, the same SNPs were derivatized with nitril-triacetic acid and reacted with His-Tag, previously labelled with 99mTc-Tricarbonyl complex. Labelled SNPs were used for different experiments: in vitro uptake kinetic in SKBR-3 and MDA-MB-468 cells (20 min, 1 h, 4h and 24h); ex vivo distribution in tumour and peripheral organs in animals implanted with MDA-MB-468 or SKBR-3 cells, at 4h from ETZ-2 injection. SNPs binding in cells was expressed as percentage of the total radioactivity counted; uptake in tumours and tissues were calculated as percentage of injected dose per gram of tissue. Slices of tumour were also fixed with 4% PAF and observed by fluorescence. In parallel, additional animals bearing SKBR-3 or MDA-MB-468 lesions were treated with liposomal doxorubicin (3 mg/kg in 40\ub5l) or vehicle, and tumour uptake of [18F]FDG and [11C]Choline was evaluated ex vivo with double autoradiography. Results: ETZ-2 specifically binds SKBR-3 cells in vitro, reaching a maximum uptake ratio of 2,1 on MDA-MB-468 cells after 4h. The same result was confirmed in tumours, after the biodistribution study and observation in fluorescence. Standard treatment particularly affected SKBR-3 lesions growth, in which we observed a 12,4% decrease of [18F]FDG and a 14.3% increase of [11C]Choline uptake, compared to control. Comparison with NPSs filled with doxorubicin are in progress. Conclusion: Labelled SNPs resulted a useful detection system for Her2 positive breast cancer and could be used for targeted therapy

FDG uptake by prosthetic arterial grafts in large vessel vasculitis Is not specific for active disease

OBJECTIVES: This study investigated the incidence and clinical significance of arterial graft-associated uptake of fluorodeoxyglucose in large-vessel vasculitis (LVV). BACKGROUND: The role of (18)F-labeled fluorodeoxyglucose-positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) in the management of LVV remains to be defined. Although [(18)F]FDG uptake at arterial graft sites raises concerns regarding active arteritis or infection, its clinical significance in LVV has never been formally studied. METHODS: An observational prospective study sought to identify patients with Takayasu arteritis (TA) undergoing [(18)F]FDG-PET/CT more than 6 months after graft surgery from a large cohort of patients from 2 tertiary referral centers. [(18)F]FDG uptake by the graft and native arteries was scored on a scale of 0 to 3 relative to hepatic uptake, and periprosthetic maximum standardized uptake value (SUVmax) was calculated. Periprosthetic [(18)F]FDG uptake in active disease was compared with that in inactive disease, and arterial progression was assessed by prospective magnetic resonance angiography (MRA). RESULTS: Twenty-six subjects with TA were enrolled. All were afebrile with negative blood culture. Periprosthetic uptake was significant in 23 of 26 patients, and the mean SUVmax was 4.21 ± 1.46. Median periprosthetic [(18)F]FDG uptake score (3; interquartile range [IQR]: 3 to 3) was higher than in native aorta (1; IQR: 0 to 1; p < 0.001). Graft-specific [(18)F]FDG uptake was unrelated to disease activity. Despite the high frequency of graft-associated [(18)F]FDG uptake, sequential MRAs did not reveal arterial progression in 25 of 26 patients; the 1 remaining case showed minor progression limited to native arteries. Nine patients underwent repeated PET/CT scanning without showing changes in graft-specific uptake, despite increased treatment. CONCLUSIONS: Significant [(18)F]FDG uptake that is confined to arterial graft sites in patients with LVV does not reflect clinically relevant disease activity or progression. To minimize exposure to immunosuppression and in the face of negative blood culture, clinically quiescent arteritis, normal or stably raised C-reactive protein levels, we elected not to escalate treatment and monitor progression with MRA

Unveiling Sub-pc Supermassive Black Hole Binary Candidates in Active Galactic Nuclei

The elusive supermassive black hole binaries (SMBHBs) are thought to be the penultimate stage of galaxy mergers, preceding a final coalescence phase. SMBHBs are sources of continuous gravitational waves, possibly detectable by pulsar timing arrays; the identification of candidates could help in performing targeted gravitational wave searches. Due to SMBHBs’ origin in the innermost parts of active galactic nuclei (AGN), X-rays are a promising tool for unveiling their presence, by means of either double Fe Kα emission lines or periodicity in their light curve. Here we report on a new method for selecting SMBHBs by means of the presence of a periodic signal in their Swift Burst Alert Telescope (BAT) 105 month light curves. Our technique is based on Fisher’s exact g-test and takes into account the possible presence of colored noise. Among the 553 AGN selected for our investigation, only the Seyfert 1.5 galaxy Mrk 915 emerges as a candidate SMBHB; from subsequent analysis of its light curve we find a period P0 = 35 ± 2 months, and the null hypothesis is rejected at the 3.7σ confidence level. We also present a detailed analysis of the BAT light curve of the only previously X-ray-selected binary candidate source in the literature, the Seyfert 2 galaxy MCG+11-11-032. We find P0 = 26.3 ± 0.6 months, consistent with the one inferred from previously reported double Fe Kα emission lines

The X-ray polarization of the Seyfert 1 galaxy IC 4329A

We present an X-ray spectro-polarimetric analysis of the bright Seyfert galaxy IC 4329A. The Imaging X-ray Polarimetry Explorer (IXPE) observed the source for ∼500 ks, supported by XMM–Newton (∼60 ks) and NuSTAR (∼80 ks) exposures. We detect polarization in the 2–8 keV band with 2.97σ confidence. We report a polarization degree of 3.3 ± 1.1 per cent and a polarization angle of 78° ± 10° (errors are 1σ confidence). The X-ray polarization is consistent with being aligned with the radio jet, albeit partially due to large uncertainties on the radio position angle. We jointly fit the spectra from the three observatories to constrain the presence of a relativistic reflection component. From this, we obtain constraints on the inclination angle to the inner disc (&amp;lt;39° at 99 per cent confidence) and the disc inner radius (&amp;lt;11 gravitational radii at 99 per cent confidence), although we note that modelling systematics in practice add to the quoted statistical error. Our spectropolarimetric modelling indicates that the 2–8 keV polarization is consistent with being dominated by emission directly observed from the X-ray corona, but the polarization of the reflection component is completely unconstrained. Our constraints on viewer inclination and polarization degree tentatively favour more asymmetric, possibly out-flowing, coronal geometries that produce more highly polarized emission, but the coronal geometry is unconstrained at the 3σ level

Uncovering the geometry of the hot X-ray corona in the Seyfert galaxy NGC 4151 with IXPE

We present an X-ray spectropolarimetric analysis of the bright Seyfert galaxy NGC 4151. The source has been observed with the Imaging X-ray Polarimetry Explorer (IXPE) for 700 ks, complemented with simultaneous XMM–Newton (50 ks) and NuSTAR (100 ks) pointings. A polarization degree Π = 4.9 ± 1.1 per cent and angle Ψ = 86° ± 7° east of north (68 per cent confidence level) are measured in the 2–8 keV energy range. The spectropolarimetric analysis shows that the polarization could be entirely due to reflection. Given the low reflection flux in the IXPE band, this requires, however, a reflection with a very large (&amp;gt;38 per cent) polarization degree. Assuming more reasonable values, a polarization degree of the hot corona ranging from ∼4 to ∼8 per cent is found. The observed polarization degree excludes a ‘spherical’ lamppost geometry for the corona, suggesting instead a slab-like geometry, possibly a wedge, as determined via Monte Carlo simulations. This is further confirmed by the X-ray polarization angle, which coincides with the direction of the extended radio emission in this source, supposed to match the disc axis. NGC 4151 is the first active galactic nucleus with an X-ray polarization measure for the corona, illustrating the capabilities of X-ray polarimetry and IXPE in unveiling its geometry