Bone marrow mononuclear cells (BMMNCs) have emerged as a potential therapeutic strategy for various incurable conditions including autism spectrum disorder (ASD). To study its safety and efficacy, we analyzed 1011 patients who underwent intrathecal administration of autologous BMMNCs along with neurorehabilitation. At mean follow-up of 19.3 months after intervention, 90.6% patients showed overall improvement. Improvements were observed in attention concentration, command following, eye contact, sitting tolerance, social interaction, hyperactivity, communication, speech, aggressiveness, stereotypical and self-injurious behavior. Statistically significant changes were observed in scores of Indian Scale of Autism Assessment and Childhood Autism Rating Scale (p<0.05). On subgroup analysis, improvements were recorded irrespective of age and disease severity and better outcome was observed in patients who took multiple doses of cell therapy compared to single dose. Comparative Brain PET-CT scan of 401 patients showed improved brain metabolism after the intervention. No major adverse events were reported. Only 9 out of 1011 patients experienced seizures which were managed using medications. 4 out of 9 had history of seizures while 5 had normal EEG with no history. However, improvements were still observed in these 9 patients. Thus, intrathecal transplantation of autologous BMMNCs along with neurorehabilitation is safe and efficacious in patients with ASD.

Scintillators play a key role in the detection chain of several applications which rely on the use of ionizing radiation, and it is often mandatory to extract and detect the generated scintillation light as efficiently as possible. In positron emission tomography (PET), for example, both energy resolution and coincidence resolving time, two of the key detection parameters, depend strongly on the total amount of light which reaches the photodetector surface as well as its spatial and temporal distribution. Typical inorganic scintillators do however feature a high index of refraction, which impacts light extraction efficiency in a negative way. Furthermore, several applications such as preclinical PET rely on pixelated scintillators with small pitch. In this case, applying reflectors on the crystal pixel surface, as done conventionally, can have a dramatic impact of the packing fraction and thus the overall system sensitivity. This paper presents a study on light extraction techniques, as well as combinations thereof, for two of the most used inorganic scintillators (LYSO and BGO). Novel approaches, employing distributed Bragg reflectors (DBRs), metal coatings, and a modified Photonic Crystal (PhC) structure, are described in detail and compared with commonly used techniques. The nanostructure of the PhC is surrounded by a hybrid organic/inorganic silica sol-gel buffer layer which ensures robustness while maintaining its performance unchanged. We observed in particular a maximum light gain of about 41% on light extraction and 21% on energy resolution for BGO, a scintillator which has gained interest in the recent past due to its prompt Cherenkov component and lower cost.

This study explores the potential to reach a circular economy for post-consumer recycled polyethylene terephthalate (rPET) packaging and bottles by using it as a distributed recycling for additive manufacturing (DRAM) feedstock. Specifically, rPET is processed using only an open source toolchain with fused particle fabrication (FPF) or fused granular fabrication (FGF) processing. In this study, first the impact of granulation, sifting and heating (and their combination) is quantified on the shape and size distribution of the rPET flakes. Then feeding studies were performed to see if they could be printed through an external feeder or needed to be direct printed with a hopper using two Gigabot X machines, one with extended part cooling and one without. Print settings were optimized based on thermal characterization and for the latter which was shown to print rPET directly from shredded water bottles mechanical testing is performed. The results showed that geometry was important for extended feeding tubes and direct printed using a hopper. Further there is a wide disparity in the physical properties of rPET from water bottles depending on source and the history of the material. Future work is needed to enable water bottles to be used as a widespread DRAM feedstock.

Objective: The study aims to evaluate the correlation between 68Ga-PSMA uptake in PSMA PET/CT in primary prostate cancer (PC) and its histopathological grading (Gleason Score and ISUP grade). Additionally, we compared preoperative biopsy histopathological findings with definitive pathology results in radical prostatectomy (RP) specimens. Methods: We retrospectively analyzed 86 patients who underwent 68Ga-PSMA PET/CT for primary PC staging, of which 40 patients later underwent radical prostatectomy. PET/CT results, including SUVmax values, were correlated with GS and PSA concentrations. Histopathology reports were analyzed and compared between biopsy and final pathology results following RP. Results: A significant positive correlation was observed between SUVmax and ISUP grades (Pearson's ρ = 0.34, p < 0.001), with higher SUVmax values associated with more advanced grades. A cut-off SUVmax value of 5.64 was determined to predict upstaging in patients, yielding a sensitivity of 76% and a specificity of 60% (AUC = 0.82, 95% CI: 0.70–0.94). Additionally, 57.5% of patients experienced a grade shift following RP, with a 35% upgrade and 22.5% downgrade in ISUP grades. Conclusion: 68Ga-PSMA PET/CT demonstrated high sensitivity in detecting high-risk prostate cancer, particularly in patients with GS > 7 or PSA levels ≥ 10 ng/ml. The findings suggest that this imaging modality may be less effective for staging of patients with lower GS or PSA values, that is low-risk PCa. Further prospective studies are necessary to validate these results.

Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial blood flow reserve (MFR), and myocardial blood flow volume fraction (MBF), and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 male, 1 female) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86±0.13 vs. 1.08±0.09, p=0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23±0.23 vs. 1.88±0.29, p=0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

Background/Objectives: Although the role of F-18 FDG PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, we retrospectively studied 134 CRC patients referred for FDG PET/CT imaging on the suspicion of recurrence based on elevated CEA and/or CA 19-9, and/or equivocal radiological findings. According to the Institutional Tumor Board CRC protocol, after initial treatment which was dependent on TNM stage (neoadjuvant therapy, primary resection or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy every 6 months. The statistics including univariate and multivariable analyses were conducted using the IBM SPSS 20.0 statistical software. P-values <0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. FDG PET/CT shows high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA shows a high sensitivity of 98.1%, but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy, for CA 19-9 and CIM for the correct diagnosis in CRC patients were: 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for FDG PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p<0.001), 0.844 (95% CI: 0.772-0.916; p<0.001), 0.753 (95% CI: 0.612-0.844; p<0.001); and 0.547 (95% CI: 0.442-0.652; p=0.358). Univariate analysis shows that both FDG PET/CT- and CIM-positive results were highly associated with CRC recurrence (p<0.001 and p<0.001, respectively), while gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) have no significance (p=0.211, p=0.158, p=0.583, and p=0.201, respectively). Our multivariate analysis shows that independent predictors for CRC recurrence are: positive FDG PET/CT scans (p<0.001), positive CIM results (p=0.001) and elevated CA19-9 levels (p=0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p=0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting CRC recurrence (p=0.023). Conclusions: FDG PET/CT shows a high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the postoperative follow-op in patients with elevated tumor markers.

Deep learning (DL) algorithms used for DOTATATE PET lesion detection typically require large, well-annotated training datasets. These are difficult to obtain due to low incidence of gastroenteopancreatic neuroendocrine tumors (GEP-NETs), and the high cost of manual annotation. Furthermore, networks trained and tested with data acquired from site specific PET/CT instrumentation, acquisition and processing protocols have reduced performance when tested with offsite data. This lack of generalizability requires even larger, more diverse training datasets. The objective of this study is to investigate the feasibility of improving DL algorithm performance by better matching the background noise in training datasets to higher noise, out-of-domain testing datasets. 68Ga-DOTATATE PET/CT datasets were obtained from two scanners: Scanner1, a state-of-the-art digital PET/CT (GE DMI PET/CT; n=83 subjects), and Scanner2, an older-generation analog PET/CT (GE STE; n=123 subjects). Set1, the data set from Scanner1 was reconstructed with standard clinical parameters (5 minutes; Q.Clear) and list-mode reconstructions (VPFXS 2, 3, 4, and 5-minutes). Set2, data from Scanner2, representing out-of-domain clinical scans, used standard iterative reconstruction (5 minutes; OSEM). Reconstructed datasets were divided into training, validation, and testing datasets in a 60%, 20%, 20% proportion, and a deep neural network was trained with each: Network1 for Scanner1 and Network2 for Scanner2. DL performance (Network1) was tested with out-of-domain test data (Set2). To evaluate the effect of training sample size, we tested DL model performance using a fraction (25%, 50%, and 75%) of Set1 for training. Scanner1, list-mode 2-minute reconstructed data demonstrated the most similar noise level compared that of Set2, resulting in the best performance (F1=0.713). This was not significantly different compared to the highest performance, upper-bound limit using in-domain training for Network2 (F1=0.755; p-value=0.103). Regarding sample size, the F1 score significantly increased from 25% training data (F1=0.478) to 100% training data (F1=0.713; p&lt;0.001). List-mode data from modern PET scanners can be reconstructed to better match the noise properties of older scanners. Using existing data and their associated annotations dramatically reduces the cost and effort in generating these datasets, and significantly improves the performance of existing DL algorithms. List-mode reconstructions can provide an efficient, low-cost method to improve DL algorithm generalizability.

The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer’s Disease (AD)-like pathology in mice, although mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report isotopic exchange reaction to obtain IDIF radiolabeled with 18F. [19F/ 18F]exchange reaction over IDIF in dimethylsulfoxide at 160 °C resulted in the formation of [18F]IDIF in 7±3% radiochemical yield in a 20 minutes reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [18F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t&gt;10 min post administration), rapid accumulation in the liver, long circulation time and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.

Within the oligometastatic state, oligo-recurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally it is an emergent situation that we are facing more frequently, mainly due to: a) the incorporation into clinical practice of the PSMA PET that provides strikingly increase superior images in comparison to conventional imaging, with higher sensitivity and specificity; b) the higher detection rates of bone and node disease with extremely low levels of PSA; and c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improve the clinical outcome. In this work we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging guided SBRT for the treatment of nodal recurrence in prostate cancer.

Progressive supranuclear palsy (PSP) is a sporadic parkinsonism tauopathy characterised by the deposition of aggregations of abnormal, hyperphosphorylated four-repeat tau (4R-tau). A revised clinical diagnostic criterion for PSP allows early presentations for the full spectrum of clinical phenotypes to be recognised enabling doctors to make a more accurate diagnosis. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT). Research into the biochemical and pathological pathways of tau is vital to improve the chances of developing an effective diagnostic biomarker to monitor tau pathogenesis. Neuroimaging biomarkers, such as tau PET ligands, are proving the most successful tool in providing a differential diagnosis between neurodegenerative disorders. There are currently no effective treatments for PSP, however tau-directed therapies in the last five years have rapidly advanced. Latest tau therapies are proposed to have disease-modifying effects by reducing toxic aggregations of tau through manipulating tau gene expression. After encouraging results from long awaited trials, additional funding is being injected into this field and with new results expected, this proves an exciting area for scientific discovery. This paper reviews advances in pathophysiology, diagnosis, biomarkers and disease-modifying therapeutic treatments for PSP.

Background: Animal-assisted therapy has positive effects on cognitive function, depression, performance ability, and social functioning in elderly patients. The aim of this study was to evaluate the effects of rearing pet insects on the cognitive function of healthy elderly participants, with fMRI (functional magnetic resonance imaging) being used for this purpose. Methods: Community-dwelling elderly women (≥60 years) with normal cognitive function were enrolled during April 2015. They were randomized at a 1:1 ratio into two groups: insect-rearing and control (n=16) groups, with the insect-rearing group being further classified into two groups for analysis according to the subjects’ scores in the Wisconsin Card Sorting Test, WCST) at the first fMRI: insect-rearing group I with a relatively high score (n=13), and insect-rearing group II with a relatively low score (n=6). All subjects were educated on a healthy lifestyle for better cognitive function at every visit, and the insect-rearing groups received and reared crickets as pet insects. The fMRI was performed at baseline and after 8 weeks using the WCST as a stimulus. The WCST consisted of two variations, a high level baseline (HLB) and semi-WCST version. Results: There were no significant differences in the baseline characteristics among the three groups. There was a significant difference accuracy of the HLB–semi-WCST (p<0.05) in insect-rearing group II after 8 weeks from the baseline test. In the fMRI analysis involving the WCST reaction test, increased activation was observed in the right dorsal lateral prefrontal cortex and parietal cortex in insect-rearing group II when the semi-WCST, rather than the HLB, was performed. There were no significant differences in the other groups. Conclusion: The rearing of pet insects as an animal-assisted therapy is cost-effective, easy, and occupies little space. In this study, it showed positive effects on executive functions and performance improvement in elderly women. Further larger studies on the effects of pet insects on cognitive function are warranted.

In the field of construction, materials referred to as sustainable are currently undergoing a process of technological development. This study aims to contribute to the understanding of the behavior of the fundamental properties of concretes prepared with recycled coarse aggregates that incorporate in their matrix a polyethylene terephthalate-based additive in an attempt to reduce their high porosity. Techniques to measure the gas adsorption, water porosity and x-ray diffraction (XRD) were used to evaluate the effect of the additive on the physical, mechanical and microstructural properties of these concretes. Porosity reductions of up to 30.60% are achieved with the addition of 1, 3, 4, 5, 7 and 9% of the additive, defining a new state in the behavioral model of the additive (the overdosage point) in the concrete matrix; in addition, the porous network of these concretes and their correlation whit other physical and mechanical properties are also explained.

Polymyalgia rheumatica (PMR) is an inflammatory disease common in people aged 50 years and older. This condition is characterized by the presence of pain and stiffness involving mainly the shoulder and pelvic girdle. Besides the frequent association with giant cell arteritis (GCA), several conditions may mimic PMR or present with PMR features. Since the diagnosis is basically clinical, an adequate diagnosis of this condition is usually required. Positron emission tomography-computed tomography (PET-CT) has proved to be a useful tool for the diagnosis of PMR. The use of 18F-FDG-PET imaging appears promising as it provides detailed information on inflammatory activity that may not be evident with traditional methods. However, since PET-CT is not strictly necessary for the diagnosis of PMR, clinicians should consider several situations in which this imaging technique can be used in patients with suspected PMR.

Present work investigates, in photon energy domains of specific interest for medical imaging, the effect of the escape of X-ray fluorescence from the scintillator materials on the energy resolution of scintillation detector itself. Monolithic as well as pixelated crystals differently sized are considered, in the case of the NaI because it is the gold standard in the field. The volumetric ratio is introduced, as a figure of merit, taking into account, alongside the surface-to-volume ratio, the geometric shape, the elemental composition and also the mean-free-path for the given scintillator and energy. The inter-crystal XRF escape is finally suggested to be considered among the effects producing image blurring in segmented scintillatros due to the spread of events between the primary pixel and the first neighbors ones.

Microplastics (MPs) quantification in benthic marine sediments is typically performed by time-consuming and moderately accurate mechanical separation and microscopy detection. In this paper we describe the results of our innovative Polymer Identification and Specific Analysis (PISA) of microplastic total mass, previously tested on either less complex sandy beach sediment or less demanding (because of the high MPs content) wastewater treatment plant sludges, applied to the analysis of benthic sediments from a sublittoral area north-west of Leghorn (Tuscany, Italy). Samples were collected from two shallow sites characterized by coarse debris in a mixed seabed of Posidonia oceanica, and by a very fine silty-organogenic sediment, respectively. After sieving at &lt;2 mm the sediment was sequentially extracted with selective organic solvents and the two polymer classes polystyrene (PS) and polyolefins (PE and PP) were quantified by pyrolysis-GC/MS. A contamination in the 8-65 ppm range by PS could be accurately detected. Acid hydrolysis on the extracted residue to achieve total depolymerization of all natural and synthetic polyamides, tagging of all aminated species in the hydrolyzate with a fluorophore, and reversed-phase HPLC (RP-HPLC) analysis, allowed to quantify within the 137-1523 ppm range the individual mass of contaminating Nylon 6 and Nylon 6,6, based on the detected amounts of the respective monomeric amines 6-aminohexanoic acid (AHA) and hexanediamine (HMDA). Finally, alkaline hydrolysis of the residue from acid hydrolysis followed by RP-HPLC analysis of the purified hydrolysate showed contamination by polyethylene terephthalate (PET) in the 12.1-2.7 ppm range, based on the content of its comonomer, terephthalic acid.

The current study assessed the influence of Anti Stripping Agents (ASA), Ground Tire Rubber (GTR) and waste polyethylene terephthalate (PET) on performance behavior of binder and Stone Matrix Asphalt (SMA) mixtures. Through this paper, the 85/100 penetration grade bitumen was utilized as original bitumen. Also, three liquid ASA’s (ASA (A), ASA (B), ASA (C)) were used as a mixture modifier. For this purpose, softening point, penetration, rotational viscosity, Dynamic Shear Rheometer, Multi Stress Creep Recovery (MSCR) and Linear Amplitude Sweep (LAS) tests were implemented to investigate the rheological properties of modified bitumen. For evaluating the behavior of modified mixtures several tests such as; Resilient Modulus, Tensile Strength, dynamic creep, wheel track and four-point beam fatigue tests were implemented. Based on MSCR test results, utilization of mentioned polymers enhanced the elasticity of bitumens and therefore the permanent deformation resistance of binders increases. Also by the addition of PET percentage, the rutting resistance improves. Results indicated that utilization of ASAs, PET and Crumb Rubber (CR) enhance the Resilient Modulus (Mr), Indirect Tensile Strength (ITS), rutting resistance, fatigue life and Fracture Energy (FE) of asphalt mixtures. Also based on results, modification of binder by PET/CR with a ratio of 50%/50% and ASA (B) have the highest fatigue life which indicates that this mixture has highest resistance against fatigue cracking.

Photophysics properties such as fluorescence quenching, and photoexcitation dynamics of bimolecular non-covalent systems consisting of cationic poly[(9,9-di(3,3’-N,N’-trimethyl-ammonium) propyl fluorenyl-2,7-diyl)-alt-co-(9,9-dioctyl-fluorenyl-2,7-diyl)] diiodide salt (PFN) and anionic graphene carboxylate (GC) have been discovered for the first time by the steady state and time-resolved femtosecond transient absorption (TA) spectroscopy with broadband capabilities. The steady-state fluorescence of PFN is quenched with high efficiency by GC acceptor. Fluorescence lifetime measurements revealed that the quenching mechanism of PFN by GC is static. Here, the quenching mechanisms are well proven by TA spectra of PFN/GC systems. For PFN/GC systems, the photo electron transfer (PET) and charge recombination (CR) processes are ultrafast (within few tens of ps) related to static interactions whereas for PFN/DCB systems the PET takes place in few hundreds ps (217.50 ps)1 suggesting diffusion-controlled PET process. In the latter case, the PFN+•-DCB-• radical ion pairs as the result of PET from the PFN to DCB are clearly resolved and they are long-lived. The slow CR process (in 30 ns time scales)1 suggest PFN+• and DCB-• may already form separated radical ion pairs through charge separation (CS) process, which recombined back to the initial state with a characteristic time constant of 30 ns. The advantage of the present positively charged polyfluorene used in this work is the control over the electrostatic interactions and electron transfers in non-covalent polyfluorene/quencher systems in DMSO solution.

Objective: To assess the spectrum of PET-CT-related large vessel vasculitis (LVV) in a Spanish tertiary center and to determine whether FDG uptake by PET-CT differs between giant cell arteritis (GCA) with predominant cranial or extracranial phenotypes. Methods: The spectrum of patients diagnosed with LVV by PET-CT in a tertiary referral hospital that cares for 450,000 people over a period of two years was reviewed. Moreover, differences in FDG uptake between LVV-GCA with predominantly cranial and extracranial phenotype were analyzed. Results: Eighty patients were diagnosed with LVV by PET-CT. Most were due to systemic vasculitis (n=64; 80%), especially GCA (n=54; 67.5%). Other conditions included the presence of rheumatic diseases (n=4; 3.2%), tumors (n=9; 7.2%), and infections (n=3; 2.4%). LVV-GCA patients with predominant extracranial GCA phenotype were younger (mean ± SD: 68.07 ± 9.91 versus 75.46 ± 7.64 years; p= 0.017) and had a longer delay to the diagnosis (median [interquartile range] 12 [4-18] versus 4 [3-8]; p=0.006), but had PMR symptoms more frequently than those with predominantly cranial GCA phenotype (46.3% versus 15.4%, p= 0.057). When FDG uptake was compared according to the two different disease patterns, no statistically significant differences were observed. However, patients with extracranial LVV-GCA showed a non-significantly higher frequency of vasculitic involvement of lower extremity arteries. Conclusion: Regardless of the predominant phenotype, LVV identified by PET-CT is more commonly due to GCA in the Spanish population. In these GCA patients, younger age, PMR and a higher frequency of lower extremity artery vasculitis suggest the presence of LVV.

Background/Aim: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. Materials and Methods: 44 melanoma patients who underwent [18F]FDG-PET/CT before first-line target therapy (28/50) or immunotherapy (16/50) were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared with Mann-Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan-Meier analysis. Results: Median(IQR) MTVwb and TLGwb were 13.1 mL and 72.4 respectively. Non-responders patients were 38/44, 26/28 and 12/16 at early evaluation, and in 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target and immunotherapy subgroup respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p<0.037) in the whole-cohort and target subgroup and also MTVwb and TLGwb (all p<0.022) in target subgroup. No significant differences were found for immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversy, MTVlfn, TLGlfn, MTVsoft+lfn, TLG-soft+lfn, MTVwb and TLGwb were significantly associated (all p<0.05) with OS in both the whole-cohort and target therapy subgroup. Conclusion: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS.

Aim To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. Materials and methods We conducted a retrospective monocentric observational study over a 3 years period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint or tyrosine kinase inhibitors (ICIs or TKIs) as of January-2017. Imaging reports were analysed by two physicians in consensus. Anatomical site responsible for discordances, as well as induced changes in treatment were noted. Results Eighty patients were included and 195 couples of scans analysed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient’s management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients’ management in 2/13 cases (15%). The more frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. Conclusions Treatment monitoring with 18F-FDG

Aim To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. Materials and methods We conducted a retrospective monocentric observational study over a 3 years period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint or tyrosine kinase inhibitors (ICIs or TKIs) as of January-2017. Imaging reports were analysed by two physicians in consensus. Anatomical site responsible for discordances, as well as induced changes in treatment were noted. Results Eighty patients were included and 195 couples of scans analysed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient’s management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients’ management in 2/13 cases (15%). The more frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. Conclusions Treatment monitoring with 18F-FDG

Objective: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are often overlapping conditions. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is useful in identifying PMR in the setting of large vessel vasculitis (LVV)-GCA. Methods: Patients diagnosed with LVV-GCA by PET-CT at a tertiary referral hospital for a population of 450,000 people over a two-year period were reviewed. Scoring was performed based on potential significant FDG uptake at up to 16 sites in nine different extravascular areas (SCORE 16). Differences in extravascular sites of significant FDG uptake were evaluated between LVV-GCA with a clinical diagnosis of PMR or not. Results: Fifty-four patients were diagnosed with LVV-GCA by 18F-FDG-PET-CT. Of them, 21 (38.8%) were clinically diagnosed with PMR. Significant extravascular FDG uptake was more frequently observed in those with a clinical diagnosis of PMR. In this sense, the SCORE 16 was higher in those with clinical PMR (5.10 ± 4.05 versus 1.73 ± 2.31 in those without a clinical diagnosis of PMR; p< 0.001). A SCORE 16 involving more than 4 sites of significant FDG uptake yielded a sensitivity of 52% and a specificity of 91% for establishing a clinical diagnosis of PMR associated with LVV-GCA. The best areas of significant FDG uptake to clinically identify PMR in patients with LVV were the shoulder, the greater trochanter and the lumbar interspinous regions with an area under the ROC curve of 0.810 (0.691-0.930). Conclusion: Significant extravascular 18F-FDG-PET-CT uptake may help establish a clinical diagnosis of PMR in patients with LVV-GCA. These patients are more commonly diagnosed with PMR if they have significant FDG uptake in the shoulder, greater trochanter, and lumbar interspinous areas.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, rheumatoid arthritis or cancer. Inflammation in the brain is marked by the upregulation of the translocator protein (TSPO) in microglia. Moreover, high TSPO levels are found, for example in macrophages during rheumatoid arthritis and in malignant tumor cells compared to its relatively low physiological expression. The same applies for cycloxygenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable to monitor the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases like rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

Immunotherapy is an effective therapeutic option for several cancers. In the last years, the introduction of checkpoint inhibitors (ICIs) has shifted the therapeutic landscape in oncology and improved patient prognosis in a variety of neoplastic diseases. However, to date, the selection of the best patients eligible for these therapies, as well as the response assessment is still challenging. Patients are mainly stratified using immunohistochemical analysis of the expression of anti-gens on biopsy specimens, such as PD-L1 and PD-1, on tumor cells, on peritumoral immune cells, and/or in the tumor microenvironment (TME). Recently, the use and development of imaging biomarkers able to assess in-vivo cancer-related processes are becoming more important. Today, positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is used routinely to evaluate tumor metabolism, and also to predict and monitor response to immunotherapy. Although highly sensitive, FDG-PET, in general, is rather unspecific. Novel radiopharmaceuticals (immuno-PET radiotracers) able to identify specific immune system targets are under investigation in pre-clinical and clinical settings. In this review, we will provide an overview of the main new immuno-PET radiotracers in development. We will also review the main players (immune cells, tumor cells, and molecular targets) involved in immunotherapy. Furthermore, we report current applications and the evidence of using [18F]FDG PET in immunotherapy, including the use of artificial intelligence (AI).

Purpose: We aimed to develop a nomogram able to predict treatment failure, skeletal events and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). Patients and Methods: Patients from Castilla-La Mancha Spanish region was prospectively included in ChoPET-Rad multicenter study, from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using Kaplan-Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. Results: Median progression-free survival (PFS) and OS for our population were 4 and 14 months (mo), respectively. The variables that showed the most robust independent significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p=0.022) and the characteristics of BM on CT portion of PET/CT (p=0.017). In the case of OS, the significant variables were therapeutic failure (p=0.038), the number of lines received after 223Ra (p

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) versus Deauville score (DS) in assessing chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (age 8-16 years) were enrolled at baseline, interim (after the 2nd or 3rd chemotherapy round), and post-therapy (upon completion of first-line chemotherapy) 18F-FDG PET-CT. Interim and post-therapy DS and ΔSUVmax% were compared as response predictors. Patients were classified as responders and non-responders based on 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively in predicting response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, with a 76.8% cutoff. Sensitivity, specificity (p<0.05) and NPV (p<0.01) were significantly higher using DS than ΔSUVmax%. In conclusion, DS can predict chemotherapy response better than ΔSUVmax% in pediatric HL patients.

Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such data for first-line ICI therapy and especially for chemotherapy-ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n=70) or as monotherapy (n=15). Maximum and mean standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis and bone marrow-/ spleen to liver ratio (BLR/SLR) were calculated. Kaplan-Meier analyses and Cox-regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p<0.001). Median PFS/OS were significantly longer in patients with MTV≤70mL versus >70mL (PFS: 10 months (M; 95% confidence interval 4-16) vs. 4M (3-5), p=0.001; OS: not reached vs. 10M (5-15), p=0.004). Disease control rate was 81% vs. 53% for MTV≤/>70mL (p=0.007). BLR ≤1.06 versus >1.06 was associated with better outcomes (PFS: 8M (4-13) vs. 4M (3-6), p=0.034; OS: 19M (12-/) vs. 6M (4-12), p=0.005). In patients with MTV>70mL, concomitant BLR≤1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI treated NSCLC, with BLR allowing additional risk stratification.

Fibroblast activation protein (FAP) is a membrane-tethered serine protease overexpressed in the reactive stromal fibroblasts of &gt; 90% human carcinomas, which makes it a promising target for developing radiopharmaceuticals for imaging and therapy of carcinomas. Here, we synthesized two novel (R)-pyrrolidin-2-yl-boronic acid-based FAP-targeted ligands; SB02055 (DOTA-conjugated (R)-(1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)glycyl)pyrrolidin-2-yl)boronic acid) and SB04028 (DOTA-conjugated ((R)-1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)-D-alanyl)pyrrolidin-2-yl)boronic acid). natGa- and 68Ga-complexes of both ligands were evaluated in preclinical studies and compared to previously reported natGa/68Ga-complexed PNT6555. Enzymatic assays showed that FAP binding affinities (IC50) of natGa-SB02055, natGa-SB04028 and natGa-PNT6555 were 0.41±0.06, 13.9±1.29 and 78.1±4.59 nM, respectively. PET imaging and biodistribution studies in HEK293T:hFAP tumor-bearing mice showed that while [68Ga]Ga-SB02055 presented with a nominal tumor uptake (1.08±0.37 %ID/g), [68Ga]Ga-SB04028 demonstrated clear tumor visualization with ~1.5-fold higher tumor uptake (10.1±0.42 %ID/g) compared to [68Ga]Ga-PNT6555 (6.38±0.45 %ID/g). High accumulation in the bladder indicated renal excretion of all three tracers. [68Ga]Ga-SB04028 displayed low background level uptake in most normal organs, and comparable to [68Ga]Ga-PNT6555. However, since its tumor uptake was considerably higher than [68Ga]Ga-PNT6555, the corresponding tumor-to-organ uptake ratios for [68Ga]Ga-SB04028 were also significantly greater than [68Ga]Ga-PNT6555. Our data demonstrate that (R)-(((quinoline-4-carbonyl)-D-alanyl)pyrrolidin-2-yl)boronic acid is a promising pharmacophore for the design of FAP-targeted radiopharmaceuticals for cancer imaging and radioligand therapy.

Loyalty is one of the greatest intangible assets that any organization can possess and improving client loyalty is a primary marketing goal that can have a significant financial impact on any business. This quantitative study examined the mediating role of communication on the relationship between satisfaction and loyalty (attitudinal and behavioral) in veterinary clinics, along with the moderating roles of trust, commitment, perceived value, and relational characteristics. Responses collected from 351 pet-owners through social media were analyzed using descriptive and inferential statistics. The results show that attitudinal loyalty (AL) has a strong positive relationship with communication at multiple points in a veterinary clinic whereas the relationship with behavioral loyalty was not as clear. Additional findings suggest that AL, which is influenced by trust in the veterinarian, communication from staff members and commitment, has a strong positive relationship with behavioral intentions, increases the number of products and services that a pet-owner consumes at his or her primary veterinary clinic, and attenuates the role of cost in receiving veterinary care. These findings can help veterinary clinic owners and managers in developing and implementing relationship strategies that improve pet-owner loyalty. The article that follows is a synopsis of the author’s dissertation.

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scan and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

This article seeks to strengthen efforts in technological developments based on the classification of PET plastic that positively impacts sustainable development and contributes to suitable solutions in collection centers in Mexico. Three experiment designs and machine learning tools for data processing were developed. For the experimentation, three factors were considered: the bottle's size, the amount of liquids inside the bottle, and the label on the bottle. The first experiment was to identify the distance of the sensor from post-consumer PET bottles. The second experiment was to determine the detection ability of the sensor with different levels of liquids inside the bottles, and the third was to determine the detection ability on the bottle labels. A digital lux meter on a microcontroller was developed to monitor illuminance on post-consumer PET plastic when it contains liquid as it passes through a conveyor belt for processing at an average rate of three bottles per second. With the implemented methodology, liquids were satisfactorily detected inside the transparent PET bottles when they had beverages between 25% and 100% of their capacity. Finally, this paper highlights that it is possible to implement an affordable design to identify bottles with liquids for collection centers.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.