Biodegradation of combined pollutants of polyethylene terephthalate and phthalate esters by esterase-integrated Pseudomonas sp. JY-Q with surface-co-displayed PETase and MHETase.

The waste pollution problem caused by polyethylene terephthalate (PET) plastics poses a huge threat to the environment and human health. As plasticizers, Phthalate esters (PAEs) are widely used in PET production and become combined pollutants with PET. Synthetic biology make it possible to construct engineered cells for microbial degradation of combined pollutants of PET and PAEs. PET hydroxylase (PETase) and monohydroxyethyl terephthalate hydroxylase (MHETase) isolated from Ideonella sakaiensis 201-F6 exhibit the capability to depolymerize PET. However, PET cannot enter cells, thus enzymatic degradation or cell surface displaying technology of PET hydrolase are the potential strategies. In this study, Pseudomonas sp. JY-Q was selected as a chassis strain, which exhibits robust stress tolerance. First, a truncated endogenous outer membrane protein cOmpA and its variant Signal (OprF)-cOmpA were selected as anchor motifs for exogenous protein to display on the cell surface. These anchor motifs were fused at the N-terminal of PET hydrolase and MHETase and transformed into Pseudomonas sp. JY-Q, the mutant strains successfully display the enzymes on cell surface, after verification by green fluorescent protein labeling and indirect immunofluorescence assay. The resultant strains also showed the catalytic activity of co-displaying PETase and MHETase for PET biodegradation. Then, the cell surface displaying PET degradation module was introduced to a JY-Q strain which genome was integrated with PAEs degrading enzymes and exhibited PAEs degradation ability. The resultant strain JY-Q-R1-R4-SFM-TPH have the ability of degradation PET and PAEs simultaneously. This study provided a promising strain resource for PET and PAEs pollution control.

Radiomics-based machine learning models for differentiating pathological subtypes in cervical cancer: a multicenter study.

Purpose: This study was designed to determine the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics-based machine learning (ML) in the classification of cervical adenocarcinoma (AC) and squamous cell carcinoma (SCC). Methods: Pretreatment 18F-FDG PET/CT data were retrospectively collected from patients who were diagnosed with locally advanced cervical cancer at two centers. Radiomics features were extracted and selected by the Pearson correlation coefficient and least absolute shrinkage and selection operator regression analysis. Six ML algorithms were then applied to establish models, and the best-performing classifier was selected based on accuracy, sensitivity, specificity, and area under the curve (AUC). The performance of different model was assessed and compared using the DeLong test. Results: A total of 227 patients with locally advanced cervical cancer were enrolled in this study (N=136 for the training cohort, N=59 for the internal validation cohort, and N=32 for the external validation cohort). The PET radiomics model constructed based on the lightGBM algorithm had an accuracy of 0.915 and an AUC of 0.851 (95% confidence interval [CI], 0.715-0.986) in the internal validation cohort, which were higher than those of the CT radiomics model (accuracy: 0.661; AUC: 0.513 [95% CI, 0.339-0.688]). The DeLong test revealed no significant difference in AUC between the combined radiomics model and the PET radiomics model in either the training cohort (z=0.940, P=0.347) or the internal validation cohort (z=0.285, P=0.776). In the external validation cohort, the lightGBM-based PET radiomics model achieved good discrimination between SCC and AC (AUC = 0.730). Conclusions: The lightGBM-based PET radiomics model had great potential to predict the fine histological subtypes of locally advanced cervical cancer and might serve as a promising noninvasive approach for the diagnosis and management of locally advanced cervical cancer.

Case report: When infection lurks behind malignancy: a unique case of primary bone lymphoma mimicking infectious process in the spine.

Primary bone lymphoma of the spine (PBL) is a rare entity that may be misdiagnosed due to its atypical location and clinical and imaging features mimicking certain pathologies as infectious processes, which complicates and delays diagnosis. Our case reports a patient in her sixties who had been suffering from chronic low back pain for a year, and had gradually started to develop cruralgia. She underwent a blood sample, magnetic resonance imaging (MRI), and positron emission tomography (18F-FDG-PET/CT) which revealed inflammatory syndrome, and an image of spondylodiscitis of the lumbar spine associated with a morphological and metabolical widespread invasion posteriorly suggesting epiduritis. No other lesions were found on the rest of the body. Neurosurgical management was performed and a biopsy was made. Histological results showed aggressive and diffuse large B-cell lymphoma, suggesting a diagnosis of PBL. This case highlights the first case of spondylodiscitis mimicking PBL in the lumbar spine, the intricacies of the diagnostic work-up, and the complexity of discriminating with an infectious process in the spine, as both have a similar, non-specific clinical presentation, while morphological and metabolic findings can be alike.

Case Report: Application of 18F-FDG PET/CT in identifying plasmacytoma in monoclonal gammopathy associated peripheral neuropathy.

Peripheral neuropathy is a prevalent complication in plasma cell disorders, posing significant diagnostic and therapeutic challenges. This study presents three cases initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Despite initial symptom regression post-immunomodulatory treatment, the patients exhibited progressive neurological deficits. Advanced laboratory evaluation confirmed monoclonal protein presence, yet traditional diagnostic methods, including bone marrow biopsy and flow cytometry, yielded normal results. Utilizing 18F-FDG PET/CT, we identified multiple hypermetabolic vertebral lesions, which upon biopsy, confirmed the diagnosis of plasmacytoma. Our findings underscore the utility of PET/CT as a reliable diagnostic tool for monoclonal gammopathy associated neuropathy, advocating for its consideration in cases with equivocal diagnosis. When the diagnosis is in doubt, biopsy of a lesion may facilitate early and accurate diagnosis, potentially influencing treatment strategies and patient outcomes.

QUALIPAED-A retrospective quality control study evaluating pediatric long axial field-of-view low-dose FDG-PET/CT.

Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-of-variance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20-50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB < 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08-0.15) equal to or lower than current clinical acceptable values (COVref ≤ 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB < 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006-0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F]FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans.

First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled leukocytes.

Introduction: Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes. Methods: Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients. Results: Successful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAO- and [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAO-labelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel. Discussion: Although the [89Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89Zr]Zr-Df-Bz-NCS-labelled leukocytes.

Case Report: Contribution of [18F]FET PET in differential diagnosis between radionecrosis and progression in metastasis-reproducibility and superiority of dynamic acquisitions.

We present the case of a 67-year-old woman with metastatic invasive ductal carcinoma of the left breast, in whom a follow-up magnetic resonance imaging, 3 months after encephalic radiotherapy, revealed a significant increase in the size of two brain metastases, potentially indicating progressive disease within the radiation field. Subsequent [18F] fluorodeoxyglucose ([18F]FDG) and [18F] fluoroethyl-L-tyrosine positron emission tomography ([18F]FET PET) scans were performed to distinguish radionecrosis from tumor progression. Despite a dynamic [18F]FET time-activity curve (TAC) against progression, the exceeding of the 1.9 cutoff by mean tumor to brain ratio (TBR) and interdisciplinary considerations led to the resection of one lesion. Histopathology revealed necrosis due to radiotherapy, without viable tumor proliferation. To verify radionecrosis, a second [18F]FET PET scan was conducted, showing consistent findings. In metastasis differentiation, the mean TBR cutoff of 1.9 and TAC analysis achieved a sensitivity of 95% and specificity of 91%. The discrepancy between the TAC and TBR emphasizes the need for consideration, and a time delay between radiotherapy and PET may impact TBR cutoffs. In addition, differences in radiosensitivity suggest a lower metastasis pre-test probability of progression, and it might be why a TAC analysis could be more effective in distinguishing true progression from treatment related changes in metastasis. This case demonstrates the accuracy of dynamic [18F]FET PET and suggests its utility for post-treatment metastasis evaluation, and further research on post-treatment delay could lead to improved performances of dynamic [18F]FET PET.

Single-voxel delay map from long-axial field-of-view PET scans.

Objective: We present an algorithm to estimate the delay between a tissue time-activity curve and a blood input curve at a single-voxel level tested on whole-body data from a long-axial field-of-view scanner with tracers of different noise characteristics. Methods: Whole-body scans of 15 patients divided equally among three tracers, namely [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, which were used in development and testing of the algorithm. Delay times were estimated by fitting the cumulatively summed input function and tissue time-activity curve with special considerations for noise. To evaluate the performance of the algorithm, it was compared against two other algorithms also commonly applied in delay estimation: name cross-correlation and a one-tissue compartment model with incorporated delay. All algorithms were tested on both synthetic time-activity curves produced with the one-tissue compartment model with increasing levels of noise and delays between the tissue activity curve and the blood input curve. Whole-body delay maps were also calculated for each of the three tracers with data acquired on a long-axial field-of-view scanner with high time resolution. Results: Our proposed model performs better for low signal-to-noise ratio time-activity curves compared to both cross-correlation and the one-tissue compartment models for non-[15O]H2O tracers. Testing on synthetically produced time-activity curves showed only a small and even residual delay, while the one-tissue compartment model with included delay showed varying residual delays. Conclusion: The algorithm is robust to noise and proves applicable on a range of tracers as tested on [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, and hence is a viable option offering the ability for delay correction across various organs and tracers in use with kinetic modeling.

Activity quantification and dosimetry in radiopharmaceutical therapy with reference to 177Lutetium.

Radiopharmaceutical therapy has been widely adopted owing primarily to the development of novel radiopharmaceuticals. To fully utilize the potential of these RPTs in the era of precision medicine, therapy must be optimized to the patient's tumor characteristics. The vastly disparate dosimetry methodologies need to be harmonized as the first step towards this. Multiple factors play a crucial role in the shift from empirical activity administration to patient-specific dosimetry-based administrations from RPT. Factors such as variable responses seen in patients with presumably similar clinical characteristics underscore the need to standardize and validate dosimetry calculations. These efforts combined with ongoing initiatives to streamline the dosimetry process facilitate the implementation of radiomolecular precision oncology. However, various challenges hinder the widespread adoption of personalized dosimetry-based activity administration, particularly when compared to the more convenient and resource-efficient approach of empiric activity administration. This review outlines the fundamental principles, procedures, and methodologies related to image activity quantification and dosimetry with a specific focus on 177Lutetium-based radiopharmaceuticals.

Cardiovascular risk factors and development of nomograms in an Italian cohort of patients with suspected coronary artery disease undergoing SPECT or PET stress myocardial perfusion imaging.

Introduction: Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive nuclear medicine techniques that can identify areas of abnormal myocardial perfusion. We assessed the prevalence of cardiovascular risk factors in patients with suspected coronary artery disease (CAD) undergoing SPECT or PET stress myocardial perfusion imaging (MPI). Based on significant risk factors associated with an abnormal MPI, we developed a nomogram for each cohort as a pretest that would be helpful in decision-making for clinicians. Methods: A total of 6,854 patients with suspected CAD who underwent stress myocardial perfusion imaging by SPECT or PET/CT was studied. As part of the baseline examination, clinical teams collected information on traditional cardiovascular risk factors: age, gender, body mass index, angina, dyspnea, diabetes, hypertension, hyperlipidemia, family history of CAD, and smoking. Results: The prevalence of cardiovascular risk factors was different in the two cohorts of patients undergoing SPECT (n = 4,397) or PET (n = 2,457) myocardial perfusion imaging. A statistical significance was observed in both cohorts for age, gender, and diabetes. At multivariable analysis, only age and male gender were significant covariates in both cohorts. The risk of abnormal myocardial perfusion imaging related to age was greater in patients undergoing PET (odds ratio 4% vs. 1% per year). In contrast, male gender odds ratio was slightly higher for SPECT compared to PET (2.52 vs. 2.06). In the SPECT cohort, smoking increased the risk of abnormal perfusion of 24%. Among patients undergoing PET, diabetes and hypertension increased the risk of abnormal perfusion by 63% and 37%, respectively. For each cohort, we obtained a nomogram by significant risk factors at multivariable logistic regression. The area under the receiver operating characteristic curve associated with the nomogram was 0.67 for SPECT and 0.73 for the PET model. Conclusions: Patients with suspected CAD belonging to two different cohorts undergoing SPECT or PET stress myocardial perfusion imaging can have different cardiovascular risk factors associated with a higher risk of an abnormal MPI study. As crude variables, age, gender, and diabetes were significant for both cohorts. Net of the effect of other covariates, age and gender were the only risk factors in common between the two cohorts. Furthermore, smoking and type of stress test were significant for the SPECT cohort, where as diabetes and hypertension were significant for the PET cohort. Nomograms obtained by significant risk factors for the two cohorts can be used by clinicians to evaluate the risk of an abnormal study.

Case report: positive pitfalls of PSMA PET/CT: diagnostic challenges in degenerative bone lesions including MODIC type 1.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an imaging technique that has demonstrated high sensitivity and specificity in detecting prostate cancer and its metastasis, especially in the bones. This case describes a 60-year-old man who presented for increased prostate-specific antigen (PSA) level and underwent [68Ga]gallium-PSMA-11 PET/CT imaging for better disease assessment. 68Ga-PSMA-11 PET/CT revealed numerous radiotracer-positive lesions in both prostate lobes with associated sclerotic lesions on L4 and L5, but only L5 showed increased radiotracer avidity raising the possibility of metastasis. Magnetic Resonance Imaging (MRI) raises the possibility of aggressive MODIC type 1 lesion vs. infectious/inflammatory process. A biopsy of the radiotracer avid area was performed and showed no evidence of metastasis. The final diagnosis was aggressive MODIC type 1, in keeping with the false positive result of 68Ga-PSMA-11 PET/CT. This example demonstrates the possible limitations of 68Ga-PSMA-11 PET/CT, particularly in detecting bone metastases, and emphasizes the need for cautious interpretation and additional study to improve its diagnostic accuracy. Understanding and resolving these limitations is critical for increasing the accuracy of PSMA PET/CT in prostate cancer management.

Advances and challenges in immunoPET methodology.

Immuno-positron emission tomography (immunoPET) enables imaging of specific targets that play a role in targeted therapy and immunotherapy, such as antigens on cell membranes, targets in the disease microenvironment, or immune cells. The most common immunoPET applications use a monoclonal antibody labeled with a relatively long-lived positron emitter such as 89Zr (T 1/2 = 78.4 h), but smaller antibody-based constructs labeled with various other positron emitting radionuclides are also being investigated. This molecular imaging technique can thus guide the development of new drugs and may have a pivotal role in selecting patients for a particular therapy. In early phase immunoPET trials, multiple imaging time points are used to examine the time-dependent biodistribution and to determine the optimal imaging time point, which may be several days after tracer injection due to the slow kinetics of larger molecules. Once this has been established, usually only one static scan is performed and semi-quantitative values are reported. However, total PET uptake of a tracer is the sum of specific and nonspecific uptake. In addition, uptake may be affected by other factors such as perfusion, pre-/co-administration of the unlabeled molecule, and the treatment schedule. This article reviews imaging methodologies used in immunoPET studies and is divided into two parts. The first part summarizes the vast majority of clinical immunoPET studies applying semi-quantitative methodologies. The second part focuses on a handful of studies applying pharmacokinetic models and includes preclinical and simulation studies. Finally, the potential and challenges of immunoPET quantification methodologies are discussed within the context of the recent technological advancements provided by long axial field of view PET/CT scanners.

Diagnosis of Hemophagocytic Lymphohistiocytosis in Pyrexia of Unknown Origin: A Case Report.

ABSTRACT: A case of a 61-year male presented with chief complaints of fever for three months. Diagnosis of hemophagocytic lymphohistiocytosis was made after liver biopsy when Positron-Emission Tomography revealed multiple fluoro deoxy glucose avid lesions in the liver. The patient of this disease typically presents with fever, splenomegaly, hyperferritinemia, hypertriglyceridemia, raised liver enzymes, and marrow features suggestive of hemophagocytosis. The treatment is usually systemic corticosteroids, chemotherapy with etoposide, cyclosporine, or hematopoietic stem cell transplantation, depending on the cause. A diagnosis like hemophagocytic lymphohistiocytosis can easily be missed in developing countries with low resources like Nepal. Hence, this disease should be suspected in patients presenting with pyrexia of unknown origin by treating physicians.

Impact of Baseline Renal Insufficiency on Piflufolastat F-18 Performance and Investigation of Changes in Renal Function Following Piflufolastat F-18 Administration: Results From the OSPREY Trial.

INTRODUCTION: Piflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function. PATIENTS AND METHODS: The OSPREY clinical trial enrolled 2 cohorts: A-high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B-patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts. RESULTS: 385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage. CONCLUSION: Piflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency.

Engineering dual-functional and thermophilic BMHETase for efficient degradation of polyethylene terephthalate.

Polyethylene terephthalate (PET) biodegradation is hindered by the intermediates bis (2-hydroxyethyl) terephthalate (BHET) and mono (2-hydroxyethyl) terephthalate (MHET). BMHETase, a thermophilic hydrolase identified from the UniParc database, exhibits degradation activity towards both BHET and MHET. BMHETase showed higher activity on BHET than LCCICCG and FASTPETase at temperatures ranging from 50 to 70℃. To enhance its activity in degrading MHET, BMHETase was engineered to mimic Ideonella sakaiensis MHETase. The resulting 6-point mutant's activities on MHET and BHET were 8 and 2 times those of the WT, with both optimal temperatures increased by 5℃. This enhancement may be attributed to the BMHETase6M's intensified binding ability with MHET and enlarged binding pocket. When combined with LCCICCG, BMHETase6M achieved complete degradation of MHET in PET films to terephthalic acid, indicating broad application potential. These findings suggest that BMHETase6M holds promise as a candidate for enhancing PET biodegradation efficiency and plastic waste management.

PSMA PET/CT patterns of recurrence after mono-brachytherapy in men with low and intermediate prostate cancer and subsequent management.

PURPOSE: Brachytherapy as monotherapy is a recommended treatment option for men with low to intermediate risk prostate cancer. Local recurrence is difficult to identify. This study investigated PSMA PET/CT for recurrence after brachytherapy, as well as their subsequent management when recurrence occurred only within the prostate. METHODS: We performed a retrospective single-center analysis for patients who were treated with brachytherapy as monotherapy for prostate cancer from May 2002 to May 2021 and who underwent a PSMA PET/CT for BCR. We report the findings on PSMA PET/CT, quantitative parameters, as well as the later management of the patients. RESULTS: Forty patients were identified, who underwent PSMA PET/CT to investigate a rising PSA at a median (IQR) of 7 years (3.0-10.8) after initial therapy. Median (IQR) PSA at time of PSMA PET/CT was 6.54 ng/mL (3.9-15.5). On PSMA PET/CT, 20/40 (50%) men had prostate-only recurrence. Of the 20 patients with prostate-only recurrence, 8/20 (40%) had recurrence in a high-dose radiation zone, versus 7/20 (35%) in an under-covered zone. On PSMA PET/CT, recurrence within the prostate had median (IQR) SUVmax 10.4 (5.1-15.7) and volume 2.9 mL (2.0-11.2). Subsequent management of these patients with local recurrence included surveillance followed by ADT (9/20, 45%). For those with surveillance followed by ADT, the mean time before introduction of ADT was 4.1 years (range 1-8 years).

Intracranial arteriosclerosis is not associated with cerebral amyloid deposition.

BACKGROUND: Intracranial arteriosclerosis and cerebral amyloid beta (Aß) are both involved in the etiology of Alzheimer's disease (AD) dementia, but the direct link between these two pathologies remains elusive. METHODS: In 633 participants (mean age 69 years, 51% women) from the population-based Rotterdam Study, we quantified cerebral Aß accumulation on amyloid positron emission tomography (PET). We assessed calcification of the intracranial internal carotid (ICAC) and vertebrobasilar arteries (VBAC) as proxies of arteriosclerosis on non-enhanced computed tomography (CT). Using logistic and linear regression, we studied the relationship of presence, burden, and type of calcification with the presence and burden of Aß. RESULTS: We found no associations of ICAC [odds ratio (OR): 0.85, 95% confidence interval (CI): 0.43, 1.72] or VBAC [OR: 0.59, CI: 0.26, 1.24] with cerebral Aß. The results did not vary across ICAC subtypes. DISCUSSION: Intracranial arteriosclerosis was not associated with cerebral Aß, underscoring their independence in the etiology of AD dementia. Highlights: Comprehensive assessment of intracranial arteriosclerosis (e.g., including subtypes).Intracranial arteriosclerosis in different arteries and cerebral Aß are not related.Arteriosclerosis and Aß likely influence Alzheimer's disease dementia independently.

Neuroinflammation and blood-brain barrier breakdown in acute, clinical intracerebral hemorrhage.

Neuroinflammation is a promising therapeutic target in intracerebral hemorrhage (ICH), characterized in the brain by microglial activation and blood-brain barrier (BBB) breakdown. In this study, 36 acute, spontaneous, supratentorial ICH patients underwent dynamic contrast-enhanced MRI to measure BBB permeability (Ktrans) 1-3 days post-onset and 16 returned for [11C](R)-PK11195 PET to quantify microglial activation (BPND), 2-7 days post-onset. We first tested if these markers were increased and co-localized in the perihematomal brain and found that perihematomal Ktrans and BPND were increased vs. the contralateral brain, but regions of high Ktrans and BPND only overlapped by a mean of 4.9%. We then tested for associations of perihematomal Ktrans and BPND with clinical characteristics (age, ICH volume & location, blood pressure), other markers of inflammation (edema, IL-6, and CRP), and long-term functional outcome (90-day mRS). Lower perihematomal BPND was associated with increasing age. Lobar hemorrhage was associated with greater Ktrans than deep, but Ktrans and BPND were not associated with ICH volume, or other inflammatory markers. While perihematomal Ktrans and BPNDwere not associated with outcome, contralateral Ktrans was significantly associated with greater 90-day mRS. Exploratory analyses demonstrated that blood pressure variability over 72 h was also associated with contralateral Ktrans.

Mechanisms of Polyethylene Terephthalate Pellet Fragmentation into Nanoplastics and Assimilable Carbons by Wastewater Comamonas.

Comamonadaceae bacteria are enriched on poly(ethylene terephthalate) (PET) microplastics in wastewaters and urban rivers, but the PET-degrading mechanisms remain unclear. Here, we investigated these mechanisms with Comamonas testosteroniKF-1, a wastewater isolate, by combining microscopy, spectroscopy, proteomics, protein modeling, and genetic engineering. Compared to minor dents on PET films, scanning electron microscopy revealed significant fragmentation of PET pellets, resulting in a 3.5-fold increase in the abundance of small nanoparticles (<100 nm) during 30-day cultivation. Infrared spectroscopy captured primarily hydrolytic cleavage in the fragmented pellet particles. Solution analysis further demonstrated double hydrolysis of a PET oligomer, bis(2-hydroxyethyl) terephthalate, to the bioavailable monomer terephthalate. Supplementation with acetate, a common wastewater co-substrate, promoted cell growth and PET fragmentation. Of the multiple hydrolases encoded in the genome, intracellular proteomics detected only one, which was found in both acetate-only and PET-only conditions. Homology modeling of this hydrolase structure illustrated substrate binding analogous to reported PET hydrolases, despite dissimilar sequences. Mutants lacking this hydrolase gene were incapable of PET oligomer hydrolysis and had a 21% decrease in PET fragmentation; re-insertion of the gene restored both functions. Thus, we have identified constitutive production of a key PET-degrading hydrolase in wastewater Comamonas, which could be exploited for plastic bioconversion.