Residual Uptake Research Articles

Navigating Pesticide Residue Accumulation in Arable Soils: Insights for Sustainable Agriculture

Adoption and application of wide range chemicals as pesticides for shielding crop against undesirable weeds, insects and pests has increased the overall agricultural productivity in recent decades. According to reports, pesticides which are exposed to a variety of environmental circumstances over an extended period of time cause many of their derivatives to survive in the environment. Accumulation of these chemicals in ecosystems lead their absorption in non-target creatures, planted crops and arable soils, and therefore, causing serious detrimental environmental hazards and many concerns have been brought to light on a worldwide scale. In fact, there may still be health hazards for people associated with the food chain transportation of these pesticide residual compounds. Pesticide residues absorption, on the other hand, is more difficult to understand. Characteristics of the planted crops, the physicochemical qualities of the pesticides and the ambient factors can all have a significant impact on the pesticide residue uptake process and bioavailable concentrations. In the meanwhile, this article will emphasize on overview of these pesticide residue forms and their fate in agricultural soils, mechanisms and factors hindering plant uptake for essential nutrients. To make reasonable risk forecasts for human health, future research must conduct field-based investigations in natural settings.

D-[5-11C]-Glutamine Positron Emission Tomography Imaging for Diagnosis and Therapeutic Monitoring of Orthopedic Implant Infections.

Orthopedic implant infections (OIIs) present diagnostic and therapeutic challenges, owing to the lack of methods to distinguish between active infection and sterile inflammation. To address this unmet need, d-amino-acid-based radiotracers with unique metabolic profiles in microorganisms have emerged as a novel class of infection-specific imaging agents. Given the pivotal role of d-glutamine in bacterial biofilm formation and virulence, herein, we explored the potential of positron emission tomography (PET) imaging with d-[5-11C]-Glutamine (d-[5-11C]-Gln) for early detection and treatment monitoring of OIIs. In vitro studies confirmed an active uptake of d-[5-11C]-Gln by Staphylococcus aureus (S. aureus) biofilm commonly associated with OIIs. In vivo evaluations included PET imaging comparisons with d-[5-11C]-Gln vs l-[5-11C]-Gln or 2-deoxy-2-[18F]-fluoroglucose ([18F]-FDG) in a rat OII model with tibial implantation of sterile or S. aureus-colonized stainless-steel screws before and after treatment. These studies demonstrated that the uptake of d-[5-11C]-Gln was significantly higher in the infected screws than that in sterile screws (∼3.4-fold, p = 0.008), which displayed significantly higher infection-to-background muscle uptake ratios (∼2-fold, p = 0.011) with d-[5-11C]-Gln as compared to l-[5-11C]-Gln. Following a 3 week vancomycin treatment, imaging with d-[5-11C]-Gln showed a significant reduction in uptake at the infected sites (∼3-fold, p = 0.0008). Further regression analyses revealed a superior correlation of residual infection-associated radiotracer uptake with the postimaging ex vivo bacterial counts for d-[5-11C]-Gln (k = 0.473, R2 = 0.796) vs [18F]-FDG (k = 0.212, R2 = 0.434), suggesting that d-[5-11C]-Gln PET had higher sensitivity for detecting residual bacterial burden than [18F]-FDG PET. Our results demonstrate the translational potential of d-[5-11C]-Gln PET imaging for noninvasive detection and treatment monitoring of OIIs.

Modification of the existing maximum residue level for flonicamid in honey.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant ISK Biosciences Europe N.V. submitted a request to the competent national authority in Finland to modify the existing maximum residue level (MRL) for the active substance flonicamid in honey. The data submitted in support of the request were not found appropriate to derive an MRL proposal for honey. The assessment was complemented by an analysis of the monitoring data available from the EU monitoring programmes (conducted during 2009-2023). The results from the monitoring data analysis suggest that the current MRL is still sufficient to account for the residue uptake in honey resulting from plant protection products uses of flonicamid on melliferious crops. Adequate analytical methods for enforcement are available to control the residues of flonicamid in honey according to the residue definition as the sum of flonicamid, TFNA and TFNG, expressed as flonicamid at the validated limit of quantification (LOQ) of 0.01 mg/kg for each compound. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues in honey at a level of 0.05 mg/kg according to the monitoring data is unlikely to present a risk to consumer health.

Adaptive radiotherapy (up to 74 Gy) or standard radiotherapy (66 Gy) for patients with stage III non-small-cell lung cancer, according to [18F]FDG-PET tumour residual uptake at 42 Gy (RTEP7–IFCT-1402): a multicentre, randomised, controlled phase 2 trial

Thoracic radiation intensification is debated in patients with stage III non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of a boost radiotherapy dose up to 74 Gy in a functional sub-volume given according to on-treatment [18F]fluorodeoxyglucose ([18F]FDG)-PET results. In this multicentre, randomised, controlled non-comparative phase 2 trial, we recruited patients aged 18 years or older with inoperable stage III NSCLC without EGFR mutation or ALK rearrangement with an Eastern Cooperative Oncology Group performance status of 0-1, and who were affiliated with or a beneficiary of a social benefit system, with evaluable tumour or node lesions, preserved lung function, and who were amenable to curative-intent radiochemotherapy. Patients were randomly allocated using a central interactive web-response system in a non-masked method (1:1; minimisation method used [random factor of 0·8]; stratified by radiotherapy technique [intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy] and by centre at which patients were treated) either to the experimental adaptive radiotherapy group A, in which only patients with positive residual metabolism on [18F]FDG-PET at 42 Gy received a boost radiotherapy (up to 74 Gy in 33 fractions), with all other patients receiving standard radiotherapy dosing (66 Gy in 33 fractions over 6·5 weeks), or to the standard radiotherapy group B (66 Gy in 33 fractions) over 6·5 weeks. All patients received two cycles of induction platinum-based chemotherapy cycles (paclitaxel 175 mg/m2 intravenously once every 3 weeks and carboplatin area under the curve [AUC]=6 once every 3 weeks, or cisplatin 80 mg/m2 intravenously once every 3 weeks and vinorelbine 30 mg/m2 intravenously on day 1 and 60 mg/m2 orally [or 30 mg/m2 intravenously] on day 8 once every 3 weeks). Then they concomitantly received radiochemotherapy with platinum-based chemotherapy (three cycles for 8 weeks, with once per week paclitaxel 40 mg/m2 intravenously and carboplatin AUC=2 or cisplatin 80 mg/m2 intravenously and vinorelbine 20 mg/m2 intravenously on day 1 and 40 mg/m2 orally (or 20 mg/m2 intravenously) on day 8 in 21-day cycles). The primary endpoint was the 15-month local control rate in the eligible patients who received at least one dose of concomitant radiochemotherapy. This RTEP7-IFCT-1402 trial is registered with ClinicalTrials.gov (NCT02473133), and is ongoing. From Nov 12, 2015, to July 7, 2021, we randomly assigned 158 patients (47 [30%] women and 111 [70%] men) to either the boosted radiotherapy group A (81 [51%]) or to the standard radiotherapy group B (77 [49%)]. In group A, 80 (99%) patients received induction chemotherapy and 68 (84%) received radiochemotherapy, of whom 48 (71%) with residual uptake on [18F]FDG-PET after 42 Gy received a radiotherapy boost. In group B, all 77 patients received induction chemotherapy and 73 (95%) received radiochemotherapy. At the final analysis, the median follow-up for eligible patients who received radiochemotherapy (n=140) was 45·1 months (95% CI 39·3-48·3). The 15-month local control rate was 77·6% (95% CI 67·6-87·6%) in group A and 71·2% (95% CI 60·8-81·6%) in group B. Acute (within 90 days from radiochemotherapy initiation) grade 3-4 adverse events were observed in 20 (29%) of 68 patients in group A and 33 (45%) of 73 patients in group B, including serious adverse events in five (7%) patients in group A and ten (14%) patients in group B. The most common grade 3-4 adverse events were febrile neutropenia (seven [10%] of 68 in group A vs 16 [22%] of 73 in group B), and anaemia (five [7%] vs nine [12%]). In the acute phase, two deaths (3%) occurred in group B (one due to a septic shock related to chemotherapy, and the other due to haemotypsia not related to study treatment), and no deaths occurred in group A. After 90 days, one additional treatment-unrelated death occurred in group A and two deaths events occurred in group B (one radiation pneumonitis and one pneumonia unrelated to treatment). A thoracic radiotherapy boost, based on interim [18F]FDG-PET, led to a meaningful local control rate with no difference in adverse events between the two groups in organs at risk, in contrast with previous attempts at thoracic radiation intensification, warranting a randomised phase 3 evaluation of such [18F]FDG-PET-guided radiotherapy dose adaptation in patients with stage III NSCLC. Programme Hospitalier de Recherche Clinique National 2014.

The prognostic role of 18F-FDG PET/CT-based response evaluation in children with stage 4 neuroblastoma.

To evaluate the association between metabolic response on 18F-FDG PET/CT and long-term survival in children with neuroblastoma (NB). A total of 39 consecutive children with newly diagnosed stage 4 NB undergoing both 18F-FDG PET/CT imaging at baseline and after chemotherapy were retrospectively analyzed. The associations between metabolic parameters, including SUVmax of the lesion with the most intense 18F-FDG uptake at baseline (SUVb), after chemotherapy (SUVe), and the percentage change between SUVb and SUVe, and long-term survival were evaluated. With a median follow-up of 56 months, 22 patients who had achieved complete resolution on PET (no residual 18F-FDG uptake higher than the surrounding backgrounds) after chemotherapy had superior 5-year overall survival (OS) (73.6% vs. 39.0%, p = 0.044). SUVb > 6.9 indicated significantly poorer 5-year event-free survival (EFS) (12.5% vs. 59.3%, p = 0.005), as did SUVe > 1.2 (18.8% vs. 41.7%, p = 0.041). Children with SUVe > 1.2 had shorter 5-year OS (33.9% vs. 75.0%, p = 0.018). Multivariate analysis identified SUVe > 1.2 as an independent predictor for both EFS [hazard ratio (HR), 3.479, 95% CI, 1.381-8.761, p = 0.008] and OS (HR, 6.948, 95% CI, 1.663-29.025, p = 0.008), while SUVb > 6.9 was a predictor for EFS (HR, 2.889, 95% CI, 1.064-7.842, p = 0.037). Among 11 children with both SUVb > 6.9 and SUVe > 1.2, all experienced disease progression or relapse within 2 years since diagnosis. 18F-FDG PET/CT could be of useful to evaluate treatment response in children with stage 4 NB. 18F-FDG PET/CT after chemotherapy exhibits prognostic significance in neuroblastoma and holds potential as an alternative imaging modality for response evaluation, especially in cases with metaiodobenzylguanidine-nonavid or persistent avid disease. The prognostic value of chemotherapy response on 18F-FDG PET/CT in advanced neuroblastoma is unknown. Higher 18F-FDG uptake after chemotherapy was associated with worse long-term event-free survival and overall survival. 18F-FDG PET/CT after chemotherapy holds prognostic significance in children with stage 4 neuroblastoma.

Abstract 2046: Overexpression Of Endothelial Lipase Enhances The Cellular Uptake Of Low-density Lipoproteins In Cultured Hepatocytes In The Absence Of Low-density Lipoprotein Receptor.

Background: Inhibitors of angiopoietin-like3 (ANGPTL3) reduce low-density lipoprotein (LDL) cholesterol, even in Familial Hypercholesterolemia (FH) patients with a dysfunctional LDL receptor (LDLR). Although the exact mechanism remains elusive, it may depend upon endothelial lipase (EL). Early studies showed that EL mediates the cellular uptake of high-density lipoproteins in hepatocytes; however, whether EL similarly mediates LDL uptake is unknown. Aim: Investigate the role of EL in mediating the cellular uptake of LDL in an LDLR-deficient model. Methods: Cas9-expressing HepG2 cells were transfected with a scrambled or an LDLR -targeting guide RNA to produce control and LDLR -knockout (KO) cells. Control and KO cells were transfected by lipofection with an empty plasmid or a plasmid containing the human LIPG gene (EL). Cellular uptake of fluorescent human LDL was measured by FACS. In addition, we measured the uptake of LDL in cells with and without the pre-incubation with 5 U/ml heparin or a cocktail of heparinases I, II, and II to test the contribution of heparan sulfate proteoglycans (HSPG). Results: LDLR -KO HepG2 cells showed a 20-25% residual uptake of LDL compared to controls (p<0.001) and 10-fold higher levels of EL mRNA. Remarkably, LIPG -transfected LDLR -KO hepatocytes showed a 2-fold increase in LDL uptake compared to LDLR-KO cells non-overexpressing EL (p<0.001). The pre-incubation with either heparinases or heparin completely blocked the uptake of LDL not only in LIPG -transfected LDLR -KO cells but also in those LDLR -KO cells transfected with the empty plasmid, suggesting a crucial role of HSPG in the LDL uptake. Conversely, overexpression of EL decreased LDL uptake in control cells (-11%, p=0.02), while unchanged or slightly increased LDL uptake was observed after incubating with heparinases or heparin. Conclusions: Our findings demonstrate that EL facilitates the uptake of LDL through an LDLR-independent, HSPG-dependent pathway. This pathway may be responsible for the residual uptake of LDL observed in LDLR -KO hepatocytes and may represent a potential druggable target to treat FH. Our data provides an alternative mechanism to explain the reduction of LDL cholesterol induced by ANGPTL3 inhibitors.

Postoperative recurrence of diffuse sclerosing thyroid cancer in an adolescent patient: A case report.

Papillary thyroid cancer is an inert malignant tumor with a good response to surgical treatment, low recurrence and metastasis rate, and good prognosis. Diffuse sclerosing thyroid cancer is an invasive subtype that is more common in young people, with a higher rate of lymph node metastasis and recurrence, and a relatively poor prognosis. A 13-year-old girl underwent radical surgery for diffuse sclerosing thyroid cancer. Eight years later, due to a large number of lymph node metastases, she underwent another radical surgery on her neck lymph nodes. The patient thyroid ultrasound and neck enhanced CT indicated that the patient had multiple enlarged lymph nodes in the neck with irregular morphology and structure, and the possibility of metastatic lymph nodes was high. Subsequently, the patient underwent thyroid fine-needle aspiration and the results showed that cancer cells were detected in both cervical lymph nodes. The patient was diagnosed with bilateral cervical lymph node metastases after thyroid surgery. After the second surgery, the patient recovered well, and no residual or focal iodine uptake tissue was found on the enhanced CT examination. As diffuse sclerosing thyroid cancer is prone to lymph node and recurrent metastases, once it is diagnosed, radical treatment should be actively performed. Postoperative adjuvant radiation therapy should be administered according to the patient condition and regular follow-ups should be conducted to monitor neck lymph node metastasis.

Modification of the temporary maximum residue levels for mepiquat in cultivated fungi and oyster mushrooms.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in Finland to modify the temporary maximum residue level (MRL) to a permanent MRL for the active substance mepiquat in cultivated fungi (with a specific MRL for oyster mushrooms). The data submitted in support of the request (monitoring data from food business operators) are not sufficient to derive permanent MRL proposals. The assessment of these data, complemented by an analysis of the most recent monitoring data available from EU monitoring programmes, supports the conclusion that the existing t-MRL for cultivated fungi is still sufficient to account for the residue uptake in cultivated mushrooms other than oyster mushrooms. It was also noted that lower t-MRLs could be derived based on the assessment of the most recent monitoring data. A risk management decision is still needed on whether to maintain the existing t-MRL value. Regarding oyster mushrooms, EFSA derived different options for risk managers to eventually update the values of the temporary MRLs based on the most recent monitoring data from food business operators. Adequate analytical methods for enforcement are available to control the residues of mepiquat (expressed as mepiquat chloride) in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the cross-contamination of untreated cultivated fungi (including oyster mushrooms) from cereal straw lawfully treated with mepiquat according to the current agricultural practices is unlikely to present a risk to consumer health.

The Interplay of Permeability, Metabolism, Transporters, and Dosing in Determining the Dynamics of the Tissue/Plasma Partition Coefficient and Volume of Distribution-A Theoretical Investigation Using Permeability-Limited, Physiologically Based Pharmacokinetic Modeling.

A permeability-limited physiologically based pharmacokinetic (PBPK) model featuring four subcompartments (corresponding to the intracellular and extracellular water of the tissue, the residual plasma, and blood cells) for each tissue has been developed in MATLAB/SimBiology and applied to various what-if scenario simulations. This model allowed us to explore the complex interplay of passive permeability, metabolism in tissue or residual blood, active uptake or efflux transporters, and different dosing routes (intravenous (IV) or oral (PO)) in determining the dynamics of the tissue/plasma partition coefficient (Kp) and volume of distribution (Vd) within a realistic pseudo-steady state. Based on the modeling exercise, the permeability, metabolism, and transporters demonstrated significant effects on the dynamics of the Kp and Vd for IV bolus administration and PO fast absorption, but these effects were not as pronounced for IV infusion or PO slow absorption. Especially for low-permeability compounds, uptake transporters were found to increase both the Kp and Vd at the pseudo-steady state (Vdss), while efflux transporters had the opposite effect of decreasing the Kp and Vdss. For IV bolus administration and PO fast absorption, increasing tissue metabolism was predicted to elevate the Kp and Vdss, which contrasted with the traditional derivation from the steady-state perfusion-limited PBPK model. Moreover, metabolism in the residual blood had more impact on the Kp and Vdss compared to metabolism in tissue. Due to its ability to offer a more realistic description of tissue dynamics, the permeability-limited PBPK model is expected to gain broader acceptance in describing clinical PK and observed Kp and Vdss, even for certain small molecules like cyclosporine, which are currently treated as perfusion-limited in commercial PBPK platforms.

Abstract 16992: Superior Vena Cava Syndrome in a Patient With Metastatic Primary Cardiac Diffuse Large B-cell Lymphoma - Case Report

Introduction: Primary cardiac tumors are uncommon, with an estimated incidence of 0.02%. Primary cardiac lymphomas (PCL), a subtype of non-Hodgkin lymphoma, account for about 10% of malignant and 1% of all primary cardiac tumors. Diffuse large B-cell lymphomas (DLBCLs) emerge as the predominant histological subtype within PCL cases. Case presentation: 54-year-old White male with no medical history presented with a few weeks of exertional dyspnea, nonproductive cough, and neck fullness. Exam was notable for tachycardia, jugular venous distension, bilateral upper extremity edema, and distended chest wall vasculature. Labs showed elevation of alkaline phosphatase and CRP. CT of the chest showed a right atrial mass extending into and obstructing the superior vena cava (SVC) and mediastinal lymphadenopathy (Panel A & B). Coronary CTA performed a few years earlier showed normal interatrial septum (Panel C) and coronary arteries. Transthoracic echo (TTE) confirmed a 7.6 x 5.0cm mass visualized in the interatrial septum extending to both atria. Cardiac MRI redemonstrated a large cardiac mass with malignant features suggestive of cardiac lymphoma vs angiosarcoma (Panel D-F). PET-CT showed enhanced fluorodeoxyglucose (FDG) uptake within cardiac mass, mediastinal, and intraabdominal lymph nodes (Panel G). Lymph node biopsy confirmed DLBCL. Patient underwent three cycles of EPOCH (etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) chemotherapy with excellent response. TTE following cycle 2 demonstrated decreased tumor size, and PET-CT after cycle 3 confirmed complete resolution of lymphadenopathy and minimal residual intracardiac FDG uptake. Conclusion: SVC syndrome can be a rare presentation of PCL. Multimodality imaging is important in cardiac mass characterization, diagnosis, treatment planning, and follow-up. Timely diagnosis and initiation of chemotherapy results in improved outcomes.

Correlation of Post-Treatment Biopsy and Fluorodeoxyglucose PET/CT Findings Following Definitive Chemotherapy and Radiation for Cervical Cancer

Concurrent chemotherapy and external beam radiation with brachytherapy boost is considered standard of care for treatment of locally advanced cervical cancer. Post treatment surveillance fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging is recommended 3-6 months after completion of therapy. Persistent FDG avidity is commonly observed at the cervix on surveillance scans, indeterminate for residual malignancy versus post treatment inflammatory change. To better understand the clinical significance of residual hypermetabolic activity, we performed an analysis of surveillance FDG-PET/CT images, correlating findings with post treatment cervical biopsy results after completion of therapy. The medical records of all patients treated with definitive chemotherapy and radiation for locally advanced (FIGO IB3 to IVA) cervical cancer at a single academic medical center between 2017 and 2022 were reviewed. Patients were treated with curative intent using a combination of pelvic external beam radiation with concurrent cisplatin chemotherapy followed by intracavitary or combined intracavitary/interstitial brachytherapy boost. Patients underwent FDG-PET/CT imaging at 3-6 months upon completion of therapy, followed by biopsy either for suspected residual disease or equivocal findings on physical exam or FDG-PET/CT scans. Biopsies were obtained within 100 days of FDG-PET/CT imaging (median, 14 days). Twenty-three patients met inclusion criteria. One patient was excluded from analysis due to lack of FDG avidity on her pre-treatment FDG-PET/CT. Among the 22 evaluable scans, median pre-treatment FDG- PET/CT SUVmax of the cervix was 16.3 (range, 4.9-55). Median post-treatment SUVmax was 4.4 (range, 2.1-7.4). Median change in SUVmax from pre-treatment to post-treatment was 11.8 (range, 1.1 to 50.6). Twenty patients had a post-treatment SUVmax of greater than 3. Among post treatment scans, eight showed no residual uptake; two showed uptakes equal to the liver; eleven showed uptakes moderately higher than liver; and one showed uptake markedly increased relative to liver. None of the biopsy specimens showed evidence of residual malignancy, instead showing fibroinflammatory necrosis and reactive changes. None of the patients developed clinical evidence of disease progression at the cervix within one year of treatment completion. Residual hypermetabolic activity at the cervix is common following definitive chemotherapy and radiation for cervical cancer. This is unlikely to represent residual viable malignancy. Post treatment FDG-PET/CT imaging remains valuable for detecting locoregional or distant disease progression/persistence following therapy.

Tumor Microenvironment Features as Predictive Biomarkers in Metastatic Differentiated Thyroid Cancer and Their Relationship With 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Metabolic Parameters.

The role of the tumor microenvironment in tumor progression and treatment response is being investigated for different types of cancer. This study aimed to determine the relationships between tumor microenvironment, histopathology, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based metabolic parameters, treatment response, and overall survival (OS) in metastatic differentiated thyroid cancer (DTC). Methods: Metastatic DTC patients who underwent 18F-FDG PET/CT between 2015-2019 were evaluated. Clinicopathological, histopathological features and PET/CT parameters of patients were recorded. Microenvironmental characteristics of the primary tumor, such as mitosis, intratumoral and peritumoral lymphocytosis, intratumoral and peritumoral fibrosis, were evaluated from the tissue samples. The relationships between these factors were statistically analyzed. Sixty-five patients (38 females, 27 males, age: 49±15 years) were included. Mitosis, intra/peritumoral lymphocytosis, and intra/peritumoral fibrosis were frequent; however, none of them had a statistically significant association with PET-positive metastases, treatment response, or OS. Univariate analysis showed that gender, size, thyroglobulin values, residual thyroid tissue, PET-positive metastases, and maximum standardized uptake value (SUVmax) were significant predictors of OS. At multivariate analysis, PET-positive metastases (HR=-2.65, 95%CI 0.007-0.707, p=0.024) and SUVmax (HR=-2.74, 95%CI 0.006-0.687, p=0.023) were the only independent predictors for OS. Conclusion:Our study revealed that microenvironmental characteristics of the primary tumor did not show prognostic significance in metastatic DTC. PET-positive metastases and SUVmax levels were the only significant factors that predicted overall survival in DTC. Supporting the results of our study with further studies with a larger sample size may be necessary to determine the relationship between the tumor microenvironment and prognosis in DTC.

Prognostic significance of delayed complete metabolic response on PET/CT after primary chemoradiation treatment of cervical cancer

ObjectiveTo investigate the prognostic significance of near-complete metabolic response on initial follow-up PET/CT after primary chemoradiation treatment of cervical cancer.MethodsSurvival data were retrospectively compared between patients who had complete metabolic...

Detection of acute myocarditis by ECG-triggered PET imaging of somatostatin receptors compared to cardiac magnetic resonance: preliminary results

AbstractSomatostatin receptors are overexpressed by inflammatory cells but not by cardiac cells, under normal conditions. This study assesses the detection of acute myocarditis by the ECG-triggered digital-PET imaging of somatostatin receptors (68Ga-DOTATOC-PET), as compared to Cardiac Magnetic Resonance (CMR) imaging, which is the reference diagnostic method in this setting. MethodsFourteen CMR-defined acute myocarditis patients had a first 15-minutes ECG-triggered 68Ga-DOTATOC PET recording, 4.4 ± 3.0 days from peak troponin, and 10 had a second 4.3 ± 0.3 months later. Myocardial/blood SUVmax ratio was analyzed relative to the normal upper limit of 2.18, which had been previously determined from oncology 68Ga-DOTATOC-PET recordings of patients with a similar age range as the myocarditis patients. ResultsAn increased myocardial 68Ga-DOTATOC uptake relative to blood activity was invariably observed during the acute phase. SUVmax ratio exceeded 2.18 in all patients during the acute phase but also in 3/10 patients at 4-months, at a time when there were no more signs of active inflammation on CMR. A residual myocardial 68Ga-DOTATOC uptake was still observed on all gated-PET cine loops at 4-months. ConclusionThese preliminary results suggest that 68Ga-DOTATOC ECG-triggered digital-PET may be as sensitive as CMR at detecting myocarditis during the acute phase and more sensitive at later stages.

Comparative Evaluation of [18F]5-Fluoroaminosuberic Acid and (4S)-4-3-[18F]fluoropropyl)-l-Glutamate as System xC--Targeting Radiopharmaceuticals.

System [Formula: see text] is an appealing biomarker for targeting oxidative stress with oncologic PET imaging and can serve as an alternative PET biomarker to other metabolic indicators. In this paper, we report a direct comparison of 2 18F-labeled amino acid radiopharmaceuticals targeting system [Formula: see text], [18F]5-fluoroaminosuberic acid ([18F]FASu) and (4S)-4-(3-[18F]fluoropropyl)-l-glutamate ([18F]FSPG), in terms of their uptake specificity and ability to image glioma and lung cancer xenografts invivo. Methods: Both tracers were synthesized according to previously published procedures. In vitro uptake specificity assays were conducted using prostate (PC-3), glioblastoma (U-87), colorectal (HT-29), ovarian (SKOV3), breast (MDA-MB-231), and lung cancer (A549) cell lines. PET/CT imaging and biodistribution studies were conducted in immunocompromised mice bearing U-87 or A549 xenografts. Results: In vitro cell uptake assays showed that the tracers accumulated in cancer cells in a time-dependent manner and that the uptake of [18F]FASu was blocked by the system [Formula: see text] inhibitor sulfasalazine and rose bengal, but not by system L inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, system [Formula: see text] inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid, or l-serine, which is a substrate for transporter systems A, ACS, B0, and B0,+ Conversely, [18F]FSPG uptake decreased significantly in the presence of an excess of L-trans-pyrrolidine-2,4-dicarboxylic acid in 2 of 3 tested cell lines, indicating some reliance on system [Formula: see text] in these cells. In an invivo setting, [18F]FASu and [18F]FSPG generated good-contrast PET images in U-87 and A549 tumor-bearing mice. Tracer accumulation in A549 tumors was 5.0 ± 0.8 percentage injected dose (%ID)/g ([18F]FASu, n ≥ 5) and 6.3 ± 1.3 %ID/g ([18F]FSPG, n ≥ 6, P = 0.7786), whereas U-87 xenografts demonstrated uptake of 6.1 ± 2.4 %ID/g ([18F]FASu, n ≥ 4) and 11.2 ± 4.1 %ID/g ([18F]FSPG, n ≥ 4, P = 0.0321) at 1 h after injection. Conclusion: [18F]FSPG had greater invitro uptake than [18F]FASu in all cell lines tested; however, our results indicate that residual uptake differences exist between [18F]FSPG and [18F]FASu, suggesting alternative transporter activity in the cell lines tested. In vivo studies demonstrated the ability of both [18F]FASu and [18F]FSPG to image glioblastoma (U-87) and non-small cell lung cancer (A549) xenografts.

Interobserver variability in interim PET assessment in Hodgkin lymphoma-reasons and solutions.

Interim PET (iPET) assessment is important for response adaptation in Hodgkin lymphoma (HL). The current standard for iPET assessment is the Deauville score (DS). The aim of our study was to evaluate the causes of interobserver variability in assigning the DS for iPET in HL patients and to make suggestions for improvement. All evaluable iPET scans from the RAPID study were re-read by two nuclear physicians, blinded to the results and patient outcomes in the RAPID trial. The iPET scans were assessed visually according to the DS and, thereafter, quantified using the qPET method. All discrepancies of more than one DS level were re-evaluated by both readers to find the reason for the discordant result. In 249/441 iPET scans (56%) a concordant visual DS result was achieved. A "minor discrepancy" of one DS level occurred in 144 scans (33%) and a "major discrepancy" of more than one DS level in 48 scans (11%). The main causes for major discrepancies were 1) different interpretation of PET-positive lymph nodes-malignant vs. inflammatory; 2) lesions missed by one reader and 3) different assessment of lesions in activated brown fat tissue. In 51% of the minor discrepancy scans with residual lymphoma uptake, additional quantification resulted in a concordant quantitative DS result. Discordant visual DS assessment occurred in 44% of all iPET scans. The main reason for major discrepancies was the different interpretation of PET positive lymph nodes as malignant or inflammatory. Disagreements in evaluation of the hottest residual lymphoma lesion can be solved by the use of semi-quantitative assessment.

Using Pop-GUIDE to Assess the Applicability of MCnest for Relative Risk of Pesticides to Hummingbirds

Hummingbirds are charismatic fauna that provide important pollination services, including in the continental US, where 15 species regularly breed. Compared to other birds in North America, hummingbirds (family Trochilidae) have a unique exposure route to pesticides because they forage on nectar. Therefore, hummingbirds may be exposed to systemic pesticides borne in nectar. They also may be particularly vulnerable to pesticide exposure due to their small size and extreme metabolic demands. We review relevant factors including hummingbird life history, nectar residue uptake, and avian bioenergetic considerations with the goal of clearly identifying and articulating the specific modeling challenges that must be overcome to develop and/or adapt existing modeling approaches. To help evaluate these factors, we developed a dataset for ruby-throated hummingbirds (Archilochus colubris) and other avian species potentially exposed to pesticides. We used the systemic neonicotinoid pesticide imidacloprid as an illustration and compared results to five other common current use pesticides. We use the structure of Pop-GUIDE to provide a conceptual modeling framework for implementation of MCnest and to compile parameter values and relevant algorithms to predict the effects of pesticide exposure on avian pollinators. Conservative screening assessments suggest the potential for adverse effects from imidacloprid, as do more refined assessments, though many important limitations and uncertainties remain. Our review found many areas in which current USEPA avian models must be improved in order to conduct a full higher-tier risk assessment for avian pollinators exposed to neonicotinoid insecticides, including addition of models suitable for soil and seed treatments within the MCnest environment, ability to include empirical residue data in both nectar and invertebrates rather than relying on existing nomograms, expansion of MCnest to a full annual cycle, and increased representation of spatial heterogeneity. Although this work focuses on hummingbirds, the methods and recommendations may apply more widely to other vertebrate pollinators.

A Rare Occurrence of Ewing’s Sarcoma Presenting as Breast Mass: A Case Report and Literature Review

Ewing’s sarcoma (EWS) typically involves the bony structures in adolescents and young adults. Extraskeletal sarcoma is a rare, aggressive, and malignant soft-tissue tumor with high recurrence rate. EWS of the breast is a rare entity with <1% cases reported in literature. A 55-year-old lady who complained of the gradual onset painless breast lump lasting for 1 year was referred to our institute in August 2021. Diagnostic ultrasound of bilateral breast identified a cystic lesion measuring 1.8 × 1.5 cm in lower inner quadrant of right breast. Diagnostic excisional biopsy of the right breast lump, which was conducted outside of the institute, showed malignant small round cell tumor. Post-excisional biopsy whole body 18-fluoro-deoxy-glucose positron emission tomography showed no residual uptake with no evidence of metastatic disease elsewhere. Immunohistochemistry work revealed positive expression of NKX2.2 and MIC2, which is consistent with the histopathological feature of EWS. Fluorescent in situ hybridization showed EWSR1 rearrangement, which is consistent with the diagnosis of EWS. The patient underwent a wide local excision of the right breast, followed by adjuvant chemotherapy consisting of 18 weekly vincristine/adriamycin D/cyclophosphamide regimen (vincristine, total dose of 2 mg; adriamycin D 100 mg; and cyclophosphamide 1.6 g). The patient was disease free after follow-up of 1 year. The rarity of primary breast EWS poses a diagnostic dilemma and hence the treatment. Local control with systemic therapy is the cornerstone of the treatment, in which breast conservation surgery is equivalent to mastectomy in patient with a good/average breast volume.

Bioaccumulation Potential of Cynodon dactylon Linn. in Crude Oil Contaminated Soil.

A greenhouse experiment was conducted to investigate the growth of Cynodon dactylon Linn. in soils contaminated by various concentrations of crude oil with a view to assessing its phytoremediating potential. The crude oil prepared at different concentrations of 0.0, 2.5, 5.0, 7.5, 10.0 and 12.5 (w/v) acted as contaminants on 3kg each of air-dried soil collected from the Obafemi Awolowo University Biological garden which is rich in organic matter. Each treatment was replicated 10 times in complete randomized design. Significantly (p<0.05) highest residual total petroleum hydrocarbon content (THC) uptake (39.26 ppm) was obtained in the plant at 12.5 ml contamination with the least residual total petroleum hydrocarbon content uptake (12.79 ppm) obtained at 2.5 ml contamination. With increased contamination, there was positive correlation with residual total petroleum hydrocarbon content uptake in the plants. No detectable amount of petroleum hydrocarbon content was found in the soil at the end of the experiment. The study concluded that C. dactylon plant could be effectively used in the phytoremediation of crude oil contaminated soil without addition of soil amendment.

Modeling banana uptake of pesticides by incorporating a peel-pulp interaction system into a multicompartment fruit tree model.

According to field research, banana peels have a significant impact on the uptake of pesticide residues by banana pulps. To predict pesticide residue concentrations in harvested bananas, however, current modeling approaches did not take into consideration the banana peel as a single simulating compartment. To address the problem, we incorporated a peel-pulp interaction system into a modified multicompartment fruit tree model in order to simulate pesticide residue concentrations in banana plants. The simulation results revealed that lipophilicity played a crucial role in regulating pesticide bioaccumulation in banana plants, showing that moderately- or highly-lipophilic compounds had a high potential for bioaccumulation in banana pulps and peels. Some model inputs, such as peel thickness, degradation rates in plant tissues, and dissipation rates in the soil, had a substantial impact on the bioaccumulation of pesticides in banana pulps and peels. Even if more aspects (such as dynamically morphological properties of banana plants and ionizable chemical compounds) must be considered for in future research, the proposed modeling approach can aid in the comprehension of the pesticide bioaccumulation mechanism in banana plants.