Search

Purpose: Plastics are used commonly in the world because of its convenience and cost-effectiveness. Microplastics, an environmental threat and human health risk, are widely detected in food, and consequently ingested. However degraded plastics are found everywhere, which cause environmental threat and human health risk. Therefore, real-time monitoring of orally administered microplastics is tremendously important to trace them in the body. Methods: In this study, to visualize their absorption path, we labeled polystyrene with [64Cu]Cu-DOTA. We prepared radiolabeled polystyrene with 64Cu after, [64Cu]Cu-DOTA-polystyrene was then orally administered to mice and evaluate its transit and absorption in mice using PET imaging. The absorption path and distribution of [64Cu]Cu-DOTA-polystyrene were determined using positron emission tomography (PET) over 48 h. Ex vivo tissue-radio thin-layer chromatography (Ex vivo-radioTLC) was used to demonstrate the existence of [64Cu]Cu-DOTA-polystyrene in tissue. Results: PET images demonstrated that [64Cu]Cu-DOTA-polystyrene began to transit to the intestine within 1 h. [64Cu]Cu-DOTA-polystyrene accumulation in the liver was also observed. Biodistribution of [64Cu]Cu-DOTA-polystyrene confirmed the observed distribution of [64Cu]Cu-DOTA-polystyrene from PET images. Ex vivo-radioTLC was used to demonstrate that the detected gamma rays originated from [64Cu]Cu-DOTA-polystyrene. Conclusion: This study provided evidence of microplastic accumulation and existence in tissue by using PET imaging, and cross confirmed by ex vivo-radioTLC. The information provided may be used as the basis for future studies on the toxicity of microplastics.

Hepsin, a cell surface serine protease, is a potential biomarker for the detection of prostate cancer due to its high expression in prostate cancer but not in normal prostate. This study aimed to develop a radioligand for positron emission tomography (PET) imaging of hepsin. Six leucine-arginine (Leu-Arg) dipeptide derivatives (two diastereomers for each of three ligands) were synthesized and evaluated for their binding affinities and selectivity for hepsin. Based on the binding assay, a

Boron neutron capture therapy (BNCT) is a precision treatment technology that ideally damages only boron-accumulating cells. The effectiveness of BNCT depends on the amount of boron in the tumor cells and the concentration ratio between normal and tumor tissues. Therefore, for successful brain-tumor treatment using BNCT, it is essential to develop a drug with high blood-brain barrier (BBB) permeability and high tumor accumulation. The benzothiazole-based boron complex 4-(benzo[

Photodynamic therapy (PDT) is an effective cancer treatment option, but it suffers from penetration limit of light, making it available only for superficial and endoscopically accessible cancers. Recently, there have been reports that Cerenkov luminescence originated from radioisotopes can be utilized as an excitation source for PDT without external light illumination. Here, cancer-selective agents, i.e., (1) clinically available 5-aminolevulinic acid (5-ALA), which promotes cancer metabolism-specific accumulation of protoporphyrin IX (PpIX), and (2)

As a high oxygenated fuel, bioethanol has already obtained more and more widespread attention in diesel engines. The present work aims to study and compare effects of various diesel-bioethanol-biodiesel ternary mixture fuels on combustion and emissions from a four-cylinder diesel engine. A series of engine experiments are conducted on neat diesel fuel (D100), 95% D100 blended with 5% bioethanol and 1% biodiesel by volume (D95E5B1), 90% D100 blended with 10% bioethanol and 1% biodiesel by volume (D90E10B1), and 85% D100 blended with 15% bioethanol and 1% biodiesel by volume (D85E15B1) according to various engine loads (40, 80 and 120 Nm). The experimental results show that the peak value of pressure and heat release rate (HRR) in the cylinder, nitrogen oxides (NOx) and smoke emissions increase with the increase in engine load, but the brake specific fuel consumption (BSFC) decreases. There is no significant variation in cylinder pressure with the addition of ethanol, but HRR is improved and NOx and smoke emissions are effectively controlled. It is exciting that the addition of ethanol can simultaneously reduce NOx and smoke emissions under medium and high load conditions. Specifically, at 120 Nm, ethanol addition simultaneously reduces NOx emissions by 2.08% and smoke opacity by 36.08% on average. Through the results of this study, it is found that the ethanol can improve the combustion of the four-cylinder diesel engine and also effectively control the emissions of NOx and smoke. Therefore, ethanol will play an important role in the future research field of energy saving and emission reduction for diesel engines.

In this Letter, the authors present a reconfigurable power divider using a hybrid matrix with variable impedance tuners. The proposed hybrid matrix-based power divider with varactor-tuned impedance tuners (VTITs) can simultaneously obtain variable power-dividing ratios at the centre frequency and variable operating frequencies for the 3 dB coupling states. The VTITs, consisting of a transmission line, an inductor, and a varactor located between the line and the inductor, are connected in parallel between two hybrid couplers for high impedance variation. Measured results demonstrate that the power-dividing ratio of the proposed divider varies from -14.3 to 13.3 dB with a return loss above 20 dB and the isolation above 20 dB at a centre frequency of 2.45 GHz. Moreover, it achieves an insertion loss of 0.7-1.45 dB and a phase variation of less than 8° across the variable power-dividing ratio at the centre frequency. The frequency-tuning range for the 3 dB coupling states is 750 MHz with a small phase variation of 5°.

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability (davg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer.

Most nanoparticles show much higher uptake in mononuclear phagocyte system (MPS) organs than in tumors, which has been a long-lasting dilemma in nanomedicine. Here, we report an imaging strategy that selectively decreases MPS organ uptakes by utilizing the differential esterase activity in tumors and other organs. When an esterase-labile radiotracer loaded liposome was injected into the body, radioactivity was rapidly excreted from the liver and spleen after breakage of the ester bond by esterase. However, the lipophilic radiotracer delivered to the tumor remained in the tumor with minimal bond cleavage. The underlying mechanism was fully characterized in vitro and in vivo in colon tumor models. As a proof of concept, the liposomal radiotracer was further optimized for the early detection of pancreatic cancer. The folate-coated liposomal radiotracer showed highly selective tumor uptake. At 4 h postinjection, a pancreatic tumor a few millimeters in size was unambiguously visualized in orthotopic tumor models by PET imaging. At 24 h, an exceptionally high tumor-to-background ratio was achieved, enabling the visualization of tumors alone with minimal background noise. More than 9% of the total radioactivity was found in the tumor. Utilizing our imaging strategy, various tumor imaging agents can be developed for sensitive detection with ultrahigh contrast.

[Image: see text] The aim of this work was to evaluate a tumor-targeting porphyrin-based gadolinium complex (Gd-TDAP) for use as an MR/optical imaging agent and potential therapeutic agent. Gd-TDAP had higher longitudinal relaxivity (11.8 mM(–1) s(–1)) than a commercial MRI contrast agent (Omniscan; 3.7 mM(–1) s(–1)) in HSA solution (0.67 mM) at 3 T. The tumor-targeting characteristics were confirmed by T(1)-weighted MR imaging and optical imaging using an orthotopic brain tumor mouse model, which showed 1.3-fold higher uptake in tumor compared to normal brain tissues. The cell fraction data using U87MG glioblastoma cells indicated the potential for gadolinium neutron capture therapy (Gd-NCT), which requires gadolinium to be inside the cell nucleus. In addition, porphyrin derivatives can be used for photodynamic therapy (PDT), and the results demonstrated that Gd-TDAP has great potential not only as a bimodal imaging agent but also for treatment.

Glioblastoma (GBM) patients can use tumor-treating fields (TTFs) with adjuvant temozolomide (TMZ) to treat their disease. TTFs involve wearing transfixed transducers to the shaved scalp, and the transducers are wired to a battery pack that is either fixed or carried (weighing 2.7 pounds). EF-14 clinical trial did evaluate health-related quality of life with standardized patient-report outcome measures but did not measure exercise behavior. We sought to evaluate the exercise behavior of GBM patients using TTFs. We consented GBM patients who intended to use TTFs with adjuvant TMZ after completion of chemoradiation. After informed consent and before starting TTFs, patients completed a self-administered questionnaire, Godin Leisure-Time Exercise Questionnaire, to assess exercise behavior/physical function. To calculate our primary outcome of total exercise behavior, the frequency of exercise sessions per week within each intensity category was multiplied by the average reported duration, weighted by an estimate of the MET, summed across all intensities, and expressed as average MET-hr/wk. Prior work has defined that physical function can be compared as < 9 MET-h/wk vs. ≥ 9 MET-h/wk. We evaluated at baseline and up to 24-week exercise behavior in patients with TTFs vs. historical controls not using TTFs. We enrolled 19 total GBM patients, with 14 proceeding to use TTFs. Of the 14 patients on TTFs, seven patients (50%) completed ≥ 9 MET-h/wk of exercise, and this level was maintained 8, 16, and 24 weeks after starting TTFs. Six months after the completion of chemoradiation, mean MET-h/wk was decreased in the TTFs group (n=6) (10.71 sd=7.06) vs. historical controls (n=38) (27.35 sd=46.94). TTFs did not interfere with exercise behavior in our GBM cohort, but when compared to GBM patients not utilizing TTFs, there could be a long-term impact on exercise behavior. More research is needed to evaluate exercise behavior in GBM patients using TTFs.

Plastics are used commonly in the world because of their convenience and cost effectiveness. Microplastics, an environmental threat and human health risk, are widely detected in food and consequently ingested. However, degraded plastics are found everywhere, creating an environmental threat and human health risk. Therefore, real-time monitoring of orally administered microplastics to trace them in the body is tremendously important.

Background It is unclear whether catheter ablation is beneficial in frail patients with AF. Purpose This study aimed to evaluate whether catheter ablation reduces death and other outcomes in real-world frail patients with atrial fibrillation (AF). Methods Out of 801,710 patients with AF in the Korean National Health Insurance Service database from 2006 to 2015, 1,411 frail patients underwent AF ablations. The Hospital Frailty Risk Score were calculated retrospectively. Inverse probability of treatment weighting (IPTW) was used to categorize ablation and non-ablation frail groups. Results After IPTW, the two cohorts had similar background characteristics. During a median follow-up of 4.7 years (interquartile range: 2.2–7.8), the risk of death in frail patients with ablations was reduced by 65% compared to frail patients without ablations (2.0 and 6.4 per 100 person-years, respectively; hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.25–0.50; P Conclussion Ablation may be associated with lower incidences of death, heart failure, and acute myocardial infarction in real-world frail patients with AF, supporting the role of AF ablation in these patients. The effect of frailty risk on the outcome of ablation should be evaluated in further studies. Funding Acknowledgement Type of funding source: None

Background There is consistent evidence of the association between ideal cardiovascular health and lower incident cardiovascular disease (CVD); however, most studies used a single measure of cardiovascular health. Purpose To examine the association of change in cardiovascular health with subsequent incident CVD and mortality in elderly population. Methods In the Korea National Health Insurance Service-Senior (≥60 years) cohort, 312,736 participants who received national health check-ups between 2005–2012 were assessed for eligibility. Using the 7metrics of the American Heart Association (nonsmoking; and ideal levels of body mass index, physical activity, diet, blood pressure, fasting blood glucose, and total cholesterol), participants with 0 to 2, 3 to 4, and 5 to 7 ideal metrics were categorized as having low, moderate, and high cardiovascular health. Change in cardiovascular health over 2 years between 2005 and 2006 was considered. Results The study population included 162,149 participants without prior CVD or malignancy (median age at baseline, 69 [IQR 66–73] years; 91,408 [56.2%] women), of whom 59,887 had data about cardiovascular health change. Over a median follow-up of 5.8 (5.5–8.0) years, 5346 incident CVD events and 6035 death occurred. In multivariable analysis and compared with individuals with persistently low cardiovascular health (consistently low group, 7.9% of participants; CVD incident rate per 1000 person-years, 21.1 [95% CI, 19.4–23.0]), a lower CVD risk was observed in the consistently moderate group (38.7% of participants; absolute rate difference per 1000 person-years, −4.8 [95% CI, −5.5 to −4.1]; HR, 0.77 [95% CI, 0.70–0.85]), the moderate to high group (11.6% of participants; absolute rate difference per 1000 person-years, −7.7 [95% CI, −8.8 to −5.5]; HR, 0.62 [95% CI, 0.55–0.70]), the high to moderate group (11.2% of participants; absolute rate difference per 1000 person-years, −7.2 [95% CI, −8.3 to −5.9]; HR, 0.64 [95% CI, 0.56–0.72]), and the consistently high group (11.3% of participants; absolute rate difference per 1000 person-years, −10.2 [95% CI, −11.2 to −9.1]; HR, 0.51 [95% CI, 0.44–0.58]). A lower mortality risk was observed in the consistently moderate group, the moderate to high group, and the high to moderate or high groups. Conclusion Among a group of elderly participants without CVD, there was benefit of moderate or high cardiovascular health for incident cardiovascular events and mortality. Funding Acknowledgement Type of funding source: None

Background Predictors are not well known for long-lasting sinus rhythm after atrial fibrillation catheter ablation (AFCA). Purpose We investigated the pre-procedural clinical factors associated with the patients with 5-year long-term atrial fibrillation (AF) free after AFCA. Methods Among 2,085 patients who underwent de novo AFCA, 934 patients (58±11 years, 73.1% male, 66.0% paroxysmal AF), who underwent guidelines-based rhythm follow-up longer than 5-years, were included in this study. We compared 340 patients who never showed AF recurrence for 5-years and 594 patients with AF/ atrial tachycardia (AT) recurrence at least a single episode. Cut-off values of pericardial fat volume and electrocardiogram (ECG) parameters were obtained by Youden index. Results 1. The patients with AF-free for 5-years (AF-Free-5yrs) had higher proportion of paroxysmal AF (p Conclusions Pericardial fat volume ( Funding Acknowledgement Type of funding source: None

We present high-density EEG datasets of auditory steady-state responses (ASSRs) recorded from the cortex of freely moving mice with or without optogenetic stimulation of basal forebrain parvalbumin (BF-PV) neurons, known as a subcortical hub circuit for the global workspace. The dataset of ASSRs without BF-PV stimulation (dataset 1) contains raw 36-channel EEG epochs of ASSRs elicited by 10, 20, 30, 40, and 50 Hz click trains and time stamps of stimulations. The dataset of ASSRs with BF-PV stimulation (dataset 2) contains raw 36-channel EEG epochs of 40-Hz ASSRs during BF-PV stimulation with latencies of 0, 6.25, 12.5, and 18.75 ms and time stamps of stimulations. We provide the datasets and step-by-step tutorial analysis scripts written in Python, allowing for descriptions of the event-related potentials, spectrograms, and the topography of power. We complement this experimental dataset with simulation results using a time-dependent perturbation on coupled oscillators. This publicly available dataset will be beneficial to the experimental and computational neuroscientists., Measurement(s) functional brain measurement • response to auditory stimulus Technology Type(s) electroencephalography (EEG) Factor Type(s) stimulation frequency • optogenetic stimulation of basal forebrain parvalbumin neurons Sample Characteristic - Organism Mus musculus Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12758720

Patients with glioblastoma have poor overall survival and experience significant burden from neurologic decline and adverse treatment effects. Despite the well-known benefits of early palliative care integration with oncology care, utilization of palliative care is low. The purpose of this quality improvement (QI) project is to investigate the feasibility, value, and effectiveness of using an adapted palliative care screening tool to improve outpatient palliative care screening and referral of glioblastoma patients. This QI project was conducted over a 10-week period. A glioma palliative care screening tool was developed and integrated into outpatient visits. Providers were required to use the screening tool during each patient visit. Patients 18 years or older who were diagnosed with a World Health Organization grade IV glioma and returning to the neuro-oncology clinic for a brain MRI evaluation were targeted. Screening, palliative care discussion, and referral rates were evaluated. Among 530 eligible patients who returned to the clinic over a 10-week period, the tool was available for 433 patients. Fifty-six percent (n = 294/530) of the patients were screened. Nine percent (n = 27) of screened patients were identified as candidates for a palliative care referral (score ≥ 5 on the screening tool). Of these 27 patients, the proportion of patients who had a palliative care discussion was 63% (n = 17). Overall, 71% (n = 12) of patients who had a palliative care discussion were referred to a palliative care provider. Integrating a glioma palliative care screening tool with outpatient visits can draw attention to palliative care needs and lead to a referral to palliative care.

Albumin is one of the most attractive nanoplatforms for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previously reported albumin-based nanoplatforms have shown inconsistent blood circulation half-life according to the modified methods, and the affecting factors were not well evaluated, which could hamper the clinical translation of albumin-based nanoplatforms. Herein, we developed a finely tuned click-chemistry based albumin nanoplatform (CAN) with a longer circulation half-life and an efficient tumor targeting ability. Methods: CAN was synthesized in two steps. First, albumin was conjugated with ADIBO-NHS (albumin-ADIBO) by reacting albumin with various molar ratios of ADIBO. The number of attached ADIBO moieties was determined using matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Second, the desired modalities including azide-functionalized chelator, a fluorescence dye, and folate were incorporated into albumin-ADIBO using strain-promoted alkyne-azide cycloaddition reaction (SPAAC reaction). The biodistribution and targeting efficiency of functionalized CANs were demonstrated in mice. Results: The degree of functionalization (DOF) and resulting in vivo biodistribution was controlled precisely using the click chemistry approach. Specifically, the numbers of attached azadibenzocyclooctyne (ADIBO) moieties on albumin, the DOF, were optimized by reacting albumin with varying molar ratios of ADIBO with a high reproducibility. Furthermore, we developed a simple and efficient method to estimate the DOF using UV-visible spectrophotometry (UV-vis), which was further validated by matrix-assisted laser desorption ionization time of flight (MALDI-TOF). The biodistribution of CAN could be controlled by DOF, and CAN with an optimized DOF showed a long circulation half-life (> 18 h). CAN was further functionalized using a simple click chemistry reaction with an azide functionalized chelator, a fluorescence dye, and folate. 64Cu- and folate-labeled CAN (64Cu-CAN-FA) showed effective and specific folate receptor targeting in vivo, with an over two-fold higher uptake than the liver at 24 h post-injection. Conclusions: Our development from the precisely controlled DOF demonstrates that an optimized CAN can be used as a multifunctional nanoplatform to obtain a longer half-life with radioisotopes and ligands, and provides an effective method for the development of albumin-based tumor theranostic agents.

We report a phase I pharmacological study of an oral formulation of CKD‐516, a vascular‐disrupting agent, in patients with refractory solid tumors. Twenty‐seven patients (16 in the dose‐escalation cohort and 11 in the expansion cohort) received a single daily dose (5‐25 mg) of CKD‐516 five days per week. Nausea (67%) and diarrhea (63%) were the most common treatment‐related adverse events. The recommended phase II dose of oral CKD‐516 was 20 mg/d (15 mg/d with a body surface area (BSA)

Isocitrate dehydrogenase 1 (IDH1) is commonly mutated in grade II-III gliomas, and the mutant enzyme leads to the production of the oncometabolite 2-hydroxyglutarate (2-HG). 2-HG is responsible for the gliomagenesis associated with these tumors and the promotion of seizures via glutamate receptors. Ivosidenib, a small molecule oral mIDH1 inhibitor, has shown promise in clinical trials to treat IDH1 mutant gliomas, and providers can utilize this agent in IDH1 mutant glioma patients. We evaluated our IDH1 mutant glioma patients treated off-label with ivosidenib and described the radiographic response and seizure control in this cohort when ivosidenib was initiated between October 2020 to February 2021. Radiographic response was determined using RANO criteria, and seizure control was determined by comparing seizures per month before and after initiation of ivosidenib. All patients represented received single-agent ivosidenib dosed at 500 mg orally once a day. One patient required a dose reduction to 250 mg orally once a day because of drug-induced diarrhea. In our cohort of six patients, patient age range was 31 to 74 years with four female patients and two male patients. Diagnoses represented were astrocytoma, IDH1 mutant (n=3) oligodendroglioma (WHO), IDH1 mutant, 1p19q co-deleted (n=2), and anaplastic astrocytoma IDH1 mutant (n=1). Three patients experienced a reduction of seizure frequency, two patients did not have seizures before or after therapy, and one patient remained with the same level of seizures (1 seizure/month). Radiographic responses recorded included three patients with stable disease, two patients with minor responses, and one patient with a partial response. Treatment with ivosidenib is ongoing for this cohort of mIDH1 glioma patients. Updated information on prolonged disease control and seizure control in this cohort of IDH1 mutant glioma patients will be presented. Therapeutics, such as ivosidenib, can lead to improved seizure control and radiographic outcomes in IDH1 mutant glioma patients.

INTRODUCTION There is increasing recognition that palliative care (PC) can benefit patients with advanced cancers. However, early referral to PC is not yet a reality for patients diagnosed with a primary brain tumor. We hypothesize that lack of knowledge and/or misperceptions regarding PC by patients, caregivers, or their providers remain barriers. METHODS This is an IRB-exempt, one-time QR-accessible REDcap questionnaire administered to patients, caregivers, and providers at the Preston Robert Tisch Brain Tumor Center between September 2020 and May 2021. We administered 9 questions regarding knowledge and beliefs about PC from the Health Information National Trends Survey 5, Cycle 2: results of this nationally representative U.S. sample are publicly available and used for comparison. RESULTS We had 141 survey respondents: 25 providers, 59 patients, and 57 caregivers. The median patient and caregiver ages were 49 (21-74) and 50 years (24-73), respectively. Caregivers were more likely female (55.2 %) and identified as a spouse or domestic partner (58.2%). Providers, were equally distributed by years of experience. Compared to patients and caregivers, providers reported more baseline knowledge of PC (p< 0.0001, p< 0.0001) and better understood the role of PC in pain/symptom management (p=0.0038, p=0.0087) and social/emotional support (p=0.0044, p=0.0279). Interestingly, most providers (76.0%) disagreed with the statement “the goal of palliative care is to give patients more time at the end of life.” Compared to a general U.S. sample (n=1,162) our patients (n=39) were better informed in only 2 of 9 questions. Whereas, caregivers (n=48) were better informed in 6 of 9 questions. CONCLUSION Neuro-oncology providers were knowledgeable, but a minor gap in understanding the goal of PC was identified. Caregivers were overall more knowledgeable than patients. However, Neuro-oncology patients, had similar knowledge and beliefs compared to a nationally representative sample. PC interventions should prioritize filling knowledge gaps for Neuro-oncology patients.

PURPOSE/OBJECTIVE(S) Radiographic density changes in normal lung parenchyma are a function of radiation dose, are associated with inflammation, and vary among patients. The purpose of this study is to evaluate these radiation-induced changes quantitatively in different patient cohorts treated with PD-1 Immune Checkpoint Inhibitors (ICI) and investigate them as possible RT-related imaging biomarker for outcome. MATERIALS/METHODS We looked at two groups of non-small cell lung cancer (NSCLC) patients drawn from two institutions: patients with metastatic disease treated with non-curative intent and normal lung in the radiation field, and patients receiving definitive chemo-radiation (CRT) followed by adjuvant PD-L1 blockade (durvalumab), some of which received durvalumab also concurrently. Normal lung parenchyma on the first post-treatment chest computer tomography (CT) scans (median time 3 months post RT) was deformably registered to the treatment plan to analyze lung density changes as function of dose, normalized to 2Gy-equivalent, and quantified as Hounsfield Unit (HU)/Gy. Differences between groups were assessed using Wilcoxon's rank sum test, correlation to progression-free and overall survival using Cox regression. RESULTS We analyzed a total of 26 patients treated with non-curative intent RT and 60 patients who received CRT. For metastatic patients, RT delivered concurrently with ICI (n = 16) led to significantly larger changes compared to patients receiving RT before initiation of ICI (median 2.21 vs 0.27 HU/Gy, P = 0.02), even though the former received significantly lower doses to the normal lung (median 27.6 vs 55.8 Gy, P = 0.02). Fraction sizes were smaller when RT was delivered concurrently with ICI (median 3.3 vs 5.5 Gy/fraction). Number of patients and events in metastatic patients were too low for survival analysis. During CRT, patients receiving concurrent durvalumab (n = 20) did not show significant lung density changes compared to those that did not (median 1.39 vs 1.28 HU/Gy, P = 0.99). All CRT patients received 1.8-2.2 Gy/fraction. The amount of change in each patient did not correlate with progression-free or overall survival (HR = 0.91, 95% CI [0.71-1.16] and HR = 0.92, [0.72-1.17] respectively). CONCLUSION RT delivered concurrently with PD-1 ICI leads to significantly increased normal lung density changes in metastatic patients but not in locally advanced patients treated with CRT, possibly related to the different fraction size. For CRT patients treated with adjuvant durvalumab, normal lung changes after CRT do not correlate with outcome. The correlation of lung density changes to oncologic outcomes in metastatic patients' needs to be studied in larger cohorts.

The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-N,N',N,″-triacetic acid trihydrochloride ([p-SCN-Bn]-NOTA), 2,2',2″-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA-N-hydroxysuccinimide ester), or 1-(p-isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([p-SCN-Bn]-DTPA) in 1.0 M NaHCO3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64Cu in 0.1 M NH4OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non-small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor-bearing mice. Results: Radiochemical yields of the 64Cu-labeled repebodies were approximately 70%-80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor-bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.

OBJECTIVE There is no validated model for delivering palliative care (PC) in the glioblastoma (GBM) population. The primary objectives were to assess the feasibility and determine the acceptability of a time-based model of integrated specialty PC to patients and providers. Secondary objectives were to estimate the impact on healthcare utilization and quality of life (QoL) compared to historical controls. METHODS We consented and referred patients to PC at their initial Neuro-Oncology consultation between 4/2018 and 5/2019. We conducted QoL assessments (NCCN Distress Tool; Functional Assessment of Cancer Therapy-Brain (FACT-BR); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); Epworth Sleepiness Scale (ESS)) at (1) baseline (2) immediately after chemoradiation, and (3) 6 months following chemoradiation. Ongoing PC follow-up was at the discretion of the PC provider. We administered the Edmonton Symptom Assessment System (ESAS) before and after PC visits. We measured patient and referring provider satisfaction using FAMCARE-16 and a PC departmental survey, respectively. RESULTS We did not meet our goal enrollment of 50 patients. 32 were offered participation, 12 consented and 8 attended at least one PC visit. The mean number of PC visits was 1.6. Mean age was 62 (42–79). 75% had a KPS ≥80. Of those that did not complete the study, 2 died and 5 either withdrew consent or declined further visits. At baseline, 91.7 % had a NCCN distress score ≥4. Patients were overall satisfied with the intervention. CONCLUSION Introduction of specialty PC at the time of GBM diagnosis is challenging. Participants reported their experience as overall positive. Results from referring providers are pending. Due to low-enrollment we did not pursue further statistical comparisons regarding healthcare utilization compared to historical controls.

Background There are limited and conflicting data regarding the prognostic implication of guideline-directed therapy, especially in heart failure (HF) patients with atrial fibrillation (AF). Thus, this study evaluated the relationship between guideline adherence to recommended therapy at discharge and relevant 60-day clinical outcomes in acute HF patients with AF having reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Methods and results Of 5,625 acute HF patients in the Korean Acute Heart Failure Registry, 2,071 with documented AF (HFrEF, n=986; HFpEF, n=1,085) were separately analysed. A guideline adherence score was calculated for the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, mineralocorticoid receptor antagonists, and anticoagulants. In HFrEF patients with AF, there was significant trend of increase in mortality (p for trend Conclusion Better adherence to guidelines was associated with a better 60-day prognosis in both HFrEF and HFpEF patients with AF. However, the beneficial effect of guideline adherence was more pronounced in HFrEF patients with AF.

Background Overall survival (OS) in glioblastoma (GBM) is poor at an average of 14 to 18 months, and long-term survivors (LTS) of GBM are rare. LTS of GBM, defined as surviving >5 years postdiagnosis, represent only 2% to 10% of all GBM patients. LTS of cancer are at high risk of developing second primary neoplasms. This study looks at occurrences of second primary neoplasms in LTS of GBM. Methods Records from adult patients newly diagnosed with GBM between January 1, 1998 and February 8, 2010, were retrospectively reviewed to identify LTS, defined as patients who survived ≥5 years. We focused on the identification of a new diagnosis of cancer occurring at least 2 years after the initial GBM diagnosis. Results We identified 155 LTS of GBM, with a median OS of 11.0 years (95% CI: 9.0 to 13.1 years) and a median follow-up of 9.6 years (95% CI: 8.7 to 10.7 years). In this cohort of patients, 13 (8.4%) LTS of GBM developed 17 secondary cancers. Eight could potentially be attributed to previous radiation and chemotherapy (skin cancer in radiation field [n = 4], leukemia [n = 2], low-grade glioma [n = 1], and sarcoma of the scalp [n = 1]). The other 9 cases included melanoma (n = 2), prostate cancer (n = 2), bladder cancer (n = 1), endometrioid adenocarcinoma (n = 1), basal cell carcinoma (n = 1), and renal cell carcinoma (n = 1). Conclusions Although second primary cancers are rare in GBM LTS, providers should continue close monitoring with appropriate oncologic care. Moreover, this highlights the need for survivorship care of patients with GBM.

The goal of this study was to suggest criteria for the determination of the optimal image reconstruction algorithm for image-based dosimetry of Cu-64 trastuzumab PET in a mouse model. Image qualities, such as recovery coefficient (RC), spill-over ratio (SOR), and non-uniformity (NU), were measured according to National Electrical Manufacturers Association (NEMA) NU4-2008. Mice bearing a subcutaneous tumor ( 200 &nbsp, mm 3 , HER2 NCI N87) were injected with monoclonal antibodies (trastuzumab) with Cu-64. Preclinical mouse PET images were acquired at 4 time points after injection (2, 15, 40 and 64 h). Phantom and Cu-64 trastuzumab PET images were reconstructed using various reconstruction algorithms (filtered back projection (FBP), 3D reprojection algorithm (FBP-3DRP), 2D ordered subset expectation maximization (OSEM 2D), and OSEM 3D maximum a posteriori (OSEM3D-MAP)) and filters. The absorbed dose for the tumor and the effective dose for organs for Cu-64 trastuzumab PET were calculated using the OLINDA/EXM program with various reconstruction algorithms. Absorbed dose for the tumor ranged from 923 mGy/MBq to 1830 mGy/MBq with application of reconstruction algorithms and filters. When OSEM2D was used, the effective osteogenic dose increased from 0.0031 to 0.0245 with an increase in the iteration number (1 to 10). In the region of kidney, the effective dose increased from 0.1870 to 1.4100 when OSEM2D was used with iteration number 1 to 10. To determine the optimal reconstruction algorithms and filters, a correlation between RC and NU was plotted and selection criteria (0.9 &lt, RC &lt, 1.0 and &lt, 10% of NU) were suggested. According to the selection criteria, OSEM2D (iteration 1) was chosen for the optimal reconstruction algorithm. OSEM2D (iteration 10) provided 154.7% overestimated effective dose and FBP with a Butterworth filter provided 20.9% underestimated effective dose. We suggested OSEM2D (iteration 1) for the calculation of the effective dose of Cu-64 trastuzumab on an Inveon PET scanner.

Correction for ‘A short PEG linker alters the in vivo pharmacokinetics of trastuzumab to yield high-contrast immuno-PET images’ by Woonghee Lee et al., J. Mater. Chem. B, 2021, 9, 2993–2997, DOI: 10.1039/D0TB02911D.

INTRODUCTION Malignant glioma (MG) patients often experience chemotherapy-induced nausea and vomiting (CINV). Olanzapine has recently been added to national anti-emesis guidelines for patients on moderately/highly emetogenic chemotherapy. In this retrospective study, we investigated the use of olanzapine for refractory-CINV (R-CINV) in MG patients. METHODS In this chart review, we queried adult MG patients with KPS ≥ 70 who received olanzapine from January 2019-March 2020. Patients were included if they were prescribed olanzapine for CINV. Data on nausea/vomiting improvement, olanzapine dosing/schedule, number of refractory anti-emetic trials, concomitant corticosteroid use, and demographics were collected. RESULTS We identified 21 MG patients who were prescribed olanzapine, with 9 of those patients receiving olanzapine specifically for CINV. Seven patients had WHO grade IV glioma, and 2 patients had anaplastic astrocytoma (WHO grade III). Five of 9 patients (55.6%) were male, all were Caucasian and median age was 54 years. Patients tried an average of 3 anti-emetics prior to initiating olanzapine for R-CINV. Only one patient was taking concomitant corticosteroids; which is not in concordance with national anti-emesis guidelines. Four of 9 patients (44.4%) achieved control of R-CINV with olanzapine. The olanzapine dose and key biomarkers (IDH-status, MGMT promoter methylation) were similar between those experiencing R-CINV and those without symptoms. CONCLUSIONS In this study, we find that approximately half of patients with R-CINV achieved improved nausea and vomiting control with the addition of olanzapine. The lack of corticosteroid use for anti-emesis in MG continues to make this population challenging to manage. The relatively high success rate in patients that had failed, on average, 3 anti-emetics, suggests that olanzapine may be a potent addition to the anti-emetic toolkit for MG patients. These results inspire further large-scale research to validate this observation and define the optimal role for olanzapine in treating R-CINV in MG patients.

BACKGROUND From the time of diagnosis to end of life, patients with primary brain tumors experience challenges to maintain quality of life. While traditional research focuses on clinical trials that involve directly treating cancer, we have designed a specific research committee at our institution that promotes supportive care research to improve patients’ and caregivers’ quality of life. Past research has shown that issues key to patients and caregivers often differ from what researchers and providers might appreciate as important. Incorporating input from brain tumor patients and caregivers is vital to direct the most relevant and necessary supportive care research. METHODS As part of an IRB-approved quality improvement project, we sought the opinions of our supportive care research committee about what are the essential quality of life issues for brain tumor patients and caregivers. We polled our committee before and after a session with patients and caregivers discussing factors relevant to their quality of life. After this patient/caregiver intervention, we used a group discussion and note comparison technique to distill down key elements to advance supportive care research for this population. RESULTS Engagement of the committee included members that were neuro-oncology providers, biostatisticians, and data/regulatory/clinical trial staff. Before the intervention, common themes about key issues for patients and caregivers were comfort, pain management, counteracting side effects, cognitive issues, and financial toxicity. While similar themes emerged after the patient/caregiver intervention, the committee gleaned that aspects of communicating outcomes and support of caregivers were consistently mentioned from the discussion session with patients and caregivers. CONCLUSIONS Opinions of brain tumor patients and caregivers are crucial in driving future direction and relevance of supportive care research in neuro-oncology. Our supportive care research committee will continue to engage patients and caregivers and are planning interventions to improve communication and support for caregivers.

Epidermal growth factor receptor (EGFR) is overexpressed and considered as a proper molecular target for diagnosis and targeted therapy of esophageal squamous cell carcinoma (ESCC). This study evaluated the usefulness of PET imaging biomarkers with 64Cu-PCTA-cetuximab and 18F-FDG-PET for anti-EGFR immunotherapy in ESCC models. In vivo EGFR status and glucose metabolism by cetuximab treatment were evaluated using 64Cu-PCTA-cetuximab and 18F-FDG-PET, respectively. Therapeutic responses with imaging biomarkers were confirmed by western blot and immunohistochemistry. TE-4 and TE-8 tumors were clearly visualized by 64Cu-PCTA-cetuximab, and EGFR expression on TE-8 tumors showed 2.6-fold higher uptake than TE-4. Tumor volumes were markedly reduced by cetuximab in TE-8 tumor (92.5 &plusmn, 5.9%), but TE-4 tumors were refractory to cetuximab treatment. The SUVs in 64Cu-PCTA-cetuximab and 18F-FDG-PET images were statistically significantly reduced by cetuximab treatment in TE-8 but not in TE-4. 64Cu-PCTA-cetuximab and 18F-FDG-PET images were well correlated with EGFR and pAkt levels. 64Cu-PCTA-cetuximab immuno-PET had a potential for determining EGFR level and monitoring therapeutic response by anti-EGFR therapy. 18F-FDG-PET was also attractive for monitoring efficacy of anti-EGFR therapy. In conclusion, PET imaging biomarkers may be useful for selecting patients that express target molecules and for monitoring therapeutic efficacy of EGFR-targeted therapy in ESCC patients.

Gadolinium-neutron capture therapy (Gd-NCT) is based on the nuclear capture reaction that occurs when 157Gd is irradiated with low energy thermal neutrons to primarily produce gamma photons. Herein, we investigated the effect of neutron capture therapy (NCT) using a small molecular gadolinium complex, Gd-DO3A-benzothiazole (Gd-DO3A-BTA), which could be a good candidate for use as an NCT drug due to its ability to enter the intracellular nuclei of tumor cells. Furthermore, MRI images of Gd-DO3A-BTA showed a clear signal enhancement in the tumor, and the images also played a key role in planning NCT by providing accurate information on the in vivo uptake time and duration of Gd-DO3A-BTA. We injected Gd-DO3A-BTA into MDA-MB-231 breast tumor-bearing mice and irradiated the tumors with cyclotron neutrons at the maximum accumulation time (postinjection 6 h); then, we observed the size of the growing tumor for 60 days. Gd-DO3A-BTA showed good therapeutic effects of chemo-Gd-NCT for the in vivo tumor models. Simultaneously, the Gd-DO3A-BTA groups ([Gd-DO3A-BTA(+), NCT(+)]) showed a significant reduction in tumor size (p<0.05), and the inhibitory effect on tumor growth was exhibited in the following order: [Gd-DO3A-BTA(+), NCT(+)] > [Gd-DO3A-BTA(+), NCT(−)] > [Gd-DO3A-BTA(−), NCT(+)] > [Gd-DO3A-BTA(−), NCT(−)]. On day 60, the [Gd-DO3A-BTA(+), NCT(+)] and [Gd-DO3A-BTA(−), NCT(−)] groups exhibited an approximately 4.5-fold difference in tumor size. Immunohistochemistry studies demonstrated that new combinational therapy with chemo-Gd-NCT could treat breast cancer by both the inhibition of tumor cell proliferation and induction of apoptosis-related proteins, with in vivo tumor monitoring by MRI.

Zirconium-89 (t(1/2)=78.41 hours) is an ideal metallic radioisotope for immuno-positron emission tomography (PET), given that its physical half-life closely matches the biological half-life of monoclonal antibodies. In this study, the authors measured the spatial resolution and image quality of Zr-89 PET and compared the results against those obtained using F-18 PET, which is widely regarded as the gold standard for comparison of imaging characteristics.The spatial resolution and image qualities of Zr-89 were measured on the Siemens Biograph Truepoint TrueV PET/CT scanner, partly according to NEMA NU2-2007 standards. For spatial resolution measurement, the Zr-89 point source was located at the center of the axial field of view (FOV) and offset 1/4 axial FOV from the center. For image quality measurements, an NEMA IEC Phantom was used. The NEMA IEC Phantom consists of six hot spheres that were filled with Zr-89 solution. Spatial resolution and image quality (%contrast, %background variability [BV], and source to background ratio [SBR]) were assessed to compare the imaging characteristics of F-18 with those of Siemens Biograph Truepoint TrueV.The transverse and axial spatial resolutions at 1 cm were 4.5 and 4.7 mm for Zr-89, respectively. The %contrast of Zr-89 was 25.5% for the smallest 10 mm sized sphere and 89.8% for the largest 37 mm sized sphere, and for F-18, it was 32.5% for the smallest 10 mm sized sphere and 103.9% for the largest 37 mm sized sphere using the ordered subset expectation maximization (OSEM) reconstruction method. The %BV of F-18 PET was 6.4% for the smallest 10 mm sized sphere and 3.5% for the largest 37 mm sized sphere using the OSEM reconstruction. The SBR of Zr-89 was 1.8 for the smallest 10 mm sized sphere and 3.7 for the largest 37 mm sized sphere, and for F-18, it was 2.0 for the smallest 10 mm sized sphere and 4.1 for the largest 37 mm sized sphere using the OSEM reconstruction method.This study assessed Zr-89 imaging characteristics using a Siemens Biograph Truepoint TrueV PET/CT scanner and compared the results with those obtained for F-18 PET. Although spatial resolution and image quality of Zr-89 PET were lower compared with F-18 PET, due to longer positron range and low positron branching ratio, Zr-89 is advantageous for immuno-PET due to well-matched half-life with monoclonal antibodies.