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Early diagnosis of radiation-induced pulmonary fibrosis (RIPF) in lung cancer patients after radiation therapy is important. A gastrin-releasing peptide receptor (GRPR) mediates the inflammation and fibrosis after irradiation in mice lungs. Previously, our group synthesized a GRPR-targeted positron emission tomography (PET) imaging probe, [

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

Immuno-positron emission tomography (immuno-PET) is a rapidly growing imaging technique in which antibodies are radiolabeled to monitor their in vivo behavior in real time. However, effecting the c...

A radiomics nomogram for pretreatment prediction of TACE refractoriness was developed and validated for hepatocellular carcinoma (HCC) without extrahepatic metastasis or macrovascular invasion. This study included 80 patients with HCC without extrahepatic metastasis or macrovascular involvement treated with TACE between July 2016 and November 2018. The datasets were divided into a training set (80%) and a test set (20%) for feature selection and tenfold cross-validation. Forty radiomic features were extracted from arterial-phase computed tomography (CT) using the Local Image Features Extraction software. The Lasso regression model was used for radiomics signature selection. The Lasso regression model was used for radiomics signature selection and the selected signatures were validated using the Mann–Whitney U-test. The radiomics nomogram was developed based on a multivariate logistic regression model incorporating the Rad-score, CT imaging factors, and clinical factors, and it was validated. The Rad-score, which consists of the Gray-Level Zone Length Matrix (GLZLM)—Long-Zone Low Gray-Level Emphasis (LZLGE) and GLZLM—Gray-Level Non-Uniformity (GLNU), T-stage, log α-fetoprotein (AFP), and bilobar distribution were significantly associated with TACE refractoriness (p

The prolonged blood circulation of the radiolabeled antibody conjugates is problematic when using immuno-PET imaging due to the increased radiation exposure and longer hospitalization required until sufficient contrast develops. In contrast to the prevailing belief that PEGylation prolongs blood retention time, we observed that a PEGylated antibody with a short PEG8 linker cleared much faster from the blood while maintaining tumor uptake compared to its non-PEGylated counterpart. Breast tumors were clearly visualized with a very high tumor-to-background ratio as early as 24 h after injection in immuno-positron emission tomography (PET) imaging.

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[

Hydrogen sulfide (Hsub2/subS) plays important roles in brain pathophysiology. However, nuclear imaging probes for the in vivo detection of brain Hsub2/subS in living animals have not been developed. Here, we report the first nuclear imaging probe that enables in vivo imaging of endogenous Hsub2/subS in the brain of live mice.Utilizing a bis(thiosemicarbazone) backbone, a fluorescent ATSM-FITC conjugate was synthesized. Its copper complex, Cu(ATSM-FITC) was thoroughly tested as a biosensor for Hsub2/subS. The same ATSM-FITC ligand was quantitatively labeled with [sup64/supCu]CuClsub2/subto obtain a radioactive [sup64/supCu][Cu(ATSM-FITC)] imaging probe. Biodistribution and positron emission tomography (PET) imaging studies were performed in healthy mice and neuroinflammation models.The Cu(ATSM-FITC) complex reacts instantly with Hsub2/subS to release CuS and becomes fluorescent. It showed excellent reactivity, sensitivity, and selectivity to Hsub2/subS. Endogenous Hsub2/subS levels in living cells were successfully detected by fluorescence microscopy. Exceptionally high brain uptake of [sup64/supCu][Cu(ATSM-FITC)] (gt; 9% ID/g) was observed in biodistribution and PET imaging studies. Subtle changes in brain Hsub2/subS concentrations in live mice were accurately detected by quantitative PET imaging. Due to its dual modality feature, increased Hsub2/subS levels in neuroinflammation models were characterized at the subcellular level by fluorescence imaging and at the whole-body scale by PET imaging.Our biosensor can be readily utilized to study brain Hsub2/subS function in live animal models and shows great potential as a novel imaging agent for diagnosing brain diseases.

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)

Immuno-positron emission tomography (immuno-PET) is a rapidly growing imaging technique in which antibodies are radiolabeled to monitor their in vivo behavior in real time. However, effecting the controlled conjugation of a chelate-bearing radioactive atom to a bulky antibody without affecting its immunoreactivity at a specific site is always challenging. The in vivo stability of the radiolabeled chelate is also a key issue for successful tumor imaging. To address these points, a facile ultra-stable radiolabeling platform is developed by using the propylene cross-bridged chelator (PCB-TE2A-alkyne), which can be instantly functionalized with various groups via the click reaction, thus enabling specific conjugation with antibodies as per choice. The PCB-TE2A-tetrazine derivative is selected to demonstrate the proposed strategy. The antibody trastuzumab is functionalized with the

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.

Gadolinium neutron capture therapy (GdNCT) is a form of binary radiotherapy. It utilizes nuclear reactions that occur when gadolinium-157 is irradiated with thermal neutrons, producing high-energy γ -rays and Auger electrons. Herein, we evaluate the potential of GdNCT for cancer treatment using PEGylated liposome incorporated with an FDA-approved MRI contrast agent. The clinical gadolinium complex (Gadovist®) was successfully encapsulated inside the aqueous core of PEGylated liposomes by repeated freeze and thaw cycling. At a concentration of 152 μM Gd, the Gd-liposome showed high cytotoxicity upon thermal-neutron irradiation. In animal experiments, when a CT26 tumor model was administered with Gd-liposomes (19 mg 157Gd per kg) followed by 20-min irradiation of thermal neutron at a flux of 1.94 × 104 cm−2 s−1, tumor growth was suppressed by 43%, compared to that in the control group, on the 23rd day of post-irradiation. After two-cycle GdNCT treatment at a 10-day interval, tumor growth was more efficiently retarded. On the 31st day after irradiation, the weight of the excised tumor in the GdNCT group (38 mg 157Gd per kg per injection) was only 30% of that of the control group. These results demonstrate the potential of GdNCT using PEGylated liposomes containing MRI contrast agents in cancer treatment.

High mobility group box 1 (HMGB1) is one of intracellular damage associated molecular patterns which is released from keratinocytes in response to external stressors and affects neighboring melanocytes by inducing apoptosis and suppressing melanogenesis. HMGB1 levels in the blood and its expression in skin tissues are increased in psoriasis, alopecia areata, dystrophic epidermolysis bullosa, and vitiligo.

[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)

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site, while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.

Although the importance of bifunctional chelators (BFCs) is well recognized, the chemophysical parameters of chelators that govern the biological behavior of the corresponding bioconjugates have not been clearly elucidated. Here, five BFCs closely related in structure were conjugated with a cyclic RGD peptide and radiolabeled with Cu-64 ions. Various biophysical and chemical properties of the Cu(II) complexes were analyzed with the aim of identifying correlations between individual factors and the biological behavior of the conjugates. Tumor uptake and body clearance of the 64Cu-labeled bioconjugates were directly compared by animal PET imaging in animal models, which was further supported by biodistribution studies. Conjugates containing propylene cross-bridged chelators showed higher tumor uptake, while a closely related ethylene cross-bridged analogue exhibited rapid body clearance. High in vivo stability of the copper–chelator complex was strongly correlated with high tumor uptake, while the overall l...

A self-shielding device for the synthesis of radiopharmaceuticals was developed and fabricated in this study. Radiation exposure was minimized by the self-shielding of the kit, installation of the disposable kit in the auxiliary chamber while in a shielded state, and discharge of the kit into a radioactive waste container upon completion of the synthesis process. The developed self-shielding synthesis kit was tested by synthesizing 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) in order to verify its performance.