Evaluation of Photobiogoverning Role of Blue Light Irradiation on Viral Replication.

Most recently, severe acute respiratory syndrome coronavirus-2 has triggered a global pandemic without successful therapeutics. The goal of the present study was to define the antiviral effect and therapeutic action of blue light irradiation in SARS-CoV-2-infected cells. Vero cells were infected with SARS-CoV-2 (NCCP43326) or mock inoculum at 50 pfu/well. After blue light irradiation, the inhibitory effect was assessed by qPCR and plaque reduction assay. When Vero cells were irradiated to blue light ranging from 1.6 to 10 J cm-2 , SARS-CoV-2 replication was inhibited by up to 80%. The antiviral effect of blue light irradiation was associated with translation suppression via the phosphorylation of eIF2α by prolonging endoplasmic reticulum (ER) stress. The levels of LC3A/B and Beclin-1, which are key markers of autophagy, and the levels of PERK and PDI for ER stress were highly increased, whereas caspase-3 cleavage was inhibited after blue light irradiation in the later stage of infection. Our data revealed that blue light irradiation exerted antiviral and photo-biogoverning activities by prolonging ER stress and stimulating autophagy progression during viral infection. The findings increase our understanding of how photo-energy acts on viral progression and have implications for use in therapeutic strategies against COVID-19.

Usefulness of cyclic thermal therapy and red blood cell scintigraphy in patients with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN. METHODS: The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient's hands. RESULTS: The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased. CONCLUSIONS: We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.

Effect of Ursodeoxycholic Acid on the Biodistribution and Excretion of Technetium-99m Radiopharmaceuticals in Rat: A Potential Image Quality Enhancer.

PURPOSE: This study aimed to investigate the effect of ursodeoxycholic acid (UDCA) on the biodistribution and excretion of technetium-99m (Tc-99m)-labeled radiopharmaceuticals. MATERIALS AND METHODS: Tc-99m hydroxy-methylene-diphosphonate (HDP), Tc-99m pertechnetate, and Tc-99m dimercaptosuccinic acid (DMSA) were injected via the tail vein of rats. After 30 min, the control group was administered saline, and the UDCA group was given UDCA orally. Scintigraphy images were acquired after 30 min and 1, 2, 3, and 4 h. Radioactivity and rate of change were compared. Tc-99m mercaptoacetyltriglycine (MAG3) imaging was also performed. RESULTS: In image analysis of Tc-99m HDP, radioactivity of the buttock was lower in the UDCA group at 4 h. Rates of change in the buttock were significantly different at 3 h-30 min and 4 h-30 min, and buttock radioactivity in the UDCA group had decreased more. In analysis of Tc-99m pertechnetate, radioactivity of the buttock was higher in the control group. Rates of change in the thyroid gland and buttock were different at 1 h-30 min, 3 h-30 min, and 4 h-30 min, with radioactivity in the UDCA group decreasing more. In the analysis of Tc-99m DMSA, while the radioactivity of the kidneys in the control group showed little decrease at 1 h-30 min, that in the UDCA group increased. In the analysis of Tc-99m MAG3 images, radioactivity and radioactivity/total body radioactivity (TBA) values for the kidneys were higher in the UDCA group at 2 min. At 5 and 10 min, radioactivity/TBA values for soft tissue in the UDCA group were lower than those in the control group. CONCLUSION: This study demonstrated that administration of UDCA increases renal excretion and soft tissue clearance of radiopharmaceuticals. This investigation could contribute to the broadening of applications of UDCA.

Conditioned media from blue light-emitting diode-exposed fibroblasts have an anti-inflammatory effect in vitro.

We have previously reported the protective effects of blue light-emitting diode (BLED)-stimulated cell metabolites on cell injury. To further examine the effect of conditioned media (CM) derived from BLED (5 J/cm2)-exposed human normal fibroblasts (CMBL5) for clinical application, we have used the choline chloride and phenol red-free media and then concentrated CMBL5 using a centrifugal filter unit. The collected CMBL5-lower part (CMBL5-LO) has evaluated the inflammatory protein expression profile in LPS-stimulated RAW264.7 cells. Comprehensive metabolomic profiling of CMBL5-LO was carried out using hybrid tandem mass spectrometry. Treatment with CMBL5-LO showed the cytoprotective effect on apoptotic cell death, but rather increased apoptotic cells after treatment with CMBL5-upper part (CMBL5-UP). In addition, CMBL5-LO inhibited several chemo-attractants, including interleukin (IL)-6, macrophage inflammatory protein (MIP)-2, chemokine (C-C motif) ligand 5 (CCL5), granulocyte colony-stimulating factor (GCSF), and monocyte chemoattractant protein-1 (MCP-1) expression. Pro-inflammatory nitric oxide was decreased after CMBL5-LO treatment, but not by CMBL5-UP treatment. Interestingly, treatment with CMBL5-LO stimulated expression of heme oxygenase-1, indicating its anti-inflammatory property. Most endoplasmic reticulum (ER) stress proteins except for transcription factor C/EBP homologous protein (CHOP) were highly expressed after irradiation with BLED in cells. Further studies are needed to examine the precise mechanism by CMBL5-LO in cells.

Rodent Leukocyte Isolation and Radiolabeling for Inflammation Imaging Study.

PURPOSE: The objective of this study was to describe to develop methods of rodent leukocyte isolation and radiolabeling for in vivo inflammation imaging. METHODS: Thigh muscle inflammation was induced by injection of collagenase. Blood was collected from the jugular vein and separated by Histopaque. The collected cells were incubated in a 37 °C CO2 incubator for 1~2 h. After incubation, 99mTc-HMPAO and 18F-FDG were used to treat leukocytes followed by incubation for 30 min. 99mTc-HMPAO and 18F-FDG labeled autologous leukocytes were injected into the tail veins of rats. The images were then acquired at various time points. Image-based lesion to normal muscle ratio was compared. RESULTS: After Histopaque separation, the proportion of lymphocytes was higher than that of other cell types. After CO2 incubation, the collected leukocytes were viable, while room temperature exposed leukocytes without CO2 incubation were non-viable. Granulocytes, especially, were more quickly influenced by various conditions than the mononuclear cells. Labeling efficiencies of 99mTc-HMPAO and 18F-FDG were 4.00 ± 2.06 and 1.8%, respectively. 99mTc-HMPAO- and 18F-FDG-labeled leukocytes targeted well the inflamed lesion. 99mTc-HMPAO-labeled leukocytes, but not 18F-FDG-labeled leukocytes, were found in the abdomen activity. CONCLUSION: Inflamed lesions of rats were well visualized using autologous radiolabeled leukocytes. This method might provide good information for understanding inflammatory diseases.

Radioactivity Reduction of 2-Deoxy-2-[18F] Fluoro-D-Glucose by Milk and Ursodeoxycholic Acid in Preclinical Study.

PURPOSE: 2-Deoxy-2-[18F] fluoro-d-glucose positron emission tomography (18F-FDG-PET) is a less-invasive and widely used diagnostic tool for detection of malignant tumors. However, prolonged retention of 18F-FDG in the body increases radiation exposure. This study evaluated the effect of oral administration of milk and ursodeoxycholic acid (UDCA) in terms of reducing radiation exposure by 18F-FDG. METHODS: 18F-FDG radioactivity was measured using a digital γ counter in the whole body and in various organs of rats after oral administration of milk and milk plus UDCA (milk + UDCA). Western blotting was performed to measure the expression levels of G6Pase, HK 2, CREB, FoxO1, and PGC-1α in the brain, liver, small intestine, and large intestine to assess the mechanism underlying the reduction in radiation exposure from 18F-FDG by oral administration of milk and UDCA. RESULTS: We found a significant reduction in 18F-FDG radioactivity in the whole body and in the brain, liver, and small and large intestines. Expression of G6Pase was significantly increased in the above-mentioned organs in the milk and milk + UDCA groups. Expression of HK 2 was significantly decreased in the brain and small intestine in the milk and milk + UDCA groups. CREB, FoxO1, and PGC-1α expression levels in the brain, liver, and small intestine were increased in the milk and milk + UDCA groups. However, expression of PGC-1α in the large intestine in the milk and milk + UDCA groups was significantly decreased compared with that in the control group. CONCLUSION: The present study demonstrated that administration of milk and UDCA increased G6Pase expression levels and 18F-FDG release from the tissue. These results suggest milk and UDCA could be used to reduce radiation exposure from 18F-FDG after image acquisition. The mechanisms underpinning this phenomenon should be explored in a human study.

Analysis of Cell Fraction of 99mTc-HMPAO Radiolabeled Leukocytes.

PURPOSE: 99mTc-HMPAO radiolabeled autologous leukocyte scintigraphy is routinely used clinically for infection imaging. Leukocytes are mostly separated via sedimentation. It is unknown whether leukocytes are clearly separated by sedimentation or selectively labeled. Therefore, in this study, the blood cell numbers were investigated after leukocyte radiolabeling to identify the cells strongly radiolabeled by 99mTc-HMPAO. METHODS: This study was performed with leftover blood samples of the patients who underwent 99mTc-HMPAO scintigraphy at Chonbuk National University Hospital (2018-2019). The blood of 22 patients was drawn for 99mTc-HMPAO scintigraphy. WBCs were separated via conventional sedimentation at our clinic and radiolabeled. The concentration of cell components was determined using an automatic hematology analyzer. The cells in the final sample injectate sample were separated using Histopaque and counted with a dose calibrator. RESULTS: The average numbers of RBCs, WBCs, and PLTs in the final injection sample were 79 ± 33, 23.26 ± 11.95, and 229.5 ± 206.57 x 103/µL, respectively. The PLT number was almost 10-fold the number of WBCs. The number of RBCs was nearly 3-fold higher than WBCs [RBC/WBC ratio = 4.67 ± 3.58, and PLT/WBC ratio = 10.65 ± 12.46]. Following Histopaque separation, the activity of each layer showed 99mTc-HMPAO labeling of WBC > RBC > PLT in order. The total activity/cell numbers of WBCs, RBCs and PLTs were 0.016 ± 0.010, 0.005 ± 0.005 and 0.003 ± 0.002, respectively (p > 0.05). CONCLUSION: Although the numbers of RBCs and PLTs were highly increased after sedimentation, their individual cellular activity was lower than that of WBCs. 99mTc-HMPAO was more selective to WBCs than RBCs or PLTs. In conclusion, a higher number of WBCs were radiolabeled compared with RBCs and PLTs.

Radioiodine ablation in thyroid cancer patients: renal function and external radiation dose rate at discharge according to patient preparation.

BACKGROUND: An elevated thyroid stimulating hormone (TSH) level is essential for the uptake of radioiodine into thyroid remnants and residual thyroid cancer in patients undergoing high-dose radioiodine therapy (HD-RIT). Recently, the use of recombinant human thyroid stimulating hormone (rh-TSH) has increased in preference over the conventional method of thyroid hormone withdrawal (THW). However, the clinical influences of the two methods, aside from the therapeutic effects, have not been widely evaluated. The aim of this work was to investigate the influences of the two methods, particularly on the renal function and external radiation dose rate (EDR) from patients undergoing HD-RIT. METHODS: From February 2012 to November 2016, 667 patients (M:F=138:529, mean age: 47.7±11.8 years), who underwent first HD-RIT (120, 150, or 180 mCi, 1 mCi=37 MBq) for ablation of remnant thyroid tissue or residual thyroid cancer, were enrolled. Patients who were proven to have distant metastasis to lung or bone were excluded. Low- to high-risk patients based on 2015 American thyroid association management guidelines who underwent first HD-RIT in our department were included. The period from total thyroidectomy to HD-RIT was limited within 12 months. The following parameters were collected and evaluated: age, gender, histology type and TNM stage of thyroid cancer, glomerular filtration rate on the admission day for total thyroidectomy (baseline GFR), GFR on the day of HD-RIT (follow-up GFR), thyroglobulin (Tg) and TSH levels on the day of HD-RIT, and EDR on the discharge day after HD-RIT. RESULTS: There were 386 patients using the THW method and 281 patients choosing the rh-TSH method. The baseline GFR of the THW group (106±16 mL/min/1.73 m2) and that of the rh-TSH group (104±17 mL/min/1.73 m2) were within normal limits and there was no significant difference. However, follow-up GFR of the THW group (84±17 mL/min/1.73 m2) was much lower than that of the rh-TSH group (104±16 mL/min/1.73 m2) (P=0.000). In the THW group, the follow-up GFR decreased significantly (P=0.000), yet the follow-up GFR of the rh-TSH group was not statistically different when compared with its baseline GFR (P=0.142). EDRs were lower in all rh-TSH subgroups compared to those of THW subgroups with statistical significance. Tg and TSH levels were not different between the two groups, excluding a few small-sized subgroups analyses. CONCLUSIONS: In this retrospective analysis of renal function and EDR, the use of rh-TSH appears to help maintain renal function and finally decrease EDR in contrast to the THW method when undergoing HD-RIT.

Characterization of malignant ovarian mass on [18F]FDG PET/CT: using metabolic indices and degree of solidity.

BACKGROUND: The utility of [18F]FDG PET/CT for characterizing malignant ovarian mass has not been extensively studied. Here, we investigated various parameters that could be useful to differentiate malignant ovarian mass. METHODS: We enrolled 51 female patients (53.4±15.0 years), with 86 ovarian masses, who underwent pretreatment [18F]FDG PET/CT. Thirty six lesions were histopathologically confirmed with ovarian serous adenocarcinoma. Thirty one ovarian masses from gastric cancer and 19 masses from colorectal cancer were diagnosed by histopathological study or clinical follow-up. Ovarian masses were evaluated by size, solidity, and metabolic indices. The degree of solidity was scored from 1 to 5 according to the portion of solid and cyst. Metabolic activity was scored to be either positive (≥ liver) or negative (< liver). SUVmax (SUVovary) and the ratio of SUVmax of ovary to SUVmean of the liver (ovary/L ratio) were performed. Age, bilaterality and level of CA 125 were also compared. In statistical analysis, categorical variables were analyzed using Pearson's chi-square test, while continuous variables were evaluated either independent student's t-test or Mann-Whitney Test. Receiveroperating-characteristic analysis was used to obtain optimal cutoff values. RESULTS: Serous adenocarcinoma had significantly higher score in all metabolic indices over metastasis. However, there were no differences in all metabolic indices in ovarian metastasis. In contrast, solidity was different between metastatic mass from gastric and colorectal cancer. Ovarian metastasis from gastric cancer was significantly solid compared with that from colorectal cancer. In comparison of all three masses, solidity and all metabolic indices were significantly different. Patients with serous adenocarcinoma were older and had higher CA-125 level. Between metastases from gastric and colorectal cancer, there were no differences in age, bilaterality and CA-125. CONCLUSIONS: Metabolic indices such as SUVovary and ovary/L ratio could be useful to differentiate serous adenocarcinoma from metastasis. Furthermore, the degree of solidity could play a role in predicting the origin of metastasis.

Incidence and severity of femoral head avascularity after femoral neck or intertrochanteric fractures on preoperative bone single photon emission computed tomography/computed tomography: preliminary study.

OBJECTIVE: The aim of the present study was to evaluate the incidence and degree of femoral head avascularity depending on the types of femoral neck or intertrochanteric fractures using preoperative bone single photon emission computed tomography (SPECT)/computed tomography (CT). PATIENTS AND METHODS: A total of 131 patients with femoral neck or intertrochanteric fractures who underwent preoperative bone SPECT/CT were enrolled. Femoral head avascularity was evaluated using bone SPECT/CT images. Visual scores ranged from 1 to 5 based on visually assessed diagnostic confidence: 1=definitely avascular femoral head, 2=likely avascular, 3=equivocal, 4=likely not avascular, and 5=definitely not avascular. In quantitative analysis, contralateral, ipsilateral, and size ratios were measured. RESULTS: Among 131 patients, 39 of 54 (72.22%) with femoral neck fractures and 23 of 77 (29.87%) with intertrochanteric fractures showed avascular femoral heads. The incidence of femoral head avascularity was significantly higher in patients with femoral neck fracture than those with intertrochanteric fracture. While the incidence and severity of femoral head avascularity increased with higher Garden stage in femoral neck fracture, neither was related to AO/Orthopaedic Trauma Association classification of intertrochanteric fracture. In addition, the number of bony fragments around intertrochanteric fractures was not a significant predictor of femoral head avascularity. CONCLUSION: Although avascular femoral head on bone SPECT/CT does not directly indicate avascular necrosis, assessing the incidence and severity of femoral head avascularity using qualitative and quantitative parameters could give clinically useful information related to the classification. Additional studies with larger sample sizes would be a next step to expand the clinical role of bone SPECT/CT.

Light-Triggered Radiochemical Synthesis: A Novel 18F-Labelling Strategy Using Photoinducible Click Reaction to Prepare PET Imaging Probes.

Novel probe development for positron emission tomography (PET) is leading to expanding the scope of molecular imaging. To begin responding to challenges, several biomaterials such as natural products and small molecules, peptides, engineered proteins including affibodies, and antibodies have been used in the development of targeted molecular imaging probes. To prepare radiotracers, a few bioactive materials are unique challenges to radiolabelling because of their complex structure, poor stability, poor solubility in aqueous or chemical organic solutions, and sensitivity to temperature and nonphysiological pH. To overcome these challenges, we developed a new radiolabelling strategy based on photoactivated 1,3-dipolar cycloaddition between alkene dipolarophile and tetrazole moiety containing compounds. Herein, we describe a light-triggered radiochemical synthesis via photoactivated click reaction to prepare 18F-radiolabelled PET tracers using small molecular and RGD peptide.

Synthesis and Evaluation of 2-[18F]Fluoroethyltriazolesuberohydroxamine Acid for Histone Deacetylase in a Tumor Model as a Positron Emission Tomography Radiotracer.

Histone deacetylases (HDACs) are an important regulator of expression and activity of numerous proteins in terms of epigenetic aberrations. This makes HDACs attractive for antitumor therapy and imaging in certain cancers. The authors report the radiochemical synthesis of 2-[18F]fluoroethyltriazolesuberohydroxamine acid ([18F]FETSAHA) as a HDAC-targeted radiolabel probe for positron imaging tomography/computed tomography. The authors also evaluated the in vivo tumor targeting in subcutaneously implanted RR1022 rats. [18F]FETSAHA was produced in less than 2 h with 31.2% ± 4.6% (n = 6) decay-corrected yields and specific activity of 21.4 ± 9.1 GBq/µmol (n = 6) at end of synthesis. [18F]FETSAHA showed significant radioactivity accumulation in tumors with rapid blood clearance and both gastrointestinal track and renal excretion. Tumor-to-blood and tumor-to-muscle uptake ratios in the RR1022 tumor bearing rat model were 1.21 and 1.83 and 2.75 and 2.76 at 30 and 60 min, respectively. An inhibition study of [18F]FETSAHA in the presence of excess amount of suberanilohydroximic acid (SAHA) revealed receptor specific activity accumulation. [18F]FETSAHA has favorable in vivo tumor imaging properties and may be useful for noninvasive evaluation of the correlation between cancer and HDACs.

Chitosan-Based Hydrogel Microparticles for Treatment of Carcinoma in a Rabbit VX2 Liver Tumor Model.

PURPOSE: To investigate potential of chitosan hydrogel microparticles (CHI) for treatment of VX2 carcinoma. MATERIALS AND METHODS: Two weeks after liver VX2 implantation, contrast-enhanced computerized tomographic scanning was conducted. Rabbits (n = 2) with successful tumor growth were treated with different sizes of 99mTc-labeled CHI (60-80 µm and 100-120 µm) via intra-arterial hepatic catheterization. Liver distribution of 99mTc-labeled CHI was determined by means of autoradiography, a radiation-based photographic technique. In the next part of this study, therapeutic effectiveness was examined with the use of CHI with the size range of 60-80 µm (n = 11). Tumor growth response and levels of blood liver enzymes were studied at baseline and 1 and 2 weeks after CHI treatment. RESULTS: Successful tumor growth was confirmed in all rabbits (24/24). Intrahepatic CHI with the size range of 60-80 µm resulted in liver localization in more close proximity to tumor nodule versus 100-120 µm. Baseline tumor volume was 1,909 ± 575 mm3 in animals receiving CHI versus 1,831 ± 249 mm3 in control animals (P = .342). In control animals, tumor volume markedly increased by 1,544 ± 512% at 2 weeks after sham operation versus baseline. In animals receiving CHI, tumor volume remained relatively unchanged (54 ± 6% increase; P = .007 vs control). Levels of blood aspartate transaminase (AST) and alanine transaminase (ALT) in animals receiving CHI increased 1 week after treatment (P = .032 vs control for AST; P = .000 vs control for ALT), but returned to control levels at 2 weeks. CONCLUSIONS: CHI embolization suppressed tumor growth without appreciable damages in liver function.

Protective Effect of BLED-exposed Conditioned Media on Cell Injury.

Previous studies have reported that 450 nm blue light emitting diode (BLED) induces apoptosis through a mitochondria-mediated pathway in cancer cells and reduces the early stage tumor growth. This study was performed to determine the effects of BLED-irradiated cell metabolites on cell injury. Our results showed that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM) inhibited apoptosis and increased cell survival. Cell protection-related proteins were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF analysis. Treatment with LCM inhibited apoptotic cell death and increased the live cell population. The cellular protective effect of LCM was associated with keratin and collagen type VI secretion from cells after low dose of BLED irradiation. Interestingly, expression of endoplasmic reticulum stress proteins was dose dependently increased after 4 h BLED irradiation. Only levels of BiP, CHOP and ERO1-Lα were decreased significantly after 24 h incubation, indicating their anti-apoptotic property in these cells. These results indicated that cell metabolites stimulated by low-dose BLED irradiation have a cytoprotective effect on cell injury via increasing transient intracellular ER stress. Further studies remain to provide the molecular mechanisms of LCM for cytoprotective activity.

αv ß3 mediated tumor imaging using 99m Tc labeled NAD/monosaccharide coated ferrihydrite nanoparticles.

This study describes the synthesis of highly water-soluble, non-toxic, and biocompatible nicotinamide adenine dinucleotide (NAD)/glucosamine (=Nga1Fh) and NAD/glucosamine/gluconic acid coated ferrihydrite nanoparticles (=Nga2Fh) and their possible uses to target tumors in living animals via 99m Tc and 125 I radioisotope labeling. The structural properties were investigated using DLS, zeta potential, TEM, FT-IR, XRD, and Raman spectroscopy. The cell toxicity in CT26 cancer cells and in vivo tumor targetability in U87MG and CT26 tumor-bearing mice was further evaluated using cRGDyK-tagged and cRGDfK-tagged ferrihydrite nanoparticles. The average diameters of the resulting Nga1Fh and Nga2Fh nanoparticles were <5 to 7 and <3 nm, respectively. The Nga2Fh nanoparticles did not show cell toxicity until 0.1 mg/mL. Using gamma camera imaging, 99m Tc-cRGDfK-Nga2Fh showed the highest tumor uptake in a U87MG tumor-bearing mouse when compared with that of 99m Tc-cRGDyK-Nga2Fh and 99m Tc-Nga2Fh. The image-based tumor-to-muscle ratio by time for 99m Tc-cRGDfK-Nga2Fh was 3.8 ± 1.7, 4.2 ± 2.0, 7 ± 1.5, 13 ± 2.0, 8 ± 3.7, and 2 ± 1.6 at 5 and 30 minutes, 1, 2, 4, and 24 hours, respectively. Although further studies are needed, the NAD/monosaccharide coated ferrihydrite nanoparticles could be presented as an interesting material for a drug delivery system.

Clinical value of intratumoral metabolic heterogeneity in [18F]FDG PET/CT for prediction of recurrence in patients with locally advanced colorectal cancer.

BACKGROUND: The aim of this study was to find a reliable predictor of recurrence in patients with locally advanced colorectal cancer. METHODS: We enrolled 96 patients for this retrospective study. We investigated metabolic (SUVmax, metabolic tumor volume, total lesion glycolysis, and heterogeneity), clinical (age, sex, stage, and CEA level) and pathologic (Ki-67, p53, CD31, COX-2, E-cadherin and EGFR) parameters. The coefficient of variation (COV) was chosen to assess heterogeneity of [18F]FDG uptake by dividing the standard deviation of the SUV by SUVmean. Recurrence-free survival was compared with each metabolic, clinical and pathologic parameters by using univariate and multivariate survival analysis. RESULTS: Among 96 patients, 19 patients (19.8%) showed disease recurrence. In the ROC analysis, the optimal cutoff values of SUVmax, metabolic tumor volume (cm3), total lesion glycolysis (cm3), and metabolic heterogeneity were determined as 17.6, 10.05, 232.46, and 0.48, respectively. In univariate analysis, probability of recurrence was statistically increased in those with metabolic tumor volume >10.05 (P=0.045), and those with metabolic heterogeneity >0.48 (P=0.031). In multivariate analysis, metabolic heterogeneity was the only independent prognostic factor (HR 4.56, 95% CI 1.57-13.23, P=0.006). CONCLUSIONS: Intratumoral metabolic heterogeneity assessed by COV is a reliable predictive factor for disease recurrence in patients with locally advanced colorectal cancer. Therefore, its application could be an important step for personalized management of colorectal cancer.

131I-labeled chitosan hydrogels for radioembolization: A preclinical study in small animals.

INTRODUCTION: The purpose of the study was to examine potential of 131I-labeled chitosan hydrogels (Chi) for treatment of liver cancer. METHODS: Orthotopic hepatoma was induced by McA-RH7777-fLuc cells (1×107) that were injected into the left hepatic lobe of rats. Ten days later, tumor-bearing rats evidenced by bioluminescence received 125I-labeled Chi with left hepatic artery access. Pharmacokinetics and excretion (n=8) and biodistribution (n=6/time point) were studied after injection. To examine therapeutic potential, animals (n=8/group) were also treated with Chi labeled with or without 131I. Changes in tumor volume by magnetic resonance (MR) imaging were studied. RESULTS: The rate of tumor induction assessed by bioluminescence imaging was 72% (68/95). Gamma counter and scintigraphy imaging analyses showed accumulation of 125I-labeled Chi dominantly in the liver. A small fraction of 125I-labeled Chi was detected in the stomach (2.02±3.07%ID) and muscle (1.37±1.48%ID) at 2 d post-treatment. Blood sample analysis showed the maximum blood concentration of 0.09±0.03%ID/mL, which peaked at 0.60±0.45 d. Over a 4-week period, 31.22±8.16%ID were excreted in the urine and 3.5±1.3% in the feces. Treatment of Chi (median, 876mm3; IQR, 496mm3-1413mm3) markedly reduced the extent of tumor growth, compared to controls (median, 12,085mm3; IQR, 7786mm3-25,832mm3; P<0.05 vs control). 131I Chi (median, 80mm3; IQR, 35mm3-172mm3; P<0.05 vs control) induced a greater tumor-suppressing effect, compared to Chi alone. CONCLUSIONS: In this study, we have characterized a new radioembolization device, 131I Chi, in vivo and provided evidence for its therapeutic potential. ADVANCES IN KNOWLEDGE: Transarterial embolization is a conceivable treatment option for patients with inoperable liver cancer to mitigate the disease progression. Recently, we have developed chitosan-based hydrogel microparticles. In the present study, the hydrogel microparticles were radiolabeled with 131I for treatment of liver cancer. Our results demonstrated that a hepatic arterial injection of 125I-labeled Chi resulted in substantial liver accumulation, which was accompanied by virtually no extrahepatic deposition. The results of the present study also showed that administration of 131I Chi markedly suppressed tumor growth, compared to controls and to animals receiving unlabeled Chi. 131I-labeled chitosan hydrogel microparticles represent a new therapeutic approach for treatment of liver cancer.

Inhibitory effect of blue light emitting diode on migration and invasion of cancer cells.

The aim of this study was to determine the effects and molecular mechanism of blue light emitting diode (LED) in tumor cells. A migration and invasion assay for the metastatic behavior of mouse colon cancer CT-26 and human fibrosarcoma HT-1080 cells was performed. Cancer cell migration-related proteins were identified by obtaining a 2-dimensional gel electrophoresis (2-DE) in total cellular protein profile of blue LED-irradiated cancer cells, followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of proteins. Protein levels were examined by immunoblotting. Irradiation with blue LED inhibited CT-26 and HT-1080 cell migration and invasion. The anti-metastatic effects of blue LED irradiation were associated with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression. P38 MAPK phosphorylation was increased in blue LED-irradiated CT-26 and HT-1080 cells, but was inhibited after pretreatment with SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK phosphorylation by SB203580 treatment increased number of migratory cancer cells in CT-26 and HT-1080 cells, indicating that blue LED irradiation inhibited cancer cell migration via phosphorylation of p38 MAPK. Additionally blue LED irradiation of mice injected with CT-26 cells expressing luciferase decreased early stage lung metastasis compared to untreated control mice. These results indicate that blue LED irradiation inhibits cancer cell migration and invasion in vitro and in vivo.

Brain Metastases Mimicking Hyperostosis Frontalis Interna on 99mTc HDP Bone Scintigraphy.

Symmetric bifrontal uptake of bone-seeking agents is usually considered as the main feature of hyperostosis frontalis interna in postmenopausal elderly women. This finding is not uncommon in elderly women because of the change in their hormonal level. However, in the present case, a 66-year-old woman with intra-axial brain metastases of breast cancer showed symmetric bifrontal uptake on bone scintigraphy. Therefore, symmetric bifrontal uptake should not always be considered as a definite indicator of hyperostosis frontalis interna. Further evaluation such as SPECT/CT is needed for evaluation of brain metastases especially in cancer patients.