Expression and purification of epitope vaccine against four virulence proteins from Helicobacter pylori and construction of label-free electrochemical immunosensor.

The epitope vaccine against four virulence proteins (FVpE) from Helicobacter pylori (H. pylori) was expressed and purified. Western blot and Enzyme-linked Immunosorbent Assays (ELISA) were used to identify and investigate the immunoreactivity of FVpE protein. The immune-sensing platform based on titanium carbide/colloidal gold nanoparticles@carbon nanofiber/ionic liquid composites electrode was constructed for immobilizing FVpE. Electrochemical impedance spectroscopy (EIS) was used to study the electrochemical properties of the modified electrodes. The relevant influenced factors were optimized including pH value, antigen concentration, and incubating time. The prepared H. pylori label-free electrochemical immunosensor was used for antibody detection using differential pulse voltammetry (DPV). Under the optimal experimental conditions, the linear ranges of H. pylori antibodies, including anti-H. pylori, cytotoxin-associated gene A (CagA), vacuolating cytotoxin-associated gene A (VacA), and urease A (UreA), were all 0.1-5 ng mL-1, except urease B (UreB, 0.1-4.5 ng mL-1). The selectivity study showed that other antibodies had little influence on the detection of H. pylori antibodies. The immunosensor could be used to detect serum samples, and the recoveries were in the range of 68.5%-100.5%.

[Diagnostic and Prognostic Value of 18F-FDG PET/CT in Bone Marrow Infiltration of Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the diagnostic value of 18F-FDG PET/CT in bone marrow infiltration (BMI) of newly diagnosed diffuse large B-cell lymphoma (DLBCL), compared with the results of bone marrow biopsy (BMB) and investigate whether the BMI diagnosed by 18F-FDG PET/CT and other factors have independent prognostic values. METHODS: Ninety-four newly diagnosed DLBCL patients who underwent PET/CT in Clinical Medical College of Shanghai General Hospital of Nanjing Medical University were included. BMB was performed within 2 weeks before or after PET/CT, and standardized treatment was performed after PET/CT. The manifestations of bone marrow (BM) FDG uptake were recorded. The diagnostic criteria of BMI were BMB positive or focal BM FDG uptake confirmed by imaging follow-up. The relationship between clinical features and BM FDG uptake and the values of PET/CT and BMB in the diagnosis of BMI was analyzed. The progression-free survival (PFS) was analyzed by Kaplan-Meier survival curves, log-rank test was used to compare PFS rate, and Cox regression model was used to analyze the independent risk factors affecting PFS. RESULTS: Among 94 DLBCL patients, 34 patients showed focal BM uptake (fPET), 7 patients showed super BM uptake (sBMU), 11 patients showed diffuse homogenous uptake higher than liver (dPET), and the other 42 patients had normal BM uptake (nPET) (lower than liver). BMB positive was found in all sBMU patients, in 20.6%(7/34) of fPET patients, and in 27.3% (3/11) of dPET patients. All nPET patients had negative BMB results. dPET patients were associated with lower hemoglobin level and leukocyte count compared with nPET group (P < 0.001, P =0.026). Compared with fPET patients, sBMU patients were more likely to have B symptoms and elevated lactate dehydrogenase (LDH). A total of 44 patients were diagnosed BMI, including 17 cases with BMB+. The sensitivity and specificity of BMB in the diagnosis of BMI was 38.6% (17/44) and 100% (50/50), respectively. Using fPET and sBMU as criteria of PET BMI, the diagnostic sensitivity and specificity of PET/CT was 93.2% (41/44) and 100% (50/50), respectively. Kaplan-Meier analysis showed that there was no significant difference in 2-year PFS rate between nPET and dPET patients (P >0.05), while sBMU patients had lower 2-year PFS rate compared with fPET patients (P < 0.001). Multivariate analysis showed that higher Ann Arbor stage (HR=9.010, P =0.04) and sBMU (HR=3.964, P =0.002) were independent risk factors affecting PFS. CONCLUSIONS: Increased BM FDG uptake of DLBCL can be manifested as dPET, fPET and sBMU. fPET and sBMU can replace BMB to diagnose BMI. Although dPET cannot completely exclude the possibility of BMI, it does not affect the prognosis, so it can be diagnosed as PET BMI negative. sBMU is an independent prognostic risk factor.

The efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary lesions and metastasis in newly diagnosed prostate cancer.

Purpose: Compared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa). Methods: A retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3-4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression. Results: The SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0% vs. 47.62%, P = 0.005; 9.09% vs. 88.89%, P = 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with 99mTc-HYNIC-PSMA SPECT/CT. Conclusion: 99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies.

A non-enzymatic electrochemical sensor based on nitrogen-doped mesoporous carbon@hydroxyl-functionalized ionic liquid composites modified electrode for the detection of fenitrothion.

The overuse of organophosphorus pesticides (OPs) results in severe environmental pollution and food safety issues. Fenitrothion (FNT) is a typical derivative of OPs, so rapid and sensitive detection of FNT plays an important role in environmental protection and public health. An FNT non-enzymatic electrochemical sensor based on nitrogen-doped mesoporous carbon@functionalized ionic liquid composites (N-CMK-3@IL) was constructed in this work. The surface topography and electrochemical properties of the sensor were investigated by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), respectively. Because N-CMK-3@IL composites could improve the conductivity and increase the active surface area of the modified electrode, the sensor exhibited good electrocatalytic activity to FNT. Under the optimal experimental conditions, a good linear relationship for FNT was obtained in the range of 0.5-100 ng mL-1, and the detection limit was 0.1 ng mL-1 (S/N = 3). The sensor was successfully applied for the detection of FNT in vegetable samples.

Investigation of Polymer Gel Reinforced by Oxygen Scavengers and Nano-SiO2 for Flue Gas Flooding Reservoir.

Polymer gel plugging is an effective technique for gas mobility control in flue gas flooding reservoirs. However, the performance of polymer gels is extremely susceptible to the injected flue gas. A reinforced chromium acetate/partially hydrolyzed polyacrylamide (HPAM) gel, using thiourea as the oxygen scavenger and nano-SiO2 as the stabilizer, was formulated. The related properties were evaluated systematically, including gelation time, gel strength, and long-term stability. The results indicated that the degradation of polymers was effectively suppressed by oxygen scavengers and nano-SiO2. The gel strength would be increased by 40% and the gel kept desirable stability after aging for 180 days at elevated flue gas pressures. Dynamic light scattering (DLS) analysis and Cryo-scanning electron microscopy (Cryo-SEM) revealed that nano-SiO2 was adsorbed on polymer chains by hydrogen bonding, which improved the homogeneity of gel structure and thus enhanced the gel strength. Besides, the compression resistance of gels was studied by creep and creep recovery tests. The failure stress of gel with the addition of thiourea and nanoparticles could reach up to 35 Pa. The gel retained a robust structure despite extensive deformation. Moreover, the flow experiment indicated that the plugging rate of reinforced gel still maintained up to 93% after flue gas flooding. It is concluded that the reinforced gel is applicable for flue gas flooding reservoirs.

Prognostic value of interim 18F-FDG PET/CT in adult follicular lymphoma treated with R-CHOP.

PURPOSE: The prognostic value of interim 18F-FDG PET/CT (I-PET) for follicular lymphoma (FL) is controversial, and may be related to the lack of strict standards in terms of age, chemotherapy regimen, and evaluation criteria in previous studies. This study aimed to investigate the prognostic value of I-PET in adult FL patients treated with R-CHOP. METHODS: I-PET was performed in 30 adult FL patients after treatment with 3-5 cycles of R-CHOP. PET/CT images were assessed using the Deauville 5-point scale (D-5PS) criteria. Baseline PET/CT (B-PET) was performed in 24 of the patients with FL before treatment. The PET/CT image parameters, such as the SUVmax, TLG, and tMTV, were recorded. The prognostic values of sex, age, grade, Ann Arbor stage, LDH level, and I-PET were evaluated. RESULTS: Kaplan-Meier analysis and Cox regression showed that sex, age, grade, Ann Arbor stage, LDH, and I-PET using the D-5PS criteria could not predict the PFS of adult patients with FL treated with R-CHOP (P>0.05). ROC curve analysis evaluated the predictive values of SUVmax, TLG, and tMTV in B-PET and I-PET and showed that none of them was predictive of PFS in adult FL patients (P>0.05). However, the variation in SUVmax (∆SUVmax) was predictive of PFS in adult FL patients (AUC=0.83, P=0.040), and the cutoff threshold was 4.85. CONCLUSIONS: I-PET using the D-5PS criteria cannot predict the PFS of adult FL patients treated with R-CHOP. However, the ∆SUVmax between B-PET and I-PET is applicable for the prognosis of adult patients with FL.

Probing the Effect and Mechanism of Flue Gas on the Performance of Resorcinol/Hexamethylenetetramine-Based Polymer Gel in Flue Gas Flooding Reservoir.

Polymer gel plugging is an effective method for gas mobility control in flue gas flooding reservoirs. However, the effect and mechanism of flue gas on the performance of polymer gels have rarely been reported. In this study, a polymer gel was prepared by cross-linking hydrolyzed polyacrylamide (HPAM) and resorcinol/ hexamethylenetetramine (HMTA) to illuminate the influencing mechanism of flue gas composition on gel. The gel rheological testing results showed that flue gas promoted gelation performance, whereas it seriously threatened gel long-term stability, especially at high pressure conditions. The influence of CO2 on the polymer gel had the characteristic of multiplicity. The hydrodynamic radius (Rh) and the initial viscosity of HPAM solution decreased in the presence of CO2. Nonetheless, the dissolved CO2 expedited the decomposition rate of HMTA into formaldehyde, which promoted the cross-linking process of the HPAM, leading to a shorter gelation time. Oxidation-reduction potential (ORP) tests and Fourier transform infrared spectroscopy (FTIR) analysis indicated that O2 played a leading role in the oxidative degradation of HPAM compared to CO2 and threatened the gel long-term stability at elevated gas pressures. To address the adverse effects caused by flue gas, it is highly desirable to develop polymer gels by adding oxygen scavengers or strengthening additives.

Deep progressive learning achieves whole-body low-dose 18F-FDG PET imaging.

OBJECTIVES: To validate a total-body PET-guided deep progressive learning reconstruction method (DPR) for low-dose 18F-FDG PET imaging. METHODS: List-mode data from the retrospective study (n = 26) were rebinned into short-duration scans and reconstructed with DPR. The standard uptake value (SUV) and tumor-to-liver ratio (TLR) in lesions and coefficient of variation (COV) in the liver in the DPR images were compared to the reference (OSEM images with full-duration data). In the prospective study, another 41 patients were injected with 1/3 of the activity based on the retrospective results. The DPR images (DPR_1/3(p)) were generated and compared with the reference (OSEM images with extended acquisition time). The SUV and COV were evaluated in three selected organs: liver, blood pool and muscle. Quantitative analyses were performed with lesion SUV and TLR, furthermore on small lesions (≤ 10 mm in diameter). Additionally, a 5-point Likert scale visual analysis was performed on the following perspectives: contrast, noise and diagnostic confidence. RESULTS: In the retrospective study, the DPR with one-third duration can maintain the image quality as the reference. In the prospective study, good agreement among the SUVs was observed in all selected organs. The quantitative results showed that there was no significant difference in COV between the DPR_1/3(p) group and the reference, while the visual analysis showed no significant differences in image contrast, noise and diagnostic confidence. The lesion SUVs and TLRs in the DPR_1/3(p) group were significantly enhanced compared with the reference, even for small lesions. CONCLUSIONS: The proposed DPR method can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment while maintaining image quality.

Deep learning-assisted PET imaging achieves fast scan/low-dose examination.

PURPOSE: This study aimed to investigate the impact of a deep learning (DL)-based denoising method on the image quality and lesion detectability of 18F-FDG positron emission tomography (PET) images. METHODS: Fifty-two oncological patients undergoing an 18F-FDG PET/CT imaging with an acquisition of 180 s per bed position were retrospectively included. The list-mode data were rebinned into four datasets: 100% (reference), 75%, 50%, and 33.3% of the total counts, and then reconstructed by OSEM algorithm and post-processed with the DL and Gaussian filter (GS). The image quality was assessed using a 5-point Likert scale, and FDG-avid lesions were counted to measure lesion detectability. Standardized uptake values (SUVs) in livers and lesions, liver signal-to-noise ratio (SNR) and target-to-background ratio (TBR) values were compared between the methods. Subgroup analyses compared TBRs after categorizing lesions based on parameters like lesion diameter, uptake or patient habitus. RESULTS: The DL method showed superior performance regarding image noise and inferior performance regarding lesion contrast in the qualitative assessment. More than 96.8% of the lesions were successfully identified in DL images. Excellent agreements on SUV in livers and lesions were found. The DL method significantly improved the liver SNR for count reduction down to 33.3% (p < 0.001). Lesion TBR was not significantly different between DL and reference images of the 75% dataset; furthermore, there was no significant difference either for lesions of > 10 mm or lesions in BMIs of > 25. For the 50% dataset, there was no significant difference between DL and reference images for TBR of lesion with > 15 mm or higher uptake than liver. CONCLUSIONS: The developed DL method improved both liver SNR and lesion TBR indicating better image quality and lesion conspicuousness compared to GS method. Compared with the reference, it showed non-inferior image quality with reduced counts by 25-50% under various conditions.

[Prognostic Value of Interim 18F-FDG PET/CT in Extranodal NK/T-Cell Lymphoma, Nasal Type].

OBJECTIVE: To explore the value of interim 18F-FDG PET/CT in the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL). METHODS: Twenty-one patients with ENKTL who were pathologically diagnosed at Shanghai General Hospital of Nanjing Medical University (Shanghai General Hospital) from January 2015 to December 2018 were retrospectively collected, and 18F-FDG PET/CT imaging was performed before and during treatment (3 weeks after 2-4 chemotherapy courses or 6 weeks after radiotherapy). The complete clinical data of the patients were followed up. The progression-free survival (PFS) and overall survival (OS) were analyzed by the Korean prognostic index (KPI), Deauville score (DS) and the maximum standard uptake reduction rate (ΔSUVmax). The independent risk factors affecting survival were evaluated by COX regression. RESULTS: After treatment, 11 patients had complete remission (CR), 3 had partial remission (PR), 1 had stable disease (SD), and 6 had disease progression (PD). The CR patients' △SUVmax was significantly higher than non-CR patients ï¼»(66.07±22.33)% vs (36.87±23.28)%, t=2.927, P=0.009ï¼½. Calculated from the receiver operating curve (ROC), the optimal cut-off point of ΔSUVmax was 51.45%. The median follow-up time was 32 months. Kaplan-Meier survival analysis showed that KPI, DS and ΔSUVmax had significance in predicting PFS and OS (P<0.05). COX regression analysis showed that DS was an independent risk factor affecting PFS (P<0.05), and KPI and ΔSUVmax were independent risk factors affecting OS (P<0.05). CONCLUSION: Interim 18F-FDG PET/CT imaging has some value in the prognostic evaluation of patients with ENKTL.

Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging and anticancer drug delivery.

BACKGROUND: Glioma is the deadliest brain cancer in adults because the blood-brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma single-photon emission computed tomography (SPECT) imaging and anticancer drug delivery. RESULTS: This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol (mPEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99mTc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac2O), the CTX-modified PEI (mPEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The formed mPEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the mPEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99mTc via DTPA, the 99mTc-labeled complex could help to visualize the drug accumulation in tumors of glioma-bearing mice and the drug delivery into the brains of rats through SPECT imaging. CONCLUSIONS: These results indicate the potential of the developed PEI-based nanocomplex in facilitating glioma-targeting SPECT imaging and chemotherapy.

Boosting the capacitive property of nickel cobalt aluminum layered double hydroxide in neutral electrolyte.

Layered double hydroxide (LDH) has shown great potential for energy storage due to their high theoretical specific capacitance, relatively low cost and eco-friendliness. LDH, however, always works in alkali aqueous electrolyte for supercapacitors, which brings serious environmental pollution. In this work, a reduced graphite oxide/Fe(CN)63-- nickel cobalt aluminum LDH (RGO/Fe(CN)63--LDH) composite has been prepared via ion-exchange reaction using RGO/LDH as precursor. RGO/Fe(CN)63--LDH electrode provides a specific capacitance of 221 F g-1 in a wide potential window of -1 ~ 0.8 V vs. SCE in Na2SO4 aqueous electrolyte, and which is much higher than that of LDH electrode (3.56 F g-1). Owing to the wide potential window of RGO/Fe(CN)63--LDH electrode, a symmetrical solid supercapacitor device (RGO/Fe(CN)63--LDH//RGO/Fe(CN)63--LDH) with a high voltage of 2.0 V can deliver a high specific energy of 25.2 Wh kg-1 at a specific power of 250 W kg-1, and a capacitance retention of 75% after galvanostatic charging/discharging at 5 A g-1 for 5000 times. This work supplies enlightenment for boosting the capacitive performance of LDHs in neutral electrolyte.

The role of CT in PET/CT for assessing diffuse infiltration of bone marrow in multiple myeloma using the Durie-Salmon PLUS staging system.

PET/CT has been identified as one of the routine methods for the assessment of multiple myeloma (MM) bone marrow infiltration. In the routine method of performing PET/CT, the 18F-Fludeoxyglucose (18F-FDG) uptake in this disease is often used in the assessment of this condition, however CT diagnosis is not currently commonly used. The aim of the present study was to investigate the importance of CT in PET/CT for assessing diffuse infiltration (DI) of bone marrow in MM. MRI was used as a control in the present study, which is the gold standard for assessing DI of bone marrow and is divided into 3 levels: Mild, moderate and severe DI. Subsequently, a total of four combinations of PET and CT results were listed using the enumeration method for the evaluation of DI in the bone marrow. These combinations were respectively compared with the three levels of MR imaging to screen the most consistent method. The concordances of the new method and routine 18F-FDG PET/CT for the assessment of DI with MR imaging were compared using the McNemar test, respectively. The results of the DI assessment from the two methods were verified by performing Durie-Salmon (D-S) PLUS staging. Compared with MR imaging, the results were as follows: PET and CT exhibited negative results, suggesting mild DI; one of them was positive, suggesting moderate DI; and two were positive, suggesting severe DI. The results of concordance between two methods (new and routine) and MR imaging are indicated as follows: For the new method, McNemar test, P=0.513 and Kappa=0.745; for the routine 18F-FDG PET/CT method, McNemar test, P=0.03 and Kappa=0.547. Re-performance of D-S PLUS staging presented the following results: New method, McNemar test, P=0.317 and Kappa=0.93; for the routine method, McNemar test, P=0.223 and Kappa=0.811. These findings indicated that the CT component of PET/CT could improve the concordance with MRI results in the assessment of DI, and the same results were obtained when D-S PLUS staging was performed. The CT in PET/CT can enhance diagnostic accuracy in the assessment of DI by reducing the false negatives when compared with the routine 18F-FDG method.

131I-labeled polyethylenimine-entrapped gold nanoparticles for targeted tumor SPECT/CT imaging and radionuclide therapy.

Purpose: Polyethylenimine (PEI) has been widely used as a versatile template to develop multifunctional nanosystems for disease diagnosis and treatment. In this study, we manufactured iodine-131 (131I)-labeled PEI-entrapped gold nanoparticles (Au PENPs) as a novel nanoprobe for single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and radionuclide therapy. Materials and methods: PEI was PEGylated and sequentially conjugated with Buthus martensii Karsch chlorotoxin (BmK CT, a tumor-specific ligand which can selectively bind to MMP2), 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate to form the multifunctional PEI template for entrapment of Au NPs. Then, the PEI surface was radiolabeled with 131I via HPAO to produce the novel nanoprobe (BmK CT-Au PENPs-131I). Results: The synthesized multifunctional Au PENPs before and after 131I radiolabeling were well-characterized as follows: structure, X-ray attenuation coefficient, colloid stability, cytocompatibility, and radiochemical stability in vitro. Furthermore, BmK CT-Au PENPs-131I were suitable for targeted SPECT/CT imaging and radionuclide therapy of tumor cells in vitro and in a xenograft tumor model in vivo. Conclusion: The developed multifunctional Au PENPs are a promising theranostic platform for targeted imaging and treatment of different MMP2-overexpressing tumors.

Design of 99mTc-Labeled Low Generation Dendrimer-Entrapped Gold Nanoparticles for Targeted Single Photon Emission Computed Tomography/Computed Tomography Imaging of Gliomas.

Chemokine receptor-4 (CXCR4) has been demonstrated to be overexpressed in glioma cells and associated with poor survival. In the present study, we designed and synthesized 99mTc-labeled low-generation dendrimer-entrapped gold nanoparticles (Au DENPs), which were modified with CXCR4-ligand for targeted single photon emission computed tomography (SPECT)/computed tomography (CT) imaging of glioma. Generation two poly(amidoamine) dendrimers were sequentially conjugated with diethylenetriamine pentacetate acid (DTPA) and polyethylene glycol (PEG) modified with FC131 peptide (a CXCR4-specific ligand), and were then utilized as a template for entrapment of gold nanoparticles (Au NPs). After radiolabeling with 99mTc via DTPA chelation, the glioma-targeting SPECT/CT dual mode nanoprobe {(Au0)6-G2-99m-DTPA-(PEG-FC131)} DENPs were generated. The FC131-functionalized Au DENPs before and after 99mTc radiolabeling were well characterized. The results revealed that prior to 99mTc radiolabeling, FC131-functionalized Au DENPs had a uniform size distribution, acceptable biocompatibility in the given Au concentration range and could specifically target glioma cells due to the attached FC131. Furthermore, the FC131-functionalized Au DENPs could be readily radiolabeled by 99m Tc with good radiochemical stability and high radiochemical purity. The {(Au0)6-G2-99mTc-DTPA-(PEG-FC131)} DENPs appeared to be effective in targeted SPECT/CT imaging of glioma cells in vitro and in vivo in a subcutaneous tumor model. The developed FC131-functionalized dendrimer-based nanoprobe may hold a great potential for utilization in SPECT/CT imaging of different CXCR4-overexpressing cancers.

Anti-metastatic effect of 131I-labeled Buthus martensii Karsch chlorotoxin in gliomas.

The present study investigated the underlying molecular mechanism by which Buthus martensii Karsch chlorotoxin (BmK CT) inhibits the invasion and metastasis of glioma cells and the possibility of 131I­labeled BmK CT (131I­BmK CT) as a novel targeted agent for the treatment of glioma. The impact of BmK CT with and without 131I radiolabeling on the invasion and metastasis of glioma cells in vitro was studied. Cell viability was assessed using Cell Counting Kit­8 and plate colony formation assays in order to confirm the cytotoxicity of BmK CT and 131I­BmK CT at different concentrations. Transwell invasion and wound­healing assays were conducted in order to investigate the inhibitory effects BmK CT and 131I­BmK CT on cell migration and invasion. Furthermore, western blotting, ELISA immunofluorescence and a gelatin zymography assay were performed to evaluate changes in the protein expression levels of glioma cells following treatment with BmK CT or 131I­BmK CT. The results indicated that BmK CT inhibits the invasion and metastasis of glioma cells via regulation of tissue inhibitor of metalloproteinase­2 expression and that 131I­BmK CT has the potential to be a novel targeted therapeutic drug for glioma.

Recurrent Leiomyosarcoma of External Oblique Muscle Detected on 99mTc-MDP SPECT/CT.

A Tc-MDP bone scintigraphy was performed in an 88-year-old man with a history of right external oblique muscle leiomyosarcoma, which was resected 8 months ago. The static images showed abnormal tracer uptake in the region of resection bed. SPECT/CT images demonstrated that the increased activity was from a partially calcified soft tissue mass in external oblique muscle. Subsequent pathological examination confirmed recurrent tumor.

SPECT imaging and radionuclide therapy of glioma using 131I labeled Buthus martensii Karsch chlorotoxin.

Gliomas, the most prevalent type of brain tumor in adults, are associated with high rates of morbidity and mortality. Recent studies on 131I labeled scorpion toxins suggest they can be developed as tumor-specific agents for glioma diagnosis and treatment. This study investigated the potential of 131I labeled Buthus martensii Karsch chlorotoxin (131I-BmK CT) as a new approach for targeted imaging and therapy of glioma. The results showed that 131I can be successfully linked to BmK CT with satisfactory radiochemical purity and stability and that 131I-BmK CT markedly inhibited glioma cell growth in a dose and time dependent manner, with significant accumulation in glioma cells in vitro. Persistent intratumoral radioiodine retention and specific accumulation of 131I-BmK CT were observed in C6 glioma tumor, which was clearly visualized by SPECT imaging. Both intratumoral and intravenous injections of 131I-BmK CT could result in significant tumor inhibition efficacy and prolonging the lifetime of tumor-bearing mice. Based on these promising results, it is concluded that 131I-BmK CT has the potential to be explored as a novel tool for SPECT imaging and radionuclide therapy of glioma.

BmK CT and 125I-BmK CT suppress the invasion of glioma cells in vitro via matrix metalloproteinase-2.

Chlorotoxin (CTX) is an established blocker of small­conductance Cl­ channels and has previously been demonstrated to inhibit the invasion of glioma cells. Buthus martensii Karsch chlorotoxin­like toxin (BmK CT) is the first chlorotoxin-like peptide. The present study aimed to determine the inhibitory effect of BmK CT on the invasive ability of glioma cells, using a Transwell assay. BmK CT was subsequently radiolabeled with radionuclide 125I and its activity was compared with BmK CT. Additionally, the underlying anti­invasive mechanism of BmK CT and 125I­BmK CT on glioma cells was investigated by ELISA and reverse transcription­quantitative polymerase chain reaction (RT­qPCR). It was revealed that BmK CT and 125I­BmK CT were able to inhibit the invasion of glioma cells and that 125I­BmK CT was superior to BmK CT. Consistent with the results of the Transwell assay, matrix metalloproteinase­2 (MMP­2) secretion by glioma cells was significantly reduced following treatment with BmK CT or 125I­BmK CT (P<0.05). However, no significant differences in MMP-2 mRNA expression levels were identified by RT­qPCR (P>0.05). In conclusion, the present study demonstrated that BmK CT and 125I­BmK CT reduced the invasion of glioma cells via downregulation of MMP-2 expression. However, inhibition of the invasion of glioma cells was not demonstrated at the mRNA level.

99mTc-MDP Uptake in Diffuse Pleural Recurrences of Pulmonary Neuroendocrine Carcinoma.

A 39-year-old woman with a history of pulmonary neuroendocrine carcinoma segmental palliative resection underwent a Tc-MDP bone scintigraphy to evaluate possible osseous metastases. The static images revealed diffuse elevated activity in the left hemithorax, more prominent in the lower thorax, which is suggestive of malignant pleural effusion. However, SPECT/CT images showed that the elevated activity was from pleura-based soft tissue masses, which were confirmed as recurrent tumor pathologically after biopsy.