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Supplementary Files contain (1) Supplementary Materials and Methods for �V�3 expression analysis, autoradiography and histological analysis, and hematology and hepatorenal function; (2) Supplementary Tables S1-S5; and (3) Supplementary Figures S1-S5. Table S1Effects of 37 MBq (1 nmol) of 64Cu-cyclam-RAFT-c(-RGDfK-)4 {plus minus} GF/Lys on hepatorenal functions of U87MG tumor-bearing mice; Table S2Blood cell counts of U87MG tumor-bearing mice at various time points post-injection of 37 MBq (1 nmol) of 64Cu-cyclam-RAFT-c(-RGDfK-)4 {plus minus} GF/Lys; Table S3Blood cell counts of U87MG tumor-bearing mice at various time points after single dose administrations of 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4; Table S4Effects of 74 MBq (2 nmol) of 64Cu-cyclam-RAFT-c(-RGDfK-)4 + GF/Lys on hepatorenal functions of normal mice; Table S5Human absorbed doses extrapolated from the biodistribution data of 64Cu-cyclam-RAFT-c(-RGDfK-)4 in U87MG tumor-bearing mice

Figure S1The treatment outcomes of radiotherapy with 37 MBq (1 nmol) of 64Cu-cyclam-RAFT-c(-RGDfK-)4; Figure S2Toxicity studies in normal mice that were injected with 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4; Figure S3Preliminary study of U87MG tumors excised at day 13 p.i. of 37 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4 for the changes in microvasculature; Figure S4Positive correlation between the tumor volume and the corresponding WBC in U87MG tumor-bearing mice; Figure S5Biodistribution of 64Cu-cyclam-RAFT-c(-RGDfK-)4 at various peptide doses (0.00510 nmol) in U87MG tumor-bearing mice.

The files contain (1) Supplementary Materials and Methods for αVβ3 expression analysis, autoradiography and histological analysis, and hematology and hepatorenal function; (2) Supplementary Tables S1-S5; and (3) Supplementary Figures S1-S5. Table S1â^'Effects of 37 MBq (1 nmole) of 64Cu-cyclam-RAFT-c(-RGDfK-)4 {plus minus} GF/Lys on hepatorenal functions of U87MG tumor-bearing mice; Table S2â^'Blood cell counts of U87MG tumor-bearing mice at various time points post-injection of 37 MBq (1 nmole) of 64Cu-cyclam-RAFT-c(-RGDfK-)4 {plus minus} GF/Lys; Table S3â^'Blood cell counts of U87MG tumor-bearing mice at various time points after single dose administrations of 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4; Table S4â^'Effects of 74 MBq (2 nmole) of 64Cu-cyclam-RAFT-c(-RGDfK-)4 + GF/Lys on hepatorenal functions of normal mice; Table S5â^'Human absorbed doses extrapolated from the biodistribution data of 64Cu-cyclam-RAFT-c(-RGDfK-)4 in U87MG tumor-bearing mice; Figure S1â^'The treatment outcomes of radiotherapy with 37 MBq (1 nmole) of 64Cu-cyclam-RAFT-c(-RGDfK-)4; Figure S2â^'Toxicity studies in normal mice that were injected with 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4; Figure S3â^'Preliminary study of U87MG tumors excised at day 13 p.i. of 37 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4 for the changes in microvasculature; Figure S4â^'Positive correlation between the tumor volume and the corresponding WBC in U87MG tumor-bearing mice; Figure S5â^'Biodistribution of 64Cu-cyclam-RAFT-c(-RGDfK-)4 at various peptide doses (0.005â^'10 nmole) in U87MG tumor-bearing mice.

64Cu-RaftRGD-based TRT (toxicity evaluation: hepatorenal functions and gastrointestinal state)

Purpose:Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors that are rarely curable. αVβ3 integrin (αVβ3) is overexpressed on tumoral neovessels and frequently on ovarian cancer cells. Here, using two clinically relevant αVβ3-positive OCPM mouse models, we studied the theranostic potential of an αVβ3-specific radiopeptide, 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD), and its intra- and intertumoral distribution in relation to the tumor microenvironment.Experimental Design:αVβ3-expressing peritoneal and subcutaneous models of ovarian carcinoma (IGR-OV1 and NIH:OVCAR-3) were established in nude mice. 64Cu-RaftRGD was administered either intravenously or intraperitoneally. We performed intratumoral distribution (ITD) studies, PET/CT imaging and quantification, biodistribution assay and radiation dosimetry, and therapeutic efficacy and toxicity studies.Results:Intraperitoneal administration was an efficient route for targeting 64Cu-RaftRGD to OCPMs with excellent tumor penetration. Using the fluorescence surrogate, Cy5.5-RaftRGD, in our unique high-resolution multifluorescence analysis, we found that the ITD of 64Cu-RaftRGD was spatially distinct from, but complementary to, that of hypoxia. 64Cu-RaftRGD–based PET enabled clear visualization of multiple OCPM deposits and ascites and biodistribution analysis demonstrated an inverse correlation between tumor uptake and tumor size (1.2–17.2 mm). 64Cu-RaftRGD at a radiotherapeutic dose (148 MBq/0.357 nmol) showed antitumor activities by inhibiting tumor cell proliferation and inducing apoptosis, with negligible toxicity.Conclusions:Collectively, these results demonstrate the all-in-one potential of 64Cu-RaftRGD for imaging guided radiotherapy of OCPM by targeting both tumoral neovessels and cancerous cells. On the basis of the ITD finding, we propose that pairing αVβ3- and hypoxia-targeted radiotherapies could improve therapeutic efficacy by overcoming the heterogeneity of ITD encountered with single-agent treatments.

Table S1-Post-PET biodistribution data of i.v.- and i.p.-administered 64Cu-RaftRGD in IGR-OV1-OCPM mice; Table S2-Biodistribution data of i.p.-administered 64Cu-RaftRGD; Table S3-Inverse regression equations; and Table S4-Estimation of human absorbed doses.

Supplementary Materials and Methods for integrin expression analysis, autoradiography, ITD of Cy5.5-RaftRGD in relation to the tumor microenvironment (in s.c. tumors), PET/CT or PET/CECT imaging and quantification, Ki-67 immunostaining, TUNEL assay, and quantification, survival study, and toxicity evaluation.

Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors that are rarely curable. αvβ3 integrin (αvβ3) is overexpressed on tumoral neovessels and frequently on ovarian cancer cells. Here, using two clinically relevant αvβ3-positive OCPM mouse models, we studied the theranostic potential of an αvβ3-specific radiopeptide, 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD), and its intra- and intertumoral distribution in relation to the tumor microenvironment.

Orthostatic hypotension (OH) is common in patients with Parkinson's disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD.This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET). According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively.CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

We have successfully developed 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD) as a multimeric RGD-based radiopeptide for specifically targeting the transmembrane cell adhesion receptor, alphaVbeta3 integrin (aVb3). Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors. Despite advances in surgical cytoreduction and drug development, the 5-year survival rate for OCPM patients remains as low as, SNMMI2021 Annual Meeting

Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors that are rarely curable. ααIntraperitoneal administration was an efficient route for targetingCollectively, these results demonstrate the all-in-one potential of

Glioblastoma is the most aggressive malignant brain tumor in humans and is difficult to cure using current treatment options. Hypoxic regions are frequently found in glioblastoma, and increased levels of hypoxia are associated with poor clinical outcomes of glioblastoma patients. Hypoxia plays important roles in the progression and recurrence of glioblastoma because of drug delivery deficiencies and induction of hypoxia-inducible factor-1α in tumor cells, which lead to poor prognosis. We focused on a promising hypoxia-targeted internal radiotherapy agent, 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), to address the need for additional treatment for glioblastoma. This compound can target the overreduced state under hypoxic conditions within tumors. Clinical positron emission tomography studies using radiolabeled Cu-ATSM have shown that Cu-ATSM accumulates in glioblastoma and its uptake is associated with high hypoxia-inducible factor-1α expression. To evaluate the therapeutic potential of this agent for glioblastoma, we examined the efficacy of 64Cu-ATSM in mice bearing U87MG glioblastoma tumors. Administration of single dosage (18.5, 37, 74, 111, and 148 MBq) and multiple dosages (37 MBq × 4) of 64Cu-ATSM was investigated. Single administration of 64Cu-ATSM in high-dose groups dose-dependently inhibited tumor growth and prolonged survival, with slight and reverse signs of adverse events. Multiple dosages of 64Cu-ATSM remarkably inhibited tumor growth and prolonged survival. By splitting the dose of 64Cu-ATSM, no adverse effects were observed. Our findings indicate that multiple administrations of 64Cu-ATSM have effective antitumor effects in glioblastoma without side effects, indicating its potential for treating this fatal disease.

Copper-67 (Cu) is one of the most promising radionuclides for internal radiation therapy. Globally, several projects have recently been initiated for developing innovative approaches for the large-scale production of Cu. Encouraged by these, we performed Cu-radiolabeling of a tetrameric cyclic Arg-Gly-Asp (cRGD) peptide conjugate, cyclam-RAFT-c(-RGDfK-)4, which selectively targets αVβ3 integrin (αVβ3), the transmembrane receptor involved in tumor invasion, angiogenesis, and metastasis. We also evaluated the therapeutic potential and safety of this radiocompound.Cu, produced through the Ni(α, p)Cu reaction, was used for the radiolabeling of cyclam-RAFT-c(-RGDfK-)4 at 70°C for 10 min. The radiolabeling efficiency and product stability were assessed using reversed-phase high-performance liquid chromatography and/or thin-layer chromatography. Mice with subcutaneous αVβ3-positive U87MG-glioblastoma xenografts received a single intravenous injection of one of the following: Cu-cyclam-RAFT-c(-RGDfK-)4 (11.1 MBq), peptide control, or vehicle solution. The tumor volumes were measured, side effects were assessed in terms of body weight, routine hematology, and hepatic and renal functions, and the mouse radiation dosimetry was estimated.Cu-cyclam-RAFT-c(-RGDfK-)4 was produced with a radiochemical purity of 97.9±2.4% and a specific activity of 2.7±0.6 MBq/nmol and showed high in-vitro and in-vivo plasma stability. The administration of a single dose of Cu-cyclam-RAFT-c(-RGDfK-)4 resulted in significant tumor growth delay in comparison with that observed upon vehicle or peptide control administration, with an estimated tumor-absorbed dose of 0.712 Gy. No significant toxicity was observed in Cu-cyclam-RAFT-c(-RGDfK-)4-treated mice.Cu-cyclam-RAFT-c(-RGDfK-)4 would be a promising therapeutic agent for αVβ3 integrin-targeted internal radiotherapy.

The present study aimed to examine whether positron emission tomography (PET) could evaluate cerebral angiogenesis. Mice were housed in a hypoxic chamber with 8–9% oxygen for 4, 7, and 14 days, and the angiogenic responses were evaluated with a radiotracer, 64Cu-cyclam-RAFT-c(-RGDfK-)4, which targeted αVβ3 integrin and was imaged with PET. The PET imaging results showed little uptake during all of the hypoxic periods. Immunofluorescence staining of the β3 integrin, CD61, revealed weak expression, while the microvessel density assessed by CD31 staining increased with the hypoxic duration. These observations suggest that the increased vascular density originated from other types of vascular remodeling, unlike angiogenic sprouting. We then searched for any signs of vascular remodeling that could be detected using PET. PET imaging of 11C-PK11195, a marker of the 18-kDa translocator protein (TSPO), revealed a transient increase at day 4 of hypoxia. Because the immunofluorescence of glial markers showed unchanged staining over the early phase of hypoxia, the observed upregulation of TSPO expression probably originated from non-glial cells (e.g. vascular cells). In conclusion, a transient increase in TSPO probe uptake was detected with PET at only the early phase of hypoxia, which indicates an early sign of vascular remodeling induced by hypoxia.

Background The present study proposed a new concept for targeted radionuclide therapy (TRT) to improve the intratumoral distribution of radioactivity using two different radiopharmaceuticals. We examined the efficacy of a combination of a tetrameric cyclic Arg-Gly-Asp (cRGD) peptide-based radiopharmaceutical, 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD, an αVβ3 integrin [αVβ3] tracer), and 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM, a supposed tracer for hypoxic metabolism) in a small animal tumor model. Results Mice with subcutaneous αVβ3-positive U87MG glioblastoma xenografts were used. The intratumoral distribution of a near-infrared dye, Cy5.5-labeled RAFT-c(-RGDfK-)4 (Cy5.5-RaftRGD), 64Cu-RaftRGD, and 64Cu-ATSM was visualized by fluorescence imaging and autoradiography of the co-injected Cy5.5-RaftRGD with 64Cu-RaftRGD or 64Cu-ATSM at 3 h postinjection. Mice were treated with a single intravenous dose of the vehicle solution (control), 18.5 or 37 MBq of 64Cu-RaftRGD or 64Cu-ATSM, or a combination (18.5 MBq of each agent). The tumor volume, tumor cell proliferation, body weight, survival, and tumor and organ uptake of radiopharmaceuticals were assessed. It was shown that Cy5.5-RaftRGD colocalized with 64Cu-RaftRGD and could be used as a surrogate for the radioactive agent. The intratumoral distribution of Cy5.5-RaftRGD and 64Cu-ATSM was discordant and nearly complementary, indicating a more uniform distribution of radioactivity achievable with the combined use of 64Cu-RaftRGD and 64Cu-ATSM. Neither 64Cu-RaftRGD nor 64Cu-ATSM showed significant effects on tumor growth at 18.5 MBq. The combination of both (18.5 MBq each) showed sustained inhibitory effects against tumor growth and tumor cell proliferation and prolonged the survival of the mice, compared to that by either single agent at 37 MBq. Interestingly, the uptake of the combination by the tumor was higher than that of 64Cu-RaftRGD alone, but lower than that of 64Cu-ATSM alone. The kidneys showed the highest uptake of 64Cu-RaftRGD, whereas the liver exhibited the highest uptake of 64Cu-ATSM. No obvious adverse effects were observed in all treated mice. Conclusions The combination of 64Cu-RaftRGD and 64Cu-ATSM achieved an improved antitumor effect owing to the more uniform intratumoral distribution of radioactivity. Thus, combining different radiopharmaceuticals to improve the intratumoral distribution would be a promising concept for more effective and safer TRT. Electronic supplementary material The online version of this article (10.1186/s13550-018-0407-3) contains supplementary material, which is available to authorized users.

Glioblastoma is the most aggressive malignant brain tumor in humans and is difficult to cure using current treatment options. Hypoxic regions are frequently found in glioblastoma, and increased levels of hypoxia are associated with poor clinical outcomes of glioblastoma patients. Hypoxia plays important roles in the progression and recurrence of glioblastoma because of drug delivery deficiencies and induction of hypoxia-inducible factor-1α in tumor cells, which lead to poor prognosis. We focused on a promising hypoxia-targeted internal radiotherapy agent, 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), to address the need for additional treatment for glioblastoma. This compound can target the overreduced state under hypoxic conditions within tumors. Clinical positron emission tomography studies using radiolabeled Cu-ATSM have shown that Cu-ATSM accumulates in glioblastoma and its uptake is associated with high hypoxia-inducible factor-1α expression. To evaluate the therapeutic potential of this agent for glioblastoma, we examined the efficacy of 64Cu-ATSM in mice bearing U87MG glioblastoma tumors. Administration of single dosage (18.5, 37, 74, 111, and 148 MBq) and multiple dosages (37 MBq × 4) of 64Cu-ATSM was investigated. Single administration of 64Cu-ATSM in high-dose groups dose-dependently inhibited tumor growth and prolonged survival, with slight and reverse signs of adverse events. Multiple dosages of 64Cu-ATSM remarkably inhibited tumor growth and prolonged survival. By splitting the dose of 64Cu-ATSM, no adverse effects were observed. Our findings indicate that multiple administrations of 64Cu-ATSM have effective antitumor effects in glioblastoma without side effects, indicating its potential for treating this fatal disease.

A kind of N-substituted maleimide - having two olefinic bonds with different reactivities, (S)-N-Maleoyl-L-leucine allyl ester ((S)-ALMI), was synthesized from maleic anhydride, L-leucine and allyl alcohol. Radical polymerizations were carried out to obtain optically active polymers using 2,2′-azobisisobutyronitrile. Structures of the monomer and polymers obtained were investigated by NMR measurements. In radical polymerizations, the solvents strongly affect the radical polymerization behaviors of (S)-ALMI.

Two kinds of cyanine dye were doped respectively in 4-cyano-4'-pentylbiphenyl (5CB) at a concentration ca. 1.0 wt%, and the mixture was sandwiched between two pieces of rubbed glass plates. The third-order nonlinear optical responses of cyanine dye-doped 5CB layers were measured for light polarized parallel to the oriented direction by the resonant femtosecond forward degenerate four-wave mixing technique at 820 nm. The time resolution of the system was ca. 0.3 ps. The amplified spontaneous emission spectra of cyanine dye-doped 5CB layers indicate that the decay of the slow response was accelerated with increasing laser power. The population grating disappears within ca. 5 ps.

Introduction The intratumoral distributions of [ 18 F]FDG and [ 64 Cu]Cu-ATSM have been reported to be similar in adenocarcinomas but different in squamous cell carcinoma (SCC) in clinical studies. In the present study, we compared the intratumoral distributions of these two tracers in cancer tissue originated spheroid (CTOS) xenografts derived from adenocarcinoma and SCC, which retain the histological characteristics of the original tumors, and in cancer cell line xenografts of corresponding origin, to investigate the underlying mechanism of the distinct FDG and Cu-ATSM distribution patterns in adenocarcinoma and SCC. Methods CTOSs derived from colon adenocarcinoma and lung SCC and cell lines established from colon adenocarcinoma and lung SCC, which were used for comparison, were subcutaneously transplanted into immunodeficient mice. One hour after administering [ 14 C]FDG and [ 64 Cu]Cu-ATSM, the intratumoral distributions were compared in the xenografts by using dual-tracer autoradiography. Adjacent sections were evaluated for necrosis, vasculature anatomy, Ki-67 antigen, and pimonidazole adducts using hematoxylin and eosin and immunohistochemical staining. Results There was a higher regional overlap of high FDG and Cu-ATSM accumulations in the adenocarcinoma CTOS xenografts than in the SCC CTOS xenografts, while the overlap in the adenocarcinoma cell line xenograft was lower than that observed in the SCC cell line. High FDG accumulation occurred primarily in proximity to necrotic or pimonidazole adduct positive regions, while high Cu-ATSM accumulation occurred primarily in live cell regions separate from the necrotic regions. The adenocarcinoma CTOS xenograft had the stereotypical glandular structure, resulting in more intricately mixed regions of live and necrotic cells compared to those observed in the SCC CTOS or the cell line xenografts. Conclusion Tumor morphological characteristics, specifically the spatial distribution of live and necrotic cell regions, appeared to be one of the most critical factors determining the regional overlap of FDG and Cu-ATSM distributions in adenocarcinoma.

Aiming at the overshoot problem of electro-hydraulic position servo system used in the process of railway rescue crane hydraulic automatic leveling, and based on its characteristics such as big output power, high control accuracy, quick response speed, et al, this paper established the linear mathematical model of railway rescue crane electro-hydraulic automatic leveling system, besides, the fractional order PID control method was proposed based on the oustaloup digital filter algorithm and the working principle of fractional order PID control method was given, and then the fractional order PID controller was designed. In order to verify the effectiveness of the proposed control strategy, the MATLAB/Simulink simulation software was used. The simulation results show that the fractional order PID controller improved the speed of electro-hydraulic servo system unit step response and the capacity of resisting disturbance compared to traditional integer order PID controller, besides it can ensure the response without overshoot at the same time, so it meets the requirements for rapidity and no overshoot of railway rescue crane hydraulic automatic leveling system very well.

Background The purpose of the current study was to investigate the long-term clinical outcomes of this technique for degenerative scoliosis (DS). Methods The records of 95 consecutive patients with DS who underwent selective segmental transforaminal interbody fusion combined with posterior-instrumented spinal fusion in our department from January 1999 to December 2007 were analysed retrospectively. Average follow-up was 7.8 years. Recorded clinical outcomes included Oswestry Disability Index (ODI), visual analogue scale (VAS) pain scores and overall patient satisfaction. Radiographic measurements included coronal Cobb angle, apical vertebra translation, Nash–Moe grade, lumbar lordosis (LL) and thoracolumbar kyphosis. Comparison of the clinical and radiographic parameters before surgery and at final follow-up was studied. Linear correlation analysis was applied to analyse the relationship between the clinical and radiological results. Results Average ODI and VAS pain scores were significantly improved at final follow-up compared with baseline (P = 0.038; P = 0.005). Specifically, the average ODI score was 32.2 ± 8.6 before surgery and 11.1 ± 6.8 at final follow-up; the average VAS score was 8.9 ± 2.0 before surgery and 2.0 ± 1.2 at final follow-up; patient satisfaction was 88.2% (84/95) at final follow-up. In addition, Cobb angle, apical vertebra translation and Nash–Moe grade were all statistically significantly decreased compared with preoperative values (P = 0.019; P = 0.035; P = 0.001). Although LL had significantly increased (P = 0.022), thoracolumbar kyphosis did not exhibit a significant change (P = 0.64). There was significant correlation between LL and decreased ODI scores (r = 0.62, P = 0.01). Eleven patients (11.6%) underwent reoperation during the study period. Conclusion Selective segmental transforaminal interbody fusion combined with posterior-instrumented spinal fusion appears to have reasonable long-term clinical and radiographic outcomes for the treatment of DS.

(64)Cu-cyclam-RAFT-c(-RGDfK-)4, an αVβ3 integrin-targeting tetrameric cyclic RGD peptide probe, is a potential theranostic compound for positron emission tomography (PET) of tumor angiogenesis and for internal radiotherapy owing to the multiple decay modes of (64)Cu. Since kidneys are dose-limiting organs in internal radiotherapy, we aimed to reduce the renal accumulation of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 by co-injection with Gelofusine (GF), a succinylated gelatin solution, and/or L-lysine (Lys), and to explore, for the first time, the related mechanisms using the noninvasive and quantitative PET imaging technology. Biodistribution assays, dynamic and static PET scans, and metabolism studies with radio-thin-layer chromatography (radio-TLC) were performed in healthy or αVβ3-positive tumor-bearing mice. In the results, co-injection with GF markedly reduced the renal uptake and slightly increased the tumor uptake of (64)Cu-cyclam-RAFT-c(-RGDfK-)4. L-Lysine alone had no effect on the probe biodistribution, but the combined use of Lys and GF tended to enhance the effect of GF. Dynamic PET and metabolite analysis by radio-TLC highly revealed that GF blocks the renal reabsorption of (64)Cu-cyclam-RAFT-c(-RGDfK-)4, but does not interfere with its metabolism and excretion. In conclusion, administration of GF and Lys is a useful strategy for kidney protection in (64)Cu-cyclam-RAFT-c(-RGDfK-)4-based internal radiotherapy.

Oncoimaging using positron emission tomography (PET) with a specific radioprobe would facilitate individualized cancer management. Evidence indicates that ectopically expressed metabotropic glutamate 1 (mGlu1) receptor independently induces melanocyte carcinogenesis, and it is therefore becoming an important target for personalized diagnosis and treatment strategies for melanomas. Here, we report the development of an oncoprotein-based PET imaging platform in melanomas for noninvasive visualization and quantification of mGlu1 with a novel mGlu1-specific radioprobe, 4-(18)F-fluoro-N-[4-[6-(isopropyl amino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ((18)F-FITM). (18)F-FITM shows excellent pharmacokinetics, namely the dense and specific accumulation in mGlu1-positive melanomas versus mGlu1-negative hepatoma and normal tissues. Furthermore, the accumulation levels of radioactivity corresponded to the extent of tumor and to levels of mGlu1 protein expression in melanomas and melanoma metastasis. The (18)F-FITM PET imaging platform, as a noninvasive personalized diagnostic tool, is expected to open a new avenue for defining individualized therapeutic strategies, clinical trials, patient management and understanding mGlu1-triggered oncologic events in melanomas.

Automatic leveling system used in railway rescue crane has characteristics such as time variance, nonlinearity and strong interference, which bring a variety of difficulties in control process into existence. This paper introduces the working principle and mathematical model of automatic leveling system used in railway rescue crane. A fuzzy PID controller based on fuzzy logic control algorithm and conventional PID algorithm is designed, MATLAB simulation results show that the effectiveness of the proposed fuzzy PID controller, and the fuzzy PID control strategy has better effect on the automatic leveling system used in railway rescue crane.

Stretch-oriented chrysophenine-doped poly(vinyl alcohol) (PVA) films were prepared at temperatures above the glass transition temperature of PVA. The optical absorption spectra of the stretch-oriented films exhibited a very high anisotropy (anisotropy ratio = 13). The third-order nonlinear optical properties of chrysophenine in stretch-oriented PVA films were measured by the resonant femtosecond degenerate four-wave mixing (DFWM) technique. The anisotropy ratio of the DFWM signal intensity was greater than 1000. The value of third-order nonlinear optical susceptibility of a uniaxially stretch-oriented chrysophenine-doped PVA film was 6.9×10-13 esu.

According to the characteristics and requirements of NCT processing system, deeper research was done on the system. The three-module design has been completed based on motion controller. The first module is completed on the design of panel, key position, machine functions and coding circuit; the second module is mainly accomplished on the tool-path generation, tool adapter and program development; the last module is used to verify the NC codes. Thus the NCT processing system is improved effectively.

The transmembrane cell adhesion receptor αVβ3 integrin (αVβ3) has been identified as an important molecular target for cancer imaging and therapy. We have developed a tetrameric cyclic RGD (Arg-Gly-Asp) peptide–based radiotracer 64Cu-cyclam-RAFT-c(-RGDfK-)4, which successfully captured αVβ3-positive tumors and angiogenesis by PET. Here, we subsequently evaluated its therapeutic potential and side effects using an established αVβ3-positive tumor mouse model. Mice with subcutaneous U87MG glioblastoma xenografts received single administrations of 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4 (37 MBq/nmol), peptide control, or vehicle solution and underwent tumor growth evaluation. Side effects were assessed in tumor-bearing and tumor-free mice in terms of body weight, routine hematology, and hepatorenal functions. Biodistribution of 64Cu-cyclam-RAFT-c(-RGDfK-)4 with ascending peptide doses (0.25–10 nmol) and with the therapeutic dose of 2 nmol were determined at 3 hours and at various time points (2 minutes–24 hours) postinjection, respectively, based on which radiation-absorbed doses were estimated. The results revealed that 64Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently slowed down the tumor growth. The mean tumor doses were 1.28 and 1.81 Gy from 37 and 74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4, respectively. Peptide dose study showed that the tumor uptake of 64Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently decreased at doses ≥1 nmol, indicating a saturation of αVβ3 with the administered therapeutic doses (1 and 2 nmol). Combined analysis of the data from tumor-bearing and tumor-free mice revealed no significant toxicity caused by 37–74 MBq of 64Cu-cyclam-RAFT-c(-RGDfK-)4. Our study demonstrates the therapeutic efficacy and safety of 64Cu-cyclam-RAFT-c(-RGDfK-)4 for αVβ3-targeted radionuclide therapy. 64Cu-cyclam-RAFT-c(-RGDfK-)4 would be a promising theranostic drug for cancer imaging and therapy. Mol Cancer Ther; 15(9); 2076–85. ©2016 AACR.

The removal of undesired chlorinated hydrocarbon contaminants through chemical destruction using ex situ Pd-based catalytic or in situ Fe-based reductive nanomaterials offers unique advantages over current physical displacement methods for groundwater treatment. While these two types of chemical methods has been studied in-depth in recent years, their respective hydrodechlorination and dechlorination transformations have not been analyzed together before. Here, the reactivities of Pd catalysts and Fe reductants were experimentally assessed for trichloroethene (TCE) degradation using room-temperature, atmospheric-pressure, dihydrogen-headspace-filled batch reactor studies under buffered and non-buffered conditions. Pseudo-first order reaction rate constants at pH 7 spanned 9 decades: 1.2 × 104, 1.0 × 103, 4.5 × 102, 2.41 × 10−4, 4.2 × 10−4, and 7.09 × 10−6 L/gactive-metal/min for Pd-on-Au nanoparticles (Pd/Au NPs), Pd NPs, Pd-on-alumina powder, and two nano-sized forms and one micron-sized form of commercial zerovalent iron, respectively. With rates measured in the range of commonly reported values, the Fe-based materials produced ethane, ethene, and vinyl chloride; ethene hydrogenated into ethane at sufficiently long reaction times. The much more active Pd-based materials produced ethane as the primary TCE degradation reaction product. This study presents, for the first time, a quantitative comparison of TCE degradation rates determined under identical experimental conditions.

Although lasing has been observed in the solid state for numerous organic molecules emitting at visible wavelengths, this is few case in the infrared. We show amplified spontaneous emission (ASE) in the near infrared (913-930 nm) from the layer of a cyanine dye-doped 4-cyano-4'-pentylbiphenyl (5CB) for laser power above 0.08 GW/cm2, the layer was prepared with the solution of 1,1',3,3,3',3'- hexamethyl-4,4',5,5'-di-benzo-2,2'-indotricarbocyanine perchlorate (NK-2014) dissolved in 5CB. Oriented NK-2014 molecules in nematic liquid crystal (NLC) must have very high amplified spontaneous emission efficiency.

Stretch-oriented cyanine-dye-doped poly(vinyl alcohol) (PVA) films were prepared at temperatures above the glass transition temperature of PVA. The optical absorption spectra of the stretch-oriented films exhibited an anisotropy. The third-order nonlinear optical susceptibilities of the stretch-oriented films were measured parallel and perpendicular to the stretching direction by the resonant femtosecond degenerate four-wave mixing (DFWM) technique, and a high anisotropic X(3) was observed for the uniaxially stretch-oriented cyanine-dye-doped PVA films.