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Sample records for high tumor uptake

  1. Reassessment of FDG uptake in tumor cells: High FDG uptake as a reflection of oxygen-independent glycolysis dominant energy production

    Energy Technology Data Exchange (ETDEWEB)

    Waki, A.; Fujibayashi, Y.; Yonekura, Y.; Sadato, N.; Ishii, Y.; Yokoyama, A

    1997-10-01

    To determine appropriate use of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) in the diagnosis of malignant tumors, the mechanism of enhanced FDG uptake in tumor cells was reassessed using in vitro cultured cell lines and {sup 3}H-deoxyglucose (DG), in combination with possible parameters of aerobic and anaerobic energy production. The high DG uptake in the tumor cells reflected the dependency of energy production on anaerobic glycolysis, and paradoxically on low levels of aerobic oxidative phosphorylation in mitochondria. We discuss here factors underlying anaerobic glycolysis in tumor cells.

  2. Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery.

    Science.gov (United States)

    Xu, Leyuan; Yeudall, W Andrew; Yang, Hu

    2017-07-15

    The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic siRNA against green fluorescent protein (siGFP)), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies. In particular, two doses of G4-FA/siVEGFA i.t. administered eight days apart resulted in a more profound inhibition of tumor growth, accompanied with significant reduction in angiogenesis, as judged by CD31 staining and microvessel counts. Tumor size reduction in the two-dose regimen study was ascertained semi-quantitatively by live fluorescence imaging of YFP tumors and independently supported antitumor effects of G4-FA/siVEGFA. Taken together, G4-FA shows high tumor uptake and sustained retention properties, making it a suitable platform for local delivery of siRNAs to treat cancers that are readily accessible such as HNSCC. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is difficult to transfect for gene therapy. We developed folate receptor (FR)-targeted polyamidoamine (PAMAM) dendrimer for enhanced delivery of genes to HNSCC and gained in-depth understanding of how gene delivery and transfection in head and neck squamous cancer cells can be enhanced via FR-targeted PAMAM dendrimers. The results we report here are encouraging and present latest advances in using dendrimers for cancer therapies, in particular for HNSCC. Our work has demonstrated that localized delivery of FR

  3. Correlation of histopathological factor of brain tumor and high thallium-201 uptake in single photon emission computed tomography

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Moritake, Takashi; Yamamoto, Tetsuya; Takano, Shingo; Tsuboi, Koji; Hyodo, Akio; Nose, Tadao; Satou, Motohiro

    1996-01-01

    This study was undertaken to investigate the relationship between several histological features and the degree of Tl-201 uptake in brain tumors. Tl-201 SPECT was performed on 52 patients with intracranial lesions. Histological examinations were carried out to determine the gradation of tumor cell density, vascularization, small-cell density, and matrix loosening, and the presence of necrosis, atypia, mitoses, and endothelial proliferation. The histological findings were classified into three categories. While the early uptake of Tl-201 depended on the degree of necrosis of glial tumor, the delayed Tl-201 uptake was closely related to the degree of necrosis, tumor cell density, and small-cell density, and may thus be of value for estimating the viability and degree of malignancy of glial tumors. In the non-glial tumors, the early and delayed Tl-201 uptakes were closely related to all histological parameters, with the increase of necrosis and vascularization in the tumor tissue being particularly closely related to high uptake levels. (author)

  4. Tumor uptake of radioruthenium compounds

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Richards, P.; Meinken, G.E.; Larson, S.M.; Grunbaum, Z.

    1980-01-01

    The use of ruthenium-97 as a scintigraphic agent, particularly for tumor localization, is investigated. The tumor uptake of ruthenium chloride and ruthenium-labelled transferrin is evaluated and their application as tumor-imagine agents is compared to gallium-67 citrate

  5. Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

    Science.gov (United States)

    Zhang, Xiao-Dong; Luo, Zhentao; Chen, Jie; Song, Shasha; Yuan, Xun; Shen, Xiu; Wang, Hao; Sun, Yuanming; Gao, Kai; Zhang, Lianfeng; Fan, Saijun; Leong, David Tai; Guo, Meili; Xie, Jianping

    2015-03-01

    Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au29-43(SG)27-37 nanoclusters (protecting shell. The GSH-coated Au29-43(SG)27-37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29-43(SG)27-37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.

  6. Radiocolloid Uptake in the Pancreas Islet Cell Tumor: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Yang, W. J.; Chung, S. K.; Yeon, S. K.; Shinn, K. S.; Bahk, Y. W. [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-03-15

    Colloid uptake in various hepatic conditions such as focal nodular hyperplasia, regenerating nodular in the cirrhotic liver, hamartoma, hemangioma and rarely hepatoma has been documented. Extrahepatic tumors may show colloid uptake and they include splenic hemangioma, malignant fibrous histiocytoma, breast carcinoma and Kaposi's sarcoma. The mechanism of colloid uptake in those lesions is associated with phagocytic activity in or around the tumors. We report a pancreas islet cell tumor that showed colloid uptake on {sup 99m}Tc-phytate liver scan without histologic evidence of phagocytosis by tumor cells or infiltration of phagocytes in the tumor. Microscopically the tumor was highly vascular and showed diffuse hemorrhage throughout the tumor. We postulated that extravasation of the colloid into the tumor interstitium caused nonspecific colloid uptake in this tumor. It is expected that hemorrhagic tumor may show nonspecific colloid uptake without phagocytosis in or about the lesion.

  7. Radiocolloid Uptake in the Pancreas Islet Cell Tumor: Case Report

    International Nuclear Information System (INIS)

    Yang, W. J.; Chung, S. K.; Yeon, S. K.; Shinn, K. S.; Bahk, Y. W.

    1994-01-01

    Colloid uptake in various hepatic conditions such as focal nodular hyperplasia, regenerating nodular in the cirrhotic liver, hamartoma, hemangioma and rarely hepatoma has been documented. Extrahepatic tumors may show colloid uptake and they include splenic hemangioma, malignant fibrous histiocytoma, breast carcinoma and Kaposi's sarcoma. The mechanism of colloid uptake in those lesions is associated with phagocytic activity in or around the tumors. We report a pancreas islet cell tumor that showed colloid uptake on 99m Tc-phytate liver scan without histologic evidence of phagocytosis by tumor cells or infiltration of phagocytes in the tumor. Microscopically the tumor was highly vascular and showed diffuse hemorrhage throughout the tumor. We postulated that extravasation of the colloid into the tumor interstitium caused nonspecific colloid uptake in this tumor. It is expected that hemorrhagic tumor may show nonspecific colloid uptake without phagocytosis in or about the lesion.

  8. Dependence of FDG uptake on tumor microenvironment

    International Nuclear Information System (INIS)

    Pugachev, Andrei; Ruan, Shutian; Carlin, Sean; Larson, Steven M.; Campa, Jose; Ling, C. Clifton; Humm, John L.

    2005-01-01

    Purpose: To investigate the factors affecting the 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake in tumors at a microscopic level, by correlating it with tumor hypoxia, cellular proliferation, and blood perfusion. Methods and Materials: Nude mice bearing Dunning prostate tumors (R3327-AT) were injected with 18 F-FDG and pimonidazole, bromodeoxyuridine, and, 1 min before sacrifice, with Hoechst 33342. Selected tumor sections were imaged by phosphor plate autoradiography, while adjacent sections were used to obtain the images of the spatial distribution of Hoechst 33342, pimonidazole, and bromodeoxyuridine. The images were co-registered and analyzed on a pixel-by-pixel basis. Results: Statistical analysis of the data obtained from these tumors demonstrated that 18 F-FDG uptake was positively correlated with pimonidazole staining intensity in each data set studied. Correlation of FDG uptake with bromodeoxyuridine staining intensity was always negative. In addition, FDG uptake was always negatively correlated with the staining intensity of Hoechst 33342. Conclusions: For the Dunning prostate tumors studied, FDG uptake was always positively correlated with hypoxia and negatively correlated with both cellular proliferation and blood flow. Therefore, for the tumor model studied, higher FDG uptake is indicative of tumor hypoxia, but neither blood flow nor cellular proliferation

  9. Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

    Directory of Open Access Journals (Sweden)

    Rachel Tréhin

    2006-04-01

    Full Text Available Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP tumors, mean overestimations of 2 and 24 µm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon and primary (Gli36 glioma brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

  10. Can tumor uptake Tc-99m MDP

    International Nuclear Information System (INIS)

    Yang, Y.S.F.; Zeng, Z.J.; Yao, Y.M.; Shi, S.M.P.; Shi, S.Z.Y.

    2002-01-01

    Aim: To study a distribution of Tc-99m MDP in mice bearing tumor cell lines. Methods: The uptake of Tc-99m MDP was analyzed in seven human tumor cell lines (SPC-A1 adenocarcinoma of lung cancer, P37 Breast cancer, T24 Bladder cancer, SKOV2 Ovary carcinoma, Hela-229 Cervical carcinoma, Osteosarcoma, A375 Melanoma) and one mouse lung cancer cell line (Lewis). They were transplanted into 13, 4, 5, 5, 4, 5 athymic mice, 6 SCID nude mice and 4 C57 black mice, respectively. Approximately 10(7) cells of each cell line were injected subcutaneously into a right chest of mouse. After 5∼6 weeks, the Tc-99m MDP scintigraphy were determined 5-6 hours after i.v. injection of 74MBq in 0.05ml every mouse. Result: Biodistribution and tumor uptake MDP was different in the various cell types investigated. Region of interests (RIOs) placed on a small part of the tumor and horizontal copied to left chest or spine of mice in Tc-99m MDP imaging and the average count ratio (tumor to background ratio: T/B, tumor to spine ratio: T/NT) in each ROI was calculated. 13 nude mice bearing the adenocarcinoma (SPC-A1) were sacrificed and biodistribution was determined after Tc-99m MDP scintigraphy. Results were expressed as % injected dose/gram (%ID/g), mean±SD. T-ulcer=ulcer of tumor, T-round=surrounding of tumor, T-center=the center of tumor, Thor-sp=thoracic spine, Lum-ver=lumbar vertebra, LN=lymph node. Conclusions: Tumor can uptake Tc-99m MDP including adenocarcinoma. Higher uptake rate in the center tissue of tumor is than other part of tumor. It maybe connected with necrosis or fibrosis of tumor

  11. 16α-[77Br]bromoestradiol-17β: a high specific-activity, gamma-emitting tracer with uptake in rat uterus and induced mammary tumors

    International Nuclear Information System (INIS)

    Katzenellenbogen, J.A.; Senderoff, S.G.; McElvany, K.D.; O'Brien, H.A. Jr.; Welch, M.J.

    1981-01-01

    16α-[ 77 Br]bromoestradiol-17β (compound 1) has been synthesized by radiobromination of estrone enoldiacetate. Tissue uptake studies performed 1 hr after administration of compound 1 to immature or mature female rats showed uterus-to-blood ratios of 13, with nontarget tissue-to-blood ratios ranging from 0.6 to 2. Co-administration of unlabeled estradiol caused a selective depression in the uterine uptake with no effect on nontarget tissue uptake. In adult animals bearing adenocarcinomas induced by DMBA (7,12-dimethylbenz(a)anthracene), tumor-to-blood ratios of 6.3 were obtained, this uptake also being depressed in animals treated with unlabeled estradiol. The studies demonstrate that compound 1 has suitable binding properties and sufficiently high specific activity so that its uptake in estrogen target tissues in vivo is mediated primarily by the estrogen receptor. Furthermore, they suggest that this compound may be suitable for imaging human breast tumors that contain estrogen receptors

  12. 16 alpha-[77Br]bromoestradiol-17 beta: a high specific-activity, gamma-emitting tracer with uptake in rat uterus and uterus and induced mammary tumors

    International Nuclear Information System (INIS)

    Katzenellenbogen, J.A.; Senderoff, S.G.; McElvany, K.D.; O'Brien, H.A. Jr.; Welch, M.J.

    1981-01-01

    16 alpha-[77Br]bromoestradiol-17 beta (Compound 1) has been synthesized by radiobromination of estrone enoldiacetate. Tissue uptake studies performed 1 h after administration of Compound 1 to immature or mature female rats showed uterus-to-blood ratios of 13, with nontarget issue-to-blood ratios ranging from 0.6 to 2. Co-administration of unlabelled estradiol caused a selective depression in the uterine uptake with no effect on nontarget tissue uptake. In adult animals bearing adenocarcinomas induced by DMBA (7,12-dimethylbenz(a)anthracene), tumor-to-blood ratios of 6.3 were obtained, this uptake also being depressed in animals treated with unlabeled estradiol. The studies demonstrate that Compound 1 has suitable binding properties and sufficiently high specific activity so that its uptake in estrogen target tissues in vivo is mediated primarily by the estrogen receptor. Furthermore, they suggest that this compound may be suitable for imaging human breast tumors that contain estrogen receptors

  13. Can tumor uptake Tc-99m MDP ?

    International Nuclear Information System (INIS)

    Yand Shun, Fang; Yao, Ming; Zeng, Jun; Shi Zhen, Yu; Zhao Lan, Xiang; Dong Qiang, Gang

    2003-01-01

    To explore the mechanism of technetium-99m-methylene diphosphonate (MDP) uptake within tumor through analyze a distribution of Tc-99m MDP in mice bearing tumor cell lines. Methods: The uptake of Tc-99m MDP was analyzed in seven human tumor cell lines ( SPC-A1 adenocarcinoma of lung cancer, Bcap-37 Breast cancer, T-24 Bladder cancer, SKOV3 Ovary carcinoma, Hela-229 Cervical carcinoma, SCI-OS Osteosarcoma, SCI-375 Melanoma) and mouse Lewis lung cancer cell line. They were transplanted into athymic mice, SCID nude mice and C57BL/6 mice, respectively. Approximately 10(6) cells of each cell line were injected subcutaneously into a right chest of mouse. After 4 and 5 weeks, the Tc-99m MDP scintigraphy were determined 6 hours after tail vein injection of 74MBq in 0.05ml every mouse. Result: Biodistribution and tumor uptake MDP was different in the various cell types investigated. According to the Region Ratio program of Siemens Power Macintosh 9500 Computer System, region of interests (RIOs) placed on a small part of the tumor and horizontal copied to left background (T/B) and thoracic spine (T/N) of mice in Tc-99m MDP imaging. The average cpm/pixel ratios were calculated by standardized uptake measure (SUM) and determined the tumor-positive value (T/B) greater than or equal to 1.2. T/B of cell lines were sorted from higher to lower as follows: SCI-OS, Lewis, SKOV3, SCI-375, T-24, SPC-A1, Bcap-37, Hela-229. T/N: SCI-OS, SKOV3, T-24, SCI-375, Lewis, SPC-A1, Bcap-37, Hela-229. The biodistribution data of 99Tcm-MDP in SPC-A1 tumor-bearing BALB/c nude mice were given as ID/g and represent the means D (n=13) in 30 hours after injection of Tc-99m MDP. ID/g of major tissue were sorted from higher to lower as follows: thoracic spine, lumbar, ribs, kidneys, the center of tumor, the ulcer of tumor, the surrounding of tumor, lymph node, blood, lungs, heart, liver. Conclusions: Most of tumor can uptake Tc-99m MDP including human adenocarcinoma. The uptake rate in the center tissue of

  14. Physiological and tumoral uptake of 68Ga-DOTATATE. Standardized uptake values and challenges in interpretation

    International Nuclear Information System (INIS)

    Kuyumcu, Serkan; Oezkan, Zeynep Goezde; Sanli, Yasemin; Yilmaz, Ebru; Mudun, Ayse; Adalet, Isik; Unal, Seher

    2013-01-01

    The objective of this study is to determine the range of standardized uptake value (SUV) max of 68Ga-DOTA-tyr3-octreotate (DOTATATE) in normal organs and tumoral lesions and establish uptake unrelated to neuroendocrine tumors (NET). One hundred and twenty patients (57 men, 63 women), who underwent 68 Ga-DOTATATE positron emission tomography (PET)/CT imaging in our institution were analyzed. Patients were indicated for 68 Ga-DOTATATE PET/CT imaging to detect primary tumor or metastasis of suspected or previously known NET, to determine somatostatin receptor (SSTR) positivity and to detect occult source of ectopic Cushing syndrome. Normal range of uptake was calculated for the organs that were proven to have no pathology by either conventional radiological imaging or clinical follow-up, using SUV max as a semiquantitative measure. Uptake and tumor to background (T/B) ratios of tumoral lesions in liver, pancreas, bone, brain and lymph nodes were calculated. Uptakes due to lesions unrelated to NET were also documented. Significant uptake was found in spleen, kidneys, adrenal glands, liver and pituitary gland with mean SUV max of 24.67, 14.30, 13.73, 9.12 and 9.74 respectively. Uptake was measured separately for the pancreatic head and body separately, however, besides a slightly heterogeneous uptake; the difference was not statistically significant. Uptake in the tumoral lesions had high (T/B) ratios with mean SUV max of 28.72, 25.21, 18.28, 34.73 and 12.59 for liver, pancreas, bone, brain and lymph nodes, respectively. Incidental benign tumoral lesions were detected in 3 patients (2.5%) which were meningioma and fibrous dysplasia demonstrating significant and breast fibroadenoma demonstrating mild 68 Ga-DOTATATE uptake. Non-neoplastic processes were detected in 4 patients (14.1%), including postsurgical inflammation, reactive lymph nodes, arthritis and demonstrated faint to mild 68 Ga-DOTATATE uptake, with the exception of significant uptake in accessory spleen. 68 Ga

  15. Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor Recurrence.

    Science.gov (United States)

    Matsui, Yusuke; Horikawa, Masahiro; Jahangiri Noudeh, Younes; Kaufman, John A; Kolbeck, Kenneth J; Farsad, Khashayar

    2017-12-01

    The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence ( P = 0.001 and Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.

  16. Quantification of radionuclide uptake levels for primary bone tumors

    Directory of Open Access Journals (Sweden)

    Hasford Francis

    2015-04-01

    Full Text Available The purpose of the study is to quantify the level of uptake of administered radionuclide in primary bone tumors for patients undergoing bone scintigraphy. Retrospective study on 48 patient's scintigrams to quantify the uptake levels of administered radiopharmaceuticals was performed in a nuclear medicine unit in Ghana. Patients were administered with activity ranging between 0.555 and 1.110 MBq (15–30 mCi, and scanned on Siemens e.cam SPECT system. Analyses on scintigrams were performed with Image J software by drawing regions of interest (ROIs over identified hot spots (pathologic sites. Nine skeletal parts namely cranium, neck, shoulder, sacrum, sternum, vertebra, femur, ribcage, and knee were considered in the study, which involved 96 identified primary tumors. Radionuclide uptakes were quantified in terms of the estimated counts of activity per patient for identified tumor sites. Average normalized counts of activity (nGMC per patient ranged from 5.2759 ± 0.6590 cts/mm2/MBq in the case of cranium tumors to 72.7569 ± 17.8786 cts/mm2/MBq in the case of ribcage tumors. The differences in uptake levels could be attributed to different mechanisms of Tc-99m MDP uptake in different types of bones, which is directly related to blood flow and degree of osteoblastic activity. The overall normalized count of activity for the 96 identified tumors was estimated to be 23.0350 ± 19.5424 cts/mm2/MBq. The study revealed highest uptake of activity in ribcage and least uptake in cranium. Quantification of radionuclide uptakes in tumors is important and recommended in assessing patient's response to therapy, doses to critical organs and in diagnosing tumors.

  17. Tumor grade-related thallium-201 uptake in chondrosarcomas

    International Nuclear Information System (INIS)

    Kaya, G.C.; Demir, Y.; Ozkal, S.

    2010-01-01

    Diagnosis of low-grade chondrosarcoma, especially discrimination between enchondroma and low-grade chondrosarcoma, may be difficult pathologically. The aim of this study was to evaluate the value of thallium-201 (Tl-201) scintigraphy in the diagnosis of chondrosarcoma and to investigate whether there was a correlation between Tl-201 uptake and tumor grade. We retrospectively evaluated 121 patients with pathologically proven bone and soft tissue tumors diagnosed between the years 1999 and 2007. All patients were followed by the Bone and Soft Tissue Tumor Working Group in our hospital. Twenty-three patients, mean age 44±15 (range 17-72) years, with a diagnosis of cartilaginous tumors were included. Increased Tl-201 uptake at the lesion sites greater than background was evaluated as malignant tumor. For the pathologic classification, a grading system (grade 1-3) based on the histopathologic findings was used. Pearson correlation coefficient was used to determine whether there was any correlation between Tl-201 uptake and tumor grade in chondrosarcoma. There were 7 enchondromas and 16 chondrosarcomas. Four of 16 patients with chondrosarcoma had lesions pathologically classified as grade 3, 5 as grade 2, and 7 had grade 1 chondrosarcoma. Increased Tl-201 uptake was observed in all patients with grade 3 chondrosarcoma and 2 patients with grade 2 chondrosarcoma. Of 10 patients with chondrosarcoma, 3 grade 2 chondrosarcomas and 7 grade 1 chondrosarcomas, there was no Tl-201 uptake in the tumor region. A significant correlation was found between Tl-201 uptake and tumor grade in chondrosarcoma (p=0.002, r=0.71). Only a few reports in literature have demonstrated false negative results in low-grade chondrosarcoma. Tl-201 uptake was related to tumor grade in chondrosarcoma. If there is a possibility of chondrosarcoma, Tl-201 scintigraphy should be reported with caution. (author)

  18. Relation between the location of elements in the periodic table and tumor-uptake rate

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A; Ando, I; Hiraki, T; Hisada, K

    1985-01-01

    The bipositive ions and anions, with few exceptions, indicated a low tumor uptake rate. On the other hand, compounds of Hg, Au and Bi, which have a strong binding power to protein, showed a high tumor uptake rate. As Hg/sup 2 +/, Au/sup +/ and Bi/sup 3 +/ are soft acids according to the classification of Lewis acids, it was thought that these ions would bind strongly to soft bases (R-SH, R-S-) present in tumor tissue. For many hard acids such as /sup 85/Sr/sup 2 +/, /sup 67/Ga/sup 3 +/, /sup 181/Hf/sup 4 +/, and /sup 95/Nb/sup 5 +/, tumor uptake rates are shown as a function of ionic potentials of the metal ions. Considering the present data and previously reported results, it was presumed that hard acids of trivalence, quadrivalence and pentavalence would replace calcium in the calcium salts of hard bases. Ionic potentials of alkaline metals and Tl were small, but the tumor-uptake rate of these elements indicated various values. As Ge and Sb are bound by covalent bonds to chloride, GeCl/sub 4/ and SbCl/sub 3/ behaved differently from many metallic compounds in tumor tissue.

  19. Relation between the location of elements in the periodic table and tumor-uptake rate.

    Science.gov (United States)

    Ando, A; Ando, I; Hiraki, T; Hisada, K

    1985-01-01

    The bipositive ions and anions, with few exceptions, indicated a low tumor uptake rate. On the other hand, compounds of Hg, Au and Bi, which have a strong binding power to protein, showed a high tumor uptake rate. As Hg2+, Au+ and Bi3+ are soft acids according to the classification of Lewis acids, it was thought that these ions would bind strongly to soft bases (R-SH, R-S-) present in tumor tissue. For many hard acids such as 85Sr2+, 67Ga3+, 181Hf4+, and 95Nb5+, tumor uptake rates are shown as a function of ionic potentials (valency/ionic radii) of the metal ions. Considering the present data and previously reported results, it was presumed that hard acids of trivalence, quadrivalence and pentavalence would replace calcium in the calcium salts of hard bases (calcium salts of acid mucopolysaccharides, etc.). Ionic potentials of alkaline metals and Tl were small, but the tumor-uptake rate of these elements indicated various values. As Ge and Sb are bound by covalent bonds to chloride, GeCl4 and SbCl3 behaved differently from many metallic compounds in tumor tissue.

  20. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  1. A mechanistic compartmental model for total antibody uptake in tumors.

    Science.gov (United States)

    Thurber, Greg M; Dane Wittrup, K

    2012-12-07

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Radioiodine-labeled disulfide: a novel radiotracer for evaluation of tumor uptake

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, E. K.; Choi, Y. S.; Byun, S. S.; Baek, J. Y.; Lee, K. H.; Kim, S. E.; Choi, Y.; Kim, B. T. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Diallyl disulfide found in garlic has been known to inhibit the growth of various cancer cells. In this study, iodine-substituted disulfides were synthesized and their growth inhibitory effects on cancer cells (SUN C5 and MCF-7) were investigated. Dibenzyl disulfide was labeled with {sup 123}I/{sup 125}I for evaluation of tumor uptake. Halogen-substituted disulfides were synthesized using 2,2'-dithiobis(benzothiazole) and one equivalent each of the corresponding thiols. Growth inhibition studies were performed on cancer cells that were grown at 37 .deg. C for 48 hr prior to exposure to the disulfides. Radioiodine-labeled disulfide was prepared by halogen exchange reaction on the 4-bromodibenzyl disulfide in the presence of Na{sup 123}I/{sup 125}I and CuCl at 150 .deg. C for 60 min, followed by HPLC purification. Uptake of the radioactivity to SUN C5 cells was measured as a function of time, and inhibition studies were performed in the presence of either S-methyl methanethiosulfonate (MMTS) or diallyl disulfide. Disulfides were synthesized in the high yields (90%). Tumor growth inhibition studies by the 3 iododisulfides showed the inhibition (>95%) comparable to diallyl disulfide (100%). Cu(I)-assisted radioiodination gave 4-{sup 123}I/{sup 125}I-iododibenzyl disulfide in overall 30-40% radiochemical yield and with high specific activity. Cell uptake studies of the radiolabeled disulfide showed a time-dependent increase of the uptake (4-fold increase from 15 min to 2 hr). Both MMTS, a glutathione depleting agent, and diallyl disulfide reduced the uptake of the radioactivity in a dose-dependent manner. Inhibition studies suggest that uptake of disulfide to the tumor cells could be mediated by thiol-disulfide exchange. This study demonstrates that radioiodine-labeled dibenzyl disulfide may be useful for evaluation of tumor uptake.

  3. Pretreatment with buthionine sulfoximine enhanced uptake and retention of BSH in brain tumor

    International Nuclear Information System (INIS)

    Yoshida, F.; Yamamoto, T.; Nakai, K.; Zaboronok, A.; Matsuda, M.; Akutsu, H.; Ishikawa, E.; Shirakawa, M.; Matsumura, A.

    2014-01-01

    To determine the influence of buthionine sulfoximine (BSO) on boron biodistribution after sulfhydryl borane (BSH) administration for boron neutron capture therapy, the effectiveness of the combination of BSO with sulfhydril- (BSH) and non-sulfhydril (B 12 H 12 and BNH 3 ) boron compounds, and the interval between BSO and BSH administration, the retention of boron in tissues have been evaluated using a 9L rat tumor model. Simultaneous administration of BSH and BSO showed significantly higher boron accumulation compared to that without BSO, however there was no difference in tissue boron level between B 12 H 12 and BNH 3 administration with BSO or without BSO. The longer interval (6 h) between BSH and BSO administration related to the highest boron concentration in the brain and subcutaneous tumors compared to shorter intervals (0.5, 3 h). Boron concentration in subcutaneous and brain tumors was maintained for 6 and 12 h after the administration of BSH following BSO pretreatment. - Highlights: • Coadministration of BSH and BSO showed higher tumor boron uptake than BSH only. • Higher boron uptake was not observed after B 12 H 12 or BNH 3 administration. • The increase in tumor boron accumulation might be related to SH-groups. • BSO injection 6 h before BSH showed further increase in tumor boron uptake. • High boron concentration maintained for 6 and 12 h after BSH with BSO administration

  4. High efficiency diffusion molecular retention tumor targeting.

    Directory of Open Access Journals (Sweden)

    Yanyan Guo

    Full Text Available Here we introduce diffusion molecular retention (DMR tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding and RAD (control probes were synthesized bearing DOTA (for (111 In(3+, a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or i.v. methods was assessed by surface fluorescence, biodistribution of [(111In] RGD and [(111In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [(111In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by i.v.. The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide, which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.

  5. Downregulation of taurine uptake in multidrug resistant Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Poulsen, K A; Litman, Thomas; Eriksen, J

    2002-01-01

    In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal...... rate constant for the initial taurine uptake was reduced by 45% (high-affinity system) and 49% (low affinity system) in the resistant subline whereas the affinity of the transporters to taurine was unchanged. By immunoblotting we identified 3 TauT protein bands in the 50-70 kDa region. A visible...... reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1...

  6. Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions.

    Directory of Open Access Journals (Sweden)

    Erica C Nakajima

    Full Text Available Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor.Cal33 cells were grown as xenograft tumors (n = 16 in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18F-fluorodeoxyglucose ((18F-FDG uptake in clinical PET scans.IR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001. IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1α, carbonic anhydrase 9, and ATP synthase subunit 5β confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors.Hypoxia is associated with increased intratumoral metabolic heterogeneity. (18F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis.

  7. Biodistribution and breast tumor uptake of 16α-[18F]-fluoro-17β-estradiol in rat

    International Nuclear Information System (INIS)

    Sasaki, Masayuki; Fukumura, Toshimitsu; Kuwabara, Yasuo; Yoshida, Tsuyoshi; Nakagawa, Makoto; Ichiya, Yuichi; Masuda, Kouji

    2000-01-01

    To evaluate the usefulness of 16α-[ 18 F]-fluoro-17β-estradiol (FES) for the assessment of estrogen receptor (ER), we examined the tissue distribution and kinetics of FES in immature female Sprague-Dawley rats and then examined FES uptake in rat breast tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA). The FES uptake by the uterus, an ER-rich tissue, was highly selective and it was 3.34±0.79%ID/g at 60 minutes and 1.57±0.57%ID/g at 120 minutes after injection. The FES uptakes in ER-negative tissues were 0.12±0.05%ID/g or less and 0.05±0.03%ID/g or less, respectively. Coadministration of unlabeled β-estradiol showed marked depression of uterine FES uptake. The FES uptake by rat breast tumors was 0.14±0.06%ID/g at 60 min and 0.12±0.09%ID/g at 120 min. The FES uptake by rat breast tumors correlated with the ER concentration (r=0.45, p<0.05). In conclusion, these results suggest that the FES uptake by tissue is mainly ER mediated and FES is thus useful for detecting ER positive breast tumors. (author)

  8. Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

    International Nuclear Information System (INIS)

    Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee; Zeon, Seok Kil; Kim, Su Jin

    2015-01-01

    The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUV max ) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV max of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUV max compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer

  9. Effect of administration route on FES uptake into MCF-7 tumors

    International Nuclear Information System (INIS)

    Downer, Joanna B.; Jones, Lynne A.; Katzenellenbogen, John A.; Welch, Michael J.

    2001-01-01

    We have observed that intraperitoneal administration of [ 18 F]fluoroestradiol (FES), a radiolabeled estrogen receptor ligand, results in higher abdominal organ uptake and slower blood clearance than intravenous administration in female mice. In SCID mice bearing MCF-7 human tumors SC, IP administration resulted in tumor uptake that was only about one third that obtained with IV administration. Thus, the route of administration of a radiopharmaceutical for imaging or radiotherapy of a tumor in the abdomen, an ovarian tumor, for example, could have a profound effect on the efficiency and selectivity of delivery of the agent to the tumor

  10. Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma

    Directory of Open Access Journals (Sweden)

    Salvesen Gerd S

    2009-12-01

    Full Text Available Abstract Background Hypoxia is associated with increased resistance to chemo- and radiation-therapy. Hyperoxic treatment (hyperbaric oxygen has previously been shown to potentiate the effect of some forms of chemotherapy, and this has been ascribed to enhanced cytotoxicity or neovascularisation. The aim of this study was to elucidate whether hyperoxia also enhances any actual uptake of 5FU (5-fluorouracil into the tumor tissue and if this can be explained by changes in the interstitium and extracellular matrix. Methods One group of tumor bearing rats was exposed to repeated hyperbaric oxygen (HBO treatment (2 bar, pO2 = 2 bar, 4 exposures à 90 min, whereas one group was exposed to one single identical HBO treatment. Animals housed under normal atmosphere (1 bar, pO2 = 0.2 bar served as controls. Three doses of 5FU were tested for dose response. Uptake of [3H]-5FU in the tumor was assessed, with special reference to factors that might have contributed, such as interstitial fluid pressure (Pif, collagen content, oxygen stress (measured as malondialdehyd levels, lymphatics and transcapillary transport in the tumors. Results The uptake of the cytostatic agent increases immediately after a single HBO treatment (more than 50%, but not 24 hours after the last repeated HBO treatment. Thus, the uptake is most likely related to the transient increase in oxygenation in the tumor tissue. Factors like tumor Pif and collagen content, which decreased significantly in the tumor interstitium after repeated HBO treatment, was without effect on the drug uptake. Conclusion We showed that hyperoxia increases the uptake of [3H]-5FU in DMBA-induced mammary tumors per se, independently of changes in Pif, oxygen stress, collagen fibril density, or transendothelial transport alone. The mechanism by which such an uptake occur is still not elucidated, but it is clearly stimulated by elevated pO2.

  11. The effect of PPAR-γ agonist on 18F-FDG uptake in tumor and macrophages and tumor cells

    International Nuclear Information System (INIS)

    Kim, Se-Lim; Kim, Eun-Mi; Cheong, Su-Jin; Lee, Chang-Moon; Kim, Dong Wook; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Yim, Chang Yeol

    2009-01-01

    Purpose: The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors, and its role in adipogenesis and glucose metabolism has been well established. PPAR-γ agonists have been shown to inhibit many cytokines and to have anti-inflammatory effects. In pathologic conditions, enhanced fluoro-2-deoxy-D-glucose (FDG) uptake is observed not only in malignant tumors but also in inflammatory lesions, and this uptake occurs through the glucose transporter in these cells. Thus, the present study was undertaken to investigate the potential of using PPAR-γ's glucose uptake ability as a diagnostic tool to differentiate between macrophage and tumor cells. Materials and Methods: Cellular uptake studies were carried out on macrophage and two tumor cell lines for comparison by using 18 F-FDG. Western blot analysis was performed to determine the expression levels of both the glucose transporter and hexokinase protein. To confirm the possibility of differentiation between tumor and inflammatory lesions using rosiglitazone based on in vitro studies, 18 F-FDG (3.7x10 6 Bq) uptake in A549 and RAW 264.7 xenograft mice was compared. Results: The cellular uptake study findings were quite different for macrophages and tumor cells. 18 F-FDG uptakes by macrophages decreased by about 60% but was increased twofold in tumor cells after rosiglitazone treatment. Moreover, the expressions of proteins related to glucose uptake correlated well with cellular glucose accumulation in both cell types. Higher tumor uptake was observed after the injection of rosiglitazone in A549 xenograft mice (1.58±0.55 to 4.66±1.16), but no significant change of 18 F-FDG uptake was shown in RAW 264.7 xenograft mice (4.04±1.16 to 4.00±0.14). Conclusion: The present study demonstrates the roles of PPAR-γ agonist on FDG uptake in macrophages and tumor cells in vitro and in vivo. Our findings suggest that rosiglitazone has the

  12. Increased tumor uptake of 67Ga citrate following a course of picibanil (NSC-B116209)

    International Nuclear Information System (INIS)

    Okuyama, Shinichi; Matsuzawa, Taiju; Mishina, Hitoshi.

    1979-01-01

    Exposure to exponential dose schedules of OK-432, penicillin-inactivated preparation of streptococcus hemolyticus (NSC-B116209), resulted in an increased retention of 67 Ga citrate. Its uptake in footpad tumors of AH 109A was also increased. The results may suggest that pretreatment with OK-432 would increase tumor uptake of 67 Ga citrate and help scintigraphic delineation of malignancies in man. It may probably augment tumor concentration of anticancer chemotherapeutics, too. Thus, the tumor affinitive property of OK-432 can be taken advantage of in anticancer strategy as well as cancer detection by 67 Ga scanning. (author)

  13. Early uptake and continuous accumulation of thallium-201 chloride in a benign mixed tumor of soft tissue: Case Report

    Directory of Open Access Journals (Sweden)

    Hamada Kenichiro

    2010-05-01

    Full Text Available Abstract A case of benign mixed tumor of the soft tissue in a 64-year-old Japanese male is presented. He noticed a painless, elastic hard mass sized 3 cm in the right knee, which gradually grew larger and harder in the last 5 years. Magnetic resonance imaging demonstrated a mass lesion embedded in the subcutaneous tissue with low and high signal intensity at T1- and T2-weighted images, respectively. Tl-201 scintigraphy showed an early uptake of Tl-201 within the lesion at 10 minutes after injection, which was slightly decreased but still continued at 2 hours later. The patient underwent a resection of tumor, and the pathological diagnosis was a benign mixed tumor of soft tissue without high vascularity, characterized by histological features similar to pleomorphic adenomas in the salivary glands. Immunohistochemical study proved expression of Na+/K+-ATPase of tumor cells. Overexpression of Na+/K+-ATPase of the tumor might be responsible for the early uptake of Tl-201, and poor vascular structure in this tumor might lead to continuous accumulation. The Tl-201 scintigraphic features of mixed tumor of soft tissue are assessed to resemble those of malignant soft tissue tumors.

  14. Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells

    Science.gov (United States)

    Chen, Eunice Y.; Hodge, Sasson; Tai, Katherine; Hou, Huagang; Khan, Nadeem; Hoopes, P. Jack; Samkoe, Kimberley S.

    2013-02-01

    Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.

  15. Uptake of radiolabeled anti-CEA antibodies in human colorectal primary tumors as a function of tumor mass

    International Nuclear Information System (INIS)

    Williams, L.E.; Bares, R.B.; Buell, U.; Fass, J.; Schumpelick, V.; Hauptmann, S.

    1993-01-01

    An inverse correlation has been demonstrated between tumor uptake (u, in units of % injected dose/kg) of monoclonal antibody (Mab) and tumor mass (m, in units of g) for colorectal carcinoma in a series of 19 consecutive patients. The correlation (ρ=-0.510), developed using surgical samples was of the form u=ab b and was significant at the 2% level of confidence. All tumors were positive for carcinoembryonic antigen (CEA) and the radiopharmaceutical was in iodine-131 labeled anti-CEA Mab. Such correlations have been predicted earlier from murine and rat tumor uptake data. The slope parameter (b) was -0.362, a number consistent with the previous value (-0.382) found in anti-CEA experiments in mice bearing human xenograft LS174T tumors. (orig.)

  16. Gallium uptake in benign tumor of liver: case report

    International Nuclear Information System (INIS)

    Belanger, M.A.; Beauchamp, J.M.; Neitzschman, H.R.

    1975-01-01

    A case of positive tracer localization in a benign tumor of the liver on a 67 Ga-citrate scan is reported. The authors were unable to find any previous reports of positive localization of gallium in this type of liver tumor. (U.S.)

  17. Effect of administration route and dose of streptavidin or biotin on the tumor uptake of radioactivity in intraperitoneal tumor with multistep targeting

    International Nuclear Information System (INIS)

    Zhang Meili; Yao Zhengsheng; Sakahara, Harumi; Saga, Tsuneo; Nakamoto, Yuji; Sato, Noriko; Zhao Songji; Nakada, Hiroshi; Yamashina, Ikuo; Konishi, Junji

    1998-01-01

    The effect of the administration route and dose of streptavidin or biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled streptavidin and a three-step method with radiolabeled biotin based on the two-step method. A monoclonal antibody, MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected intravenously (IV) or IP in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, IP-injected streptavidin showed a higher tumor uptake and tumor-to-nontumor ratios than IV-injected streptavidin regardless of administration route of pretargeting. The tumor uptake of radiolabeled streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of streptavidin. In the three-step targeting, IP injection also gave a higher tumor uptake of radiolabeled biotin than IV injection. In conclusion, IP administration of radiolabeled streptavidin or biotin resulted in more efficient IP tumor targeting with the multistep methods

  18. Increased Plasma Colloid Osmotic Pressure Facilitates the Uptake of Therapeutic Macromolecules in a Xenograft Tumor Model

    Directory of Open Access Journals (Sweden)

    Matthias Hofmann

    2009-08-01

    Full Text Available Elevated tumor interstitial fluid pressure (TIFP is a characteristic of most solid tumors. Clinically, TIFP may hamper the uptake of chemotherapeutic drugs into the tumor tissue reducing their therapeutic efficacy. In this study, a means of modulating TIFP to increase the flux of macromolecules into tumor tissue is presented, which is based on the rationale that elevated plasma colloid osmotic pressure (COP pulls water from tumor interstitium lowering the TIFP. Concentrated human serum albumin: (20% HSA, used as an agent to enhance COP, reduced the TIFP time-dependently from 8 to 2 mm Hg in human tumor xenograft models bearing A431 epidermoid vulva carcinomas. To evaluate whether this reduction facilitates the uptake of macromolecules, the intratumoral distribution of fluorescently conjugated dextrans (2.5 mg/ml and cetuximab (2.0 mg/ml was probed using novel time domain nearinfrared fluorescence imaging. This method permitted discrimination and semiquantification of tumor-accumulated conjugate from background and unspecific probe fluorescence. The coadministration of 20% HSA together with either dextrans or cetuximab was found to lower the TIFP significantly and increase the concentration of the substances within the tumor tissue in comparison to control tumors. Furthermore, combined administration of 20%HSA plus cetuximab reduced the tumor growth significantly in comparison to standard cetuximab treatment. These data demonstrate that increased COP lowers the TIFP within hours and increases the uptake of therapeutic macromolecules into the tumor interstitium leading to reduced tumor growth. This model represents a novel approach to facilitate the delivery of therapeutics into tumor tissue, particularly monoclonal antibodies.

  19. FDG uptake and glut-1 expression in primary tumors and loco-regional lymph nodes in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Lee, Won Woo; Nguyen, Xuan Canh; Chung, Jin Haeng; Park, So Yeon; Kim, Sang Eun

    2007-01-01

    FDG uptake level by primary tumors in NSCLC may affect the likelihood of malignant involvement in loco-regional lymph nodes (LNs). FDG uptake in tumors has been reported to be mediated by glucose transporter type 1 (Glut-I). Here, we investigated the correlations between primary tumors and loco-regional LNs in NSCLC regarding FDG uptake and Glut-1 expression. 126 NSCLC patients (M: F=103: 23, age=659.7y) who underwent curative resection and loco-regional LN dissection within 4 week period after FDG-PET study were enrolled. Maximum standardized uptake value (maxSUV) by PET and %Glut-1 expression by immunostaining were compared between primary tumors and FDG uptake positive loco-regional LNs. Significant correlations were found between 52 malignant LNs and 37 primary tumors in terms of maxSUV (r=0.6451, p<0.0001) and %Glut-1 expression (r=0.8341, p<0.0001). Linear regression of the relation between maxSUVs of malignant LNs (Y) and maxSUVs of primary tumors (X) yielded the expression Y = 0.5938 + 0.4808 X with an r2 value of 0.4162. On the other hand, no significant correlation was observed between 144 benign LNs and 75 primary tumors in terms of maxSUVs (r= -0.0125, p 0.8831). Moreover, %Glut-1 expressions of pathologically proven benign LNs and primary tumors were found to be correlated (r=0.3863, p=0.0004), but r2 value was low at 0.1492. High correlations were found between primary tumors and loco-regional metastatic LNs in NSCLC regarding FDG uptake and Glut-1 expression. Mediastinal LN staging of NSCLC by FDG-PET may be improved by considering the linear correlation between FDG uptakes of metastatic LNs and primary tumors

  20. Evaluation of uptake and distribution of gold nanoparticles in solid tumors

    Science.gov (United States)

    England, Christopheri G.; Gobin, André M.; Frieboes, Hermann B.

    2015-11-01

    Although nanotherapeutics offer a targeted and potentially less toxic alternative to systemic chemotherapy in cancer treatment, nanotherapeutic transport is typically hindered by abnormal characteristics of tumor tissue. Once nanoparticles targeted to tumor cells arrive in the circulation of tumor vasculature, they must extravasate from irregular vessels and diffuse through the tissue to ideally reach all malignant cells in cytotoxic concentrations. The enhanced permeability and retention effect can be leveraged to promote extravasation of appropriately sized particles from tumor vasculature; however, therapeutic success remains elusive partly due to inadequate intra-tumoral transport promoting heterogeneous nanoparticle uptake and distribution. Irregular tumor vasculature not only hinders particle transport but also sustains hypoxic tissue kregions with quiescent cells, which may be unaffected by cycle-dependent chemotherapeutics released from nanoparticles and thus regrow tumor tissue following nanotherapy. Furthermore, a large proportion of systemically injected nanoparticles may become sequestered by the reticulo-endothelial system, resulting in overall diminished efficacy. We review recent work evaluating the uptake and distribution of gold nanoparticles in pre-clinical tumor models, with the goal to help improve nanotherapy outcomes. We also examine the potential role of novel layered gold nanoparticles designed to address some of these critical issues, assessing their uptake and transport in cancerous tissue.

  1. Study of the cellular uptake and distribution of 57cobalt bleomycin in Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Metelmann, H.R.

    1980-01-01

    We investigated the dependence of the cellular uptake of 57 cobalt-bleomycin on the exposure time and on the dose. In addition we observed the influences due to the incubation temperature, to the growth phase of the tumor cells and due to the composition of the suspensory medium. In supplementary experiments we investigated the binding of the labelled cytostatic agent to erythrocytes, its adsorption to broken Ehrlich ascites tumor cells and the 57 cobalt-bleomycin outflow from pre-loaded intact Ehrlich ascites tumor cells. The 57 cobalt-bleomycin uptake of intact Ehrlich ascites tumor cells is determined by characteristic kinetics. Moreover, the erythrocytes and injured Ehrlich ascites tumor cells show a qualitatively similar graph of the 57 cobalt-bleomycin binding, which can clearly be distinguished from the kinetics found with intact Ehrlich ascites tumor cells. The uptake of this cytostatic agent depends on an unequivocal time-dose-temperature relationship. The transport mechanism of the 57 cobalt-bleomycin uptake was considered as endocytosis. An endocytosis-stimulating inducer could not be detected. However, we obtained indications that the cell-bound cytostatic agent is taken up in two compartments: on the cellular surface and in the interior of the cell. (orig./MG) [de

  2. Correlation of primary tumor FDG uptake with histopathologic features of advanced gastric cancer

    International Nuclear Information System (INIS)

    Kim, Hae Won; Won, Kyoung Sook; Song, Bong Il; Kang, Yu Na

    2015-01-01

    Histopathologic features could affect the FDG uptake of primary gastric cancer and detection rate on FDG PET/CT. The aim of this study was to evaluate the FDG uptake of primary gastric cancer by correlating it with the histopathologic features of the tumors. Fifty patients with locally advanced gastric adenocarcinoma who were referred for preoperative FDG-PET/CT scans were enrolled in this study. The detection rate of PET/CT and maximum standardized uptake values (SUV max ) of the primary tumor were compared using the WHO, Lauren, Ming and Borrmann classifications and tumor size and location. In 45 of the 50 patients (90 %), the primary gastric tumors were detected by FDG PET/CT. On comparison using the WHO classification, the detection rate and SUV max of the tubular type were significantly higher than those of the poorly cohesive type. On comparison using the Lauren and Ming classifications, the SUV maxs of the intestinal type and expanding type were significantly higher than those of the diffuse and infiltrative type, respectively. On comparison using the Borrmann classification and tumor size and location, there was no significant difference in the detection rate and SUV max of primary gastric tumors. This study demonstrates that the poorly cohesive type according to the WHO classification, diffuse type according to the Lauren classification and infiltrative type according to the Ming classification have low FDG uptake in patients with locally advanced gastric carcinoma. Understanding the relationship between primary tumor FDG uptake and histopathologic features would be helpful in detecting the primary tumor by FDG PET/CT in patients with gastric cancer

  3. Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice

    International Nuclear Information System (INIS)

    Liniecki, J.; Rembelska, M.; Koniarek, B.

    1983-01-01

    Tumor and normal tissue uptake of 51 Cr- or 57 Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 μg of each complex with an activity of 40-120 μCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57 Co than for the 51 Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin. (orig.) [de

  4. The effect of steroid on FDG uptake in experimental tumors, granulomatous and inflammatory lesions

    International Nuclear Information System (INIS)

    Zhao Songji; Yuji Kuge; Kunihiro Nakada; Masayuki Sato; Toshiki Takei; Zhao Yan; Nagara Tamaki; Masashi Kohanawa; Ken-ichi Seki

    2004-01-01

    Objectives: FDG accumulates not only in malignant tumors but also inflammatory lesions, especially in granulomatous lesions, which makes differentiate malignant tumors from benign lesions difficult. To obtain a clue for differentiating malignant lesions from benign ones by FDG-PET, we determined the effect of steroid on FDG uptake in granulomatous and inflammatory lesions, and compared them with those in malignant tumors in rats. Methods: Rats were inoculated with a suspension of allogenic hepatoma cells (KDH-8), Bacille bili e de Calmette-Guerin-(BCG) or Staphylococcus aureus (S. aureus), or with turpentine oil into the left calf muscle. Two weeks after KDH-8, 19 days after BCG, or one week after S. aureus or turpentine oil inoculations, the rats were fasted overnight and divided into two subgroups (n=5-6, in each group): Prednisolone (PRE)-pretreated (Methylprednisolone acetate, 8 mg/kg body weight, i.m. injection 20 hour before the FDG intravenous injection) and control (untreated) groups. Radioactivity in tissues was determined one hour after i.v. injection of FDG. FDG uptake in tissues were expressed as the percentage of injected dose per gram of tissue after normalization to animal's weight (%ID/g tissue/kg body weight). Results: FDG uptake in the tumor, granulomatous and inflammatory lesions were shown in Table. In the untreated animals, remarkably higher accumulations of FDG were observed in the tumor and granulomatous lesions, compared with those in the inflammatory lesions induced by S. aureus and turpentine oil. There was no significant difference in the level of FDG uptake between the tumor and granulomatous lesions, and between the two inflammatory lesions. PRE pre-treatment significantly decreased the level of FDG uptake in granulomatous lesions induced by BCG, inflammatory lesions induced by S. aureus and turpentine oil to 52%, 73% and 76% of the control value, respectively. The level of FDG uptake in the tumor was not significantly decreased by PRE

  5. Difluoromethylornithine enhanced uptake of tritiated putrescine in 9L rat brain tumors

    International Nuclear Information System (INIS)

    Redgate, E.S.; Grudziak, A.G.; Deutsch, M.; Boggs, S.S.

    1997-01-01

    Difluoromethylornithine (DFMO) depletes endogenous putrescine and enhances the uptake of and retention of [ 3 H] putrescine in vitro. To determine if DFMO also enhances uptake of [ 3 H] putrescine in vivo, DFMO and trace doses of [ 3 H] putrescine, dissolved in artificial CSF, were infused into growing (6-9 day) 9L brain tumors by means of osmotic pumps. When 7-day osmotic pumps were loaded with 1 μCi [ 3 H] putrescine, with or without 10 or 100 mM DFMO, pumped at 1 μl/h, the mean uptake after 3 days was 168 ± 62 cpm/mg tumor (17 rats) without DFMO, 300 ± 197 cpm/mg tumor (11 rats) with 10 mM DFMO and 1088 ± 421 cpm/mg tumor (11 rats) with 100 mM DFMO (p ≤ 0.05 vs. control). Significantly less radioactivity was detected in the contralateral brain and in nonbrain tissues (0.5 ± 0.1 to 14 ± 5 cpm/mg). To measure the extent of [ 3 H] putrescine distribution in the tumor, the same dose of drugs was delivered for a longer period of time, using 14-day pumps to allow tumors to become large enough to be divided into 1.4 mm thick transections. The mean radioactivity in the sections from eight control rats receiving [ 3 H] putrescine without DFMO were not significantly different between the sections (174 ± 61 cpm/mg tumor for sections containing the cannulas, 273 ± 61 and 259 ± 91 cpm/mg for adjacent sections). In the six rats given 100 mM DFMO there was a significant increase in mean radioactivity in the cannula containing section (2251 ± 919 cpm/mg tumor). Mean counts from adjacent sections in these rats were 97 ± 44 and 33 ± 13 cpm/mg. Values for contralateral corpus striatum and nonbrain tissues ranged from 0.7 ± 0.3 to 4.3 ± 1.5 cpm/mg tissue. When DFMO was delivered directly to the tumors while [ 3 H] putrescine was infused intraperitoneally, the uptake in the tumor slices was low (5-10 cpm/mg in different slices). These results demonstrate that infusion of DFMO directly into growing 9L brain tumors can selectively enhance the uptake of exogenous [ 3 H

  6. Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

    Directory of Open Access Journals (Sweden)

    Chávez Mireya

    2010-01-01

    Full Text Available Abstract Background von Hippel-Lindau (VHL disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Results Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02. Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01. Conclusions The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening

  7. False Positive Radioiodinated Metaiodobenzylguanidine (123I-MIBG Uptake in Undifferentiated Adrenal Malignant Tumor

    Directory of Open Access Journals (Sweden)

    Hee Soo Jung

    2015-01-01

    Full Text Available 123I-Metaiodobenzylguanidine (123I-MIBG scintigraphy is a widely used functional imaging tool with a high degree of sensitivity and specificity in diagnosis of pheochromocytoma. However, rare cases of false positive reactions have been reported. A 67-year-old male patient was admitted with epigastric pain. Abdominal computed tomography (CT revealed a heterogeneous left adrenal mass 6 cm in diameter; following hormone testing, 123I-MIBG scintigraphy was performed to determine the presence of pheochromocytoma, which confirmed eccentric uptake by a large left adrenal gland mass. Chest CT and PET-CT confirmed metastatic lymphadenopathy; therefore, endobronchial ultrasound transbronchial needle aspiration was performed. Metastatic carcinoma of unknown origin was suspected from a lymph node biopsy, and surgical resection was performed for definitive diagnosis and correction of excess hormonal secretion. A final diagnosis of undifferentiated adrenal malignant tumor was rendered, instead of histologically malignant pheochromocytoma, despite the uptake of 123I-MIBG demonstrated by scintigraphy.

  8. Effect of pH on tumor cell uptake of radiogallium in vitro and in vivo

    International Nuclear Information System (INIS)

    Vallabhajosula, S.R.; Hartwig, J.F.; Wolf, W.

    1982-01-01

    When injected at tracer levels into the blood, radiogallium as 67 Ga-citrate binds to, and is transported to, the site of the tumor by transferrin. The process by which transferrin-bound Ga is converted to tumor-bound Ga is not fully unterstood, but may involve the differential physicology of neoplasmas compared with normal tissues. Based on the slight acidity known to be exhibited by the extracellular fluid of many animal and human tumors, we have studied the effect of pH on stability and dissociation of the Ga-transferrin complex and on the uptake of Ga by tumor cells in vitro and animal tumors in vivo. When plasma from rabbits injected with 67 Ga-citrate was dialyzed at pH 6.5-7.5, disociation of Ga from transferrin showed an inverse pH-dependence. A similar inverse dependence on pH was observed for the uptake of Ga by L1210 leukemia cells and Ehrlich ascites cells incubated with Ga-transferrin complex. Tumor uptake of Ga in rats bearing Walker-256 carcinosarcoma or Murphystum lymphosarcoma whose tumor pH had been further lowered by administration of glucose showed a statistically significant increase over control rats receiving no glucose. These results demonstrate that the stability of the Ga-transferrin complex is pH-dependent and suggest that dissociation of this complex due to decreased pH at the tumor site may be one factor involved in tumor localization and binding of Ga. (orig.)

  9. Dose painting based on tumor uptake of Cu-ATSM and FDG

    DEFF Research Database (Denmark)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

    2014-01-01

    definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting...

  10. Dose painting based on tumor uptake of Cu-ATSM and FDG

    DEFF Research Database (Denmark)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

    2014-01-01

    Background: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[18 F]- fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis...

  11. The intensity of 18FDG uptake does not predict tumor growth in patients with metastatic differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Terroir, Marie; Dercle, Laurent; Lumbroso, Jean; Baudin, Eric; Berdelou, Amandine; Deandreis, Desiree; Schlumberger, Martin; Leboulleux, Sophie [Gustave Roussy and Universite Paris Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif (France); Borget, Isabelle [University Paris Sud, Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif (France); Bidault, Francois [Gustave Roussy, Department of Radiology, Villejuif (France); Ricard, Marcel [Gustave Roussy, Department of Physic, Villejuif (France); Deschamps, Frederic; Tselikas, Lambros [Department of Interventional Radiology, Villejuif (France); Hartl, Dana [Gustave Roussy, Department of Surgery, Villejuif (France)

    2017-04-15

    In patients with metastatic differentiated thyroid carcinoma (DTC), fluorodeoxyglucose (FDG) uptake as well as age, tumor size and radioactive iodine (RAI) uptake are prognostic factors for survival. High FDG uptake is a poor prognostic factor and lesions with high FDG uptake are often considered aggressive, but the predictive value of FDG uptake for morphological progression is unknown. The principal aim of this retrospective single center study was to determine whether the intensity of FDG uptake was correlated on a per lesion analysis with tumor growth rate (TGR) expressed as the percentage of increase in tumor size during 1 year (1-year TGR). Fifty five patients with DTC were included between July 2012 and May 2014 with the following criteria: (i) at least one distant metastasis measuring ≥ 1 cm in diameter on CT scan (ii) evaluation by FDG-positron emission tomography/computed tomography (PET/CT) performed at our center (iii) at least one CT or another FDG-PET/CT performed 3 to 12 months after the reference FDG-PET/CT in the absence of systemic or local treatment between the two imaging procedures. One hundred and fifty-six metastatic lesions located in lungs (63), neck lymph nodes (28), chest lymph nodes (42), bone (11), liver (2) and other sites (12) were studied. The median size was 16 mm, median SUVmax/lesion: 8.7; median metabolic tumor volume/lesion (Metab.TV/lesion): 3.7 cm{sup 3}. The median 1-year TGR was 40.68 %. SUVmax and Metab.TV/lesion were not correlated to their 1-year TGR (p = 0.38 and p = 0.74 respectively). Among single patients with multiple lesions, the lesions with the highest SUVmax/lesion or the highest Metab.TV/lesion did not disclose the higher 1-year TGR. The intensity of FDG uptake on a per lesion analysis is not correlated to its 1-year TGR and cannot be used as a surrogate marker of tumour progression. (orig.)

  12. Dose-dependent effects of (anti)folate preinjection on 99mTc-radiofolate uptake in tumors and kidneys

    International Nuclear Information System (INIS)

    Mueller, Cristina; Schibli, Roger; Forrer, Flavio; Krenning, Eric P.; Jong, Marion de

    2007-01-01

    Introduction: The folate receptor (FR) is frequently overexpressed in tumors and can be targeted with folate-based (radio)pharmaceuticals. However, significant accumulation of radiofolates in FR-positive kidneys represents a drawback. We have shown that preadministration of the antifolate pemetrexed (PMX) significantly improved the tumor-to-kidney ratio of radiofolates in mice. The aim of this study was to investigate the dose dependence of these effects and whether the same results could be achieved with folic acid (FA) or 5-methyl-tetrahydrofolate (5-Me-THF). Methods: Biodistribution was assessed 4 h postinjection of the organometallic 99m Tc-picolylamine monoacetic acid folate in nude mice bearing FR-positive KB tumor xenografts. PMX (50-400 μg/mouse) was injected 1 h previous to radioactivity. The effects of FA and 5-Me-THF (0.5-50 μg/mouse) were investigated likewise. Tissues and organs were collected and counted for radioactivity and the values tabulated as percentage of injected dose per gram tissue (% ID/g). Results: PMX administration reduced renal retention ( 10% ID/g), while the tumor uptake (average 1.35%±0.40% ID/g vs. control: 1.79%±0.49% ID/g) was only slightly affected independent of the PMX dose. Replacement of PMX by FA or 5-Me-THF (50 μg/mouse) resulted in a significant renal blockade (<0.1% ID/g) but at the same time in an undesired reduction of tumor uptake (<0.2% ID/g). Conclusions: Selective reduction of radiofolate uptake in kidneys under retention of high tumor accumulation could be achieved in combination with PMX over a broad dose range but not with FA or 5-Me-THF

  13. Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study

    International Nuclear Information System (INIS)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael; Hollensen, Christian; Pommer, Tobias; Munck af Rosenschöld, Per; Kristensen, Annemarie Thuri; Kjær, Andreas; McEvoy, Fintan J; Engelholm, Svend Aage

    2014-01-01

    Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[ 18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N 4 )-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64 Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64 Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64 Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64 Cu-ATSM at two

  14. Side-by-Side Comparison of Commonly Used Biomolecules That Differ in Size and Affinity on Tumor Uptake and Internalization

    Science.gov (United States)

    Leelawattanachai, Jeerapond; Kwon, Keon-Woo; Michael, Praveesuda; Ting, Richard; Kim, Ju-Young; Jin, Moonsoo M.

    2015-01-01

    The ability to use a systemically injected agent to image tumor is influenced by tumor characteristics such as permeability and vascularity, and the size, shape, and affinity of the imaging agent. In this study, six different imaging biomolecules, with or without specificity to tumor, were examined for tumor uptake and internalization at the whole body, ex-vivo tissue, and cellular levels: antibodies, antibody fragments (Fab), serum albumin, and streptavidin. The time of peak tumor uptake was dependent solely on the size of molecules, suggesting that molecular size is the major factor that influences tumor uptake by its effect on systemic clearance and diffusion into tumor. Affinity to tumor antigen failed to augment tumor uptake of Fab above non-specific accumulation, which suggests that Fab fragments of typical monoclonal antibodies may fall below an affinity threshold for use as molecular imaging agents. Despite abundant localization into the tumor, albumin and streptavidin were not found on cell surface or inside cells. By comparing biomolecules differing in size and affinity, our study highlights that while pharmacokinetics are a dominant factor in tumor uptake for biomolecules, affinity to tumor antigen is required for tumor binding and internalization. PMID:25901755

  15. 99mTcO(MAG2-3G3-dimer): a new integrin αvβ3-targeted SPECT radiotracer with high tumor uptake and favorable pharmacokinetics

    International Nuclear Information System (INIS)

    Shi, Jiyun; Wang, Lijun; Kim, Young-Seung; Zhai, Shizhen; Liu, Shuang; Jia, Bing; Wang, Fan

    2009-01-01

    This report presents the synthesis of a cyclic RGD dimer conjugate, MAG 2 -G 3 -E[G 3 -c(RGDfK)] 2 (MAG 2 -3G 3 -dimer, G 3 = Gly-Gly-Gly, MAG 2 = S-benzoyl mercaptoacetylglycylglycyl), and evaluation of its 99m Tc complex, 99m TcO(MAG 2 -3G 3 -dimer), as a new radiotracer for imaging the tumor integrin α v β 3 expression. An in vitro displacement assay was used to determine the integrin α v β 3 binding affinity of MAG 2 -3G 3 -dimer against 125 I-c(RGDyK) bound to U87MG human glioma cells. The athymic nude mice bearing U87MG glioma xenografts were used for biodistribution and planar imaging studies. We found that (1) MAG 2 is such a highly effective bifunctional chelator that 99m TcO(MAG 2 -3G 3 -dimer) can be prepared in high yield (radiochemical purity >95%) and with high specific activity (∝5 Ci/μmol) using a kit formulation; (2) 99m TcO(MAG 2 -3G 3 -dimer) has very high solution stability in the kit matrix; and (3) 99m TcO(MAG 2 -3G 3 -dimer) has very fast clearance kinetics from the intestine, liver, and kidneys. Among the 99m Tc-labeled cyclic RGD peptides evaluated in the xenografted U87MG glioma models, 99m TcO(MAG 2 -3G 3 -dimer) has the best pharmacokinetics and tumor to background ratios (tumor/liver = 4.29 ± 1.00 at 30 min postinjection and 8.29 ± 1.50 at 120 min postinjection; tumor/kidney = 1.16 ± 0.19 at 30 min postinjection and 2.49 ± 0.25 at 120 min postinjection). Planar imaging studies showed that tumors in the glioma-bearing mice administered with 99m TcO(MAG 2 -3G 3 -dimer) can be visualized with excellent contrast as early as 15 min postinjection. 99m TcO(MAG 2 -3G 3 -dimer) was able to maintain its chemical integrity in kidneys (>80% intact) and liver (>95% intact) over the 2-h period. However, there was significant metabolism (>50% of the injected radioactivity) detected in both urine and feces samples. 99m TcO(MAG 2 -3G 3 -dimer) is a very attractive radiotracer for early detection of integrin α v β 3 -positive tumors and has

  16. Extensive FDG uptake and its modification with corticosteroid in a granuloma rat model: an experimental study for differentiating granuloma from tumors

    International Nuclear Information System (INIS)

    Zhao, Songji; Takei, Toshiki; Zhao, Yan; Tamaki, Nagara; Kuge, Yuji; Kohanawa, Masashi; Takahashi, Toshiyuki; Kawashima, Hidekazu; Temma, Takashi; Seki, Koh-ichi

    2007-01-01

    Increased 18 F-fluorodeoxyglucose (FDG) uptake in inflammatory lesions, particularly in granulomatous inflammation (e.g., sarcoidosis), makes it difficult to differentiate malignant tumors from benign lesions and is the main source of false-positive FDG-PET findings in oncology. Here, we developed a rat granuloma model and examined FDG uptake in the granuloma. The effects of corticosteroid on FDG uptake in the granuloma were compared with those in a malignant tumor. Rats were inoculated with Mycobacterium bovis bacillus Calmette-Guerin (BCG) or allogenic hepatoma cells, and subdivided into control and pretreated (methylprednisolone acetate, 8 mg/kg i.m.) groups. Radioactivity in tissues was determined 1 h after the FDG injection. FDG-PET was performed in rats bearing BCG granulomas or tumors before and after prednisolone treatment. Mature epithelioid cell granuloma-formation and massive lymphocyte-infiltration were observed in the control group of granuloma, histologically similar to sarcoidosis. The mean FDG uptake in the granuloma was comparable to that in the hepatoma. Prednisolone reduced epithelioid cell granuloma-formation and lymphocyte-infiltration. Prednisolone significantly decreased the level of FDG uptake in the granuloma (52% of control), but not in the hepatoma. The FDG uptake levels in the granulomas and tumors were clearly imaged with PET. We developed an intramuscular granuloma rat model that showed a high FDG uptake comparable to that of the tumor. The effect of prednisolone pretreatment on FDG uptake was greater in the granuloma than in the tumor. These results suggest that BCG-induced granuloma may be a valuable model and may provide a biological basis for FDG studies. (orig.)

  17. Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Wahl, R.L.; Piko, C.R.; Beers, B.A.; Geatti, O.; Johnson, J.; Sherman, P. (Michigan Univ., Ann Arbor, MI (USA). Dept. of Internal Medicine)

    1989-01-01

    The authors evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times. The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +- 5.1%) than for those perfused at 24h post i.v. antibody injection (32.9 +- 2.9%). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively by computer image analysis enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor. These studies show that much background antibody radioactivity can be removed using whole-body perfusion with saline, that the decline in whole body activity is larger with 4 than 24h perfusion and that tumor imaging can be enhanced by this approach. This and similar approaches that increase relative tumor antibody uptake such as plasmapheresis may be useful in imaging and therapy with radiolabeled antibodies.

  18. Comparative evaluation of SUV, tumor-to-blood standard uptake ratio (SUR), and dual time point measurements for assessment of the metabolic uptake rate in FDG PET.

    Science.gov (United States)

    Hofheinz, Frank; Hoff, Jörg van den; Steffen, Ingo G; Lougovski, Alexandr; Ego, Kilian; Amthauer, Holger; Apostolova, Ivayla

    2016-12-01

    We have demonstrated recently that the tumor-to-blood standard uptake ratio (SUR) is superior to tumor standardized uptake value (SUV) as a surrogate of the metabolic uptake rate K m of fluorodeoxyglucose (FDG), overcoming several of the known shortcomings of the SUV approach: excellent linear correlation of SUR and K m from Patlak analysis was found using dynamic imaging of liver metastases. However, due to the perfectly standardized uptake period used for SUR determination and the comparatively short uptake period, these results are not automatically valid and applicable for clinical whole-body examinations in which the uptake periods (T) are distinctly longer and can vary considerably. Therefore, the aim of this work was to investigate the correlation between SUR derived from clinical static whole-body scans and K m-surrogate derived from dual time point (DTP) measurements. DTP (18)F-FDG PET/CT was performed in 90 consecutive patients with histologically proven non-small cell lung cancer (NSCLC). In the PET images, the primary tumor was delineated with an adaptive threshold method. For determination of the blood SUV, an aorta region of interest (ROI) was delineated manually in the attenuation CT and transferred to the PET image. Blood SUV was computed as the mean value of the aorta ROI. SUR values were computed as ratio of tumor SUV and blood SUV. SUR values from the early time point of each DTP measurement were scan time corrected to 75 min postinjection (SURtc). As surrogate of K m, we used the SUR(T) slope, K slope, derived from DTP measurements since it is proportional to the latter under the given circumstances. The correlation of SUV and SURtc with K slope was investigated. The prognostic value of SUV, SURtc, and K slope for overall survival (OS) and progression-free survival (PFS) was investigated with univariate Cox regression in a homogeneous subgroup (N=31) treated with primary chemoradiation. Correlation analysis revealed for both, SUV and SURtc, a

  19. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    Directory of Open Access Journals (Sweden)

    Hui Guo

    2016-07-01

    Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

  20. The effect of the administration of iron on Ga-67 uptake in animal tumor and biodistribution

    International Nuclear Information System (INIS)

    Furukawa, Keiji

    1983-01-01

    In 1979 Larson reported that the uptake of Ga-67 in tumor cell was preceded by binding of the Ga-67 to transferrin. Since that time there have been many papers concerning changes in Ga-67 accumulation in experimental tumor by administration of iron before and after Ga-67 injection. This study was undertaken in the attempt to discern what changes are produced in Ga-67 images of tumor-bearing rabbits (VX-II) when iron was administered before and after Ga-67 injection. Additionally, the relationships between the change in the serum iron concentration in the tumor tissue in mice bearing Ehrlich's ascites tumor were studied. The following results were obtained. 1) The tumor uptake and biodistribution of Ga-67 following administration of iron in the form of Fesin (saccharated ferric oxide) or ferric-citrate is obviously diminished. This iron administration leads to an elevated excretion of Ga-67 from tumor and other organs except from bone. From this results, it was found that Ga-67 binds somewhat less avidity than iron to various iron transport protein. Accordingly, Ga-67 biodistribution may be markedly influenced by iron-loading. 2) The Ga-67 activity in blood following administration of iron was noted to suddenly markedly decrease. However, 24-48 hours after iron injection the Ga-67 activity in blood gradually increased. This result suggests that the Ga-67 displaced into the extravascular space by iron-loading reentered the vascular space when the iron concentration of serum returned to normal. 3) The accumulation of Ga-67 in the tumor and soft tissues was slightly decreased compared with controls after iron administration. However, the tumor to blood ratio (T/B) of Ga-67 in mice by iron loading was several time greater than that of Ga-67 alone because the clearance of Ga-67 from the blood was more accelated than that of tumor. The large tumor to blood ratio (T/B) would be advantageous in obtaining a more distinct tumor scan. (author)

  1. Polyamine deprivation-induced enhanced uptake of methylglyoxal bis(guanylhydrazone) by tumor cells.

    Science.gov (United States)

    Seppänen, P; Alhonen-Hongisto, L; Jänne, J

    1981-05-05

    1. Putrescine and spermidine depletion produced by alpha-difluoromethylornithine, an irreversible inhibitor or ornithine decarboxylase (EC 4.1.1.17), resulted in a strikingly enhanced cellular uptake of methylglyoxal bis(guanylhydrazone) in cultured Ehrlich ascites carcinoma cells and human lymphocytic leukemia cells. 2. A prior priming of the cells with difluoromethylornithine followed by a short exposure of the cells to methylglyoxal bis(guanylhydrazone) rapidly established intracellular concentrations of the latter drug approaching 10 mM. 3. The enhanced transport of methylglyoxal bis(guanylhydrazone) into the tumor cells apparently required metabolic energy as the uptake of extracellular drug rapidly ceased and intracellular methylglyoxal bis(guanylhydrazone) was excreted into the medium when the glycolysis of the tumor cells was inhibited by iodoacetate. 4. A sequential treatment of cultured tumor cells with difluoromethylornithine until established polyamine depletion followed by an addition of low concentrations of methylglyoxal bis(guanylhydrazone) produced an antiproliferative action not achieved with either of the drugs alone. 5. A similar treatment schedule, i.e a priming of mice inoculated with Ehrlich ascites cells with difluoromethylornithine for a few days, likewise enhanced the uptake of methylglyoxal bis(guanylhydrazone) by the carcinoma cells, but only marginally increased the drug concentration in the liver and small intestine of the animals.

  2. High radio-isotope uptakes in patients with hypothyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Wing, J.; Kalk, W.J.; Ganda, C. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Medicine)

    1982-12-04

    Hypothyroidism is usually associated with a low radio-isotope uptake by the thyriod gland. We report 8 cases of Hashimoto's thyroiditis with clinical and biochemical hypothyroidism and with borderline high or overtly increased technetium-99m pertechnetate and/or iodine-131 uptakes.

  3. The effect of tumor size on F-18-labeled fluorodeoxyglucose and fluoroerythronitroimidazole uptake in a murine sarcoma model

    International Nuclear Information System (INIS)

    Chung, June-Key; Chang, Young Soo; Lee, Yong Jin; Kim, Young Ju; Jeong, Jae Min; Lee, Dong Soo; Jang, Ja June; Lee, Myung Chul

    1999-01-01

    The purpose of this study was to evaluate the effect of tumor size on the uptake of 18 F-fluorodeoxyglucose (FDG) and fluoroerythronitroimidazole (FETNIM) in a murine sarcoma model. ICR mice were xenografted with sarcoma 180 cell line and tumors were allowed to grow to a weight of 0.26-5.82 grams. 18 F-FDG and 18 F-FETNIM were injected intravenously in separate groups of mice, and after 1 hr, the tumors were excised and radiotracer uptake was measured. In another group of mice tumors were autoradiographically analyzed and subjected to H and E staining. In both the FDG and FETNIM group, per-gram radiotracer uptake by a tumor was inversely proportional to tumor weight. 18 F-FETNIM correlated more (r=-0.593, p 18 F-FDG (r=-0.447, p 18 F-FETNIM, a direct correlation between tumor weight and the no-uptake-area to total-tumor-area was demonstrated. We concluded that increased tumor size is associated with decreased uptake of 18 F-FDG and FETNIM, though this depends on the type of radiotracers and distribution of necrosis. (author)

  4. A Case of Esophageal Leiomyoma Showing High FDG Uptake on F-18 FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jai Hyuen [College of Medicine, Cheonan (Korea, Republic of); Ryu, Jin Sook [Asan Medical Center, University of Ulsan College of Medicine (Korea, Republic of)

    2008-08-15

    An esophageal leiomyoma is the most common benign tumor of the esophagus mainly occurred in intramural portion. Occasionally, it is difficult to discriminate esophageal malignancy from large leiomyoma. Although F-18 FDG PET has been used for differentiating malignant from benign disease, false-positive cases have been reported. Recently, uterine leiomyoma has been reported to have relatively high F-18 FDG uptake in some patients but little is known about how an esophageal leiomyoma might be showed on F-18 FDG PET. We report a case of esophageal leiomyoma that showed high FDG uptake on PET images.

  5. A Case of Esophageal Leiomyoma Showing High FDG Uptake on F-18 FDG PET

    International Nuclear Information System (INIS)

    Lee, Jai Hyuen; Ryu, Jin Sook

    2008-01-01

    An esophageal leiomyoma is the most common benign tumor of the esophagus mainly occurred in intramural portion. Occasionally, it is difficult to discriminate esophageal malignancy from large leiomyoma. Although F-18 FDG PET has been used for differentiating malignant from benign disease, false-positive cases have been reported. Recently, uterine leiomyoma has been reported to have relatively high F-18 FDG uptake in some patients but little is known about how an esophageal leiomyoma might be showed on F-18 FDG PET. We report a case of esophageal leiomyoma that showed high FDG uptake on PET images

  6. Tumor and liver drug uptake following hepatic artery and portal vein infusion

    International Nuclear Information System (INIS)

    Sigurdson, E.R.; Ridge, J.A.; Kemeny, N.; Daly, J.M.

    1987-01-01

    Anatomic dye injection studies of the blood supply of colorectal hepatic metastases suggest that tumors are supplied predominantly by the hepatic artery. Using 13 N amino acids with dynamic gamma camera imaging in patients with colorectal hepatic metastases, it has been shown that hepatic artery infusion results in a significantly greater nutrient delivery to tumor compared with portal vein infusion. However, direct measurements of drug levels in tumor following hepatic artery and portal vein infusion in humans have not previously been reported. Patients with metastatic colorectal cancer confined to the liver received fluorodeoxyuridine (FUdR) through the hepatic artery or through the portal vein. All patients had previously failed systemic chemotherapy. Five patients with hepatic artery catheters were matched (by age, serum lactic dehydrogenase levels, percent hepatic replacement, and tumor size) with five patients with portal vein catheters. At operation, 3 H-FUdR (1 microCi/kg) and /sup 99m/Tc-macroaggregated albumin (MAA) (6 mCi) were injected into the hepatic artery or portal vein. Liver and tumor biopsies were obtained two and five minutes later. 3 H and /sup 99m/Tc were measured per gram tissue by scintillation and gamma counting. The mean liver levels following hepatic artery infusion (23.9 +/- 11.4 nmol/g) and portal vein infusion (18.4 +/- 14.5 nmol/g) did not differ. However, the mean tumor FUdR level following hepatic artery infusion was 12.4 +/- 12.2 nmol/g, compared with a mean tumor FUdR level following portal vein infusion of 0.8 +/- 0.7 nmol/g (P less than .01). This low level of tumor drug uptake after portal vein infusion of FUdR predicts minimal tumor response to treatment via this route. Thus, regional chemotherapy for established colorectal hepatic metastases should be administered through the hepatic artery

  7. Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xuemei [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Wu, Xinchao [Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Maimaiti, Yusufu [Department of Thyroid and Breast Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Gao, Zairong, E-mail: gaobonn@163.com [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Zhang, Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China)

    2016-01-15

    Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

  8. Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

    International Nuclear Information System (INIS)

    Gao, Xuemei; Wu, Xinchao; Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing; Maimaiti, Yusufu; Gao, Zairong; Zhang, Yongxue

    2016-01-01

    Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine "1"3"1I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from "1"3"1I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced "1"3"1I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

  9. Prognostic value of tumor-to-blood standardized uptake ratio in patients with resectable non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Seung Hyeon; Pak, Kyoung June; Kim, In Joo [Dept. of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan(Korea, Republic of); Kim, Bum Soo; Kim, Seong Jang [Dept. of Nuclear Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2017-09-15

    Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUVmax). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery.

  10. Prognostic value of tumor-to-blood standardized uptake ratio in patients with resectable non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Shin, Seung Hyeon; Pak, Kyoung June; Kim, In Joo; Kim, Bum Soo; Kim, Seong Jang

    2017-01-01

    Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUVmax). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery

  11. Factors affecting 18 F FDOPA standardized uptake value in patients with primary brain tumors after treatment

    International Nuclear Information System (INIS)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

    2015-01-01

    Aim: To investigate the factors affecting 18 F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. Materials and methods: 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent 18 F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (± 42.27), 16.04 (± 29.08) and 28.62 (± 34.49) months respectively. Results: 18 F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. Conclusions: The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect 18 F FDOPA uptake

  12. Investigations of (99m)Tc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism.

    Science.gov (United States)

    Meng, Lanfang; Xiu, Yan; Li, Yanli; Xu, Xiaobo; Li, Shanqun; Li, Xiao; Pak, Koon Y; Shi, Hongcheng; Cheng, Dengfeng

    2015-07-01

    This study attempted to evaluate the feasibility of (99m)Tc-labeled glucarate ((99m)Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of (99m)Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of (99m)Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in (99m)Tc-GLA uptake by H292 and H1975 cells when fructose was added. The (99m)Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. (99m)Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of (99m)Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that (99m)Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors.

    Science.gov (United States)

    Kaewput, Chalermrat; Suppiah, Subapriya; Vinjamuri, Sobhan

    2018-01-01

    The aim of our study was to correlate tumor uptake of 68 Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68 Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUV max ) and averaged SUV SUV mean of "main tumor lesions" were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUV max of tumor and Ki-67 index ( r = -0.241) and negatively poor agreement between SUV mean of tumor and Ki-67 index ( r = -0.094). SUV max of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUV mean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUV max and SUV mean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68 Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68 Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68 Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.

  14. Reproducibility of O-(2-{sup 18}F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Stegmayr, Carina; Schoeneck, Michael; Oliveira, Dennis; Willuweit, Antje [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); Filss, Christian; Coenen, Heinz H.; Langen, Karl-Josef [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Galldiks, Norbert [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Juelich (Germany)

    2016-06-15

    Positron emission tomography (PET) using O-(2-{sup 18}F-fluoroethyl)-L-tyrosine ({sup 18}F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of {sup 18}F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy. F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of {sup 18}F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of {sup 18}F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC). The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC. TBR of {sup 18}F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation. (orig.)

  15. Antibody Drug Conjugates Differentiate Uptake and DNA Alkylation of Pyrrolobenzodiazepines in Tumors from Organs of Xenograft Mice.

    Science.gov (United States)

    Ma, Yong; Khojasteh, S Cyrus; Hop, Cornelis E C A; Erickson, Hans K; Polson, Andrew; Pillow, Thomas H; Yu, Shang-Fan; Wang, Hong; Dragovich, Peter S; Zhang, Donglu

    2016-12-01

    Pyrrolobenzodiazepine (PBD)-dimer is a DNA minor groove alkylator, and its CD22 THIOMAB antibody drug conjugate (ADC) demonstrated, through a disulfide linker, an efficacy in tumor reduction for more than 7 weeks with minimal body weight loss in xenograft mice after a single 0.5-1 mg/kg i.v. dose. The DNA alkylation was investigated here in tumors and healthy organs of mice to understand the sustained efficacy and tolerability. The experimental procedures included the collection of tumors and organ tissues of xenograft mice treated with the ADC followed by DNA isolation/hydrolysis/quantitation and payload recovery from reversible DNA alkylation. PBD-dimer formed a considerable amount of adducts with tissue DNA, representing approximately 98% (at 24 hours), and 99% (at 96 hours) of the total PBD-dimer in tumors, and 78-89% in liver and lung tissues, suggesting highly efficient covalent binding of the released PBD-dimer to tissue DNA. The amount of PBD-DNA adducts in tumor tissues was approximately 24-fold (at 24 hours) and 70-fold (at 96 hours) greater than the corresponding amount of adducts in liver and lung tissues. In addition, the DNA alkylation levels increased 3-fold to 4-fold from 24 to 96 hours in tumors [41/10 6 base pairs (bp) at 96 hours] but remained at the same level (1/10 6 bp) in livers and lungs. These results support the typical target-mediated cumulative uptake of ADC into tumors and payload release that offers an explanation for its sustained antitumor efficacy. In addition, the low level of DNA alkylation in normal tissues is consistent with the tolerability observed in mice. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. An observational study of circulating tumor cells and (18F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Viswam S Nair

    Full Text Available We investigated the relationship of circulating tumor cells (CTCs in non-small cell lung cancer (NSCLC with tumor glucose metabolism as defined by (18F-fluorodeoxyglucose (FDG uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs". We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6 and median maximum standardized uptake value (SUVmax was 7.2 (IQR 3.7-15.5. More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71 or in stage I disease (27 of 43. HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03 and not correlated with tumor diameter (r = 0.07; p-value = 0.60. For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

  17. Tc-99m TRODAT uptake in an osteoid tumor of clivus.

    Science.gov (United States)

    Taywade, Sameer; Tripathi, Madhavi; Tandon, Vivek; Das, Chandan Jyoti; Damle, Nishikant Avinash; Shamim, Shamim Ahmed; Thukral, Parul; Bal, Chandrasekhar

    2016-01-01

    Tc-99m TRODAT is cocaine analog and binds to the dopamine transporter in vivo . Tc-99m TRODAT single-photon emission computed tomography/computed tomography. (SPECT/CT) is useful for demonstrating presynaptic dopaminergic dysfunction in patients with Parkinsonism. However, few reports have shown extrastriatal uptake of Tc-99m TRODAT. We present the case of a 67-year-old male who underwent Tc-99m TRODAT SPECT/CT for evaluation of Parkinsonism. In addition to tracer binding in the striatum, tracer uptake was noted in an osteoid tumor of the clivus. Integrated SPECT/CT enabled precise localization and characterization of the extrastriatal site of tracer binding and emphasizes the importance of such coincidental findings.

  18. Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET.

    Science.gov (United States)

    Tixier, Florent; Hatt, Mathieu; Le Rest, Catherine Cheze; Le Pogam, Adrien; Corcos, Laurent; Visvikis, Dimitris

    2012-05-01

    (18)F-FDG PET measurement of standardized uptake value (SUV) is increasingly used for monitoring therapy response and predicting outcome. Alternative parameters computed through textural analysis were recently proposed to quantify the heterogeneity of tracer uptake by tumors as a significant predictor of response. The primary objective of this study was to evaluate the reproducibility of these heterogeneity measurements. Double baseline (18)F-FDG PET scans were acquired within 4 d of each other for 16 patients before any treatment was considered. A Bland-Altman analysis was performed on 8 parameters based on histogram measurements and 17 parameters based on textural heterogeneity features after discretization with values between 8 and 128. The reproducibility of maximum and mean SUV was similar to that in previously reported studies, with a mean percentage difference of 4.7% ± 19.5% and 5.5% ± 21.2%, respectively. By comparison, better reproducibility was measured for some textural features describing local heterogeneity of tracer uptake, such as entropy and homogeneity, with a mean percentage difference of -2% ± 5.4% and 1.8% ± 11.5%, respectively. Several regional heterogeneity parameters such as variability in the intensity and size of regions of homogeneous activity distribution had reproducibility similar to that of SUV measurements, with 95% confidence intervals of -22.5% to 3.1% and -1.1% to 23.5%, respectively. These parameters were largely insensitive to the discretization range. Several parameters derived from textural analysis describing heterogeneity of tracer uptake by tumors on local and regional scales had reproducibility similar to or better than that of simple SUV measurements. These reproducibility results suggest that these (18)F-FDG PET-derived parameters, which have already been shown to have predictive and prognostic value in certain cancer models, may be used to monitor therapy response and predict patient outcome.

  19. Differentiation of Glioblastomas from Metastatic Brain Tumors by Tryptophan Uptake and Kinetic Analysis: A Positron Emission Tomographic Study with Magnetic Resonance Imaging Comparison

    Directory of Open Access Journals (Sweden)

    David O. Kamson

    2013-07-01

    Full Text Available Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional magnetic resonance imaging (MRI; molecular imaging may facilitate such discrimination. We tested the accuracy of α[11C]methyl-L-tryptophan (AMT–positron emission tomography (PET to differentiate newly diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs. Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution [VD] from unidirectional uptake rates using dynamic PET and blood input function. Differentiating the accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74% and the tumor/cortex VD ratio had the highest positive predictive value (82%. The combined accuracy of MRI (size of contrast-enhancing lesion and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with > 90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pretreatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly diagnosed solitary ring-enhancing mass.

  20. Effect of Chelator Conjugation Level and Injection Dose on Tumor and Organ Uptake of 111In Labeled MORAb-009, an Anti-mesothelin Antibody

    Science.gov (United States)

    Shin, I. S.; Lee, S.-M.; Kim, H. S.; Yao, Z.; Regino, C.; Sato, N.; Cheng, K. T.; Hassan, R.; Campo, M. F.; Albone, E. F.; Choyke, P. L.; Pastan, I.; Paik, C. H.

    2012-01-01

    demonstrates that the number of chelate conjugation and the injected dose are two important parameters to achieve high tumor and low non-target organ uptake of 111In labeled MORAb-009. This study also suggests that the injected dose of mAb could be individualized based on the tumor size or the blood level of shed-antigen in a patient to achieve the ideal tumor-to-organ radioactivity ratios. PMID:21741258

  1. Uptake of radionuclides by vegetation at a High Arctic location

    International Nuclear Information System (INIS)

    Dowdall, M.; Gwynn, J.P.; Moran, C.; O'Dea, J.; Davids, C.; Lind, B.

    2005-01-01

    Radionuclide levels in vegetation from a High Arctic location were studied and compared to in situ soil concentrations. Levels of the anthropogenic radionuclide 137 Cs and the natural radionuclides 40 K, 238 U, 226 Ra and 232 Th are discussed and transfer factor (TF) values and aggregated transfer (Tag) values are calculated for vascular plants. Levels of 137 Cs in vegetation generally followed the order mosses > lichen > vascular plants. The uptake of 137 Cs in vascular plants showed an inverse relationship with the uptake of 40 K, with 137 Cs TF and Tag values generally higher than 40 K TF and Tag values. 40 K activity concentrations in all vegetation showed little correlation to associated soil concentrations, while the uptake of 238 U, 226 Ra and 232 Th by vascular and non-vascular plants was generally low. - Uptake of the anthropogenic radionuclide 137 Cs is highest for moss species

  2. Accumulation of Tc-99m-MIBI and Tc-99m-tetrofosmin in tumor cells. Uptake and washout studies

    International Nuclear Information System (INIS)

    Rodrigues, M.; Aghajanian, A.A.; Sinzinger, H.; Kalinowska, W.; Zielinski, C.

    2002-01-01

    Tc-99m-tetrofosmin seem to be promising for the in-vivo imaging and characterization of tumors with high cellular metabolic activity, such as cells rich in mitochondria or enhanced mitochondrial activity

  3. Biodistribution and tumor uptake of C60(OH)x in mice

    International Nuclear Information System (INIS)

    Ji Zhiqiang; Sun Hongfang; Wang Haifang; Xie Qunying; Liu Yuangfang; Wang Zheng

    2006-01-01

    Radiolabeling of fullerol, 125 I-C 60 (OH) x , was performed by the traditional chloramine-T method. The C-I covalent bond in I-C 60 (OH) x was characterized by X-ray photoelectron spectroscopy (XPS) that was sufficiently stable for in vivo study. Laser light scattering spectroscopy clearly showed that C 60 (OH) x aggregated to large nanoparticle clumps with a wide range of distribution. The clumps formed were also visualized by transmission electron microscope (TEM). We examined the biodistribution and tumor uptake of C 60 (OH) x in five mouse bearing tumor models, including mouse H22 hepatocarcinoma, human lung giantcellcarcinoma PD, human colon cancer HCT-8, human gastric cancer MGC803, and human OS732 osteosarcoma. The accumulation ratios of 125 I-C 60 (OH) x in mouse H22 hepatocarcinoma to that in normal muscle tissue (T/N) and blood (T/B) at 1, 6, 24 and 72 h, reveal that 125 I-C 60 (OH) x gradually accumulates in H22 tumor, and retains for a quite long period (e.g., T/N 3.41, T/B 3.94 at 24 h). For the other four tumor models, the T/N ratio at 24 h ranges within 1.21-6.26, while the T/B ratio ranges between 1.23 and 4.73. The accumulation of C 60 (OH) x in tumor is mostly due to the enhanced permeability and retention effect (EPR) and the phagocytosis of mononuclear phagocytes. Hence, C 60 (OH) x might serve as a photosensitizer in the photodynamic therapy of some kinds of tumor

  4. Biodistribution and tumor uptake of C{sub 60}(OH){sub x} in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhiqiang, Ji; Sun Hongfang, E-mail: shf@pku.edu.cn; Haifang, Wang; Qunying, Xie; Yuangfang, Liu [Peking University, Department of Chemical Biology, College of Chemistry and Molecular Engineering (China); Zheng, Wang [Chinese Academy of Medical Sciences, Cancer Institute (China)

    2006-02-15

    Radiolabeling of fullerol, {sup 125}I-C{sub 60}(OH){sub x}, was performed by the traditional chloramine-T method. The C-I covalent bond in I-C{sub 60}(OH){sub x} was characterized by X-ray photoelectron spectroscopy (XPS) that was sufficiently stable for in vivo study. Laser light scattering spectroscopy clearly showed that C{sub 60}(OH){sub x} aggregated to large nanoparticle clumps with a wide range of distribution. The clumps formed were also visualized by transmission electron microscope (TEM). We examined the biodistribution and tumor uptake of C{sub 60}(OH){sub x} in five mouse bearing tumor models, including mouse H22 hepatocarcinoma, human lung giantcellcarcinoma PD, human colon cancer HCT-8, human gastric cancer MGC803, and human OS732 osteosarcoma. The accumulation ratios of {sup 125}I-C{sub 60}(OH){sub x} in mouse H22 hepatocarcinoma to that in normal muscle tissue (T/N) and blood (T/B) at 1, 6, 24 and 72 h, reveal that {sup 125}I-C{sub 60}(OH){sub x} gradually accumulates in H22 tumor, and retains for a quite long period (e.g., T/N 3.41, T/B 3.94 at 24 h). For the other four tumor models, the T/N ratio at 24 h ranges within 1.21-6.26, while the T/B ratio ranges between 1.23 and 4.73. The accumulation of C{sub 60}(OH){sub x} in tumor is mostly due to the enhanced permeability and retention effect (EPR) and the phagocytosis of mononuclear phagocytes. Hence, C{sub 60}(OH){sub x} might serve as a photosensitizer in the photodynamic therapy of some kinds of tumor.

  5. Impact of muscular uptake and statistical noise on tumor quantification based on simulated FDG-PET studies

    International Nuclear Information System (INIS)

    Silva-Rodríguez, Jesús; Domínguez-Prado, Inés; Pardo-Montero, Juan; Ruibal, Álvaro

    2017-01-01

    Purpose: The aim of this work is to study the effect of physiological muscular uptake variations and statistical noise on tumor quantification in FDG-PET studies. Methods: We designed a realistic framework based on simulated FDG-PET acquisitions from an anthropomorphic phantom that included different muscular uptake levels and three spherical lung lesions with diameters of 31, 21 and 9 mm. A distribution of muscular uptake levels was obtained from 136 patients remitted to our center for whole-body FDG-PET. Simulated FDG-PET acquisitions were obtained by using the Simulation System for Emission Tomography package (SimSET) Monte Carlo package. Simulated data was reconstructed by using an iterative Ordered Subset Expectation Maximization (OSEM) algorithm implemented in the Software for Tomographic Image Reconstruction (STIR) library. Tumor quantification was carried out by using estimations of SUV max , SUV 50 and SUV mean from different noise realizations, lung lesions and multiple muscular uptakes. Results: Our analysis provided quantification variability values of 17–22% (SUV max ), 11–19% (SUV 50 ) and 8–10% (SUV mean ) when muscular uptake variations and statistical noise were included. Meanwhile, quantification variability due only to statistical noise was 7–8% (SUV max ), 3–7% (SUV 50 ) and 1–2% (SUV mean ) for large tumors (>20 mm) and 13% (SUV max ), 16% (SUV 50 ) and 8% (SUV mean ) for small tumors (<10 mm), thus showing that the variability in tumor quantification is mainly affected by muscular uptake variations when large enough tumors are considered. In addition, our results showed that quantification variability is strongly dominated by statistical noise when the injected dose decreases below 222 MBq. Conclusions: Our study revealed that muscular uptake variations between patients who are totally relaxed should be considered as an uncertainty source of tumor quantification values. - Highlights: • Distribution of muscular uptake from 136 PET

  6. Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine

    Science.gov (United States)

    Doloff, J.C.; Khan, N.; Ma, J.; Demidenko, E.; Swartz, H.M.; Jounaidi, Y.

    2010-01-01

    Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2nd CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO2, starting at 48 hr, which further increased after the 3rd CPA injection. pO2 levels were, however, stable in growing untreated tumors. A strong negative correlation (−0.81) between tumor pO2 and tumor volume during 21 days of weekly CPA chemotherapy was observed, indicating increasing tumor pO2 with decreasing tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day 1, and in PLGF RNA which was sustained throughout the treatment, while anti-angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA treatment. Weekly cyclophosphamide treatment was anticipated to generate exploitable hypoxia. However, our findings suggest that weekly CPA treatment induces a functional improvement of tumor vasculature, which is characterized by increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively, benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs. PMID:19754361

  7. Combined Scintigraphy and Tumor Marker Analysis Predicts Unfavorable Histopathology of Neuroblastic Tumors with High Accuracy.

    Directory of Open Access Journals (Sweden)

    Wolfgang Peter Fendler

    Full Text Available Our aim was to improve the prediction of unfavorable histopathology (UH in neuroblastic tumors through combined imaging and biochemical parameters.123I-MIBG SPECT and MRI was performed before surgical resection or biopsy in 47 consecutive pediatric patients with neuroblastic tumor. Semi-quantitative tumor-to-liver count-rate ratio (TLCRR, MRI tumor size and margins, urine catecholamine and NSE blood levels of neuron specific enolase (NSE were recorded. Accuracy of single and combined variables for prediction of UH was tested by ROC analysis with Bonferroni correction.34 of 47 patients had UH based on the International Neuroblastoma Pathology Classification (INPC. TLCRR and serum NSE both predicted UH with moderate accuracy. Optimal cut-off for TLCRR was 2.0, resulting in 68% sensitivity and 100% specificity (AUC-ROC 0.86, p < 0.001. Optimal cut-off for NSE was 25.8 ng/ml, resulting in 74% sensitivity and 85% specificity (AUC-ROC 0.81, p = 0.001. Combination of TLCRR/NSE criteria reduced false negative findings from 11/9 to only five, with improved sensitivity and specificity of 85% (AUC-ROC 0.85, p < 0.001.Strong 123I-MIBG uptake and high serum level of NSE were each predictive of UH. Combined analysis of both parameters improved the prediction of UH in patients with neuroblastic tumor. MRI parameters and urine catecholamine levels did not predict UH.

  8. Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice.

    Science.gov (United States)

    Oyewumi, Moses O; Yokel, Robert A; Jay, Michael; Coakley, Tricia; Mumper, Russell J

    2004-03-24

    The purpose of these studies was to compare the cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium (Gd) nanoparticles. Gd is a potential agent for neutron capture therapy (NCT) of tumors. Gd nanoparticles were engineered from oil-in-water microemulsion templates. To obtain folate-coated nanoparticles, a folate ligand [folic acid chemically linked to distearoylphosphatidylethanolamine (DSPE) via a PEG spacer MW 3350] was included in nanoparticle preparations. Similarly, control nanoparticles were coated with DSPE-PEG-MW 3350 (PEG-coated). Nanoparticles were characterized based on size, size distribution, morphology, biocompatibility and tumor cell uptake. In vivo studies were carried out in KB (human nasopharyngeal carcinoma) tumor-bearing athymic mice. Biodistribution and tumor retention studies were carried out at pre-determined time intervals after injection of nanoparticles (10 mg/kg). Gd nanoparticles did not aggregate platelets or activate neutrophils. The retention of nanoparticles in the blood 8, 16 and 24 h post-injection was 60%, 13% and 11% of the injected dose (ID), respectively. A maximum Gd tumor localization of 33+/-7 microg Gd/g was achieved. Both folate-coated and PEG-coated nanoparticles had comparable tumor accumulation. However, the cell uptake and tumor retention of folate-coated nanoparticles was significantly enhanced over PEG-coated nanoparticles. Thus, the benefits of folate ligand coating were to facilitate tumor cell internalization and retention of Gd-nanoparticles in the tumor tissue. The engineered nanoparticles may have potential in tumor-targeted delivery of Gd thereby enhancing the therapeutic success of NCT.

  9. FDG uptake in cold and heat treated MCF-7 cells, comparison with cell viability, apoptosis, and tumor marker changes

    International Nuclear Information System (INIS)

    Zhang, C.; Sun, X.; Huang, G.; Liu, J.

    2007-01-01

    Full text: Objectives-To investigate the FDG uptake changes in cold and hyperthermia therapy and its correlation with cell viability, apoptosis and tumor marker changes. Methods: An in vitro cultured breast adenocarcinoma cell line, MCF- 7, was divided into 5 groups. Hyperthermia group: cell was treated in 43 degree centigrade 30 min. Hypothermia group: cell was treated in 0 degree centigrade 30 min. Hypo- and hyperthermia group: cell was treated in 0 degree centigrade 30 min and 43 degree centigrade 30 min. chemotherapy group: cell was treated with 21 microgram Cisplatin for 6 hours. And Control group: cell was untreated. The levels 18F-labelled FDG uptake, a 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazoliumbromide viability assay, flow cytometry assay and tumor markers (CA153, CA125) were detected at 24 hour and 48 hour. Results: The change of 18F- FDG uptake (which came out at the 24h) is early than tumor marker (which came out at the 48h) under our study conditions. In treated MCF-7 cells, the levels of 18F-labelled FDG uptake were significantly lower than control group. The levels of 18F-FDG uptake depression were well correlated with cell viability and apoptosis data. Conclusion: FDG uptake is sensitive and well correlated with cell viability and apoptosis assay, and can be used for early response monitoring in hypo- and hyperthermia therapy. (author)

  10. Unexpectedly high uptake of palladium by bituminous coals

    Energy Technology Data Exchange (ETDEWEB)

    Lakatos, J. [Research Lab. for Mining Chemistry, Hungarian Academy of Sciences, Miskolc-Egyetemvaros (Hungary); Brown, S.D.; Snape, C.E. [Univ. of Strathclyde, Dept. of Pure and Applied Chemistry, Glasgow (United Kingdom)

    1997-12-31

    The uptake of palladium as a conversion catalyst onto coals of different rank was investigated. Palladium fixation occurs by a different mode to that for alkaline earth and first row transition metals. Therefore, the dispersion of relatively high concentration of palladium by an ion sorption process is even possible for bituminous coals. (orig.)

  11. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of 18F-Fluorodeoxyglucose After Radiation Treatment

    International Nuclear Information System (INIS)

    Wilson, George D.; Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L.; Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John; Oliver Wong, Ching Yee; Yan, Di; Marples, Brian; Huang, Jiayi

    2014-01-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm 3 they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: 18 F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism

  12. Tumor Uptake of 64Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer.

    Science.gov (United States)

    Mortimer, Joanne E; Bading, James R; Park, Jinha M; Frankel, Paul H; Carroll, Mary I; Tran, Tri T; Poku, Erasmus K; Rockne, Russell C; Raubitschek, Andrew A; Shively, John E; Colcher, David M

    2018-01-01

    The goal of this study was to characterize the relationship between tumor uptake of 64 Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods: Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including 18 F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent 64 Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h after 64 Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUV max Average intrapatient SUV max ( pt ) was compared between HER2+ and HER2- patients. Results: Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2- (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median pt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2- patients ( P pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease ( P DOTA-trastuzumab in MBC is strongly associated with patient HER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for 64 Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  13. Optimizing fluorescently tethered Hsp90 inhibitor dose for maximal specific uptake by breast tumors

    Science.gov (United States)

    Crouch, Brian T.; Duer, Joy; Wang, Roujia; Gallagher, Jennifer; Hall, Allison; Soo, Mary Scott; Hughes, Philip; Haystead, Timothy A. J.; Ramanujam, Nirmala

    2018-03-01

    Despite improvements in surgical resection, 20-40% of patients undergoing breast conserving surgery require at least one additional re-excision. Leveraging the unique surface expression of heat shock protein 90 (Hsp90), a chaperone protein involved in several key hallmarks of cancer, in breast cancer provides an exciting opportunity to identify residual disease during surgery. We developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens using a fluorescence microendoscope with a field of view of 750 μm and subcellular resolution of 4 μm. HS-27 consists of an FDA approved Hsp90 inhibitor tethered to fluorescein isothiocyanate (EX 488nm, EM 525nm). Here, we optimized ex vivo HS-27 administration in pre-clinical breast cancer models and validated our approach on 21 patients undergoing standard of care ultrasound guided core needle biopsy. HS-27 administration time was fixed at 1- minute to minimize imaging impact on clinical workflow. HS-27 and HS-217 (non-specific control) doses were modulated from 1 μM up to 100 μM to identify the dose maximizing the ratio of specific uptake (HS-27 fluorescence) to non-specific uptake (HS-217 fluorescence). The specificity ratio was maximized at 100 μM and was significantly greater than all other doses (pcancer makes this technology attractive for assessing tumor margins, as one agent can be used for all subtypes.

  14. Three-dimensional positron emission tomography image texture analysis of esophageal squamous cell carcinoma: relationship between tumor 18F-fluorodeoxyglucose uptake heterogeneity, maximum standardized uptake value, and tumor stage.

    Science.gov (United States)

    Dong, Xinzhe; Xing, Ligang; Wu, Peipei; Fu, Zheng; Wan, Honglin; Li, Dengwang; Yin, Yong; Sun, Xiaorong; Yu, Jinming

    2013-01-01

    To explore the relationship of a new PET image parameter, (18)F-fluorodeoxyglucose ((18)F-FDG) uptake heterogeneity assessed by texture analysis, with maximum standardized uptake value (SUV(max)) and tumor TNM staging. Forty consecutive patients with esophageal squamous cell carcinoma were enrolled. All patients underwent whole-body preoperative (18)F-FDG PET/CT. Heterogeneity of intratumoral (18)F-FDG uptake was assessed on the basis of the textural features (entropy and energy) of the three-dimensional images using MATLAB software. The correlations between the textural parameters and SUV(max), histological grade, tumor location, and TNM stage were analyzed. Tumors with higher SUV(max) were seen to be more heterogenous on (18)F-FDG uptake. Significant correlations were observed between T stage and SUV(max) (r(s)=0.390, P=0.013), entropy (rs=0.693, Pheterogeneity and the commonly used simplistic parameter of SUV and tumor stage. Our findings suggest a complementary role of these parameters in the staging and prognosis of esophageal squamous cell carcinoma.

  15. Impact of clinically tested NEP/ACE inhibitors on tumor uptake of [(111)In-DOTA]MG11-first estimates for clinical translation.

    Science.gov (United States)

    Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Valkema, Roelf; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

    2016-12-01

    We have recently shown that treatment of mice with the neutral endopeptidase (NEP) inhibitor phosphoramidon (PA) improves the bioavailability and tumor uptake of biodegradable radiopeptides. For the truncated gastrin radiotracer [(111)In-DOTA]MG11 ([(DOTA)DGlu(10)]gastrin(10-17)), this method led to impressively high tumor-to-kidney ratios. Translation of this concept in the clinic requires the use of certified NEP inhibitors, such as thiorphan (TO) and its orally administered prodrug racecadotril (Race). Besides NEP, angiotensin-converting enzyme (ACE) has also been implicated in the catabolism of gastrin analogs. In the present study, we first compared the effects induced by NEP inhibition (using PA, TO, or Race) and/or by ACE inhibition (using lisinopril, Lis) on the biodistribution profile of [(111)In-DOTA]MG11 in mice. In addition, we compared the efficacy of PA and TO at different administered doses to enhance tumor uptake. [(111)In-DOTA]MG11 was coinjected with (a) vehicle, (b) PA (300 μg), (c) TO (150 μg), (d) Lis (100 μg), (e) PA (300 μg) plus Lis (100 μg), or (f) 30-40 min after intraperitoneal (ip) injection of Race (3 mg) in SCID mice bearing AR42J xenografts. In addition, [(111)In-DOTA]MG11 was coinjected with vehicle, or with progressively increasing amounts of PA (3, 30, or 300 μg) or TO (1.5, 15, and 150 μg) in SCID mice bearing twin A431-CCK2R(+/-) tumors. In all above cases, biodistribution was conducted at 4 h postinjection (pi). During NEP inhibition, the uptake of [(111)In-DOTA]MG11 in the AR42J tumors impressively increased from 1.8 ± 1.0 % ID/g (controls) to 15.3 ± 4.7 % ID/g (PA) and 12.3 ± 3.6 % ID/g (TO), while with Race tumor values reached 6.8 ± 2.8 % ID/g. Conversely, Lis had no effect on tumor uptake and no additive effect when coinjected with PA. During the dose dependence study in mice, PA turned out to be more efficacious in enhancing tumor uptake of [(111)In-DOTA]MG11 in the CCK2R

  16. SU-F-R-13: Decoding 18F-FDG Uptake Heterogeneity for Primary and Lymphoma Tumors by Using Texture Analysis in PET Images

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Yin, Y [Shandong Cancer Hospital and Institute, Jinan, Shandong (China)

    2016-06-15

    Purpose: To explore 18F-FDG uptake heterogeneity of primary tumor and lymphoma tumor by texture features of PET image and quantify the heterogeneity difference between primary tumor and lymphoma tumor. Methods: 18 patients with primary tumor and lymphoma tumor in lung cancer were enrolled. All patients underwent whole-body 18F-FDG PET/CT scans before treatment. Texture features, based on Gray-level Co-occurrence Matrix, second and high order matrices are extracted from code using MATLAB software to quantify 18F-FDG uptake heterogeneity. The relationships of volume between energy, entropy, correlation, homogeneity and contrast were analyzed. Results: For different cases, tumor heterogeneity was not the same. Texture parameters (contrast, entropy, and correlation) of lymphoma were lower than primary tumor. On the contrast, the texture parameters (energy, homogeneity and inverse different moment) of lymphoma were higher than primary tumor. Significantly, correlations were observed between volume and energy (primary, r=−0.194, p=0.441; lymphoma, r=−0.339, p=0.582), homogeneity (primary, r=−0.146, p=0.382; lymphoma, r=−0.193, p=0.44), inverse difference moment (primary, r=−0.14, p=0.374; lymphoma, r=−0.172, p=0.414) and a positive correlation between volume and entropy (primary, r=0.233, p=0.483; lymphoma, r=0.462, p=0.680), contrast (primary, r=0.159, p=0.399; lymphoma, r=0.341, p=0.584), correlation (primary, r=0.027, p=0.165; lymphoma, r=0.046, p=0.215). For the same patient, energy for primary and lymphoma tumor is equal. The volume of lymphoma is smaller than primary tumor, but the homogeneity were higher than primary tumor. Conclusion: This study showed that there were effective heterogeneity differences between primary and lymphoma tumor by FDG-PET image texture analysis.

  17. SU-F-R-13: Decoding 18F-FDG Uptake Heterogeneity for Primary and Lymphoma Tumors by Using Texture Analysis in PET Images

    International Nuclear Information System (INIS)

    Ma, C; Yin, Y

    2016-01-01

    Purpose: To explore 18F-FDG uptake heterogeneity of primary tumor and lymphoma tumor by texture features of PET image and quantify the heterogeneity difference between primary tumor and lymphoma tumor. Methods: 18 patients with primary tumor and lymphoma tumor in lung cancer were enrolled. All patients underwent whole-body 18F-FDG PET/CT scans before treatment. Texture features, based on Gray-level Co-occurrence Matrix, second and high order matrices are extracted from code using MATLAB software to quantify 18F-FDG uptake heterogeneity. The relationships of volume between energy, entropy, correlation, homogeneity and contrast were analyzed. Results: For different cases, tumor heterogeneity was not the same. Texture parameters (contrast, entropy, and correlation) of lymphoma were lower than primary tumor. On the contrast, the texture parameters (energy, homogeneity and inverse different moment) of lymphoma were higher than primary tumor. Significantly, correlations were observed between volume and energy (primary, r=−0.194, p=0.441; lymphoma, r=−0.339, p=0.582), homogeneity (primary, r=−0.146, p=0.382; lymphoma, r=−0.193, p=0.44), inverse difference moment (primary, r=−0.14, p=0.374; lymphoma, r=−0.172, p=0.414) and a positive correlation between volume and entropy (primary, r=0.233, p=0.483; lymphoma, r=0.462, p=0.680), contrast (primary, r=0.159, p=0.399; lymphoma, r=0.341, p=0.584), correlation (primary, r=0.027, p=0.165; lymphoma, r=0.046, p=0.215). For the same patient, energy for primary and lymphoma tumor is equal. The volume of lymphoma is smaller than primary tumor, but the homogeneity were higher than primary tumor. Conclusion: This study showed that there were effective heterogeneity differences between primary and lymphoma tumor by FDG-PET image texture analysis.

  18. Alterations of tumor suppressor genes (Rb, p16, p27 and p53) and an increased FDG uptake in lung cancer

    International Nuclear Information System (INIS)

    Sasaki, Masayuki; Sugio, Kenji; Kuwabara, Yasuo

    2003-01-01

    The FDG uptake in lung cancer is considered to reflect the degree of malignancy, while alterations of some tumor suppressor genes are considered to be related to the malignant biological behavior of tumors. The aim of this study is to examine the relationship between FDG-PET and alterations in the tumor suppression genes of lung cancer. We examined 28 patients with primary lung cancer who underwent FDG-PET before surgery consisting of 17 patients with adenocarcinoma, 10 with squamous cell carcinoma and 1 with large cell carcinoma. The FDG-PET findings were evaluated based on the standardized uptake value (SUV). Alterations in the tumor suppressor genes, Rb, p16, p27 and p53, were evaluated immunohistochemically. The FDG uptake in lung cancer with alteration in each tumor suppressor gene tended to be higher than in those genes without alterations, although the differences were not significant. In 15 tumors with alterations in either tumor suppressor genes, the FDG uptake was 6.83±3.21. On the other hand, the mean FDG uptake was 1.95 in 2 tumors without alterations in any genes. The difference in the FDG uptake between the 2 groups was statistically significant (p<0.001). In conclusion, the presence of abnormalities in the tumor suppressor genes, which results in an accelerated cell proliferation, is thus considered to increase the FDG uptake in lung cancer. (author)

  19. Novel antibody conjugates for enhanced tumor uptake. Final report, September 1, 1992--August 31, 1997

    International Nuclear Information System (INIS)

    Thakur, M.

    1997-01-01

    Progress in three areas of research is summarized. These are as follows: Labeling Monoclonal antibodies (MAbs) with Tc-99m and Re-186; human melanoma tumors and specific MAbs; evaluation of biological response modifiers (BRM). The techniques of labeling MAbs (IgM, IgG, F(ab') 2 or F(ab')) with Tc-99m was developed in the author's laboratory in 1989 and that with Re-186 in 1992. The techniques are in daily use in the laboratory since then and are adapted to a convenient kit formulation. The metal ions are bound at MAb sulfhydryls generated by a controlled reduction of a pair of disulfide groups. At least two types of MAbs labeled with Tc-99m by this method have been administered into patients and excellent diagnostic results have been obtained. Over the past two and a half years the author has been successfully growing human melanoma tumors in athymic Balb/c nude mice. The cell LINE, WM-9, was obtained from Dr. D Herlyn's laboratory at Wistar Institute in Philadelphia. Sufficient quantities of antihuman melanoma specific antibodies ME 31.3 (Wistar, IgG-1) and MEM-136 (Hybritech, IgG-2A) and their F(ab') 2 fragments are also available in the laboratory. The use of BRM is a rapidly evolving field. Over the past four years, the author has evaluated a number of BRMs in a quest for agents that may augment MAb tumor uptake. These included interferon-α; a pokeweed mitogen and Ukrain, an alkaloid separated from a plant Chelideonium Majis. In these preliminary studies, normal Balb/c mice were used and the BRMs were given i.p. one hour prior to the i.v. administration of tumor necrosis factor or an MAb (TNT-F(ab') 2 ) labeled with Tc-99m which served as an imaging agent. Animals were sacrificed at 1.5 hr or 4 hrs post-injection. Highlights of the work are given here in a table

  20. Novel antibody conjugates for enhanced tumor uptake. Final report, September 1, 1992--August 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, M.

    1997-12-31

    Progress in three areas of research is summarized. These are as follows: Labeling Monoclonal antibodies (MAbs) with Tc-99m and Re-186; human melanoma tumors and specific MAbs; evaluation of biological response modifiers (BRM). The techniques of labeling MAbs (IgM, IgG, F(ab{prime}){sub 2} or F(ab{prime})) with Tc-99m was developed in the author`s laboratory in 1989 and that with Re-186 in 1992. The techniques are in daily use in the laboratory since then and are adapted to a convenient kit formulation. The metal ions are bound at MAb sulfhydryls generated by a controlled reduction of a pair of disulfide groups. At least two types of MAbs labeled with Tc-99m by this method have been administered into patients and excellent diagnostic results have been obtained. Over the past two and a half years the author has been successfully growing human melanoma tumors in athymic Balb/c nude mice. The cell LINE, WM-9, was obtained from Dr. D Herlyn`s laboratory at Wistar Institute in Philadelphia. Sufficient quantities of antihuman melanoma specific antibodies ME 31.3 (Wistar, IgG-1) and MEM-136 (Hybritech, IgG-2A) and their F(ab{prime}){sub 2} fragments are also available in the laboratory. The use of BRM is a rapidly evolving field. Over the past four years, the author has evaluated a number of BRMs in a quest for agents that may augment MAb tumor uptake. These included interferon-{alpha}; a pokeweed mitogen and Ukrain, an alkaloid separated from a plant Chelideonium Majis. In these preliminary studies, normal Balb/c mice were used and the BRMs were given i.p. one hour prior to the i.v. administration of tumor necrosis factor or an MAb (TNT-F(ab{prime}){sub 2}) labeled with Tc-99m which served as an imaging agent. Animals were sacrificed at 1.5 hr or 4 hrs post-injection. Highlights of the work are given here in a table.

  1. Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

    Science.gov (United States)

    Hoopes, P. Jack; Petryk, Alicia A.; Tate, Jennifer A.; Savellano, Mark S.; Strawbridge, Rendall R.; Giustini, Andrew J.; Stan, Radu V.; Gimi, Barjor; Garwood, Michael

    2013-02-01

    The predicted success of nanoparticle based cancer therapy is due in part to the presence of the inherent leakiness of the tumor vascular barrier, the so called enhanced permeability and retention (EPR) effect. Although the EPR effect is present in varying degrees in many tumors, it has not resulted in the consistent level of nanoparticle-tumor uptake enhancement that was initially predicted. Magnetic/iron oxide nanoparticles (mNPs) have many positive qualities, including their inert/nontoxic nature, the ability to be produced in various sizes, the ability to be activated by a deeply penetrating and nontoxic magnetic field resulting in cell-specific cytotoxic heating, and the ability to be successfully coated with a wide variety of functional coatings. However, at this time, the delivery of adequate numbers of nanoparticles to the tumor site via systemic administration remains challenging. Ionizing radiation, cisplatinum chemotherapy, external static magnetic fields and vascular disrupting agents are being used to modify the tumor environment/vasculature barrier to improve mNP uptake in tumors and subsequently tumor treatment. Preliminary studies suggest use of these modalities, individually, can result in mNP uptake improvements in the 3-10 fold range. Ongoing studies show promise of even greater tumor uptake enhancement when these methods are combined. The level and location of mNP/Fe in blood and normal/tumor tissue is assessed via histopathological methods (confocal, light and electron microscopy, histochemical iron staining, fluorescent labeling, TEM) and ICP-MS. In order to accurately plan and assess mNP-based therapies in clinical patients, a noninvasive and quantitative imaging technique for the assessment of mNP uptake and biodistribution will be necessary. To address this issue, we examined the use of computed tomography (CT), magnetic resonance imaging (MRI), and Sweep Imaging With Fourier Transformation (SWIFT), an MRI technique which provides a

  2. Water uptake and motion in highly densified bentonite

    International Nuclear Information System (INIS)

    Kahr, G.; Mueller-Vonmoos, F.; Kraehenbuehl, F.; Stoeckli, H.F.

    1986-07-01

    Water uptake by the bentonites MX-80 and Montigel was investigated according to the classical method of determination of the heat immersion and the adsorption-desorption isotherms. In addition, the layer expansion of the montmorillonite was measured as a function of the water content. The evaluation of the adsorption isotherms according to Dubinin-Radushkevich and the stratification distances determined by x-ray confirmed gradual water uptake. Up to 10% water content, the water is adsorbed as a monolayer, up to 20%, as a bimolecular layer around the interlayer cations. The partial specific entropy could be determined from the approximative calculation of the partial specific enthalpy from the heats of immersion and the free enthalpy from the adsorption isotherms. From this it is evident that the interlayer water shows a high degree of order. In this condition, the mobility of the water molecules is considerably lower than in free water. From the adsorption isotherm and the layer expansion observed, it can be assumed that water can appear in the pore space only from approximately 25% water content. The spaces outwith the interlayer space and the surfaces of the montmorillonite particles are considered as pore space. If free swelling is prevented and with dry densities greater than 1.8 Mg/m/sup 3/ for the highly compacted bentonites, water uptake causes a drastic reduction of the original pore space so that practically all the water is in the interlayer space. Calculation of the swelling pressure from the adsorption isotherms gives a good approximation of the measured swelling pressures. A montmorillonite surface of ca. 750 m/sup 2//g for both bentonites can be derived from a Dubinin-Radushkevich analysis of the adsorption isotherm. Water uptake into the compacted unsaturated bentonites can be described as diffusion with a diffusion coefficient of the order of magnitude of 3.10/sup -10/ m/sup 2//s. (author)

  3. Constructing aptamer anchored nanovesicles for enhanced tumor penetration and cellular uptake of water soluble chemotherapeutics.

    Science.gov (United States)

    Li, Xin; Zhu, Xiumei; Qiu, Liyan

    2016-04-15

    Polymersomes represent a promising pharmaceutical vehicle for the delivery of hydrophilic therapeutic agents. However, modification of polymersomes with molecules that confer targeting functions remains challenging because of the strict requirements regarding the weight fractions of the hydrophilic and hydrophobic block polymers. In this study, based on the compatibility between cholesterol and polymeric carriers, polymersomes self-assembled by amphiphilic graft polyphosphazenes were endowed with a targeting function by incorporating the cholesterol-linked aptamer through a simple dialysis method. The aqueous interior of the polymersomes was employed to encapsulate water-soluble doxorubicin hydrochloride. In vivo experiments in tumor-bearing mice showed that the aptamer-anchored vesicle targeted accumulation at the tumor site, favorable penetration through tumor tissue, and incremental endocytosis into tumor cells. Correspondingly, the aptamer-anchored vesicle decreased systemic toxicity and effectively suppressed the growth of subcutaneous MCF-7 xenografts. These findings suggested that vesicles modified with targeted groups via hydrophobic supermolecular interactions could provide a platform for selective delivery of hydrophilic drug. Polymersomes have represented a promising type of pharmaceutical vehicles due to their predominant physical properties. However, it is still a challenge to endow polymersomes with active target function because of strict requirements of the weight fractions of hydrophilic polymer block to hydrophobic one. In this research, by taking advantage of the supermolecular interactions between amphiphilic graft polyphosphazene and cholesterol which was linked to aptamer AS1411, we prepared a targeted functional polymersome (PEP-DOX·HCl-Ap) through a simple method with high loading of water soluble anti-cancer drug doxorubicin hydrochloride. The in vivo experiments in MCF-7 tumor-bearing mice demonstrated several advantages of PEP

  4. Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

    Science.gov (United States)

    Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

    2012-01-01

    Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

  5. Cadmium-109 uptake by tumors derived from Balb C/3T3 cell lines with varying degrees of the transformed phenotype

    International Nuclear Information System (INIS)

    Morton, K.; Alazraki, N.; Winge, D.; Lynch, R.E.

    1986-01-01

    To determine if tumors are rich in metallothionein, the authors measured the vivo uptake of subcutaneously-injected carrier-free cadmium-109 in tumors and in normal tissues of Balb/C mice. The tumors were grown in the mice from cultured Balb/3T3 cells transformed by the Moloney murine sarcoma virus. Uptake of cadmium-109 per gram of tissue was greatest for liver, kidney, and spleen. However, tumor uptake of cadmium-109 was markedly greater than that in blood, skeletal muscle, bones, intestine or adipose tissue. B Sephadex G-75 chromatography, the radioactivity in tumor and in liver lysates eluted with cytochrome-C, a molecule similar in molecular weight to metal-lothionein. To determine if metallothionein levels are related to the degree of malignancy of tumors, cadmium-109 uptake in the tumors from the virally-transformed cells was compared to that in tumors from non-transformed Balb/3T3 cells and two derivative chemically transformed cell lines. There was strong correlation between the substrate-independent growth in soft agarose of the four cell lines, the rate of growth of the corresponding tumors, and the amount of cadmium-109 uptake in the tumors. The authors conclude that metallothionein levels may be elevated in tumors as a function of the degree of expression of the transformed phenotype

  6. Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans

    DEFF Research Database (Denmark)

    Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj

    2003-01-01

    BACKGROUND: Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin....../or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow....... Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (Palpha...

  7. Effect of tumour mass animal gender on specific uptake of [99Tc] pertechnetate in the EMT6 tumor in mice

    International Nuclear Information System (INIS)

    Maddalena, D.J.; Snowdon, G.M.

    1990-01-01

    The effects of tumour mass and animal gender on tumour uptake of [ 99m Tc] pertechnetate were examined in balb/c mice bearing an EMT-6 tumour showing high affinity for pertechnetate. The injected dose per gram found in the tumours appears to be inversely related to the tumour mass with good correlation suggesting a high specific uptake. The tumours grown in female mice had greater uptakes and rates of uptake than those grown in the male mice. Studies carried out in animals treated with perchlorate to block active anion transport showed low pertechnetate uptake into the tumours suggesting that the high affinity of 99m TcO 4 - for the tumour was due to a specific 99m TcO 4 - transport mechanism. 15 refs., 3 tabs., 3 figs

  8. Co-administration of succinylated gelatine with a 99mTc-bombesin analogue, effects on pharmacokinetics and tumor uptake

    International Nuclear Information System (INIS)

    Liolios, Christos C.; Xanthopoulos, Stavros; Loudos, George; Varvarigou, Alexandra D.; Sivolapenko, Gregory B.

    2016-01-01

    The bombesin analogue, [ 99m Tc-GGC]-(Ornithine) 3 -BN(2-14), 99m Tc-BN-O, targeting gastrin releasing peptide receptors (GRPrs) on the surface of tumors, was pre-clinically investigated as potential imaging agent for single photon emission computed tomography (SPECT). In addition, the improvement of its pharmacokinetic profile (PK) was investigated through the co-administration of a succinylated gelatin plasma expander (Gelofusine), aiming to reduce its kidney accumulation and enhance its tumor-to-normal tissue contrast ratios. Biodistribution data were collected from normal mice and rats, and PC-3 tumor bearing mice, in reference to its PK, metabolism and tumor uptake. Imaging data were also collected from PC-3 tumor bearing mice. Biodistribution and imaging experiments showed that 99m Tc-BN-O was able to efficiently localize the tumor (5.23 and 7.00% ID/g at 30 and 60 min post injection, respectively), while at the same time it was rapidly cleared from the circulation through the kidneys. HPLC analysis of kidney samples, collected at 60 min p.i. from normal mice and rats, showed that the majority of radioactivity detected was due to intact peptide i.e. 56% for mice and 73% for rats. Co-administration of 99m Tc-BN-O with Gelo resulted in the reduction of kidney uptake in both animal models. The integrated area under the curve (AUC 30–60 min ) from the concentration–time plots of kidneys was decreased in both mice and rats by 25 and 50%, respectively. In PC-3 tumor bearing mice, an increase of tumor uptake (AUC tumor increased by 69%) was also observed with Gelo. An improvement in tumor-to-blood and tumor-to-normal tissue ratios was noted in all cases with the exception of the pancreas, which normally expresses GRPr. The results of this preclinical study may also be extended to other similar peptides, which are utilized in prostate cancer imaging and present similar PK profile.

  9. Correlation of intra-tumor 18F-FDG uptake heterogeneity indices with perfusion CT derived parameters in colorectal cancer.

    Science.gov (United States)

    Tixier, Florent; Groves, Ashley M; Goh, Vicky; Hatt, Mathieu; Ingrand, Pierre; Le Rest, Catherine Cheze; Visvikis, Dimitris

    2014-01-01

    Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis. Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-valueheterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization.

  10. In vitro study of tumor seeking radiopharmaceutical uptake by human breast cancer cell line MCF-7 after paclitaxel treatment

    International Nuclear Information System (INIS)

    Choi, Joon Young; Choi, Yong; Choe, Yearn Seong; Lee, Kyung Han; Kim, Byung Tae

    2007-01-01

    This study was designed to investigate the cellular uptake of various tumor imaging radiopharmaceuticals in human breast cancer cells before and after paclitaxel exposure considering viable cell number. F-18-fluorodeoxyglucose, C-11-methionine. TI-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin were used to evaluate the cellular uptake in MCF-7 cells. MCF-7 cells were cultured in multi-well plates. Wells were divided into DMSO exposure control group, and paclitaxel exposure group. The exposure durations of paclitaxel with 10 nM or 100 nM were 2 h, 6 h, 12 h, 24 h, and 48 h. Viable cell fraction was reduced as the concentration and exposure time of paclitaxel increased. After 10 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was not reduced significantly, irrespective of exposure time and viable cell fraction. After 100 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was enhanced significantly irrespective of viable cell fraction. The peak uptake was observed in experimental groups with paclitaxel exposure for 6 to 48 h according the type of radiopharmaceutical. When the cellular uptake was adjusted for the viable cell fraction and cell count, the peak cellular uptake was observed in experimental groups with paclitaxel exposure for 48 h, irrespective of the type of radiopharmaceutical. The cellular uptake of F-18-fluorodeoxyglucose, C-11-methionine, TI-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin did not reflect viable cell number in MCF-7 cells after paclitaxel exposure for up to 48 h

  11. Smart Nanoparticles Undergo Phase Transition for Enhanced Cellular Uptake and Subsequent Intracellular Drug Release in a Tumor Microenvironment.

    Science.gov (United States)

    Ye, Guihua; Jiang, Yajun; Yang, Xiaoying; Hu, Hongxiang; Wang, Beibei; Sun, Lu; Yang, Victor C; Sun, Duxin; Gao, Wei

    2018-01-10

    Inefficient cellular uptake and intracellular drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. To overcome both problems, we designed a smart nanoparticle that undergoes phase transition in a tumor microenvironment (TME). The smart nanoparticle is generated using a lipid-polypetide hybrid nanoparticle, which comprises a PEGylated lipid monolayer shell and a pH-sensitive hydrophobic poly-l-histidine core and is loaded with the antitumor drug doxorubicin (DOX). The smart nanoparticle undergoes a two-step phase transition at two different pH values in the TME: (i) At the TME (pH e : 7.0-6.5), the smart nanoparticle swells, and its surface potential turns from negative to neutral, facilitating the cellular uptake; (ii) After internalization, at the acid endolysosome (pH endo : 6.5-4.5), the smart nanoparticle dissociates and induces endolysosome escape to release DOX into the cytoplasm. In addition, a tumor-penetrating peptide iNRG was modified on the surface of the smart nanoparticle as a tumor target moiety. The in vitro studies demonstrated that the iNGR-modified smart nanoparticles promoted cellular uptake in the acidic environment (pH 6.8). The in vivo studies showed that the iNGR-modified smart nanoparticles exerted more potent antitumor efficacy against late-stage aggressive breast carcinoma than free DOX. These data suggest that the smart nanoparticles may serve as a promising delivery system for sequential uptake and intracellular drug release of antitumor agents. The easy preparation of these smart nanoparticles may also have advantages in the future manufacture for clinical trials and clinical use.

  12. Effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate in animals: concise communication

    International Nuclear Information System (INIS)

    Bradley, W.P.; Alderson, P.O.; Weiss, J.F.

    1979-01-01

    To investigate the effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate, 20 weanling Sprague-Dawley rats were maintained for 6 to 8 weeks on a low-iron diet. Eighteen littermates were maintained on a normal iron diet and served as controls. Animals received 10 μCi Ga-67 citrate, and urine and feces were collected for 48 h. The animals were then killed, tissue samples were obtained, and serum iron and unsaturated iron-binding capacity (UIBC) were measured. The accumulation of Ga-67 in the liver and spleen (% injected dose) was markedly increased in iron-deficient animals and urinary excretion was reduced. Tumor uptake was not significantly different in iron-deficient and control animals, but tumor-to-blood ratios were elevated (p < 0.001) in the iron-deficient animals because of low blood levels of Ga-67. The liver and spleen accumulation of Ga-67 correlated significantly (p < 0.001) with the UIBC. The results show that iron deficiency alters the distribution of Ga-67 citrate, and suggest that the variable liver-spleen uptake seen in clinical Ga-67 images may be explained, in part, by changes in serum iron and UIBC

  13. Prognostic value of lymph node-to-primary tumor standardized uptake value ratio in endometrioid endometrial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

    2018-01-15

    To determine whether the relative metabolic activity of pelvic or para-aortic LN compared with that of primary tumor measured by preoperative [{sup 18}F]FDG PET/CT scan has prognostic value in patients with endometrioid endometrial carcinoma. We retrospectively reviewed patients with endometrioid endometrial carcinoma who underwent preoperative [{sup 18}F]FDG PET/CT scans. Prognostic values of PET/CT-derived metabolic variables such as maximum standardized uptake value (SUV) of the primary endometrial carcinoma (SUV{sub Tumor}) and LN (SUV{sub LN}), and the LN-to-endometrial carcinoma SUV ratio (SUV{sub LN} / SUV{sub Tumor}) were assessed. Clinico-pathological data, imaging data, and treatment results were reviewed for 107 eligible patients. Median post-surgical follow-up was 23 months (range, 6-60), and 7 (6.5%) patients experienced recurrence. Regression analysis showed that SUV{sub LN} / SUV{sub Tumor} (P < 0.001), SUV{sub LN} (P = 0.003), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.006), and tumor grade (P = 0.011) were risk factors of recurrence. Multivariate regression analysis revealed that FIGO stage (P = 0.034) was the independent risk factor of recurrence. SUV{sub LN} / SUV{sub Tumor} showed significant correlation with FIGO stage (P < 0.001), LN metastasis (P < 0.001), lymphovascular space invasion (P < 0.001), recurrence (P = 0.001), tumor grade (P < 0.001), and deep myometrial invasion of tumor (P = 0.022). Patient groups categorized by SUV{sub LN} / SUV{sub Tumor} showed significant difference in progression-free survival (Log-rank test, P = 0.001). Preoperative SUV{sub LN} / SUV{sub Tumor} measured by [{sup 18}F]FDG PET/CT was significantly associated with recurrence, and may become a novel prognostic factor in patients with endometrioid endometrial carcinoma. (orig.)

  14. Predicting pathologic tumor response to chemoradiotherapy with histogram distances characterizing longitudinal changes in 18F-FDG uptake patterns

    Science.gov (United States)

    Tan, Shan; Zhang, Hao; Zhang, Yongxue; Chen, Wengen; D’Souza, Warren D.; Lu, Wei

    2013-01-01

    Purpose: A family of fluorine-18 (18F)-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) features based on histogram distances is proposed for predicting pathologic tumor response to neoadjuvant chemoradiotherapy (CRT). These features describe the longitudinal change of FDG uptake distribution within a tumor. Methods: Twenty patients with esophageal cancer treated with CRT plus surgery were included in this study. All patients underwent PET/CT scans before (pre-) and after (post-) CRT. The two scans were first rigidly registered, and the original tumor sites were then manually delineated on the pre-PET/CT by an experienced nuclear medicine physician. Two histograms representing the FDG uptake distribution were extracted from the pre- and the registered post-PET images, respectively, both within the delineated tumor. Distances between the two histograms quantify longitudinal changes in FDG uptake distribution resulting from CRT, and thus are potential predictors of tumor response. A total of 19 histogram distances were examined and compared to both traditional PET response measures and Haralick texture features. Receiver operating characteristic analyses and Mann-Whitney U test were performed to assess their predictive ability. Results: Among all tested histogram distances, seven bin-to-bin and seven crossbin distances outperformed traditional PET response measures using maximum standardized uptake value (AUC = 0.70) or total lesion glycolysis (AUC = 0.80). The seven bin-to-bin distances were: L2 distance (AUC = 0.84), χ2 distance (AUC = 0.83), intersection distance (AUC = 0.82), cosine distance (AUC = 0.83), squared Euclidean distance (AUC = 0.83), L1 distance (AUC = 0.82), and Jeffrey distance (AUC = 0.82). The seven crossbin distances were: quadratic-chi distance (AUC = 0.89), earth mover distance (AUC = 0.86), fast earth mover distance (AUC = 0.86), diffusion distance (AUC = 0.88), Kolmogorov-Smirnov distance (AUC = 0.88), quadratic form distance

  15. Tumor implantation model for rapid testing of lymphatic dye uptake from paw to node in small animals

    Science.gov (United States)

    DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2015-03-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue - used in the sentinel lymph node procedure - in normal and tumor-bearing animals, and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

  16. Avid 18F-FDG Uptake in Idiopathic Tumoral Calcinosis Mimicking Lymph Node Metastasis

    DEFF Research Database (Denmark)

    Strandberg, Jesper; Zacho, Helle D

    2017-01-01

    Tumoral calcinosis is a benign condition characterized by periarticular calcified lesions that is frequently observed in patients with chronic renal failure. Tumoral calcinosis often presents with subcutaneous masses and joint swelling. We present a case of tumoral calcinosis with dramatically in...

  17. Factors affecting ¹⁸F FDOPA standardized uptake value in patients with primary brain tumors after treatment.

    Science.gov (United States)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

    2015-04-01

    To investigate the factors affecting (18)F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent (18)F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (±42.27), 16.04 (±29.08) and 28.62 (±34.49) months respectively. (18)F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect (18)F FDOPA uptake. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Carbogen Breathing Differentially Enhances Blood Plasma Volume and 5-Fluorouracil Uptake in Two Murine Colon Tumor Models with a Distinct Vascular Structure

    Directory of Open Access Journals (Sweden)

    Hanneke W.M. van Laarhoven

    2006-06-01

    Full Text Available For the systemic treatment of colorectal cancer, 5-fluorouracil (FU-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2 may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.

  19. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake

    Energy Technology Data Exchange (ETDEWEB)

    Dearling, Jason L.J. [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)], E-mail: j.dearling@hotmail.com; Flynn, Aiden A.; Qureshi, Uzma [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom); Whiting, Stephen [Department of Clinical Biochemistry, Royal Free and University College Medical School, UCL, Royal Free Campus, London NW3 2PF (United Kingdom); Boxer, Geoffrey M.; Green, Alan; Begent, Richard H.J.; Pedley, R. Barbara [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)

    2009-11-15

    Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([{sup 125}I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [{sup 131}I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., {approx}15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., {approx}80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6{+-}12.9 vs. treated mean survival of 39.1{+-}30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.

  20. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake

    International Nuclear Information System (INIS)

    Dearling, Jason L.J.; Flynn, Aiden A.; Qureshi, Uzma; Whiting, Stephen; Boxer, Geoffrey M.; Green, Alan; Begent, Richard H.J.; Pedley, R. Barbara

    2009-01-01

    Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([ 125 I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [ 131 I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., ∼15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., ∼80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6±12.9 vs. treated mean survival of 39.1±30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.

  1. Low carbohydrate diet before 18F-FDG tumor imaging contributes to reduce myocardial 18F-FDG uptake

    International Nuclear Information System (INIS)

    Miao Weibing; Chen Shaoming; Zheng Shan; Wu Jing; Peng Jiequan; Jiang Zhihong

    2014-01-01

    Objective: To evaluate whether low carbohydrate diet before 18 F-FDG tumor imaging could reduce myocardial 18 F-FDG uptake. Methods: From April 2011 to January 2012, 70 patients were enrolled in this study.They were randomly divided into control group (34 cases) and test group (36 cases). Patients in control group were on regular diet, while those in test group had low carbohydrate diet in the evening before imaging. Blood samples were taken before injection of 18 F-FDG for the measurement of serum glucose, free fatty acid,insulin and ketone body. Whole body 18 F-FDG tomography was performed with dual-head coincidence SPECT. The myocardial uptake of FDG was assessed visually and scored as 0 for no uptake, 1 for uptake lower than liver, 2 for uptake similar to liver, 3 for uptake higher than liver, and 4 for remarkable uptake.The ratio of myocardium to liver (H/L) was calculated. Two-sample t test, Wilcoxon rank sum test and linear correlation analysis were performed. Results: The myocardial uptake in test group was significantly lower than that in control group with H/L ratios of 0.94±0.57 and 1.50±1.04, respectively (t=-2.75, P<0.05). The concentrations of serum free fatty acid and ketone body in test group were significantly higher than those in control group: (0.671±0.229) mmol/L vs (0.547±0.207) mmol/L and (0.88±0.60) mmol/L vs (0.57±0.32) mmol/L, t=2.38 and 2.67, both P<0.05. The concentrations of glucose and insulin were (5.28±1.06) mmol/L and (35.16±33.70) pmol/L in test group, which showed no significant difference with those in control group ((5.19±0.78) mmol/L and (41.64±35.13) pmol/L, t=0.39 and-0.79, both P>0.05). A negative correlation was found between the myocardial uptake of 18 F-FDG and serum free fatty acid/ketone body concentration (r=-0.40, -0.33, both P<0.01), respectively. There was no correlation between the myocardial uptake of 18 F-FDG and glucose/insulin (r=-0.02, 0.13, both P>0.05), respectively. Conclusion: Low carbohydrate

  2. Assessment of early changes in 3H-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression

    International Nuclear Information System (INIS)

    Zhao, Songji; Kuge, Yuji; Zhao, Yan; Takeuchi, Satoshi; Hirata, Kenji; Takei, Toshiki; Shiga, Tohru; Dosaka-Akita, Hirotoshi; Tamaki, Nagara

    2013-01-01

    The purpose of this study was to evaluate whether early changes in 3′-deoxy-3′- 3 H-fluorothymidine ( 3 H-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR). An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of 3 H-FLT and 18 F-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed. High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of 3 H-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 ± 0.09, 0.36 ± 0.06, 0.59 ± 0.11%ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p < 0.01 vs. control), but those of 18 F-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 ± 2.4%, 6.2 ± 1.8%, and 10.4 ± 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p < 0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p < 0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in

  3. Tumor and liver uptake models of /sup 67/Ga-citrate

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A; Ando, I; Sanada, S; Hiraki, T; Hisada, K

    1985-03-01

    After administration /sup 67/Ga concentrates with time in lysosomes from the cytoplasm of liver cells. The lysosomal role in the accumulation of /sup 67/Ga in the liver cell is weakened upon transformation of the liver cell into a malignant tumor cell. In malignant tumors (except for hepatoma) the lysosome does not play a major role in the tumor concentration of /sup 67/Ga. /sup 67/Ga is bound to acid mucopolysaccharides (keratan polysulfate, etc.) in both tumor and liver. In liver cells, large amounts of /sup 67/Ga are transported into lysosomes with these acid mucopolysaccharides, and in hepatoma cells, quite large amounts of /sup 67/Ga are transported into lysosomes with these acid mucopolysaccharides. In malignant tumor cells (except for hepatoma) the effect is much smaller, the acid mucopolysaccharides transporting very little /sup 67/Ga into lysosome. The /sup 67/Ga is concentrated in viable tumor tissue within malignant tissue but hardly at all in necrotic tumor tissue, and concentrates avidly in inflammatory infiltration around tumor cells. Plenty of /sup 67/Ga is found in liver but very little in connective tissue associated with the liver.

  4. Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT

    International Nuclear Information System (INIS)

    Büsing, Karen A.; Schönberg, Stefan O.; Brade, Joachim; Wasser, Klaus

    2013-01-01

    Introduction: Chronically altered glucose metabolism interferes with 18 F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in 18 F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on 18 F-FDG uptake in tumors and biodistribution in normal organ tissues. Methods: 18 F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index > 25. The maximum standardized uptake value (SUV max ) of normal organs and the main tumor site was measured. Differences in SUV max in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance. Results: Increased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUV max in muscle cells and fat, whereas the mean cerebral SUV max was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity. Conclusions: Changes in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases

  5. Nutrient Uptake by High-Yielding Cotton Crop in Brazil

    Directory of Open Access Journals (Sweden)

    José Luís Vilela Vieira

    2018-02-01

    Full Text Available ABSTRACT: Determining nutrient uptake and accumulation rates by cotton crops is important to define management strategies, especially for transgenic varieties, which are cultivated using high-technology approaches that require substantial investment to maximize yield. Currently in Brazil, the states of Bahia and Mato Grosso are responsible for 84.4 % of the total cotton growing area. In the present study, two trials were conducted in 2013, one that involved planting FM 940 GLT, FM 980 GLT, and FM 913 GLT varieties in the state of Bahia and the other which involved FM 940 GLT and FM 980 GLT varieties in the state of Mato Grosso. The aim of the two trials was to represent the two regions that currently encompass the largest areas of cotton cultivation. Tissue samples, consisting of leaves, stems, and reproductive components, were collected eleven times during the crop cycle for determination of nutrient content and shoot dry matter. After weighing, plant tissue samples were dried and ground to determine nutrient contents. Because there were no overall differences in nutrient contents and biomass accumulation of the varieties during the crop cycle, we undertook joint analysis of the data from all varieties at each site. Favorable climatic conditions in Bahia promoted plant biomass production that was twice as much as plants grown in Mato Grosso, with cotton yields of 6.2 and 3.8 t ha−1 of lint and seed, respectively. The maximum nutrient accumulation occurred between 137-150 days after emergence (DAE for N; 143-148 for P; 172-185 for K; 100 for Ca; 144-149 for Mg; and 153-158 for S. Maximum uptake ranged from 218-362 kg ha−1 N; 26-53 kg ha−1 P; 233-506 kg ha−1 K; 91-202 kg ha−1 Ca; 28-44 kg ha−1 Mg; and 19-61 kg ha−1 S. On average, the sites revealed nutrient export of 14, 2, 23, 3, 2, and 2 kg t−1 of lint and seed for N, P, K, Ca, Mg, and S, respectively, with little variation among sites. Extraction of nutrients per area by cotton

  6. [111In-DTPA]octreotide tumor uptake in GEPNET liver metastases after intra-arterial administration: An overview of preclinical and clinical observations and implications for tumor radiation dose after peptide radionuclide therapy

    NARCIS (Netherlands)

    S.E. Pool (Stefan); B.L. Kam (Boen); G.A. Koning (Gerben); M. Konijnenberg (Mark); T.L.M. ten Hagen (Timo); W.A.P. Breeman (Woulter); E.P. Krenning (Eric); M. de Jong (Marcel); C.H.J. van Eijck (Casper)

    2014-01-01

    textabstractAims: With the aim to improve peptide receptor radionuclide therapy effects in patients with gastroenteropancreatic neuroendocrine tumor (GEPNET) liver metastases we explored the effect of intra-arterial (IA) administration of [111In-DTPA]octreotide (111In-DTPAOC) on tumor uptake in an

  7. Defining PET standardized uptake value threshold for tumor delineation with metastatic lymph nodes in head and neck cancer

    International Nuclear Information System (INIS)

    Suzuki, Osamu; Nishiyama, Kinji; Morimoto, Masahiro; Nakajima, Aya; Nakamura, Satoaki; Yoshino, Kunitoshi; Hashiguchi, Hajime; Tanaka, Kanji

    2012-01-01

    Hot spots of F-18 fluorodeoxyglucose positron emission tomograms are variable in size according to window settings of standardized uptake values. The purpose of this study was to determine the standardized uptake value threshold that represents the target volume. Sixty-three patients who underwent fluorodeoxyglucose positron emission tomographic computed tomography and were diagnosed as having head and neck cancer with cervical lymphadenopathy were studied. The horizontal and vertical diameters of metastatic lymph nodes (LN-CT) were measured at the center of computed tomographic images. Of the corresponding nodes, the maximal standardized uptake value (SUVmax) and standardized uptake value profiles along the central horizontal and vertical axes were calculated on positron emission tomographic images (LN-PET). On the standardized uptake value profiles, the standardized uptake value levels (SUVeq) where the size of LN-PET was equivalent to the diameters of LN-CT were obtained. The regression formula between SUVeq and SUVmax was obtained. The regression formula of SUVeq was validated in subsequent 30 positron emission tomographic computed tomography studies. The mean horizontal and vertical diameters of LN-CT were 14.9 and 16.4 mm, respectively. SUVmax ranged from 1.88 to 9.07, and SUVeq was between 1.16 and 6.42. The regression formula between SUVeq and SUVmax was as follows: SUVeq =1.21+0.34 x SUVmax (coefficient of correlation: R=0.69). The validation study resulted in a good correlation between the volume of lymph nodes on computed tomography and positron emission tomographic computed tomography (R 2 =0.93). The formula with a relatively high coefficient of correlation is considered to indicate that SUVeq is not constant, but is a complex of an absolute standardized uptake value and is proportional to SUVmax. (author)

  8. Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

    International Nuclear Information System (INIS)

    Nguyen, Xuan Canh; Nguyen, Van Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

    2014-01-01

    To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUV pt ), maxSUV of whole-body tumors (maxSUV wb ) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSCLC were enrolled. Seventeen patients had Stage IIIA, 21 Stage IIIB, and 45 Stage IV. maxSUV pt , maxSUV wb , sumaxSUV, age, gender, tumor-cell type, T stage, N stage, overall stage, primary tumor size, and specific treatment were analyzed for correlation with overall survival. Median follow-up duration was 13 months. Fifty patients were dead during a median follow-up time of 11 months and 33 patients were alive with a median time of 15 months. Univariate analysis revealed that overall survival was significantly correlated with sumaxSUV (≥35 vs. <35, P = 0.004), T stage (T4 vs. T1-T3, P = 0.025), overall stage (IV vs. III, P = 0.002), gender (male vs. female, P = 0.029) and specific treatment (no vs. yes, P = 0.011). maxSUV pt and maxSUV wb were not correlated with overall survival with P value of 0.139 and 0.168, respectively. Multivariate analysis identified sumaxSUV, T stage, gender, and specific treatment as independent prognostic indicators. Patients with a sumaxSUV of ≥35 were 1.921 times more likely to die than those with a sumaxSUV of < 35 (P = 0.047). Median survival time was 14 months for patients with sumaxSUV ≥ 35 compared with 20 months for those with sumaxSUV < 35. In patients with metastatic NSCLC, sumaxSUV with cut-off of 35 was much more significant for survival prognosis (P = 0.021). sumaxSUV is a new prognostic measure, independent of tumor stage, gender, and specific treatment in advanced NSCLC. sumaxSUV may be better than maxSUV pt and maxSUV wb in

  9. A Comparison between Radiolabeled Fluorodeoxyglucose Uptake and Hyperpolarized 13C-Labeled Pyruvate Utilization as Methods for Detecting Tumor Response to Treatment

    Directory of Open Access Journals (Sweden)

    Timothy H. Witney

    2009-06-01

    Full Text Available Detection of early tumor responses to treatment can give an indication of clinical outcome. Positron emission tomography measurements of the uptake of the glucose analog, [18F] 2-fluoro-2-deoxy-d-glucose (FDG, have demonstrated their potential for detecting early treatment response in the clinic. We have shown recently that 13C magnetic resonance spectroscopy and spectroscopic imaging measurements of the uptake and conversion of hyperpolarized [1-13C]pyruvate into [1-13C]lactate can be used to detect treatment response in a murine lymphoma model. The present study compares these magnetic resonance measurements with changes in FDG uptake after chemotherapy. A decrease in FDG uptake was found to precede the decrease in flux of hyperpolarized 13C label between pyruvate and lactate, both in tumor cells in vitro and in tumors in vivo. However, the magnitude of the decrease in FDG uptake and the decrease in pyruvate to lactate flux was comparable at 24 hours after drug treatment. In cells, the decrease in FDG uptake was shown to correlate with changes in plasma membrane expression of the facilitative glucose transporters, whereas the decrease in pyruvate to lactate flux could be explained by an increase in poly(ADP-ribose polymerase activity and subsequent depletion of the NAD(H pool. These results show that measurement of flux between pyruvate and lactate may be an alternative to FDG-positron emission tomography for imaging tumor treatment response in the clinic.

  10. FDG uptake in the stomach

    International Nuclear Information System (INIS)

    Yun, M. J.; Cho, H. J.; Cho, E. H.; Kim, T. S.; Kang, W. J.; Lee, J. D.

    2007-01-01

    This study was performed to evaluate histopathologic features of advanced gastric cancer (AGC) to predict FDG uptake on PET. 153 patients(102 men; mean age, 55 y) were diagnosed with AGC by surgery were included in this study. PET images were evaluated by visual and semi-quantitative analysis of FDG uptake in primary tumors. Primary tumors size were measured and divided according to Borrmann classification. Tumor histology was classified under WHO classification, depth of invasion and Iymphovascular invasion. The tumors were also grouped by high cellular(cellularity = 50%) and low cellular group (<50%). Microscopic growth type was based on Lauren classification. Stromal fibrosis degree and inflammatory cell infiltration amount was graded as low(none∼mild), or high(moderate∼severe). Lymph node metastases was assessed in all patients. Statistical analyses were performed to evaluate differences in SUV as to histopathologic factors. Of the 153 patients, 21 patients(14%) had primary tumor invisible on initial whole body images. After water ingestion, the tumors became visible in 15 of the 21 patients due to disappearance of physiologic stomach uptake. Polypoid or ulcerofungating tumors, high cellularity, intestinal growth pattern, and larger tumors significantly predicted increased tumor SUVs. Well or moderately differentiated adenocarcinoma tended to show high cellularity and intestinal growth pattern. Poorly differentiated adenocarcinoma had diverse spectrum of histopathology. Signet ring cell carcinomas were mostly ulceroinfiltrative or diffusely infiltrative in macroscopic type and diffuse in microscopic tumor growth. Mucinous adenocarcinomas were mostly low in cellularity. FDG uptake patterns are useful in representing histopathologic characteristics of the entire tumor in gastric cancers. The degree of FDG uptake depends on tumor size, macroscopic type, cellularity, and microscopic growth pattern and it shows no association with well known important prognostic

  11. Tumor-Associated Macrophages Derived from Circulating Inflammatory Monocytes Degrade Collagen through Cellular Uptake

    DEFF Research Database (Denmark)

    Madsen, Daniel Hargbøl; Jürgensen, Henrik Jessen; Siersbæk, Majken Storm

    2017-01-01

    -associated macrophage (TAM)-like cells that degrade collagen in a mannose receptor-dependent manner. Accordingly, mannose-receptor-deficient mice display increased intratumoral collagen. Whole-transcriptome profiling uncovers a distinct extracellular matrix-catabolic signature of these collagen-degrading TAMs. Lineage......-ablation studies reveal that collagen-degrading TAMs originate from circulating CCR2+ monocytes. This study identifies a function of TAMs in altering the tumor microenvironment through endocytic collagen turnover and establishes macrophages as centrally engaged in tumor-associated collagen degradation. Madsen et...

  12. Steroid-induced suppression of gallium uptake in tumors of the central nervous system: concise communication

    International Nuclear Information System (INIS)

    Waxman, A.D.; Beldon, J.R.; Richli, W.; Tanasescu, D.E.; Siemsen, J.K.

    1978-01-01

    The effect of steroids given in greater than replacement doses on the gallium and technetium glucoheptonate brain scan is evaluated by comparing the relative sensitivity of both radiopharmaceuticals in patients both on and off steroids. The study shows a significant steroid effect on the sensitivity of 95% to 64% following steroids. Steroids did not significantly alter the sensitivity of the technetium glucoheptonate study. The superiority of the TcGH brain scan over the gallium citrate brain scan in the steroid population suggests a difference in the uptake mechanism for the two radiopharmaceuticals

  13. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of {sup 18}F-Fluorodeoxyglucose After Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, George D., E-mail: george.wilson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Oliver Wong, Ching Yee [Department of Diagnostic Radiology and Molecular Imaging Medicine, William Beaumont Hospital, Royal Oak, Michigan (United States); Yan, Di; Marples, Brian [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Huang, Jiayi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm{sup 3} they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: {sup 18}F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

  14. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  15. Impact of third-line treatment with irinotecan plus cetuximab on non-tumor standardized uptake values in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Skougaard, Kristin; Nielsen, Anne Lerberg

    2012-01-01

    The correct interpretation of metabolic response in cancer cells to therapy requires knowledge of how tumor-free tissue responds to the same treatment. The aim of this study was to evaluate standardized uptake values (SUVs) in tumor-free regions of patients with metastatic colorectal cancer prior...... body mass were registered. The procedure was repeated for a follow-up scan two weeks following a single administration of the third-line treatment with irinotecan plus cetuximab. The mean differences in SUV prior to and following therapy were non-significant (P>0.05) in all the registered tumor...

  16. Reproducibility study of [{sup 18}F]FPP(RGD){sub 2} uptake in murine models of human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Edwin; Liu, Shuangdong; Chin, Frederick; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Gowrishankar, Gayatri; Yaghoubi, Shahriar [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Wedgeworth, James Patrick [Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Berndorff, Dietmar; Gekeler, Volker [Bayer Schering Pharma AG, Global Drug Discovery, Berlin (Germany); Gambhir, Sanjiv S. [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Canary Center at Stanford for Cancer Early Detection, Nuclear Medicine, Departments of Radiology and Bioengineering, Molecular Imaging Program at Stanford, Stanford, CA (United States)

    2011-04-15

    with level of tracer uptake. Mouse body weight, injected dose, and fasting state did not contribute to the variability of the scans; however, consistent scanning parameters were necessary to ensure accurate studies, in particular, noting tumor volume, as well as making uniform: the time of imaging after injection and the ROI size. Reanalysis of ROI placement displayed variability for %ID{sub mean}/g of 6.6 {+-} 3.9% and 0.28 {+-} 0.12% for %ID{sub max}/g. [ {sup 18}F ]FPP(RGD){sub 2} small animal PET mouse tumor xenograft studies are reproducible with relatively low variability. (orig.)

  17. Concurrent low brain and high liver uptake on FDG PET are associated with cardiovascular risk factors

    International Nuclear Information System (INIS)

    Nam, Hyun Yeol; Jun, Sung Min; Pak, Kyoung June; Kim, In Joo

    2017-01-01

    Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without

  18. Concurrent low brain and high liver uptake on FDG PET are associated with cardiovascular risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Hyun Yeol [Dept. of Nuclear Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon (Korea, Republic of); Jun, Sung Min [Dept. of Nuclear Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan (Korea, Republic of); Pak, Kyoung June; Kim, In Joo [Dept. of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of)

    2017-04-15

    Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without.

  19. Mapping water exchange rates in rat tumor xenografts using the late-stage uptake following bolus injections of contrast agent.

    Science.gov (United States)

    Bailey, Colleen; Moosvi, Firas; Stanisz, Greg J

    2014-05-01

    To map the intra-to-extracellular water exchange rate constant in rat xenografts using a two-compartment model of relaxation with water exchange and a range of contrast agent concentrations and compare with histology. MDA-MB-231 cells were xenografted into six nude rats. Three bolus injections of gadodiamide were administered. When uptake in the tumor demonstrated a steady-state, T1 data were acquired by spoiled gradient recalled acquisitions at four flip angles. A global fit of data to a two-compartment model incorporating exchange was performed, assuming a distribution volume of 20% of the rat. Voxels that did not reach steady-state and were excluded from parametric maps tended to be in large necrotic areas. TUNEL-negative (nonapoptotic) regions tended to have well-defined error bounds, with an average intra-to-extracellular exchange rate constant of 0.6 s(-1) . Apoptotic regions had higher exchange, but poorly determined upper bounds, with goodness of fit similar to that for a model assuming infinitely fast exchange. A lower bound of >3 s(-1) was used to establish voxels where the exchange rate constant was fast despite a large upper bound. Water exchange rates were higher in apoptotic regions, but examination of statistical errors was an important step in the mapping process. Copyright © 2013 Wiley Periodicals, Inc.

  20. Foliar water uptake of Tamarix ramosissima from an atmosphere of high humidity.

    Science.gov (United States)

    Li, Shuang; Xiao, Hong-lang; Zhao, Liang; Zhou, Mao-Xian; Wang, Fang

    2014-01-01

    Many species have been found to be capable of foliar water uptake, but little research has focused on this in desert plants. Tamarix ramosissima was investigated to determine whether its leaves can directly absorb water from high humidity atmosphere and, if they can, to understand the magnitude and importance of foliar water uptake. Various techniques were adopted to demonstrate foliar water uptake under submergence or high atmospheric humidity. The mean increase in leaf water content after submergence was 29.38% and 20.93% for mature and tender leaves, respectively. In the chamber experiment, obvious reverse sap flow occurred when relative humidity (RH) was persistently above 90%. Reverse flow was recorded first in twigs, then in branches and stems. For the stem, the percentage of negative sap flow rate accounting for the maximum value of sap flow reached 10.71%, and its amount accounted for 7.54% of diurnal sap flow. Small rainfall can not only compensate water loss of plant by foliar uptake, but also suppress transpiration. Foliar uptake can appear in the daytime under certain rainfall events. High atmospheric humidity is beneficial for enhancing the water status of plants. Foliar uptake should be an important strategy of water acquisition for desert plants.

  1. Foliar Water Uptake of Tamarix ramosissima from an Atmosphere of High Humidity

    Directory of Open Access Journals (Sweden)

    Shuang Li

    2014-01-01

    Full Text Available Many species have been found to be capable of foliar water uptake, but little research has focused on this in desert plants. Tamarix ramosissima was investigated to determine whether its leaves can directly absorb water from high humidity atmosphere and, if they can, to understand the magnitude and importance of foliar water uptake. Various techniques were adopted to demonstrate foliar water uptake under submergence or high atmospheric humidity. The mean increase in leaf water content after submergence was 29.38% and 20.93% for mature and tender leaves, respectively. In the chamber experiment, obvious reverse sap flow occurred when relative humidity (RH was persistently above 90%. Reverse flow was recorded first in twigs, then in branches and stems. For the stem, the percentage of negative sap flow rate accounting for the maximum value of sap flow reached 10.71%, and its amount accounted for 7.54% of diurnal sap flow. Small rainfall can not only compensate water loss of plant by foliar uptake, but also suppress transpiration. Foliar uptake can appear in the daytime under certain rainfall events. High atmospheric humidity is beneficial for enhancing the water status of plants. Foliar uptake should be an important strategy of water acquisition for desert plants.

  2. A study of the uptake of chloroquine in malaria-infected erythrocytes. High and low affinity uptake and the influence of glucose and its analogues.

    Science.gov (United States)

    Diribe, C O; Warhurst, D C

    1985-09-01

    A study of concentration- and substrate-dependence of chloroquine uptake has been carried out on mouse erythrocytes infected with the chloroquine-sensitive NK65 and the chloroquine-resistant RC strains of Plasmodium berghei. The presence of drug binding sites of high and low affinity in such strains of P. berghei was confirmed. High affinity uptake sites in cells parasitized with chloroquine-sensitive and chloroquine-resistant parasites have similar characteristics, but in the sensitive strain the major component of chloroquine-uptake is at high affinity and dependent on the availability of ATP whilst in the resistant strain the major component of uptake is at low affinity and independent of energy. An absolute increase in the quantity of the low affinity site in erythrocytes parasitized with chloroquine-resistant P. berghei was noted, which may be related to an increase in quantity of parasite membrane.

  3. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    International Nuclear Information System (INIS)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

    1999-01-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

  4. High affinity, ligand specific uptake of complexed copper-67 by brain tissue incubated in vitro

    International Nuclear Information System (INIS)

    Barnea, A.; Hartter, D.E.

    1987-01-01

    Copper is an essential metal that is highly concentrated in the brain. The blood, the sole source of tissue Cu, contains 16-20 μM Cu, of which >95% is complexed to proteins and 2 was 10 times greater than that of CuAlbumin or Cu(II). Within the range of 0.2-150μM Cu, multiple uptake sites for CuHis were apparent. Increasing the molar ratio of His:Cu had a differential effect on Cu uptake: enhancing uptake at [Cu] 1 μM. Thus, using a His:Cu ratio of 1000, they observed a high affinity process exhibiting saturating and half saturating values of 5 μM and 1.5 μM Cu, respectively; using a His:Cu ratio of 2, they observed a low affinity process exhibiting saturating and half-saturating values of 100 μM and 40 μM Cu, respectively. Both processes required thermic but not metabolic energy, suggestive of facilitated diffusion. Considering the blood brain barrier for proteins, CuHis appears to be the major substrate for Cu uptake by neuronal tissue. They demonstrate the existence of a ligand specific, high affinity (apparent Km about 1.5 μM Cu) uptake process for CuHis in the brain, operative at the physiological concentration range of CuHis and histidine

  5. Comparison of the uptake of [123/125I]-2-iodo-D-tyrosine and [123/125I]-2-iodo-L-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo

    International Nuclear Information System (INIS)

    Bauwens, Matthias; Lahoutte, Tony; Kersemans, Ken; Gallez, Carol; Bossuyt, Axel; Mertens, John

    2006-01-01

    Introduction: Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [ 123 I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[ 123/125 I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats. Methods: The uptake of [ 125 I]-2-iodo-L-tyrosine and [ 125 I]-2-iodo-D-tyrosine into R1M cells was determined in appropriate buffers, allowing the study of the involved transport systems. In vivo, the biodistribution in R1M-bearing rats of [ 123 I]-2-iodo-L-tyrosine and [ 123 I]-2-iodo-D-tyrosine was performed by both dynamic and static planar imaging with a gamma camera. Results: In in vitro conditions, the uptake of both [ 125 I]-2-iodo-L-tyrosine and [ 125 I]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na + ions. In the absence of Na + ions, [ 125 I]-2-iodo-D-tyrosine was taken up reversibly in the R1M cells, with an apparent accumulation, probably for the larger part by the LAT1 system. Dynamic planar imaging showed that the uptake in the tumors of [ 123 I]-2-iodo-D-tyrosine was somewhat lower than that of [ 123 I]-2-iodo-L-tyrosine. At 30 min postinjection, the mean differential uptake ratio values of the L- and D-enantiomers are 2.5±0.7 and 1.7±0.6, respectively. Although the uptake of the D-isomer is lower, probably due to a faster clearance from the blood, the tumor-background ratio is the same as that of the L-analogue. Conclusion: A large part (75%) of [ 125 I]-2-iodo-D-tyrosine in vitro and [ 123 I]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in R1M tumor cells by Na + -independent LAT transport systems, more likely by the LAT1. The clearance from the blood of [ 123 I]-2-iodo-D-tyrosine in the rats is faster than that of the

  6. Kinetics and autoradiography of high affinity uptake of serotonin by primary astrocyte cultures

    International Nuclear Information System (INIS)

    Katz, D.M.; Kimelberg, H.K.

    1985-01-01

    Primary astrocyte cultures prepared from the cerebral cortices of neonatal rats showed significant accumulation of serotonin (5-hydroxytryptamine; [ 3 H]-5-HT). At concentrations in the range of 0.01 to 0.7 microM [ 3 H]-5-HT, this uptake was 50 to 85% Na+ dependent and gave a Km of 0.40 +/- 0.11 microM [ 3 H]-5-HT and a Vmax of 6.42 +/- 0.85 (+/- SEM) pmol of [ 3 H]-5-HT/mg of protein/4 min for the Na+-dependent component. In the absence of Na+ the uptake was nonsaturable. Omission of the monoamine oxidase inhibitor pargyline markedly reduced the Na+-dependent component of [ 3 H]-5-HT uptake but had a negligible effect on the Na+-independent component. This suggest significant oxidative deamination of serotonin after it has been taken up by the high affinity system, followed by release of its metabolite. The authors estimated that this system enabled the cells to concentrate [ 3 H]-5-HT up to 44-fold at an external [ 3 H]-5-HT concentration of 10(-7) M. Inhibition of [ 3 H]-5-HT uptake by a number of clinically effective antidepressants was also consistent with a specific high affinity uptake mechanism for 5-HT, the order of effectiveness of inhibition being chlorimipramine greater than fluoxetine greater than imipramine = amitriptyline greater than desmethylimipramine greater than iprindole greater than mianserin. Uptake of [ 3 H]-5-HT was dependent on the presence of Cl- as well as Na+ in the medium, and the effect of omission of both ions was nonadditive. Varying the concentration of K+ in the media from 1 to 50 mM had a limited effect on [ 3 H]-5-HT uptake

  7. Effect of quinolinic acid in the nucleus basalis magnocellularis on cortical high-affinity choline uptake

    Energy Technology Data Exchange (ETDEWEB)

    Metcalf, R.H.; Boegman, R.J.; Quirion, R.; Riopelle, R.J.; Ludwin, S.K.

    1987-08-01

    A transient 45% increase in cortical high-affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific (/sup 3/H)hemicholinium-3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM. The increase in cortical HACU elicited by QUIN appeared to be dose dependent.

  8. Quantitative analysis of receptor-mediated uptake and pro-apoptotic activity of mistletoe lectin-1 by high content imaging.

    Science.gov (United States)

    Beztsinna, N; de Matos, M B C; Walther, J; Heyder, C; Hildebrandt, E; Leneweit, G; Mastrobattista, E; Kok, R J

    2018-02-09

    Ribosome inactivating proteins (RIPs) are highly potent cytotoxins that have potential as anticancer therapeutics. Mistletoe lectin 1 (ML1) is a heterodimeric cytotoxic protein isolated from European Mistletoe and belongs to RIP class II. The aim of this project was to systematically study ML1 cell binding, endocytosis pathway(s), subcellular processing and apoptosis activation. For this purpose, state of the art cell imaging equipment and automated image analysis algorithms were used. ML1 displayed very fast binding to sugar residues on the membrane and energy-dependent uptake in CT26 cells. The co-staining with specific antibodies and uptake blocking experiments revealed involvement of both clathrin-dependent and -independent pathways in ML1 endocytosis. Co-localization studies demonstrated the toxin transport from early endocytic vesicles to Golgi network; a retrograde road to the endoplasmic reticulum. The pro-apoptotic and antiproliferative activity of ML1 were shown in time lapse movies and subsequently quantified. ML1 cytotoxicity was less affected in multidrug resistant tumor cell line 4T1 in contrast to commonly used chemotherapeutic drug (ML1 resistance index 6.9 vs 13.4 for doxorubicin; IC 50 : ML1 1.4 ng/ml vs doxorubicin 24000 ng/ml). This opens new opportunities for the use of ML1 as an alternative treatment in multidrug resistant cancers.

  9. STUDY OF POSTERIOR FOSSA TUMORS BY HIGH RESOLUTION MRI

    Directory of Open Access Journals (Sweden)

    Sree Hari

    2016-01-01

    Full Text Available INTRODUCTION Magnetic Resonance Imaging (MRI is the imaging modality used for the assessment of infratentorial neoplasms. Although Computed Tomography (CT provides better demonstration of small or subtle calcifications within tumors. OBJECTIVES Study is done to assess the potential of MRI in characterisation of different tumors in posterior fossa by evaluating various unenhanced and gadolinium enhanced sequences and to compare high resolution FSE MRI sequences with routine FSE MRI sequences in diagnosing posterior fossa brain tumors. Also correlate findings on Magnetic Resonance Imaging with Pathological diagnosis. MATERIALS AND METHODS A total of 52 patients were diagnosed by CT brain as having posterior fossa brain for a year of 2 years were included in the study. In all studies MR imaging was performed with a clinical 1.5 T system (General electrical medical systems. A dedicated phased-array coil was used. RESULTS The age group ranged from 1 year to 60 years, majority were between 1 to 20 years (39%. Slight male preponderance was seen (males 29, females 23. Commonest tumor encountered in our study was vestibular schwannoma. DWI alone can differentiate different pediatric posterior fossa brain tumors. One case of pilocytic astrocytoma showed solid lesion instead of typical cystic lesion with mural nodule. One case AT-RT showed 2 lesions one in cerebrum, one in CP angle. Common feature being intra-axial lesion involving cerebellum. MRI was able to predict diagnosis in 50 of the 52 tumors. CONCLUSION Magnetic Resonance Imaging was found to be a highly sensitive imaging procedure and method of choice for posterior fossa brain tumors.

  10. Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

    Science.gov (United States)

    Scheulen, M E; Hoensch, H; Kappus, H; Seeber, S; Schmidt, C G

    1987-01-01

    From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

  11. Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

    Science.gov (United States)

    Kramer, G M; Liu, Y; de Langen, A J; Jansma, E P; Trigonis, I; Asselin, M-C; Jackson, A; Kenny, L; Aboagye, E O; Hoekstra, O S; Boellaard, R

    2018-06-01

    3'-deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18 F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18 F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five 18 F-FLT repeatability cohorts in solid tumors. 18 F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUV max , SUV mean , SUV peak , proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all 18 F-FLT uptake metrics (R 2  ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUV peak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUV max  ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. In multi-center studies

  12. High-field MR imaging of spinal cord tumors

    International Nuclear Information System (INIS)

    Halimi, P.; Sigal, R.; Blas, C.; Doyon, D.; Hurth, M.; Bittoun, J.

    1986-01-01

    In 60 patients with spinal cord tumors, MR imaging was performed using a 1.5-T unit (GE Signa) and a planar surface coil, 5-mm-thick sections, and spin-echo pulse sequences (TE/TR = 25/600 and 25-100/2,000-2,500 msec). There were 32 astrocytomas, 13 ependymomas, and five hemangioblastomas. Ten patients were not operated on. Surgical follow-up was available in 35 patients. The MR imaging results were correlated with findings on CT, myelography, intraoperative US, surgery, and pathologic examination. In all cases the tumor appeared markedly inhomogeneous. Four imaging patterns corresponding to structural abnormalities were observed: low signal intensity of the tumor core on both T1- and T2-weighted images; hypointensity on T1-weighted images and hyperintensity on T2-weighted images (low-protein cyst, syrinx, edema); isointensity on T1-weighted and slight hypertensity on T2-weighted images (high-protein tumoral necrotic cyst); and high spinal intensity on both T1- and T2-weighted images (chronic hemorrhage). MR imaging contributes the most information in the diagnosis of spinal cord tumors and delineation of their extent, and consequently has a potential impact on surgical management

  13. Effect of high carbohydrate or high protein diets on the uptake of [57Co] cyanocobalamin in the rat organs

    International Nuclear Information System (INIS)

    Inamdar-Deshmukh, A.B.; Jathar, V.S.

    1978-01-01

    The mean total body radiocyanocobalamin uptake in rats fed high casein or high carbohydrate diet did not show any significant difference, though there was marked variation in their body-weights. It seems that the body possesses the mechanism to maintain its B 12 store constant though the protein status altered at an early stage of under or over protein nutrition. (author)

  14. 64Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin αvβ3 Expression in Human Neuroendocrine Tumor Xenografts

    DEFF Research Database (Denmark)

    Oxbøl, Jytte; Schjøth-Eskesen, Christina; El Ali, Henrik H.

    2012-01-01

    727) were administered (64)Cu-NODAGA-c(RGDyK) i.v. for study of biodistribution as well as for dynamic PET. Gene expression of angiogenesis markers integrin α(V), integrin β(3), and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors (%ID/g). From biodistribution data......Purpose. The purpose of this paper is to evaluate a new PET tracer (64)Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures. Nude mice with human neuroendocrine tumor xenografts (H...... was estimated to be 0.038 and 0.029 mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion. (64)Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use....

  15. Uptake of manganese in potatoes tolerant of high tissue manganese levels

    Energy Technology Data Exchange (ETDEWEB)

    Marsh, K.B.

    1987-01-01

    Observations on the accumulations of Mn in potatoes (Solanum tuberosum cv. Norland) focused on factors which enabled plants in field studies to withstand high concentrations of Mn in their foliage. A microculture method for assessing nutrient uptake was introduced and applied to studies of the effects of P and temperature on Mn toxicity. Potato plants in microculture behaved similarly in the symptomatology of Mn toxicity to those grown in solution culture but were more responsive to P. The effects of both P and temperature on Mn toxicity in microculture correlated with changes in Mn uptake and with growth reductions due to low P or temperature stress. The uptake of Mn from solution culture increased with increasing P level in solution. This increase was attributed to an increased health and vitality of potato plants under high P and to changes in pH and nutrient solution concentration as plants matured at different rates. When limited control over solution pH and nutrient concentration was provided the effects of P on Mn uptake were largely eliminated. The well-documented time dependence of Mn accumulation was confirmed in a fractionation experiment.

  16. Intratumoral Heterogeneous F 18 Fluorodeoxyglucose Uptake Corresponds with Glucose Transporter 1 and Ki-67 Expression in a Case of Krukenberg Tumor: Localization of Intratumoral Hypermetabolic Focus by Fused PET/MR

    International Nuclear Information System (INIS)

    Im, Hyung Jun; Kim, Youg il; Kim, Woo Ho; Kim, Seung Hyup; Kang, Keon Wook

    2011-01-01

    The expression of glucose transporters (Glut 1, Glut 3), Hexokinase II, and Ki-67 has been proposed to explain intratumoral heterogeneous F-18 fluorodeoxyglucose (FDG) uptake. We report a case of Krukenberg tumor with intratumoral heterogeneous FDG uptake which corresponded well with the expression tomography (PET)/magnetic resonance (MR) imaging was helpful for localizing the metabolically active area in the tumor specimen. This report elucidates the relationship between the intratumoral heterogeneous FDG uptake and biologic heterogeneity, and shows the usefulness of PET/MR in research on intratumoral heterogeneity.

  17. MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Kim, Joonyoung; Jones, Lynne A.; Mercer, Nicole M.; Engelbach, John A.; Sharp, Terry L.; Welch, Michael J. E-mail: welchm@mir.wustl.edu

    2002-11-01

    PET has been used to monitor changes in tumor metabolism in breast cancer following hormonal therapy. This study was undertaken to determine whether PET imaging could evaluate early metabolic changes in prostate tumor following androgen ablation therapy. Studies were performed comparing two positron-emitting tracers, {sup 18}F-FDG and {sup 11}C-acetate, in Sprague-Dawley male rats to monitor metabolic changes in normal prostate tissue. Additional studies were performed in nude mice bearing the CWR22 androgen-dependent human prostate tumor to evaluate metabolic changes in prostate tumor. In rats, for the androgen ablation pretreatment, 1 mg diethylstilbestrol (DES) was injected subcutaneously 3 and 24 hours before tracer injection. For androgen pretreatment, 500 {mu}g dihydrotestosterone (DHT) was injected intraperitoneally 2 and 6 hours before tracer injection. The rats were divided into three groups, Group A (no-DES, no-DHT, n = 18), Group B (DES, no-DHT, n = 18) and Group C (DES, DHT, n = 18). In each group, 10 animals received {sup 18}F-FDG, whereas the remaining eight animals were administered {sup 11}C-acetate. Rats were sacrificed at 120 min post-injection of {sup 18}F-FDG or 30 min post-injection of {sup 11}C-acetate. Pretreatment of the mouse model using DHT (200 {mu}g of DHT in 0.1 mL of sunflower seed oil) or DES (200 {mu}g of DES in 0.1 mL of sunflower seed oil) was conducted every 2 days for one week. Mice were imaged with both tracers in the microPET scanner (Concorde Microsystems Inc.). DES treatment caused a decrease in acetate and glucose metabolism in the rat prostate. Co-treatment with DHT maintained the glucose metabolism levels at baseline values. In the tumor bearing mice, similar effects were seen in {sup 18}F-FDG study, while there was no significant difference in {sup 11}C-acetate uptake. These results indicate that changes in serum testosterone levels influence {sup 18}F-FDG uptake in the prostate gland, which is closely tied to glucose

  18. Characterization of cartilaginous tumors with 201Tl scintigraphy

    International Nuclear Information System (INIS)

    Higuchi, Takahiro; Taki, Junichi; Sumiya, Hisashi; Kinuya, Seigo; Nakajima, Kenichi; Tonami, Norihisa

    2005-01-01

    Histological diagnosis and grading of cartilaginous tumors are closely correlated with patient prognosis; consequently, they are essential elements. We attempted to clarify the characteristics of 201 Tl uptake in various histological types of cartilaginous tumors and to assess its clinical value. Twenty-two cases with histologically proven cartilaginous tumors (3 enchondromas, 15 conventional chondrosarcomas (grade I=9, II=5, III=1), 3 mesenchymal chondrosarcomas, and 1 de-differentiated chondrosarcoma) were examined retrospectively. Planar 201 Tl images were recorded 15 mm following intravenous injection of 201 Tl (111 MBq). 201 Tl uptake in the tumor was evaluated visually employing a five-grade scoring system: 0=no appreciable uptake, 1=faint uptake above the background level, 2=moderate uptake, 3=intense uptake but lower than heart uptake and 4=uptake higher than heart uptake. 201 Tl uptake scores were 0 in 3 of 3 enchondromas, 9 of 9 grade I, and 4 of 5 grade II conventional chondrosarcomas. 201 Tl uptake scores were 1 among 1 of 5 grades II and a grade III conventional chondrosarcoma. Mesenchymal chondrosarcoma and de-differentiated chondrosarcoma displayed 201 Tl uptake scores of 2 or 3. Absence of elevated 201 Tl uptake in cartilaginous tumors was indicative of enchondroma or low-grade conventional chondrosarcoma. However, in instances in which 201 Tl uptake is obvious, high-grade chondrosarcoma or variant types should be considered. (author)

  19. Correlation between 11C-choline or 18F-FDG uptake and tumor proliferation: a rabbit bearing lung cancer model study

    International Nuclear Information System (INIS)

    Li Yajun; Bai Renju; Gao Shuo; Li Yansheng; Liu Lei; Jia Wei; Cai Li; Xing Xiling

    2009-01-01

    Objective: Tumor proliferative activity has been recognized as an indicator of malignant degree in lung cancer and related to prognosis. The purpose of this study was to evaluate the feasibility of assessing proliferative activity with 11 C-choline and 18 F-fluorodeoxyglucose (FDG) PET on a rabbit bearing lung VX2 tumor model. Methods: About 0.5 ml of viable VX2 tumor cell suspension was slowly injected into the right lungs of 54 New Zealand white rabbits through a transthoracical needle insertion. 11 C-choline and 18 F-FDG PET scan were performed 10-11 d after tumor implantation. One ear vein was cannulated for administration of the tracers, 11 C-choline PET scan (with Discovery LS PET/CT scanner, GE) was performed 5 rain after intravenously injection of 37 MBq 11 C-choline. Then 18.7 MBq 18 F-FDG was infused at 60 min after 11 C-choline administration and 18 F-FDG PET scan was performed at 60 min after 18 F-FDG administration. The maximal standardized uptake value of tumor was calculated. The animals were euthanized after examination. Histochemical stain with proliferating cell nuclear antigen (PCNA) was performed and PCNA index was obtained to assess tumor proliferation. The difference of 11 C-choline and 18 F-FDG was analyzed using paired student t-test. The correlation of 11 C-choline 18 F-FDG and tumor cell density and PCNA index was analyzed using Pearson linear regression. Results: Of the 54 rabbits, 36 had a solitary pulmonary tumor. The rate of successful generation of a solitary VX2 tumor was 66.7% (36/54). Only 33 rabbits underwent both 11 C-choline and 18 F-FDG PET, and enrolled in this study. The mean cellular density was (547.36 ± 64.78) cells/field and the mean PCNA index was (42.34 ± 15.26)%. 18 F-FDG was higher than 11 C-choline (5.70 ± 3.45 vs 4.02 ± 3.07, t=-3.188, P=0.003). 11 C-choline significantly and positively correlated with PCNA index (r=0.786, P 11 C-choline and tumor cellular density (r=-0.176, P=0.327). 18 F-FDG significantly and

  20. The high-risk HPV infection and urinary system tumor

    Directory of Open Access Journals (Sweden)

    Yang Wenyan

    2018-04-01

    Full Text Available HPV is classified into high-risk and low-risk types depending on its probability of leading to tumorigenesis. Many studies have shown that HPV infection, especially the infection caused by the high-risk type, is always related to prostate cancer, bladder cancer, penile cancer, testicular cancer, and other urinary system tumors. However, previous studies differed in sexual openness and racial genetic susceptibility of the study object, sample size, and experimental methods. Hence, the correlation between high-risk HPV infection and urinary system tumors remains controversial. The early open reading frame of the HPV genome is composed of E1–E7, among which E6 and E7 are the key transfer proteins. The combination of these proteins with oncogene and anti-oncogene may be one of the mechanisms leading to tumorigenesis.

  1. Differential effect of alpha-difluoromethylornithine on the in vivo uptake of 14C-labeled polyamines and methylglyoxal bis(guanylhydrazone) by a rat prostate-derived tumor

    International Nuclear Information System (INIS)

    Heston, W.D.; Kadmon, D.; Covey, D.F.; Fair, W.R.

    1984-01-01

    The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both [ 14 C]putrescine and [14 C]spermidine. The in vitro uptake of [ 14 C]putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting [ 14 C]putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of [ 14 C]putrescine and [ 14 C]-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines

  2. Differential effect of alpha-difluoromethylornithine on the in vivo uptake of 14C-labeled polyamines and methylglyoxal bis(guanylhydrazone) by a rat prostate-derived tumor

    Energy Technology Data Exchange (ETDEWEB)

    Heston, W.D.; Kadmon, D.; Covey, D.F.; Fair, W.R.

    1984-03-01

    The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both (/sup 14/C)putrescine and (14 C)spermidine. The in vitro uptake of (/sup 14/C)putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting (/sup 14/C)putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of (/sup 14/C)putrescine and (/sup 14/C)-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines.

  3. Highly selective and stable carbon dioxide uptake in polyindole-derived microporous carbon materials.

    Science.gov (United States)

    Saleh, Muhammad; Tiwari, Jitendra N; Kemp, K Christain; Yousuf, Muhammad; Kim, Kwang S

    2013-05-21

    Adsorption with solid sorbents is considered to be one of the most promising methods for the capture of carbon dioxide (CO₂) from power plant flue gases. In this study, microporous carbon materials used for CO₂ capture were synthesized by the chemical activation of polyindole nanofibers (PIF) at temperatures from 500 to 800 °C using KOH, which resulted in nitrogen (N)-doped carbon materials. The N-doped carbon materials were found to be microporous with an optimal adsorption pore size for CO₂ of 0.6 nm and a maximum (Brunauer-Emmett-Teller) BET surface area of 1185 m(2) g(-1). The PIF activated at 600 °C (PIF6) has a surface area of 527 m(2) g(-1) and a maximum CO₂ storage capacity of 3.2 mmol g(-1) at 25 °C and 1 bar. This high CO₂ uptake is attributed to its highly microporous character and optimum N content. Additionally, PIF6 material displays a high CO₂ uptake at low pressure (1.81 mmol g(-1) at 0.2 bar and 25 °C), which is the best low pressure CO₂ uptake reported for carbon-based materials. The adsorption capacity of this material remained remarkably stable even after 10 cycles. The isosteric heat of adsorption was calculated to be in the range of 42.7-24.1 kJ mol(-1). Besides the excellent CO₂ uptake and stability, PIF6 also exhibits high selectivity values for CO₂ over N₂, CH₄, and H₂ of 58.9, 12.3, and 101.1 at 25 °C, respectively, and these values are significantly higher than reported values.

  4. Methylcellulose-Directed Synthesis of Nanocrystalline Zeolite NaA with High CO₂ Uptake.

    Science.gov (United States)

    Shakarova, Dilshod; Ojuva, Arto; Bergström, Lennart; Akhtar, Farid

    2014-07-28

    Zeolite NaA nanocrystals with a narrow particle size distribution were prepared by template-free hydrothermal synthesis in thermo-reversible methylcellulose gels. The effects of the amount of methylcellulose, crystallization time and hydrothermal treatment temperature on the crystallinity and particle size distribution of the zeolite NaA nanocrystals were investigated. We found that the thermogelation of methylcellulose in the alkaline Na₂O-SiO₂-Al₂O₃-H₂O system played an important role in controlling the particle size. The synthesized zeolite nanocrystals are highly crystalline, as demonstrated by X-ray diffraction (XRD), and scanning electron microscopy (SEM) shows that the nanocrystals can also display a well-defined facetted morphology. Gas adsorption studies on the synthesized nanocrystalline zeolite NaA showed that nanocrystals with a size of 100 nm displayed a high CO₂ uptake capacity (4.9 mmol/g at 293 K at 100 kPa) and a relatively rapid uptake rate compared to commercially available, micron-sized particles. Low-cost nanosized zeolite adsorbents with a high and rapid uptake are important for large scale gas separation processes, e.g., carbon capture from flue gas.

  5. Increased uptake on 99mTc bone scintigraphy in a case of tumoral calcinosis in a child

    Directory of Open Access Journals (Sweden)

    N Jawad

    2015-06-01

    Full Text Available Tumoral calcinosis is an idiopathic condition resulting in the periarticular deposition of calcium crystals and salts in soft tissues. It is rare in children, and even rarer in idiopathic form. We present a case of a 2-year-old female with tumoral calcinosis in the supraclavicular region, and, in particular, focus on the pertinent radiological findings with radiography, MRI and bone scintigraphy.

  6. Water uptake, migration and swelling characteristics of unsaturated and saturated, highly compacted bentonite

    International Nuclear Information System (INIS)

    Pusch, R.

    1980-09-01

    The report presents the results of a number of laboratory tests and field observations to form the basis of a physical and mathematical model that can be used for predicting water uptake and swelling in highly compacted bentonite components of an actual deposition plant. The clay buffer masses have been suggested as barriers in the Swedish KBS concepts. Two commercially available bentonites were used for the production of samples. The rate of water uptake suggests a mathematical model based on a simple diffusion equation. The rate is determined by the access of water and thousands of years may pass before saturation is obtained. The rate of swelling is governed by the negative pore pressure and the permeability. There is reasonable agreement with field observations. The observed swelling potential of old smectite-rich clays has offered the evidence. (G.B.)

  7. High HPV vaccination uptake rates for adolescent girls after regional governmental funding in Shiki City, Japan.

    Science.gov (United States)

    Hayashi, Y; Shimizu, Y; Netsu, S; Hanley, S; Konno, R

    2012-08-10

    In Japan, the bivalent HPV vaccine was approved in October, 2009 and became available as a non-routine vaccine from December, 2009. While routine vaccinations are free, the cost and responsibility for non-routine vaccinations are left to the individual. In exceptional circumstances regional governments fund non-routine vaccinations. This was the case in Shiki City, Saitama Prefecture, where a high uptake rate for individual (non-school based) HPV vaccination was obtained. On January 20, 2010, the mayor of Shiki City announced to the media his decision to vaccinate adolescent girls in Shiki City against HPV. A project team for HPV vaccination was set up in the city's Health Promotion Center. To gain mutual consent for HPV vaccination, senior health professionals, city officials, the head of the board of education, school principals and health-care teachers met several times. The cohort to be vaccinated was 1254 girls aged 12-15 years. Individual notifications were mailed to each girl on April 23, 2010, along with information about the HPV vaccine. As of April 10th, 2011, the uptake rate for girls aged 15 years old was 90.7% for the 1st dose. The vaccine registry is managed by the health care system of the city. The success of the HPV vaccination program and high uptake rates in Shiki City is a good model for the nationwide HPV vaccination program that started in February, 2011. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. High contrast tumor imaging with radio-labeled antibody Fab fragments tailored for optimized pharmacokinetics via PASylation.

    Science.gov (United States)

    Mendler, Claudia T; Friedrich, Lars; Laitinen, Iina; Schlapschy, Martin; Schwaiger, Markus; Wester, Hans-Jürgen; Skerra, Arne

    2015-01-01

    Although antigen-binding fragments (Fabs) of antibodies constitute established tracers for in vivo radiodiagnostics, their functionality is hampered by a very short circulation half-life. PASylation, the genetic fusion with a long, conformationally disordered amino acid chain comprising Pro, Ala and Ser, provides a convenient way to expand protein size and, consequently, retard renal filtration. Humanized αHER2 and αCD20 Fabs were systematically fused with 100 to 600 PAS residues and produced in E. coli. Cytofluorimetric titration analysis on tumor cell lines confirmed that antigen-binding activities of the parental antibodies were retained. The radio-iodinated PASylated Fabs were studied by positron emission tomography (PET) imaging and biodistribution analysis in mouse tumor xenograft models. While the unmodified αHER2 and αCD20 Fabs showed weak tumor uptake (0.8% and 0.2% ID/g, respectively; 24 h p.i.) tumor-associated radioactivity was boosted with increasing PAS length (up to 9 and 26-fold, respectively), approaching an optimum for Fab-PAS400. Remarkably, 6- and 5-fold higher tumor-to-blood ratios compared with the unmodified Fabs were measured in the biodistribution analysis (48 h p.i.) for αHER2 Fab-PAS100 and Fab-PAS200, respectively. These findings were confirmed by PET studies, showing high imaging contrast in line with tumor-to-blood ratios of 12.2 and 5.7 (24 h p.i.) for αHER2 Fab-PAS100 and Fab-PAS200. Even stronger tumor signals were obtained with the corresponding αCD20 Fabs, both in PET imaging and biodistribution analysis, with an uptake of 2.8% ID/g for Fab-PAS100 vs. 0.24% ID/g for the unmodified Fab. Hence, by engineering Fabs via PASylation, plasma half-life can be tailored to significantly improve tracer uptake and tumor contrast, thus optimally matching reagent/target interactions.

  9. Strong association of epidermal growth factor receptor status with breast cancer FDG uptake

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joohee; Moon, Seung Hwan; Hyun, Seung Hyup; Cho, Young Seok; Choi, Joon Young; Kim, Byung-Tae; Lee, Kyung-Han [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Eun Jeong [Seoul Medical Center, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Seokhwi [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of)

    2017-08-15

    Imaging tumor FDG uptake could complement breast cancer biomarkers of risk and treatment response. Although breast cancer FDG uptake is reputedly influenced by major biomarker states, the role of epidermal growth factor receptor (EGFR) expression remains largely unexplored. This is a retrospective study that included 499 patients with primary breast cancer at initial presentation. Tumor FDG uptake was measured on pretreatment PET/CT as maximum standardized uptake value (SUVmax), and biomarkers were assessed by immunohistochemistry of tumor tissue. Regression analysis was performed for predictors of high tumor FDG uptake (SUVmax ≥ 8.6). SUVmax was higher in ER- (36.5%; 11.2 ± 6.0 vs. 8.3 ± 5.3), PR- (42.3%; 10.9 ± 6.0 vs. 8.2 ± 5.2), and triple-negative tumors (19.8%; 12.0 ± 6.9 vs. 8.7 ± 5.2; all p < 0.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6) + and mutant P53 (mP53) + tumors (all p < 0.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9 ± 6.0 vs. 8.3 ± 5.3), ER- tumors (p < 0.0001), PR- and + tumors (p < 0.0001 and 0.027), hormone receptor- and + tumors (p < 0.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors (p < 0.0001 and 0.006), non-triple negative tumors (p < 0.0001), CK5/6- and + tumors (p = 0.021 and <0.0001), and mP53- and + tumors (p < 0.0001 and 0.008). Tumors had high FDG uptake in 73.2% of EGFR+ and 40.6% of EGFR- tumors. On regression analysis, significant multivariate predictors of high tumor FDG uptake were large size, EGFR+ and CK5/6+ for the entire subjects, and EGFR+ and CK5/6+ for ER- and hormone receptor negative subgroups. High FDG uptake was able to sub-stratify EGFR+ tumors that were more likely to be ER- and CK5/6+, and EGFR- tumors more likely to be mP53 +. Primary breast tumor FDG uptake is strongly influenced by EGFR status beyond that by other major biomarkers including hormone receptor and HER2 status, and EGFR

  10. Carbonate-sensitive phytotransferrin controls high-affinity iron uptake in diatoms

    Science.gov (United States)

    McQuaid, Jeffrey B.; Kustka, Adam B.; Oborník, Miroslav; Horák, Aleš; McCrow, John P.; Karas, Bogumil J.; Zheng, Hong; Kindeberg, Theodor; Andersson, Andreas J.; Barbeau, Katherine A.; Allen, Andrew E.

    2018-03-01

    In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton. Although most dissolved iron in the marine environment is complexed with organic molecules, picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone and serve as an important source of iron for eukaryotic phytoplankton and particularly for diatoms. Genome-enabled studies of labile iron utilization by diatoms have previously revealed novel iron-responsive transcripts, including the ferric iron-concentrating protein ISIP2A, but the mechanism behind the acquisition of picomolar labile iron remains unknown. Here we show that ISIP2A is a phytotransferrin that independently and convergently evolved carbonate ion-coordinated ferric iron binding. Deletion of ISIP2A disrupts high-affinity iron uptake in the diatom Phaeodactylum tricornutum, and uptake is restored by complementation with human transferrin. ISIP2A is internalized by endocytosis, and manipulation of the seawater carbonic acid system reveals a second-order dependence on the concentrations of labile iron and carbonate ions. In P. tricornutum, the synergistic interaction of labile iron and carbonate ions occurs at environmentally relevant concentrations, revealing that carbonate availability co-limits iron uptake. Phytotransferrin sequences have a broad taxonomic distribution and are abundant in marine environmental genomic datasets, suggesting that acidification-driven declines in the concentration of seawater carbonate ions will have a negative effect on this globally important eukaryotic iron acquisition mechanism.

  11. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  12. (99m)Tc-labeled gastrins of varying peptide chain length: Distinct impact of NEP/ACE-inhibition on stability and tumor uptake in mice.

    Science.gov (United States)

    Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

    2016-06-01

    In situ inhibition of neutral endopeptidase (NEP) has been recently shown to impressively increase the bioavailability and tumor uptake of biodegradable gastrin radioligands. Furthermore, angiotensin converting enzyme (ACE) has been previously shown to cleave gastrin analogs in vitro. In the present study, we have assessed the effects induced by single or dual NEP/ACE-inhibition on the pharmacokinetic profile of three (99m)Tc-labeled gastrins of varying peptide chain length: [(99m)Tc]SG6 ([(99m)Tc-N4-Gln(1)]gastrin(1-17)), [(99m)Tc]DG2 ([(99m)Tc-N4-Gly(4),DGlu(5)]gastrin(4-17)) and [(99m)Tc]DG4 ([(99m)Tc-N4-DGlu(10)]gastrin(10-17)). Mouse blood samples were collected 5min after injection of each of [(99m)Tc]SG6/DG2/DG4 together with: a) vehicle, b) the NEP-inhibitor phosphoramidon (PA), c) the ACE-inhibitor lisinopril (Lis), or d) PA plus Lis and were analyzed by RP-HPLC for radiometabolite detection. Biodistribution was studied in SCID mice bearing A431-CCK2R(+/-) xenografts at 4h postinjection (pi). [(99m)Tc]SG6 or [(99m)Tc]DG4 was coinjected with either vehicle or the above described NEP/ACE-inhibitor regimens; for [(99m)Tc]DG2 control and PA animal groups were only included. Treatment of mice with PA induced significant stabilization of (99m)Tc-radiotracers in peripheral blood, while treatment with Lis or Lis+PA affected the stability of des(Glu)5 [(99m)Tc]DG4 only. In line with these findings, PA coinjection led to notable amplification of tumor uptake of radiopeptides compared to controls (PTc]DG4 profited by single Lis (2.06±0.39%ID/g vs 0.99±0.13%ID/g in controls) or combined Lis+PA coinjection (8.91±1.61%ID/g vs 4.89±1.33%ID/g in PA-group). Furthermore, kidney uptake remained favourably low and unaffected by PA and/or Lis coinjection only in the case of [(99m)Tc]DG4 (Tc-radioligands based on different-length gastrins. Truncated [(99m)Tc]DG4 exhibited overall the most attractive profile during combined NEP/ACE-inhibition in mouse models, providing new

  13. When is reacquisition necessary due to high extra-cardiac uptake in myocardial perfusion scintigraphy?

    DEFF Research Database (Denmark)

    Johansen, Allan; Lomsky, Milan; Gerke, Oke

    2013-01-01

    Technetium-labeled agents, which are most often used for assessing myocardial perfusion in myocardial perfusion scintigraphy (MPS), are cleared by the liver and excreted by the biliary system. Spillover from extra-cardiac activity into the myocardium, especially the inferior wall, might conceal d...... defects and lower the diagnostic accuracy of the study. The objective was to determine rules of thumb for when reacquisition is useful due to high extra-cardiac uptake, i.e., when interpretation of the studies was affected by poor image quality....

  14. What significance can be attributed to high bone uptake of 67GA citrate in patients with HIV infection?

    International Nuclear Information System (INIS)

    Sabbatini, S.; Bini, A.; Turba, E.

    1989-01-01

    The authors observed high uptake of 67 Ga citrate in the spine and in some cases also in the ribs in 15 patients with HIV infection. 12 were also carriers of opportunistic infections, 14 had anaemia with reduced Hb synthesis. 9 were undergoing treatment with antifolic drugs or AZT. The high bone uptake of the radio-indicator was related to the presence of opportunistic infections, the eventual treatment with myelotoxic drugs and the reduction of Hb values. (orig.) [de

  15. Fluorescent derivatives of σ receptor ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a tool for uptake and cellular localization studies in pancreatic tumor cells.

    Science.gov (United States)

    Abate, Carmen; Hornick, John R; Spitzer, Dirk; Hawkins, William G; Niso, Mauro; Perrone, Roberto; Berardi, Francesco

    2011-08-25

    Fluorescent derivatives of σ(2) high affinity ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) were synthesized. NBD or dansyl fluorescent tags were connected through a 5- or 6-atom linker in two diverse positions of 1 structure. Good σ(2) affinities were obtained when the fluorescent tag was linked to 5-methoxytetralin nucleus replacing the methyl function. NBD-bearing compound 16 displayed high σ(2) affinity (K(i) = 10.8 nM) and optimal fluorescent properties. Its uptake in pancreatic tumor cells was evaluated by flow cytometry, showing that it partially occurs through endocytosis. In proliferating cells, the uptake was higher supporting that σ(2) receptors are markers of cell proliferation and that the higher the proliferation is, the stronger the antiproliferative effect of σ(2) agonists is. Colocalization of 16 with subcellular organelles was studied by confocal microscopy: the greatest was in endoplasmic reticulum and lysosomes. Fluorescent σ(2) ligands show their potential in clarifying the mechanisms of action of σ(2) receptors. © 2011 American Chemical Society

  16. Studies on uptake and distribution of chemotherapeutic agents to malignant tumors of the head and neck in rabbits, 2

    International Nuclear Information System (INIS)

    Yamada, Ryuichi

    1981-01-01

    Experiments were performed to investigate incorporation and distribution of chemotherapeutic agents into malignant tumors of the head and neck by microautoradiographic and electron microscopic-autoradiographic observations of VX2 carcinoma transplanted in the lower genial region of rabbits after injection of 3 H-Adriamycin as a tracer. The following findings were obtained. 1. On microautoradiograms, 3 H-Adriamycin was distributed predominantly in the nucleoplasm, rather than in the cytoplasm, of tumor tissues. 2. At the ultrastructural level, 3 H-Adriamycin was localized in the nuclear membrane and nucleoli within the nucleoplasm and in the rough endoplasmic reticulum and secretory granules within the cytoplasm. 3. These findings seem to indicate that Adriamycin may inhibit the synthesis of DNA and RNA in the nucleoplasm. (author)

  17. Prognostic importance of lymph node-to-primary tumor standardized uptake value ratio in invasive squamous cell carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang; Cheon, Gi Jeong

    2017-01-01

    Using integrated PET/CT, we evaluated the prognostic value of [ 18 F]FDG uptake ratio between pelvic lymph node (LN) and primary tumor in invasive squamous cell carcinoma (SCCA) of the uterine cervix. We retrospectively reviewed patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB to IIA cervical SCCA who underwent preoperative [ 18 F]FDG PET/CT scans. PET/CT parameters such as maximum standardized uptake value (SUV) of the primary cervical cancer (SUV cervix ) and LN (SUV LN ), and the LN-to-cervical cancer SUV ratio (SUV LN /SUV cervix ) were assessed. Prognostic values of PET/CT-derived metabolic and volumetric variables and clinicopathology parameters were analyzed to predict progression-free survival (PFS) in regression analyses. Clinical data, treatment modalities, and results were reviewed for 103 eligible patients. Median post-surgical follow-up was 29 months (range, 6-89), and 19 (18.5%) patients experienced recurrence. Multivariate logistic regression analysis showed that SUV LN / SUV cervix > 0.1747(P = 0.048) was the independent risk factor of recurrence. Patient group categorized by SUV LN /SUV cervix showed significant difference in PFS (log-rank test, P < 0.001). Preoperative SUV LN /SUV cervix measured by [ 18 F]FDG PET/CT was significantly associated with recurrence, and has an incremental prognostic value for PFS in patients with cervical SCCA. (orig.)

  18. Tellurium-123m-labeled isosteres of palmitoleic and oleic acids show high myocardial uptake

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Ambrose, K.R.; Callahan, A.P.; Grigsby, R.A.; Irgolic, K.J.

    1979-01-01

    These studies were directed at determining if the telluro fatty acids prepared by the isosteric replacement of the Δ 9 -double bonds of oleic and palmitoleic acids with /sup 123m/Te would show heart uptake in rats. The isostere of palmitoleic acid, 9-tellurapentadecanoic acid(II), was prepared by basic hydrolysis of the product formed by the coupling of /sup 123m/Te-sodium hexyl tellurol with methyl-8-bromooctadecanoate. Similarly, the isostere of oleic acid, 9-telluraheptadecanoic acid(IV), was prepared by the same route beginning with the reaction of /sup 123m/Te-sodium octyl tellurol with methyl-8-bromooctadecanoate. Both /sup 123m/Te-(II) and /sup 123m/Te-(IV) showed remarkably high heart uptake in rats (2 to 3% dose/gm) ten minutes after intravenous administration, and the heart/blood ratios were high (20-30/1). Finally, the hearts of rats injected with /sup 123m/Te-(IV) have been clearly imaged with a rectilinear scanner

  19. Inhibition of high affinity choline uptake by N-allyl-3-quinuclidinol

    International Nuclear Information System (INIS)

    Asermely, K.E.; O'Neill, J.J.

    1986-01-01

    The peripheral actions of N-allyl-3-quinuclidinol (N-Al-3-OHQ) on high affinity choline uptake (HAChU) on rat phrenic nerve diaphragm are described. Endplate regions (EPA) identified by the Koelle histochemical techniques for acetylcholinesterase, were dissected from adult rat hemidiaphragms and placed in cold Krebs solution (pH-7.35). All measurements of HAChU were at 37 0 C in buffers containing tritium choline (5 μM 0.124 μC/mmole) at intervals of 1, 2, 4, 8, 15 and 30 min. Tissues were washed 3x, digested in 1N NaOH and counted for tritium in Chaikoff's solution. All data are expressed as pmole Ch/g wet weight. Comparison between EPA and non-EPA tissue demonstrate HAChU and slow choline diffusion, respectively. Steady state is observed in 15 min. N-Al-3-OHQ produces 15% inhibition at 5 x 10 -5 M compared with 50% inhibition on brain synaptosomes. At 5 x 10 -4 M N-Al-3-OHQ, 30% inhibition is observed. Attempts to deplete ACh by pre-stimulation with high K + -ion (25 mM) were unsuccessful; tissue 3 H-choline uptake appeared to oscillate over a 30 min period

  20. Inhibition of high affinity choline uptake by N-allyl-3-quinuclidinol

    Energy Technology Data Exchange (ETDEWEB)

    Asermely, K.E.; O' Neill, J.J.

    1986-03-01

    The peripheral actions of N-allyl-3-quinuclidinol (N-Al-3-OHQ) on high affinity choline uptake (HAChU) on rat phrenic nerve diaphragm are described. Endplate regions (EPA) identified by the Koelle histochemical techniques for acetylcholinesterase, were dissected from adult rat hemidiaphragms and placed in cold Krebs solution (pH-7.35). All measurements of HAChU were at 37/sup 0/C in buffers containing tritium choline (5 ..mu..M 0.124 ..mu..C/mmole) at intervals of 1, 2, 4, 8, 15 and 30 min. Tissues were washed 3x, digested in 1N NaOH and counted for tritium in Chaikoff's solution. All data are expressed as pmole Ch/g wet weight. Comparison between EPA and non-EPA tissue demonstrate HAChU and slow choline diffusion, respectively. Steady state is observed in 15 min. N-Al-3-OHQ produces 15% inhibition at 5 x 10/sup -5/ M compared with 50% inhibition on brain synaptosomes. At 5 x 10/sup -4/ M N-Al-3-OHQ, 30% inhibition is observed. Attempts to deplete ACh by pre-stimulation with high K/sup +/-ion (25 mM) were unsuccessful; tissue /sup 3/H-choline uptake appeared to oscillate over a 30 min period.

  1. Effects of high NH4+ on K+ uptake, culm mechanical strength and grain filling in wheat

    Directory of Open Access Journals (Sweden)

    Lingan eKong

    2014-12-01

    Full Text Available It is well established that a high external NH4+ concentration depresses many processes in plant development, but the underlying mechanisms are still not well understood. To determine whether the negative effects of high levels of NH4+ are related to competitive cation uptake, wheat was grown in a field with moderate (18 g N m-2 and high (30 g N m-2 supplies of NH4+ in the presence or absence of additional K+ (6 g K2O m-2 to examine culm mechanical strength, the main components of the vascular bundle, nitrogen (N remobilization and the grain-filling rate. The results indicated that an excessive supply of NH4+ significantly decreased culm mechanical strength, the cellulose and lignin contents of vascular bundles, the N remobilization efficiency (NRE and the grain-filling rate compared with a moderate level of NH4+. The additional provision of K+ considerably alleviated these negative effects of high NH4+, resulting in a 19.41%-26.95% increase in culm mechanical strength during grain filling and a 34.59% increase in the NRE. An assay using the scanning ion-selective electrode technique (SIET showed that the net rate of transmembrane K+ influx decreased by 84.62%, and measurements using flame photometry demonstrated that the K+ content decreased by 36.13% in wheat plants subjected to high NH4+. This study indicates that the effects of high NH4+ on culm mechanical strength, cellulose and lignin contents, the NRE and the grain-filling rate are probably associated with inhibition of K+ uptake in wheat.

  2. Tc-99m Hydroxymethylene Diphosphonate (HMDP) Renal Uptake as a Surrogate Marker of Postoperative Impairment of the Glomerular Filtration Rate in Renal Tumor Patients Following Nephron-Sparing Surgery.

    Science.gov (United States)

    Choi, Hongyoon; Lee, Won Woo; So, Young; Ha, Seunggyun; Byun, Seok-Soo; Kim, Sang Eun

    2014-12-01

    We investigated Tc-99m hydroxymethylene diphosphonate (HMDP) scintigraphy findings in renal tumor patients from the perspective of postoperative renal dysfunction following nephron-sparing surgery (NSS). Forty-three renal tumor patients (M:F = 28:15, age 53.9 ± 12.5 years) who had undergone Tc-99m HMDP scintigraphy after NSS were enrolled. The patients were divided into HMDP(+) or HMDP(-) groups by visual assessment, and the asymmetric index (ASI) was calculated using a region-of-interest analysis. In 16 patients, the total and split glomerular filtration rate (GFR) was assessed using Tc-99m diethylenetriaminepentaacetic acid (DTPA) scintigraphy at baseline and at 3 and 6 months post-NSS. High Tc-99m HMDP uptake was observed in the operated kidneys, but this did not persist later than 7 days post-NSS. Split GFR of the operated kidneys at baseline (58.5 ± 9.3 ml/min) was significantly reduced at 6 months post-NSS (40.1 ± 5.9 ml/min, p Tc-99m HMDP. Declines in both total GFR (p = 0.010 and p = 0.002 for 3 and 6 months, respectively) and split GFR of the operated kidneys (p Tc-99m HMDP in the operated kidneys. The ASI was negatively correlated with %change in the split GFR of these operated kidneys at 6 months post-NSS (rho =-0.578, p = 0.0304). Tc-99m HMDP uptake within 1 week following NSS is a surrogate marker of GFR impairment over 6 months post-NSS.

  3. 99mTc-labeled gastrins of varying peptide chain length: Distinct impact of NEP/ACE-inhibition on stability and tumor uptake in mice

    International Nuclear Information System (INIS)

    Kaloudi, Aikaterini; Nock, Berthold A.; Lymperis, Emmanouil; Krenning, Eric P.; Jong, Marion de; Maina, Theodosia

    2016-01-01

    Introduction: In situ inhibition of neutral endopeptidase (NEP) has been recently shown to impressively increase the bioavailability and tumor uptake of biodegradable gastrin radioligands. Furthermore, angiotensin converting enzyme (ACE) has been previously shown to cleave gastrin analogs in vitro. In the present study, we have assessed the effects induced by single or dual NEP/ACE-inhibition on the pharmacokinetic profile of three 99m Tc-labeled gastrins of varying peptide chain length: [ 99m Tc]SG6 ([ 99m Tc-N 4 -Gln 1 ]gastrin(1–17)), [ 99m Tc]DG2 ([ 99m Tc-N 4 -Gly 4 ,DGlu 5 ]gastrin(4–17)) and [ 99m Tc]DG4 ([ 99m Tc-N 4 -DGlu 10 ]gastrin(10–17)). Methods: Mouse blood samples were collected 5 min after injection of each of [ 99m Tc]SG6/DG2/DG4 together with: a) vehicle, b) the NEP-inhibitor phosphoramidon (PA), c) the ACE-inhibitor lisinopril (Lis), or d) PA plus Lis and were analyzed by RP-HPLC for radiometabolite detection. Biodistribution was studied in SCID mice bearing A431-CCK2R(+/−) xenografts at 4 h postinjection (pi). [ 99m Tc]SG6 or [ 99m Tc]DG4 was coinjected with either vehicle or the above described NEP/ACE-inhibitor regimens; for [ 99m Tc]DG2 control and PA animal groups were only included. Results: Treatment of mice with PA induced significant stabilization of 99m Tc-radiotracers in peripheral blood, while treatment with Lis or Lis + PA affected the stability of des(Glu) 5 [ 99m Tc]DG4 only. In line with these findings, PA coinjection led to notable amplification of tumor uptake of radiopeptides compared to controls (P < 0.01). Only [ 99m Tc]DG4 profited by single Lis (2.06 ± 0.39%ID/g vs 0.99 ± 0.13%ID/g in controls) or combined Lis + PA coinjection (8.91 ± 1.61%ID/g vs 4.89 ± 1.33%ID/g in PA-group). Furthermore, kidney uptake remained favourably low and unaffected by PA and/or Lis coinjection only in the case of [ 99m Tc]DG4 (< 1.9%ID/g) resulting in the most optimal tumor-to-kidney ratios. Conclusions: In situ NEP

  4. Positron imaging feasibility studies: characteristics of 2-deoxyglucose uptake in rodent and canine neoplasms

    International Nuclear Information System (INIS)

    Larson, S.M.; Weiden, P.L.; Grunbaum, J.

    1981-01-01

    Uptake of [ 3 H]2-deoxyglucose was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in eight dogs with spontaneous neoplasms: five osteosarcomas and three diffuse lymphomas. High tumor-to-tissue ratios were observed for all tumor types studies. In rodents, peak levels of uptake occurred between 30 min and 1 hr, with a slow loss from the tumor of about 10% per hour thereafter. In dogs there was considerable variability in uptake, both between individuals and at different tumor sites within an individual. Necrotic tumor did not take up the radiotracer. Absolute uptakes, when normalized for body weight, were similar for spontaneous and transplanted neoplasms. These studies provide additional support for the concept that positron emission tomography can be used to obtain functional images of important metabolic processes of tumors, including glycolysis

  5. 18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and neck Cancer: a correlation study between suitable uptake value threshold and tumor parameters

    International Nuclear Information System (INIS)

    Kao, Chia-Hung; Hsieh, Te-Chun; Yu, Chun-Yen; Yen, Kuo-Yang; Yang, Shih-Neng; Wang, Yao-Ching; Liang, Ji-An; Chien, Chun-Ru; Chen, Shang-Wen

    2010-01-01

    To define a suitable threshold setting for gross tumor volume (GTV) when using 18 Fluoro-deoxyglucose positron emission tomography and computed tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC). Fifteen HNC patients prospectively received PET/CT simulation for their radiation treatment planning. Biological target volume (BTV) was derived from PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity volumes when adjusting different percentage of the maximal standardized uptake value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based primary GTV (C-pGTV) that had been previously defined by radiation oncologists was compared with the BTV. Suitable threshold level (sTL) could be determined when BTV value and its morphology using a certain threshold level was observed to be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was calculated as the sTL multiplied by the SUVmax. Our result demonstrated no single sTL or sSUV method could achieve an optimized volumetric match with the C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98 (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln (SUVmax) + 0.4464; R 2 = 0.81]. The sSUV showed a linear correlation with the SUVmax (sSUV = 0.0842 SUVmax + 1.248; R 2 = 0.89). The sTL was not associated with the value of C-pGTVs. In PET/CT-based BTV for HNC, a suitable threshold or SUV level can be established by correlating with SUVmax rather than using a fixed threshold

  6. Effects of anticonvulsants in vivo on high affinity choline uptake in vitro in mouse hippocampal synaptosomes.

    Science.gov (United States)

    Miller, J. A.; Richter, J. A.

    1985-01-01

    The effects of several anticonvulsant drugs on sodium-dependent high affinity choline uptake (HACU) in mouse hippocampal synaptosomes was investigated. HACU was measured in vitro after in vivo administration of the drug to mice. HACU was inhibited by drugs which have in common the ability to facilitate gamma-aminobutyric acid (GABA) transmission, pentobarbitone, phenobarbitone, barbitone, diazepam, chloridiazepoxide, and valproic acid. Dose-response relationships were determined for these drugs and the drugs' potencies at inhibiting HACU correlated well with their anticonvulsant potencies. Clonazepam, ethosuximide, carbamazepine, and barbituric acid had no effect on HACU in the doses used while phenytoin and trimethadione stimulated HACU. These results suggest that certain anticonvulsants may elicit a part of their anticonvulsant activity by modulating cholinergic neurones. This effect may be mediated through a GABA mechanism. PMID:3978310

  7. Elevated tumor-to-liver uptake ratio (TLR) from 18F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    International Nuclear Information System (INIS)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin; Duan, Yinghua; Zhang, Zhanwen; Hu, Ping; Wang, Xiaoyan

    2017-01-01

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from 18 F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent 18 F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative 18 F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with elevated TLR. Cox

  8. Elevated tumor-to-liver uptake ratio (TLR) from {sup 18}F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin [6th Affiliated Hospital, Sun Yat-sen University, Department of Colorectal Surgery, Guangzhou, Guangdong (China); Duan, Yinghua [1st Affiliated Hospital, Sun Yat-sen University, Department of Traditional Chinese Medicine, Guangzhou (China); Zhang, Zhanwen; Hu, Ping [6th Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China); Wang, Xiaoyan [1st Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China)

    2017-11-15

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from {sup 18}F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent {sup 18}F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative {sup 18}F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with

  9. Interactions Between Structure and Processing that Control Moisture Uptake in High-Performance Polycyanurates (Briefing Charts)

    Science.gov (United States)

    2015-03-24

    Motivation • SOTA Theories of Moisture Uptake in Thermosetting Networks • New Tools and New Discoveries • Unresolved Issues and Ways to Address Them...Temperature Thermosetting Polymers: Cyanate Esters • Glass transition temperatures at full cure of 200 – 400°C • Uncured resins exist as low-melting solids...Summary: Basic Studies of Moisture Uptake in Cyanate Ester Networks • Many aspects of moisture uptake (and its minimization) in thermosetting polymer

  10. Prognostic importance of lymph node-to-primary tumor standardized uptake value ratio in invasive squamous cell carcinoma of uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of)

    2017-10-15

    Using integrated PET/CT, we evaluated the prognostic value of [{sup 18}F]FDG uptake ratio between pelvic lymph node (LN) and primary tumor in invasive squamous cell carcinoma (SCCA) of the uterine cervix. We retrospectively reviewed patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB to IIA cervical SCCA who underwent preoperative [{sup 18}F]FDG PET/CT scans. PET/CT parameters such as maximum standardized uptake value (SUV) of the primary cervical cancer (SUV{sub cervix}) and LN (SUV{sub LN}), and the LN-to-cervical cancer SUV ratio (SUV{sub LN}/SUV{sub cervix}) were assessed. Prognostic values of PET/CT-derived metabolic and volumetric variables and clinicopathology parameters were analyzed to predict progression-free survival (PFS) in regression analyses. Clinical data, treatment modalities, and results were reviewed for 103 eligible patients. Median post-surgical follow-up was 29 months (range, 6-89), and 19 (18.5%) patients experienced recurrence. Multivariate logistic regression analysis showed that SUV{sub LN} / SUV{sub cervix} > 0.1747(P = 0.048) was the independent risk factor of recurrence. Patient group categorized by SUV{sub LN}/SUV{sub cervix} showed significant difference in PFS (log-rank test, P < 0.001). Preoperative SUV{sub LN}/SUV{sub cervix} measured by [{sup 18}F]FDG PET/CT was significantly associated with recurrence, and has an incremental prognostic value for PFS in patients with cervical SCCA. (orig.)

  11. Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha.

    Science.gov (United States)

    Szymocha, R; Akaoka, H; Dutuit, M; Malcus, C; Didier-Bazes, M; Belin, M F; Giraudon, P

    2000-07-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of a chronic progressive myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In this disease, lesions of the central nervous system (CNS) are associated with perivascular infiltration by lymphocytes. We and others have hypothesized that these T lymphocytes infiltrating the CNS may play a prominent role in TSP/HAM. Here, we show that transient contact of human or rat astrocytes with T lymphocytes chronically infected by HTLV-1 impairs some of the major functions of brain astrocytes. Uptake of extracellular glutamate by astrocytes was significantly decreased after transient contact with infected T cells, while the expression of the glial transporters GLAST and GLT-1 was decreased. In two-compartment cultures avoiding direct cell-to-cell contact, similar results were obtained, suggesting possible involvement of soluble factors, such as cytokines and the viral protein Tax-1. Recombinant Tax-1 and tumor necrosis factor alpha (TNF-alpha) decreased glutamate uptake by astrocytes. Tax-1 probably acts by inducing TNF-alpha, as the effect of Tax-1 was abolished by anti-TNF-alpha antibody. The expression of glutamate-catabolizing enzymes in astrocytes was increased for glutamine synthetase and decreased for glutamate dehydrogenase, the magnitudes of these effects being correlated with the level of Tax-1 transcripts. In conclusion, Tax-1 and cytokines produced by HTLV-1-infected T cells impair the ability of astrocytes to manage the steady-state level of glutamate, which in turn may affect neuronal and oligodendrocytic functions and survival.

  12. Opioid receptor subtypes mediating the noise-induced decreases in high-affinity choline uptake in the rat brain.

    Science.gov (United States)

    Lai, H; Carino, M A

    1992-07-01

    Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.

  13. Positron imaging feasibility studies: characteristics of [3H]thymidine uptake in rodent and canine neoplasms

    International Nuclear Information System (INIS)

    Larson, S.M.; Weiden, P.L.; Grunbaum, J.

    1981-01-01

    Uptake [ 3 H]thymidine was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in nine dogs with spontaneous neoplasms: four lymphomas, two osteosarcomas, two soft-tissue sarcomas, and a thyroid carcinoma. High tumor-to-tissue ratios were observed for all tumor types assayed, and absolute uptakes, when computed as percent dose per gram tumor normalized for body weight, were similar for transplanted and spontaneous tumors. In the rodent tumors, radiothymidine was retained for at least 3 hr in the tumor without appreciable loss. In canine neoplasms, although the highest uptakes were observed in cellular tumors with many mitotic figures, tumor uptake showed significant variability that did not correlate with any obvious histologic change, and thus may reflect true biologic differences in metabolism among tumors at different sites in the same animal. These studies provide additional experimental evidence that the ratios of neoplastic to normal tissue and the kinetics of thymidine uptake by tumors are suitable for positron emission tomography of neoplasms in small and large, animals, including both transplanted and spontaneous tumors

  14. High prevalence of thyroid FDG uptake on PET study in patients with thyroid hormone replacement

    International Nuclear Information System (INIS)

    Yu, J.-Q.; Kumar, R.; Xiu, Y.; Dadparvar, S.; Kung, J.W.; Kunjunmen, B.D.; Feng, Q.; Alavi, A.; Zhuang, H.

    2004-01-01

    Thyroid uptake is commonly seen on whole-body FDG-PET images. One well-known cause for this uptake is hyperthyroidism. The purpose of this study was to determine whether hypothyroidism also affects FDG uptake by the thyroid gland. Hospital records of 2765 patients who had undergone whole-body FDG-PET imaging for malignancies were retrospectively reviewed. Among them, those who had thyroid cancer, history of thyroid ablation for hyperthyroidism, neck lymphoma, and other types of head and neck cancer or recent neck surgery were excluded from analysis. The prevalence and level of thyroid FDG uptake in the remaining 1939 patients was compared with the state of patients' thyroid function. There were 141 hypothyroid subjects and the rest (n=1798) were euthyroid. The prevalence of thyroid tissue uptake in euthyroid subjects was 2.34% (42 of 1798), while it was 22% (31 out of 141) in hypothyroid patients. This was statistically significant. Similarly, the prevalence of hypothyroidism in patients in patients showing thyroid uptake was 42.5% (31 of 73), while it was 5.9% (110 of 1866) in patients without thyroid uptake. This was again statistically significant (p<0.001). Based on this retrospective analysis it was concluded that the prevalence of increased thyroid FDG uptake is significantly higher in patients with hypothyroidism than those who are euthyroid. (author)

  15. High Intra- and Inter-Tumoral Heterogeneity of RAS Mutations in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Marion Jeantet

    2016-12-01

    Full Text Available Approximately 30% of patients with wild type RAS metastatic colorectal cancer are non-responders to anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs, possibly due to undetected tumoral subclones harboring RAS mutations. The aim of this study was to analyze the distribution of RAS mutations in different areas of the primary tumor, metastatic lymph nodes and distant metastasis. A retrospective cohort of 18 patients with a colorectal cancer (CRC was included in the study. Multiregion analysis was performed in 60 spatially separated tumor areas according to the pathological tumor node metastasis (pTNM staging and KRAS, NRAS and BRAF mutations were tested using pyrosequencing. In primary tumors, intra-tumoral heterogeneity for RAS mutation was found in 33% of cases. Inter-tumoral heterogeneity for RAS mutation between primary tumors and metastatic lymph nodes or distant metastasis was found in 36% of cases. Moreover, 28% of tumors had multiple RAS mutated subclones in the same tumor. A high proportion of CRCs presented intra- and/or inter-tumoral heterogeneity, which has relevant clinical implications for anti-EGFR mAbs prescription. These results suggest the need for multiple RAS testing in different parts of the same tumor and/or more sensitive techniques.

  16. Properties of internalization factors contributing to the uptake of extracellular DNA into tumor-initiating stem cells of mouse Krebs-2 cell line.

    Science.gov (United States)

    Dolgova, Evgeniya V; Potter, Ekaterina A; Proskurina, Anastasiya S; Minkevich, Alexandra M; Chernych, Elena R; Ostanin, Alexandr A; Efremov, Yaroslav R; Bayborodin, Sergey I; Nikolin, Valeriy P; Popova, Nelly A; Kolchanov, Nikolay A; Bogachev, Sergey S

    2016-05-25

    Previously, we demonstrated that poorly differentiated cells of various origins, including tumor-initiating stem cells present in the ascites form of mouse cancer cell line Krebs-2, are capable of naturally internalizing both linear double-stranded DNA and circular plasmid DNA. The method of co-incubating Krebs-2 cells with extracellular plasmid DNA (pUC19) or TAMRA-5'-dUTP-labeled polymerase chain reaction (PCR) product was used. It was found that internalized plasmid DNA isolated from Krebs-2 can be transformed into competent Escherichia coli cells. Thus, the internalization processes taking place in the Krebs-2 cell subpopulation have been analyzed and compared, as assayed by E. coli colony formation assay (plasmid DNA) and cytofluorescence (TAMRA-DNA). We showed that extracellular DNA both in the form of plasmid DNA and a PCR product is internalized by the same subpopulation of Krebs-2 cells. We found that the saturation threshold for Krebs-2 ascites cells is 0.5 μg DNA/10(6) cells. Supercoiled plasmid DNA, human high-molecular weight DNA, and 500 bp PCR fragments are internalized into the Krebs-2 tumor-initiating stem cells via distinct, non-competing internalization pathways. Under our experimental conditions, each cell may harbor 340-2600 copies of intact plasmid material, or up to 3.097 ± 0.044×10(6) plasmid copies (intact or not), as detected by quantitative PCR. The internalization dynamics of extracellular DNA, copy number of the plasmids taken up by the cells, and competition between different types of double-stranded DNA upon internalization into tumor-initiating stem cells of mouse ascites Krebs-2 have been comprehensively analyzed. Investigation of the extracellular DNA internalization into tumor-initiating stem cells is an important part of understanding their properties and possible destruction mechanisms. For example, a TAMRA-labeled DNA probe may serve as an instrument to develop a target for the therapy of cancer, aiming at elimination of

  17. Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart

    International Nuclear Information System (INIS)

    Farde, L.; Halldin, C.; Naagren, K.; Suhara, Tetsuya; Karlsson, P.; Schoeps, K.O.; Swahn, C.G.; Bone, D.

    1994-01-01

    (-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [ 11 C]norepinephrine indicates that enatiomerically pure(-)-[ 11 C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium. (orig.)

  18. Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart

    Energy Technology Data Exchange (ETDEWEB)

    Farde, L [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Halldin, C [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Naagren, K [Turku Univ., Cyclotron/PET Center (Finland); Suhara, Tetsuya [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Karlsson, P [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Schoeps, K O [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Swahn, C G [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Bone, D [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden)

    1994-04-01

    (-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [[sup 11]C]norepinephrine indicates that enatiomerically pure(-)-[[sup 11]C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium. (orig.)

  19. High failure rates after (131)I therapy in Graves hyperthyroidism patients with large thyroid volumes, high iodine uptake, and high iodine turnover.

    Science.gov (United States)

    de Jong, Jeroen A F; Verkooijen, Helena M; Valk, Gerlof D; Zelissen, Pierre M J; de Keizer, Bart

    2013-06-01

    The objective of this study was to identify patient characteristics positively and independently associated with I-iodide treatment failure in a large cohort of patients with Graves hyperthyroidism treated with either a calculated "standard" activity of 3.7 MBq/mL (0.1 mCi) or 7.4 MBq/mL (0.2 mCi) of thyroid volume. Data on 385 consecutive patients were prospectively collected. Clinical treatment outcome up to 1 year in relation to thyroid volume, 5- and 24-hour I uptake, 5/24-hour I uptake ratio, and the administered activity of radioiodine were analyzed. Overall treatment results were hypothyroidism in 46%, euthyroidism in 29%, and recurrent hyperthyroidism in 26% of patients. Thyroid volume (P = 0.000), 5/24-hour uptake ratio (P = 0.000), and 5- and 24-hour uptake alone (respectively, P = 0.000 and P = 0.002) were significantly associated with therapy outcome. Patients with a combination of a thyroid volume greater than 50 mL and a 5/24-hour uptake ratio 0.8 or greater showed treatment failure in 70% and 42% (respectively, 3.7 MBq/mL, n = 20; and 7.4 MBq/mL, n = 41).Thyroid volume and 5/24-hour uptake ratio were positively and independently associated with recurrent hyperthyroidism (respectively, odds ratio [OR], 5.3; 95% confidence interval [CI], 2.39-11.76; and OR, 2.97; 95% CI, 1.59-5.59). Higher activities of 7.4 MBq/mL I were associated with a lower risk of treatment failure (OR, 0.34; 95% CI, 0.18-0.62). Large thyroid volumes and high 5/24-hour uptake ratios are positively and independently associated with recurrent hyperthyroidism following I therapy in Graves hyperthyroidism. Higher success rates can be achieved when account is taken of these poor prognostic factors. In consequence, these patients should be treated with activities greater than 7.4 MBq/mL.

  20. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

    2016-01-15

    hold in multivariate analysis. Determination of uptake heterogeneity in pre-therapeutic FET-PET using textural features proved valuable for the (sub-)grading of high-grade glioma as well as prediction of tumor progression and patient survival, and showed improved performance compared to standard parameters such as TBR and tumor volume. Our results underscore the importance of intratumoral heterogeneity in the biology of high-grade glial cell tumors and may contribute to individual therapy planning in the future, although they must be confirmed in prospective studies before incorporation into clinical routine. (orig.)

  1. The influence of proteasome inhibitor MG132, external radiation and unlabeled antibody on the tumor uptake and biodistribution of 188Re-labeled anti-E6 C1P5 antibody in cervical cancer in mice

    Science.gov (United States)

    Phaeton, Rébécca; Wang, Xing Guo; Einstein, Mark H.; Goldberg, Gary L.; Casadevall, Arturo; Dadachova, Ekaterina

    2009-01-01

    Background Human Papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer and >95% of all cervical cancers have detectable HPV sequences. We have recently demonstrated the efficacy of radioimmunotherapy (RIT) which targeted viral oncoprotein E6 in treatment of experimental cervical cancer We hypothesized that pre-treatment of tumor cells with various agents which cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors. Methods HPV-16 positive CasKi cells were treated in vitro with up to 6 Gy of external radiation, or proteasome inhibitor MG-132 or unlabeled anti-E6 antibody C1P5 and cell death was assessed. Biodistribution of 188Rhenium (188Re)-labeled C1P5 antibody was performed in both control and radiation MG-132 treated CasKi tumor-bearing nude mice. Results . 188Re-C1P5 antibody demonstrated tumor specificity and very low uptake and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG-132 but was unaffected by pre-treatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by our previous in vivo studies in CasKi tumor model. Conclusion We demonstrated that pre-treatment of cervical tumors with proteasome inhibitor MG-132 and with unlabeled antibody to E6 can serve as a means to generate non-viable cancer cells and to elevate the levels of target oncoproteins in the cells for increasing the accumulation of targeted radiolabeled antibodies in tumors. These results favor further development of RIT of cervical cancers targeting viral antigens. PMID:20127955

  2. Irradiation of meningioma: a prototype circumscribed tumor for planning high-dose irradiation of the brain

    International Nuclear Information System (INIS)

    Friedman, M.

    1977-01-01

    The purpose of this report is to provide specific data concerning the radiation dose required to destroy meningioma, and to demonstrate that radiation doses much greater than the alleged tolerance dose, can be administered to the brain in some patients. Most meninglomas are not responsive to irradiation, but, some surgically incurable lesions benefit from irradiation with radically high doses to small volumes of tissue. The arrest of 7 of 12 consecutive meningiomas in adults for periods of 2 to 17 years following maximum tumor doses up to 8800 R in 40 days is reported in this paper. All patients, when irradiated, had active tumor in the form of inoperable primary tumor, recurrence, or known postoperative residual tumor. Three of the successful results were achieved with orthovoltage radiation. The incidence of brain damage may be acceptable to the patient when it is related to arrest of tumor growth but he must be forewarned of possible brain damage. The factors influencing the radioresponsiveness of meningioma are: the required tumor lethal dose, histology and vascularity of the tumor, anatomical site in the brain, treatment technique for each tumor site, small size of the treated volume, growth rate of the tumor, displacement of normal brain tissue by tumor, inherent individual variations of tumor and normal tissues, quality of the radiation, and tolerance of normal brain tissues. The role of these factors is discussed in the light of modern radiobiological concepts

  3. Correlation of high {sup 18}F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Groheux, David; Moretti, Jean-Luc; Hindie, Elif [Department of Nuclear Medicine, Saint-Louis Hospital,Assistance publique Hopitaux de Paris, Paris Cedex 10 (France); IUH, Doctoral School, University of Paris VII, Paris (France); Giacchetti, Sylvie; Espie, Marc; Hamy, Anne-Sophie; Cuvier, Caroline [Breast Diseases Unit, Saint-Louis Hospital, Department of Medical Oncology, Paris (France); Porcher, Raphael [Saint-Louis Hospital, Department of Biostatistics and Medical Information, Paris (France); Lehmann-Che, Jacqueline [Saint-Louis Hospital, Department of Biochemistry, Paris (France); Roquancourt, Anne de [Saint-Louis Hospital, Department of Pathology, Paris (France); Vercellino, Laetitia [Department of Nuclear Medicine, Saint-Louis Hospital, Assistance publique Hopitaux de Paris, Paris Cedex 10 (France)

    2011-03-15

    The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on {sup 18}F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20 mm (T2-T4) were included in order to minimize bias of partial volume effect. In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUV{sub max}) were compared to tumour characteristics as assessed on core biopsy. There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUV{sub max} was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p < 0.0001); negativity for oestrogen receptors (ER) was associated with higher SUV (ER+ SUV = 5.5; ER- SUV = 7.6; p = 0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p < 0.0001). Overexpression of c-erbB-2 had no effect on the SUV value. Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging. (orig.)

  4. Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer

    International Nuclear Information System (INIS)

    Groheux, David; Moretti, Jean-Luc; Hindie, Elif; Giacchetti, Sylvie; Espie, Marc; Hamy, Anne-Sophie; Cuvier, Caroline; Porcher, Raphael; Lehmann-Che, Jacqueline; Roquancourt, Anne de; Vercellino, Laetitia

    2011-01-01

    The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on 18 F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20 mm (T2-T4) were included in order to minimize bias of partial volume effect. In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUV max ) were compared to tumour characteristics as assessed on core biopsy. There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUV max was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p < 0.0001); negativity for oestrogen receptors (ER) was associated with higher SUV (ER+ SUV = 5.5; ER- SUV = 7.6; p = 0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p < 0.0001). Overexpression of c-erbB-2 had no effect on the SUV value. Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging. (orig.)

  5. Evaluation of the Effect of Tumor Position on Standardized Uptake Value Using Time-of-Flight Reconstruction and Point Spread Function

    Directory of Open Access Journals (Sweden)

    Yasuharu Wakabayashi

    2016-01-01

    Full Text Available Objective(s: The present study was conducted to examine whether the standardized uptake value (SUV may be affected by the spatial position of a lesion in the radial direction on positron emission tomography (PET images, obtained via two methods based on time-of-flight (TOF reconstruction and point spread function (PSF. Methods: A cylinder phantom with the sphere (30mm diameter, located in the center was used in this study. Fluorine-18 fluorodeoxyglucose (18F-FDG concentrations of 5.3 kBq/ml and 21.2 kBq/ml were used for the background in the cylinder phantom and the central sphere respectively. By the use of TOF and PSF, SUVmax and SUVmean were determined while moving the phantom in a horizontal direction (X direction from the center of field of view (FOV: 0 mm at 50, 100, 150 and 200 mm positions, respectively. Furthermore, we examined 41 patients (23 male, 18 female, mean age: 68±11.2 years with lymph node tumors , who had undergone 18F-FDG PET examinations. The distance of each lymph node from FOV center was measured, based on the clinical images. Results: As the distance of a lesion from the FOV center exceeded 100 mm, the value of SUVmax, which was obtained with the cylinder phantom, was overestimated, while SUVmean by TOF and/or PSF was underestimated. Based on the clinical examinations, the average volume of interest was 8.5 cm3. Concomitant use of PSF increased SUVmax and SUVmean by 27.9% and 2.8%, respectively. However, size of VOI and distance from the FOV center did not affect SUVmax or SUVmean in clinical examinations. Conclusion: The reliability of SUV quantification by TOF and/or PSF decreased, when the tumor was located at a 100 mm distance (or farther from the center of FOV. In clinical examinations, if the lymph node was located within 100 mm distance from the center of FOV, SUV remained stable within a constantly increasing range by use of both TOF and PSF. We conclude that, use of both TOF and PSF may be helpful.

  6. High and typical 18F-FDG bowel uptake in patients treated with metformin

    International Nuclear Information System (INIS)

    Gontier, Eric; Bonardel, Gerald; Mantzarides, Marina; Foehrenbach, Herve; Fourme, Emmanuelle; Wartski, Myriam; Pecking, Alain-Paul; Alberini, Jean-Louis; Blondet, Cyrille; Le Stanc, Elise

    2008-01-01

    This prospective and bi-centric study was conducted in order to determine the impact of antidiabetic treatments (AD) on 18 F-FDG bowel uptake in type 2 diabetic patients. Fifty-five patients with previously diagnosed and treated type 2 diabetes mellitus (group 1) were divided in two subgroups: AD treatment including metformin (n=32; group 1a) and AD treatment excluding metformin (n=23; group 1b). The 95 patients without diabetes mellitus made up controls (group 2). 18 F-FDG uptake in small intestine and colon was visually graded and semi-quantitatively measured using the maximum standardized uptake value. 18 F-FDG bowel uptake was significantly increased in AD patients (group 1) as compared to controls (group 2) (p 18 F-FDG uptake in colon and, to a lesser extent, in small intestine. It raises the question of stopping metformin treatment before an 18 F-FDG PET/CT scan is performed for intra-abdominal neoplasic lesion assessment. (orig.)

  7. Effect of colony-stimulating factor and conventional- or high-dose chemotherapy on FDG uptake in bone marrow

    International Nuclear Information System (INIS)

    Kazama, Toshiki; Swanston, Nancy; Podoloff, Donald A.; Macapinlac, Homer A.

    2005-01-01

    Granulocyte or granulocyte-macrophage colony stimulating factor (CSF), usually used in conjunction with chemotherapy, may interfere with the 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) reading. The purpose of this study is to evaluate the effects of CSF, conventional-or high-dose chemotherapy on bone marrow FDG uptake. Two hundred and forty-one FDG PET scans obtained in 163 patients with lymphoma and no pathologically and radiologically proven bone marrow involvement were analyzed. The standardized uptake value (SUV) of each patient's spine was measured. Among patients with no recent history of CSF use, the average SUV in 36 patients with no history of chemotherapy was 1.60±0.34, that in 49 patients with a history of conventional-dose chemotherapy was 1.37±0.32, and that in 12 patients with a history of high-dose chemotherapy was 1.26±0.25 (P=0.008 and 0.002, respectively by Mann-Whitney U test). In 80 patients treated with conventional-dose chemotherapy and CSF, the average SUV after discontinuation of CSF was as follows: 0-7 days, 2.37±1.19; 8-14 days: 2.04±0.67; 15-21 days: 1.87±0.52; 22-30 days: 1.59±0.18; 31-90 days: 1.54±0.36. In 45 patients treated with high-dose chemotherapy and CSF, no significant increase in bone marrow uptake was seen in most of them. Bone marrow FDG uptake may be increased by CSF treatment and may be decreased by chemotherapy. In patients treated with conventional-dose chemotherapy and CSF, increased marrow uptake will return to the pretreatment value approximately 1 month after discontinuation of CSF. (orig.)

  8. Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Lucia Natarelli

    Full Text Available Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG. In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9 and effector caspases (caspase 7 and 3 and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.

  9. Uptake of [3H]vitamin D3 from low and high density lipoproteins by cultured human fibroblasts

    International Nuclear Information System (INIS)

    Shireman, R.B.; Williams, D.; Remsen, J.F.

    1986-01-01

    The plasma distribution and cellular uptake of [ 3 H]vitamin D 3 was studied in vitro using cultured human fibroblasts. Incubation of [ 3 H]vitamin D 3 (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from [ 3 H] 1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of [ 3 H]vitamin D 3 from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D 3 was time, concentration, and temperature dependent. At a concentration of 50 μg LDL/ml of medium, the uptake of [ 3 H]vitamin D 3 from LDL at 37 0 C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D 3 absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver

  10. 201Tl scintigraphic evaluation of tumor mass and viability of bone and soft-tissue tumors

    International Nuclear Information System (INIS)

    Tsuda, Takatoshi; Kubota, Masahiro; Yoshida, Satoru; Shibata, Masahito; Wakabayashi, Jun-ichi; Obata, Hiroyuki; Matsuyama, Toshikatsu; Usui, Masamichi; Ishii, Sei-ichi.

    1994-01-01

    To characterize 201 Tl uptake in patients with bone and soft-tissue tumor, we studied 49 patients with surgically proven tumors and one patient with a tumor diagnosed arteriographically. In 37 of our 50 patients, the tumor was evaluated with 201 Tl and arteriography. Moreover, in 14 of patients with pre-operative chemotherapy, pathologic changes were graded on the basis of percent tumor necrosis as defined histologically. The percent tumor necrosis histologically was compared with changes in the scintigraphic and conventional angiographic studies. Radiologic comparisons demonstrated a high degree of correlation with images of 201 Tl and both arterial and blood pool phase of 99m Tc-HMDP. Ninety-six percent of 28 malignant tumors had positive 201 Tl uptake. None of the patients showed any thallium accumulation in the soft tissues or skeleton adjacent to the lesion. Activity of 201 Tl was mainly dependent upon a tumor blood flow and a vascular density. In of 14 cases with the preoperative chemotherapeutic treatment, 201 Tl scintigraphic changes showed concordance with % tumor necrosis. Thallium-201 was superior to 99m Tc-HMDP in predicting tumor response to chemotherapy. Interestingly, delayed images of 99m Tc-HMDP of 5 responders with >90% tumor necrosis showed decreased uptake in the adjacent bone to the tumor mass lesions. It seems to be quite all right to consider that a major determinant of 201 Tl uptake is intratumoral angiogenecity, which is closely connected with tumor viability. Therefore, 201 Tl is a sensitive radiopharmaceutical for detection of vascular rich bone and soft-tissue tumors, and appears to be a simple and an accurate test for evaluating the response to specific therapeutic regimens of malignant bone and soft-tissue tumors. (author)

  11. Amide proton transfer imaging of high intensity focused ultrasound-treated tumor tissue

    NARCIS (Netherlands)

    Hectors, S.J.C.G.; Jacobs, I.; Strijkers, G.J.; Nicolay, K.

    2014-01-01

    Purpose: In this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. Methods: APT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

  12. Amide Proton Transfer Imaging of High Intensity Focused Ultrasound-Treated Tumor Tissue

    NARCIS (Netherlands)

    Hectors, Stefanie J. C. G.; Jacobs, Igor; Strijkers, Gustav J.; Nicolay, Klaas

    2014-01-01

    PurposeIn this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. MethodsAPT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

  13. T1 ρ mapping for the evaluation of high intensity focused ultrasound tumor treatment

    NARCIS (Netherlands)

    Hectors, Stefanie J. C. G.; Moonen, Rik P. M.; Strijkers, Gustav J.; Nicolay, Klaas

    2015-01-01

    This study was aimed to assess the effects of High Intensity Focused Ultrasound (HIFU) thermal ablation on tumor T1ρ . In vivo T1ρ measurements of murine tumors at various spin-lock amplitudes (B1 = 0-2000 Hz) were performed before (n = 13), directly after (n = 13) and 3 days (n = 7) after HIFU

  14. Correlation of 18F-fluoroethyl tyrosine positron-emission tomography uptake values and histomorphological findings by stereotactic serial biopsy in newly diagnosed brain tumors using a refined software tool

    Directory of Open Access Journals (Sweden)

    Lopez WO

    2015-12-01

    Full Text Available William Omar Contreras Lopez,1,2 Joacir Graciolli Cordeiro,1 Ulrich Albicker,3 Soroush Doostkam,4 Guido Nikkhah,1,5 Robert D Kirch,6 Michael Trippel,1 Thomas Reithmeier1,7 1Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Freiburg im Breisgau, Germany; 2Division of Functional Neurosurgery, Department of Neurology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil; 3Inomed, Emmendingen, 4Department of Neuropathology, University Medical Center Freiburg, Freiburg im Breisgau, 5Department of Neurosurgery, University Clinic Erlangen, Erlangen, 6Neuroelectronic Systems, Department of Neurosurgery, University Medical Center Freiburg, Freiburg im Breisgau, 7Department of Neurosurgery, Schwabing Academic Teaching Hospital of Technical University and Ludwig Maximilian University of Munich, Munich, Germany Background: Magnetic resonance imaging (MRI is the standard neuroimaging method to diagnose neoplastic brain lesions, as well as to perform stereotactic biopsy surgical planning. MRI has the advantage of providing structural anatomical details with high sensitivity, though histological specificity is limited. Although combining MRI with other imaging modalities, such as positron-emission tomography (PET, has proven to increment specificity, exact correlation between PET threshold uptake ratios (URs and histological diagnosis and grading has not yet been described.Objectives: The aim of this study was to correlate exactly the histopathological criteria of the biopsy site to its PET uptake value with high spatial resolution (mm3, and to analyze the diagnostic value of PET using the amino acid O-(2-[18F]fluoroethyl-L-tyrosine (18F-FET PET in patients with newly diagnosed brain lesions in comparison to histological findings obtained from stereotactic serial biopsy.Patients and methods: A total of 23 adult patients with newly diagnosed brain tumors on MRI were enrolled in this study

  15. [Characteristics of phosphorus uptake and use efficiency of rice with high yield and high phosphorus use efficiency].

    Science.gov (United States)

    Li, Li; Zhang, Xi-Zhou; Li, Tinx-Xuan; Yu, Hai-Ying; Ji, Lin; Chen, Guang-Deng

    2014-07-01

    efficiencies to the yield was in order of P uptake efficiency > P utilization efficiency > P transportation efficiency. The greatest contribution rate of P accumulation to the yield was noticed at the jointing-heading stage with the normal P application while it reached the maximal value at the tillering-jointing stage with the low P application. Therefore, these two stages may be the critical periods to coordinate high yield and high P efficiency in rice.

  16. Accelerated growth of B16BL6 tumor in mice through efficient uptake of their own exosomes by B16BL6 cells

    OpenAIRE

    Matsumoto, Akihiro; Takahashi, Yuki; Nishikawa, Makiya; Sano, Kohei; Morishita, Masaki; Charoenviriyakul, Chonlada; Saji, Hideo; Takakura, Yoshinobu

    2017-01-01

    Exosomes are extracellular vesicles released by various cell types and play roles in cell?cell communication. Several studies indicate that cancer cell?derived exosomes play important pathophysiological roles in tumor progression. Biodistribution of cancer cell?derived exosomes in tumor tissue is an important factor for determining their role in tumor proliferation; however, limited studies have assessed the biodistribution of exosomes in tumor tissues. In the present study, we examined the e...

  17. Reduction of Cadmium Uptake of Rice Plants Using Soil Amendments in High Cadmium Contaminated Soil: A Pot Experiment

    Directory of Open Access Journals (Sweden)

    Dian Siswanto

    2013-05-01

    Full Text Available The aims of this study were to investigate the effect of agricultural residues on reducing cadmium uptake in rice plants. The rice plants growing on no cadmium/free cadmium soils (N, Cd soils (Cds, and Cd soils each amended with 1% w/w of coir pith (CP, coir pith modified with sodium hydroxide (CPm and corncob (CC under high cadmium contaminated soil with an average 145 mg Cd kg-1 soil were investigated. The results showed that the cumulative transpiration of rice grown in various treatments under high cadmium contaminated soil followed the order: Cds > CPm ≥ CP ≥ CC. These transpirations directly influenced cadmium accumulation in shoots and husks of rice plants. The CC and CP seemed to work to reduce the cadmium uptake by rice plants indicated by accumulated cadmium in the husk that were 2.47 and 7.38 mg Cd kg-1 dry weight, respectively. Overall, transpiration tended to drive cadmium accumulation in plants for rice grown in high cadmium contaminated soil. The more that plants uptake cadmium, the lower cadmium that remains in the soil.

  18. In vivo regulation of scavenger receptor BI and the selective uptake of high density lipoprotein cholesteryl esters in rat liver parenchymal and Kupffer cells

    NARCIS (Netherlands)

    Fluiter, K.; van der Westhuijzen, D. R.; van Berkel, T. J.

    1998-01-01

    High density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake. This selective uptake route forms an important step in the so-called reverse cholesterol transport. Scavenger receptor BI (SR-BI) is the only known HDL

  19. Highly-sensitive and large-dynamic diffuse optical tomography system for breast tumor detection

    Science.gov (United States)

    Du, Wenwen; Zhang, Limin; Yin, Guoyan; Zhang, Yanqi; Zhao, Huijuan; Gao, Feng

    2018-02-01

    Diffuse optical tomography (DOT) as a new functional imaging has important clinical applications in many aspects such as benign and malignant breast tumor detection, tumor staging and so on. For quantitative detection of breast tumor, a three-wavelength continuous-wave DOT prototype system combined the ultra-high sensitivity of the photon-counting detection and the measurement parallelism of the lock-in technique was developed to provide high temporal resolution, high sensitivity, large dynamic detection range and signal-to-noise ratio. Additionally, a CT-analogous scanning mode was proposed to cost-effectively increase the detection data. To evaluate the feasibility of the system, a series of assessments were conducted. The results demonstrate that the system can obtain high linearity, stability and negligible inter-wavelength crosstalk. The preliminary phantom experiments show the absorption coefficient is able to be successfully reconstructed, indicating that the system is one of the ideal platforms for optical breast tumor detection.

  20. In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

    Science.gov (United States)

    Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

    2017-02-01

    Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (pbladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

  1. Is it beneficial to selectively boost high-risk tumor subvolumes? A comparison of selectively boosting high-risk tumor subvolumes versus homogeneous dose escalation of the entire tumor based on equivalent EUD plans

    International Nuclear Information System (INIS)

    Kim, Yusung; To me, Wolfgang A.

    2008-01-01

    Purpose. To quantify and compare expected local tumor control and expected normal tissue toxicities between selective boosting IMRT and homogeneous dose escalation IMRT for the case of prostate cancer. Methods. Four different selective boosting scenarios and three different high-risk tumor subvolume geometries were designed to compare selective boosting and homogeneous dose escalation IMRT plans delivering the same equivalent uniform dose (EUD) to the entire PTV. For each scenario, differences in tumor control probability between both boosting strategies were calculated for the high-risk tumor subvolume and remaining low-risk PTV, and were visualized using voxel based iso-TCP maps. Differences in expected rectal and bladder complications were quantified using radiobiological indices (generalized EUD (gEUD) and normal tissue complication probability (NTCP)) as well as %-volumes. Results. For all investigated scenarios and high-risk tumor subvolume geometries, selective boosting IMRT improves expected TCP compared to homogeneous dose escalation IMRT, especially when lack of control of the high-risk tumor subvolume could be the cause for tumor recurrence. Employing, selective boosting IMRT significant increases in expected TCP can be achieved for the high-risk tumor subvolumes. The three conventional selective boosting IMRT strategies, employing physical dose objectives, did not show significant improvement in rectal and bladder sparing as compared to their counterpart homogeneous dose escalation plans. However, risk-adaptive optimization, utilizing radiobiological objective functions, resulted in reduction in NTCP for the rectum when compared to its corresponding homogeneous dose escalation plan. Conclusions. Selective boosting is a more effective method than homogeneous dose escalation for achieving optimal treatment outcomes. Furthermore, risk-adaptive optimization increases the therapeutic ratio as compared to conventional selective boosting IMRT

  2. Activity of MM-398, nanoliposomal irinotecan (nal-IRI), in Ewing's family tumor xenografts is associated with high exposure of tumor to drug and high SLFN11 expression.

    Science.gov (United States)

    Kang, Min H; Wang, Jing; Makena, Monish R; Lee, Joo-Sang; Paz, Nancy; Hall, Connor P; Song, Michael M; Calderon, Ruben I; Cruz, Riza E; Hindle, Ashly; Ko, Winford; Fitzgerald, Jonathan B; Drummond, Daryl C; Triche, Timothy J; Reynolds, C Patrick

    2015-03-01

    To determine the pharmacokinetics and the antitumor activity in pediatric cancer models of MM-398, a nanoliposomal irinotecan (nal-IRI). Mouse plasma and tissue pharmacokinetics of nal-IRI and the current clinical formulation of irinotecan were characterized. In vivo activity of irinotecan and nal-IRI was compared in xenograft models (3 each in nu/nu mice) of Ewing's sarcoma family of tumors (EFT), neuroblastoma (NB), and rhabdomyosarcoma (RMS). SLFN11 expression was assessed by Affymetrix HuEx arrays, Taqman RT-PCR, and immunoblotting. Plasma and tumor concentrations of irinotecan and SN-38 (active metabolite) were approximately 10-fold higher for nal-IRI than for irinotecan. Two doses of NAL-IRI (10 mg/kg/dose) achieved complete responses maintained for >100 days in 24 of 27 EFT-xenografted mice. Event-free survival for mice with RMS and NB was significantly shorter than for EFT. High SLFN11 expression has been reported to correlate with sensitivity to DNA damaging agents; median SLFN11 mRNA expression was >100-fold greater in both EFT cell lines and primary tumors compared with NB or RMS cell lines or primary tumors. Cytotoxicity of SN-38 inversely correlated with SLFN11 mRNA expression in 20 EFT cell lines. In pediatric solid tumor xenografts, nal-IRI demonstrated higher systemic and tumor exposures to SN-38 and improved antitumor activity compared with the current clinical formulation of irinotecan. Clinical studies of nal-IRI in pediatric solid tumors (especially EFT) and correlative studies to determine if SLFN11 expression can serve as a biomarker to predict nal-IRI clinical activity are warranted. ©2015 American Association for Cancer Research.

  3. Characteristic Uptake Pattern of Bone Scintigraphy in Patients with Hepatocellular Carcinoma Following Treatment with High-Intensity Focused Ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Waihan; Ho, Waiyin; Lai, Andrew S. H.; Wong, Kwongkuen; Law, Martin [Queen Mary Hospital, Pokfulam (Hong Kong)

    2013-12-15

    This study retrospectively reviews the characteristic bone scintigraphic findings in 18 patients with hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU). A potential complication of HIFU is damage to the tissues along the path of the ultrasound beam and structures superficial to the lesion of interest. Patients with hepatocellular carcinoma who underwent a bone scan between 1st December 2005 and 31st December 2011 were considered for this study. Among these patients, only those who had bone scans after the HIFU treatment were included. The time between HIFU treatment and bone scans, HIFU energy, HCC sites, tumour sizes and related radiological findings were evaluated. In total, 20 bone scans of 18 patients were reviewed. Of these scans, two patients were normal; three patients showed decreased uptake, four patients showed increased uptake and nine patients showed mixed uptakes of the bony tracer in their rib cages. The defects were located in the anterior, lateral, anterolateral or posterolateral aspects of the rib cage. The majority of those cold defects were in the right anterior rib cages. SPECT/CT was used to localise the decreased uptake in ribs. The magnetic resonance imaging in individual patients invariably showed ill-defined rim enhancement along the right chest wall, signifying chest wall injury. The results showed that tissue ablation using HIFU caused tissue injury along the pathway of high-intensity ultrasound beams. The harm to tissues is presented as photopenic area on the rib cages due to necrosis or hot spots due to rib fractures in the bone scan. Since these cold defects are subtle, they are easily overlooked or mistaken as aggressive bony metastasis.

  4. In vitro and in vivo evaluation of a (18F-labeled high affinity NOTA conjugated bombesin antagonist as a PET ligand for GRPR-targeted tumor imaging.

    Directory of Open Access Journals (Sweden)

    Zohreh Varasteh

    Full Text Available Expression of the gastrin-releasing peptide receptor (GRPR in prostate cancer suggests that this receptor can be used as a potential molecular target to visualize and treat these tumors. We have previously investigated an antagonist analog of bombesin (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26 conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA via a diethylene glycol (PEG2 spacer (NOTA-P2-RM26 labeled with (68Ga and (111In. We found that this conjugate has favorable properties for in vivo imaging of GRPR-expression. The focus of this study was to develop a (18F-labelled PET agent to visualize GRPR. NOTA-P2-RM26 was labeled with (18F using aluminum-fluoride chelation. Stability, in vitro binding specificity and cellular processing tests were performed. The inhibition efficiency (IC50 of the [(natF]AlF-NOTA-P2-RM26 was compared to that of the (natGa-loaded peptide using (125I-Tyr(4-BBN as the displacement radioligand. The pharmacokinetics and in vivo binding specificity of the compound were studied. NOTA-P2-RM26 was labeled with (18F within 1 h (60-65% decay corrected radiochemical yield, 55 GBq/µmol. The radiopeptide was stable in murine serum and showed high specific binding to PC-3 cells. [(natF]AlF-NOTA-P2-RM26 showed a low nanomolar inhibition efficiency (IC50=4.4±0.8 nM. The internalization rate of the tracer was low. Less than 14% of the cell-bound radioactivity was internalized after 4 h. The biodistribution of [(18F]AlF-NOTA-P2-RM26 demonstrated rapid blood clearance, low liver uptake and low kidney retention. The tumor uptake at 3 h p.i. was 5.5±0.7 %ID/g, and the tumor-to-blood, -muscle and -bone ratios were 87±42, 159±47, 38±16, respectively. The uptake in tumors, pancreas and other GRPR-expressing organs was significantly reduced when excess amount of non-labeled peptide was co-injected. The low uptake in bone suggests a high in vivo stability of the Al-F bond. High contrast PET image was obtained 3 h p

  5. Second malignancies in high-dose areas of previous tumor radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Welte, Birgitta; Suhr, Peter; Bottke, Dirk; Bartkowiak, Detlef; Wiegel, Thomas [Dept. of Radiotherapy and Radiation Oncology, Univ. of Ulm (Germany); Doerr, Wolfgang [Dept. of Radiotherapy and Radiation Oncology, Radiobiology Lab., Univ. of Technology Dresden (Germany); Trott, Klaus Ruediger [UCL Cancer Centre, Univ. Coll. London (United Kingdom)

    2010-03-15

    Purpose: To characterize second tumors that developed in or near the high-dose areas of a previous radiotherapy, regarding their frequency, entities, latency, and dose dependence. Patients and Methods: 9,995/15,449 tumor patients of the Radiation Oncology Department in Ulm, Germany, treated between 1981 and 2003, survived at least 1 year after radiotherapy. By long-term follow-up and review of treatment documentation, 100 of them were identified who developed an independent second cancer in or near the irradiated first tumor site. Results: Major primary malignancies were breast cancer (27%), lymphoma (24%), and pelvic gynecologic tumors (17%). Main second tumors were carcinomas of the upper (18%) and lower (12%) gastrointestinal tract, head and neck tumors (10%), lymphoma (10%), breast cancer (9%), sarcoma (9%), and lung cancer (8%). Overall median second tumor latency was 7.4 years (1-42 years). For colorectal cancer it was 3.5 and for leukemia 4.3 years, but for sarcoma 11.7 and for breast cancer 17.1 years. The relatively frequent second tumors of the upper gastrointestinal tract were associated with median radiation doses of 24 Gy. By contrast, second colorectal cancer and sarcoma developed after median doses of 50 Gy. Conclusion: The 5- and 15-year probability to develop a histopathologically independent second tumor in or near the irradiated first tumor site, i.e., after intermediate or high radiation doses, was 0.5% and 2.2%, respectively. To identify potentially radiogenic second malignancies, a follow-up far beyond 5 years is mandatory. The incidence and potential dose-response relationship intermediate will be analyzed by a case-case and a case-control study of the Ulm data. (orig.)

  6. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.

    Science.gov (United States)

    Adalsteinsson, Viktor A; Ha, Gavin; Freeman, Samuel S; Choudhury, Atish D; Stover, Daniel G; Parsons, Heather A; Gydush, Gregory; Reed, Sarah C; Rotem, Denisse; Rhoades, Justin; Loginov, Denis; Livitz, Dimitri; Rosebrock, Daniel; Leshchiner, Ignaty; Kim, Jaegil; Stewart, Chip; Rosenberg, Mara; Francis, Joshua M; Zhang, Cheng-Zhong; Cohen, Ofir; Oh, Coyin; Ding, Huiming; Polak, Paz; Lloyd, Max; Mahmud, Sairah; Helvie, Karla; Merrill, Margaret S; Santiago, Rebecca A; O'Connor, Edward P; Jeong, Seong H; Leeson, Rachel; Barry, Rachel M; Kramkowski, Joseph F; Zhang, Zhenwei; Polacek, Laura; Lohr, Jens G; Schleicher, Molly; Lipscomb, Emily; Saltzman, Andrea; Oliver, Nelly M; Marini, Lori; Waks, Adrienne G; Harshman, Lauren C; Tolaney, Sara M; Van Allen, Eliezer M; Winer, Eric P; Lin, Nancy U; Nakabayashi, Mari; Taplin, Mary-Ellen; Johannessen, Cory M; Garraway, Levi A; Golub, Todd R; Boehm, Jesse S; Wagle, Nikhil; Getz, Gad; Love, J Christopher; Meyerson, Matthew

    2017-11-06

    Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.

  7. Zeolite Y Adsorbents with High Vapor Uptake Capacity and Robust Cycling Stability for Potential Applications in Advanced Adsorption Heat Pumps.

    Science.gov (United States)

    Li, Xiansen; Narayanan, Shankar; Michaelis, Vladimir K; Ong, Ta-Chung; Keeler, Eric G; Kim, Hyunho; McKay, Ian S; Griffin, Robert G; Wang, Evelyn N

    2015-01-01

    Modular and compact adsorption heat pumps (AHPs) promise an energy-efficient alternative to conventional vapor compression based heating, ventilation and air conditioning systems. A key element in the advancement of AHPs is the development of adsorbents with high uptake capacity, fast intracrystalline diffusivity and durable hydrothermal stability. Herein, the ion exchange of NaY zeolites with ingoing Mg 2+ ions is systematically studied to maximize the ion exchange degree (IED) for improved sorption performance. It is found that beyond an ion exchange threshold of 64.1%, deeper ion exchange does not benefit water uptake capacity or characteristic adsorption energy, but does enhance the vapor diffusivity. In addition to using water as an adsorbate, the uptake properties of Mg,Na-Y zeolites were investigated using 20 wt.% MeOH aqueous solution as a novel anti-freeze adsorbate, revealing that the MeOH additive has an insignificant influence on the overall sorption performance. We also demonstrated that the labscale synthetic scalability is robust, and that the tailored zeolites scarcely suffer from hydrothermal stability even after successive 108-fold adsorption/desorption cycles. The samples were analyzed using N 2 sorption, 27 Al/ 29 Si MAS NMR spectroscopy, ICP-AES, dynamic vapor sorption, SEM, Fick's 2 nd law and D-R equation regressions. Among these, close examination of sorption isotherms for H 2 O and N 2 adsorbates allows us to decouple and extract some insightful information underlying the complex water uptake phenomena. This work shows the promising performance of our modified zeolites that can be integrated into various AHP designs for buildings, electronics, and transportation applications.

  8. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease. Copyright © 2017 Endocrine Society

  9. A perillyl alcohol-conjugated analog of 3-bromopyruvate without cellular uptake dependency on monocarboxylate transporter 1 and with activity in 3-BP-resistant tumor cells.

    Science.gov (United States)

    Chen, Thomas C; Yu, Jiali; Nouri Nigjeh, Eslam; Wang, Weijun; Myint, Phyo Thazin; Zandi, Ebrahim; Hofman, Florence M; Schönthal, Axel H

    2017-08-01

    The anticancer agent 3-bromopyruvate (3-BP) is viewed as a glycolytic inhibitor that preferentially kills glycolytic cancer cells through energy depletion. However, its cytotoxic activity is dependent on cellular drug import through transmembrane monocarboxylate transporter 1 (MCT-1), which restricts its anticancer potential to MCT-1-positive tumor cells. We created and characterized an MCT-1-independent analog of 3-BP, called NEO218. NEO218 was synthesized by covalently conjugating 3-BP to perillyl alcohol (POH), a natural monoterpene. The responses of various tumor cell lines to treatment with either compound were characterized in the presence or absence of supplemental pyruvate or antioxidants N-acetyl-cysteine (NAC) and glutathione (GSH). Drug effects on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) enzyme activity were investigated by mass spectrometric analysis. The development of 3-BP resistance was investigated in MCT-1-positive HCT116 colon carcinoma cells in vitro. Our results show that NEO218: (i) pyruvylated GAPDH on all 4 of its cysteine residues and shut down enzymatic activity; (ii) severely lowered cellular ATP content below life-sustaining levels, and (iii) triggered rapid necrosis. Intriguingly, supplemental antioxidants effectively prevented cytotoxic activity of NEO218 as well as 3-BP, but supplemental pyruvate powerfully protected cells only from 3-BP, not from NEO218. Unlike 3-BP, NEO218 exerted its potent cytotoxic activity irrespective of cellular MCT-1 status. Treatment of HCT116 cells with 3-BP resulted in prompt development of resistance, based on the emergence of MCT-1-negative cells. This was not the case with NEO218, and highly 3-BP-resistant cells remained exquisitely sensitive to NEO218. Thus, our study identifies a mechanism by which tumor cells develop rapid resistance to 3-BP, and presents NEO218 as a superior agent not subject to this cellular defense. Furthermore, our results offer alternative interpretations of previously

  10. Aging, tumor suppression and cancer: High-wire act!

    Energy Technology Data Exchange (ETDEWEB)

    Campisi, Judith

    2004-08-15

    Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropy--protecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms.

  11. Imaging of radiocesium uptake dynamics in a plant body using a newly developed high-resolution gamma camera for radiocesium

    Energy Technology Data Exchange (ETDEWEB)

    Kawachi, Naoki; Yin, Yong-Gen; Suzui, Nobuo; Ishii, Satomi; Fujimaki, Shu [Radiotracer Imaging Gr., Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA), 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Yoshihara, Toshihiro [Plant Molecular Biology, Laboratory of Environmental Science, Central Research Institute of Electric Power Industry (CRIEPI), 1646 Abiko, Chiba 270-1194 (Japan); Watabe, Hiroshi [Cyclotron and Radioisotope Center (CYRIC), Tohoku University, 6-3Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578 (Japan); Yamamoto, Seiichi [Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya 461-8673 (Japan)

    2014-07-01

    Vast agricultural and forest areas around the Tokyo Electric Power Company Fukushima Daiichi Nuclear Power Station in Japan were contaminated with radiocesium (Cs-134 and Cs-137) after the accident following the earthquake and tsunami in March 2011. A variety of agricultural studies, such as fertilizer management and plant breeding, have been undertaken intensively for reduction of radiocesium uptake in crops, or, enhancement of uptake in phyto-remediation. In this study, we newly developed a gamma camera specific for plant nutritional research, and performed quantitative analyses on uptake and partitioning of radiocesium in intact plant bodies. In general, gamma camera is a common technology in medical imaging, but it is not applicable to high-energy gamma rays such as emissions from Cs-137 (662 keV). Therefore, we designed our new gamma camera to prevent the penetration and scattering of the high-energy gamma rays. A single-crystal scintillator, Ce-doped Gd{sub 3}Al{sub 2}Ga{sub 3}O{sub 12} (Ce:GAGG), was employed, which has a relatively high density, a large light output, no natural radioactivity and no hygroscopicity. A 44 x 44 matrix of the Ce:GAGG pixels, with dimensions of 0.85 mm x 0.85 mm x 10 mm for each pixel, was coupled to a high-quantum efficiency position sensitive photomultiplier tube. This gamma detector unit was encased in a 20-mm-thick tungsten container with a tungsten pinhole collimator on the front. By using this gamma camera, soybean plants (Glycine max), grown in hydroponic solutions and fed with 1-2 MBq of Cs-137, were imaged for 6.5 days in maximum to investigate and visualize the uptake dynamics into/within the areal part. As a result, radiocesium gradually appeared in the shoot several hours after feeding of Cs-137, and then accumulated intensively in the maturing pods and seeds in a characteristic pattern. Our results also demonstrated that this gamma-camera method enables quantitative evaluation of plant ability to absorb, transport

  12. Risk-adaptive optimization: Selective boosting of high-risk tumor subvolumes

    International Nuclear Information System (INIS)

    Kim, Yusung; Tome, Wolfgang A.

    2006-01-01

    Background and Purpose: A tumor subvolume-based, risk-adaptive optimization strategy is presented. Methods and Materials: Risk-adaptive optimization employs a biologic objective function instead of an objective function based on physical dose constraints. Using this biologic objective function, tumor control probability (TCP) is maximized for different tumor risk regions while at the same time minimizing normal tissue complication probability (NTCP) for organs at risk. The feasibility of risk-adaptive optimization was investigated for a variety of tumor subvolume geometries, risk-levels, and slopes of the TCP curve. Furthermore, the impact of a correlation parameter, δ, between TCP and NTCP on risk-adaptive optimization was investigated. Results: Employing risk-adaptive optimization, it is possible in a prostate cancer model to increase the equivalent uniform dose (EUD) by up to 35.4 Gy in tumor subvolumes having the highest risk classification without increasing predicted normal tissue complications in organs at risk. For all tumor subvolume geometries investigated, we found that the EUD to high-risk tumor subvolumes could be increased significantly without increasing normal tissue complications above those expected from a treatment plan aiming for uniform dose coverage of the planning target volume. We furthermore found that the tumor subvolume with the highest risk classification had the largest influence on the design of the risk-adaptive dose distribution. The parameter δ had little effect on risk-adaptive optimization. However, the clinical parameters D 5 and γ 5 that represent the risk classification of tumor subvolumes had the largest impact on risk-adaptive optimization. Conclusions: On the whole, risk-adaptive optimization yields heterogeneous dose distributions that match the risk level distribution of different subvolumes within the tumor volume

  13. Thyroid uptake test

    International Nuclear Information System (INIS)

    Ganatra, R.D.

    1992-01-01

    The uptake of radioiodine by the thyroid gland is altered by the iodine content of diet or drugs. American diet has a high iodine content because each slice of the white bread contains nearly 150μg of iodine due to the bleaching process employed in the production of the bread. This carrier content of iodine reduces the uptake so much, that the normal American uptakes are usually three to four times lower than the uptakes in the developing countries. The other drawback of the thyroid uptake test is that it is affected by the iodine containing drugs. Anti-diarrhoea medications are quire common in the developing countries and many of them contain iodine moiety. Without a reliable drug history, a low thyroid uptake value may lead to a misleading conclusion

  14. Resveratrol-Loaded Albumin Nanoparticles with Prolonged Blood Circulation and Improved Biocompatibility for Highly Effective Targeted Pancreatic Tumor Therapy

    Science.gov (United States)

    Geng, Tao; Zhao, Xia; Ma, Meng; Zhu, Gang; Yin, Ling

    2017-06-01

    Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances across cell membranes. Herein, we have designed and prepared resveratrol (RV)-loaded HSA nanoparticles conjugating RGD (arginine-glycine-aspartate) via a polyethylene glycol (PEG) "bridge" (HRP-RGD NPs) for highly effective targeted pancreatic tumor therapy. HRP-RGD NPs possess an average size of 120 ± 2.6 nm with a narrow distribution, a homodisperse spherical shape, a RV encapsulation efficiency of 62.5 ± 4.21%, and a maximum RV release ratio of 58.4.2 ± 2.8% at pH 5.0 and 37 °C. In vitro biocompatibility of RV is improved after coating with HSA and PEG. Confocal fluorescence images show that HRP-RGD NPs have the highest cellular uptake ratio of 47.3 ± 4.6% compared to HRP NPs and HRP-RGD NPs with free RGD blocking, attributing to an RGD-mediated effect. A cell counting kit-8 (CCK-8) assay indicates that HRP-RGD NPs without RV (HP-RGD NPs) have nearly no cytotoxicity, but HRP-RGD NPs are significantly more cytotoxic to PANC-1 cells compared to free RV and HRP NPs in a concentration dependent manner, showing apoptotic morphology. Furthermore, with a formulated PEG and HSA coating, HRP-RGD NPs prolong the blood circulation of RV, increasing approximately 5.43-fold (t1/2). After intravenous injection into tumor-bearing mice, the content of HRP-RGD NPs in tumor tissue was proven to be approximately 3.01- and 8.1-fold higher than that of HRP NPs and free RV, respectively. Based on these results, HRP-RGD NPs were used in an in vivo anti-cancer study and demonstrated the best tumor growth suppression effect of all tested drugs with no relapse, high in vivo biocompatibility, and no significant systemic toxicity over 35 days treatment. These results demonstrate that HRP-RGD NPs with prolonged blood circulation and improved biocompatibility have high anti-cancer effects with promising future applications in cancer therapy.

  15. Sulfonated poly(fluorenyl ether ketone nitrile) electrolyte membrane with high proton conductivity and low water uptake

    Energy Technology Data Exchange (ETDEWEB)

    Tian, S.H.; Wang, S.J.; Xiao, M.; Meng, Y.Z. [State Key Laboratory of Optoelectronic Materials and Technologies/Institute of Optoelectronic and Functional Composite Materials, Sun Yat-sen University, Guangzhou 510275 (China); Shu, D. [School of Chemistry and Environmental, South China Normal University, Guangzhou 510006 (China)

    2010-01-01

    High molecular weight sulfonated poly(fluorenyl ether ketone nitrile)s with different equivalent weight (EW) from 681 to 369 g mequiv.{sup -1} are synthesized by the nucleophilic substitution polycondensation of various amounts of sulfonated difluorobenzophenone (SDFBP) and 2,6-difluorobenzonitrile (DFBN) with bisphenol fluorene (BPF). The synthesized copolymers are characterized by {sup 1}H NMR, FT-IR, TGA, and DSC techniques. The membranes cast from the corresponding copolymers exhibit superior thermal stability, good oxidative stability and high proton conductivity, but low water uptake due to the strong nitrile dipole interchain interactions that combine to limit swelling. Among all the membranes, the membrane with EW of 441 g mequiv.{sup -1} shows optimum properties of both high proton conductivity of 41.9 mS cm{sup -1} and low water uptake of 42.6%. Accordingly, That membrane is fabricated into a membrane electrode assembly (MEA) and evaluated in a single proton exchange membrane fuel cell (PEMFC). The experimental results indicate its similar cell performance as that of Nafion {sup registered} 117 at 70 C, but much better cell performance at higher temperatures. At the potential of 0.6 V, the current density of fuel cell using the prepared membrane and Nafion {sup registered} 117 is 0.46 and 0.25 A cm{sup -2}, respectively. The highest current density of the former reaches as high as 1.25 A cm{sup -2}. (author)

  16. A high surface area Zr(IV)-based metal–organic framework showing stepwise gas adsorption and selective dye uptake

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Xiu-Liang [Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing 100124 (China); Tong, Minman; Huang, Hongliang [College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Wang, Bin; Gan, Lei [Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing 100124 (China); Yang, Qingyuan [College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Zhong, Chongli [College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Li, Jian-Rong, E-mail: jrli@bjut.edu.cn [Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing 100124 (China); State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China)

    2015-03-15

    Exploitation of new metal–organic framework (MOF) materials with high surface areas has been attracting great attention in related research communities due to their broad potential applications. In this work, a new Zr(IV)-based MOF, [Zr{sub 6}O{sub 4}(OH){sub 4}(eddb){sub 6}] (BUT-30, H{sub 2}eddb=4,4′-(ethyne-1,2-diyl)dibenzoic acid) has been solvothermally synthesized, characterized, and explored for gases and dyes adsorptions. Single-crystal X-ray diffraction analysis demonstrates a three-dimensional cubic framework structure of this MOF, in which each Zr{sub 6}O{sub 4}(OH){sub 4} building unit is linked by 12 linear eddb ligands. BUT-30 has been found stable up to 400 °C and has a Brunauer–Emmett–Teller (BET) surface area as high as 3940.6 m{sup 2} g{sup −1} (based on the N{sub 2} adsorption at 77 K) and total pore volume of 1.55 cm{sup 3} g{sup −1}. It is more interesting that this MOF exhibits stepwise adsorption behaviors for Ar, N{sub 2}, and CO{sub 2} at low temperatures, and selective uptakes towards different ionic dyes. - Graphical abstract: A new Zr(IV)-based MOF with high surface area has been synthesized and structurally characterized, which shows stepwise gas adsorption at low temperature and selective dye uptake from solution. - Highlights: • A new Zr-based MOF was synthesized and structurally characterized. • This MOF shows a higher surface area compared with its analogous UiO-67 and 68. • This MOF shows a rare stepwise adsorption towards light gases at low temperature. • This MOF performs selective uptakes towards cationic dyes over anionic ones. • Using triple-bond spacer is confirmed feasible in enhancing MOF surface areas.

  17. Evidence of arterial wall uptake of fluorodeoxyglucose on imaging can indicate recent or future cardiovascular events in high-risk patients

    International Nuclear Information System (INIS)

    Paulmier, B.; Khayat, R.; Duet, M.; Pierquet-Ghazzar, N.; Maunoury, C.; Sauvaget, E.; Faraggi, M.; Laissy, J.P.

    2007-01-01

    With this study, we sought to identify plaque inflammation as assessed by 18 FDG uptake on positron emission tomography (PET)/computed tomography (CT) as an independent cardiovascular risk factor in patients at high risk for cardiovascular events. We compared 31 consecutive cancer patients presenting with visually enhanced 18 FDG uptake in arterial walls on PET/CT (Group 1) to a selection of 34 matched cancer patients not showing arterial uptake (Group 2). All patients were followed for two years before and six months after PET/CT... Cardiovascular events were classified as older (>6 months before PET/CT) or recent ( 18 FDG uptake was computed on non-attenuation corrected data by a AW/L ratio: mean Arterial Wall uptake/Lung uptake in a normal area, and by SUV on corrected data. A calcium score (CS) was also calculated. 18 FDG uptake and CS were higher in Group 1 than Group 2 (both p = 0.02), and older and recent cardiovascular events were significantly more frequent in Group 1 than Group 2 (p = 0.001 and p = 0.03. respectively). Among the following parameters: number of conventional risk factor, calcium score and presence of 18 FDG uptake, only the latter was significantly related to the occurrence of a recent event by multivariate analysis (p = 0.02). Patients with elevated arterial 18 FDG uptake have a high risk of immediate or future cardiovascular events. Arterial 18 FDG uptake is an indicator of evolving atherosclerotic process and can indicate future cardiovascular events. (authors)

  18. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    Science.gov (United States)

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  19. Identification of a Polyomavirus microRNA Highly Expressed in Tumors

    Science.gov (United States)

    Chen, Chun Jung; Cox, Jennifer E.; Azarm, Kristopher; Wylie, Karen N.; Woolard, Kevin D.; Pesavento, Patricia A.; Sullivan, Christopher S.

    2014-01-01

    Polyomaviruses (PyVs) are associated with tumors including Merkel cell carcinoma (MCC). Several PyVs encode microRNAs (miRNAs) but to date no abundant PyV miRNAs have been reported in tumors. To better understand the function of the Merkel cell PyV (MCPyV) miRNA, we examined phylogenetically-related viruses for miRNA expression. We show that two primate PyVs and the more distantly-related raccoon PyV (RacPyV) encode miRNAs that share genomic position and partial sequence identity with MCPyV miRNAs. Unlike MCPyV miRNA in MCC, RacPyV miRNA is highly abundant in raccoon tumors. RacPyV miRNA negatively regulates reporters of early viral (T antigen) transcripts, yet robust viral miRNA expression is tolerated in tumors. We also identify raccoon miRNAs expressed in RacPyV-associated neuroglial brain tumors, including several likely oncogenic miRNAs (oncomiRs). This work describes the first PyV miRNA abundantly expressed in tumors and is consistent with a possible role for both host and viral miRNAs in RacPyV-associated tumors. PMID:25514573

  20. Uptake and effect of highly fluorescent silver nanoclusters on Scenedesmus obliquus.

    Science.gov (United States)

    Zhang, Li; He, Yiliang; Goswami, Nirmal; Xie, Jianping; Zhang, Bo; Tao, Xianji

    2016-06-01

    The release of silver nanoparticles (Ag NPs) in aquatic environment has caused wide public concern about their effects on living organisms (e.g., algae). However, how these small NPs exert cytotoxicity in the living organisms has always been under heated debate. In this study, the uptake and toxicity effects of strongly red-emitting fluorescent silver nanoclusters (r-Ag NCs) exposed to the green algae Scenedesmus obliquus was investigated. Upon exposure to pure r-Ag NCs and r-Ag NCs containing l-cysteine, the algae growth inhibition test showed that Ag(+) ions released from r-Ag NCs played an important role in the toxicity of r-Ag NCs along with the toxicity of intact r-Ag NCs. Furthermore, no signals of intracellular reactive oxygen species (ROS) were observed indicating that r-Ag NCs or released Ag(+) ions - mediated growth inhibition of algae cells was independent of ROS production. Transmission electron microscopy (TEM) and laser scanning confocal microscopy (LSCM) were employed to study cellular uptake and cytotoxicity. Furthermore, analysis of differential expressed gene demonstrated that r-Ag NCs as well as the released Ag(+) ions can simultaneously exist inside the algae cells, and inhibit the transcriptomic process of genes by their "joint-toxicity" mechanism. Taken together, our study provides a new insight into the molecular mechanisms of r-Ag NCs and Ag(+) ions exposure to the aquatic organism and can be applied to early diagnosis of ecologic risk mediated by others metal-based NPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Tumor Classification Using High-Order Gene Expression Profiles Based on Multilinear ICA

    Directory of Open Access Journals (Sweden)

    Ming-gang Du

    2009-01-01

    Full Text Available Motivation. Independent Components Analysis (ICA maximizes the statistical independence of the representational components of a training gene expression profiles (GEP ensemble, but it cannot distinguish relations between the different factors, or different modes, and it is not available to high-order GEP Data Mining. In order to generalize ICA, we introduce Multilinear-ICA and apply it to tumor classification using high order GEP. Firstly, we introduce the basis conceptions and operations of tensor and recommend Support Vector Machine (SVM classifier and Multilinear-ICA. Secondly, the higher score genes of original high order GEP are selected by using t-statistics and tabulate tensors. Thirdly, the tensors are performed by Multilinear-ICA. Finally, the SVM is used to classify the tumor subtypes. Results. To show the validity of the proposed method, we apply it to tumor classification using high order GEP. Though we only use three datasets, the experimental results show that the method is effective and feasible. Through this survey, we hope to gain some insight into the problem of high order GEP tumor classification, in aid of further developing more effective tumor classification algorithms.

  2. Detection of high GS risk group prostate tumors by diffusion tensor imaging and logistic regression modelling.

    Science.gov (United States)

    Ertas, Gokhan

    2018-07-01

    To assess the value of joint evaluation of diffusion tensor imaging (DTI) measures by using logistic regression modelling to detect high GS risk group prostate tumors. Fifty tumors imaged using DTI on a 3 T MRI device were analyzed. Regions of interests focusing on the center of tumor foci and noncancerous tissue on the maps of mean diffusivity (MD) and fractional anisotropy (FA) were used to extract the minimum, the maximum and the mean measures. Measure ratio was computed by dividing tumor measure by noncancerous tissue measure. Logistic regression models were fitted for all possible pair combinations of the measures using 5-fold cross validation. Systematic differences are present for all MD measures and also for all FA measures in distinguishing the high risk tumors [GS ≥ 7(4 + 3)] from the low risk tumors [GS ≤ 7(3 + 4)] (P Logistic regression modelling provides a favorable solution for the joint evaluations easily adoptable in clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression.

    Directory of Open Access Journals (Sweden)

    Aya Matsui

    Full Text Available BACKGROUND: Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1, recruits immature myeloid-derived cells and enhances early tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+Gr1(+ myeloid-derived cells at tumor sites in mice and promoted CD31(+ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+Gr1(highF4/80(- cells (≈ 90% with a neutrophil-like morphology in vitro. Although CXCL17 expression could not increase the number of CD11b(+Gr1(+ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.

  4. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    DEFF Research Database (Denmark)

    Egerod, Frederikke N S Lihme; Bartels, Annette; Fristrup, Niels

    2009-01-01

    bladder cancer. RESULTS: The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling...... than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling...

  5. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.

    Science.gov (United States)

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias; Stummer, Walter

    2016-03-01

    Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

  6. Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor size versus CT perfusion parameters.

    Science.gov (United States)

    Chen, Chao; Kang, Qinqin; Xu, Bing; Guo, Hairuo; Wei, Qiang; Wang, Tiegong; Ye, Hui; Wu, Xinhuai

    To compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC). Tumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed. High-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did. Tumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

    Science.gov (United States)

    Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

    2017-03-01

    Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

  8. High Birth Weight Increases the Risk for Bone Tumor: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Songfeng Chen

    2015-09-01

    Full Text Available There have been several epidemiologic studies on the relationship between high birth weight and the risk for bone tumor in the past decades. However, due to the rarity of bone tumors, the sample size of individual studies was generally too small for reliable conclusions. Therefore, we have performed a meta-analysis to pool all published data on electronic databases with the purpose to clarify the potential relationship. According to the inclusion and exclusion criteria, 18 independent studies with more than 2796 cases were included. As a result, high birth weight was found to increase the risk for bone tumor with an Odds Ratio (OR of 1.13, with the 95% confidence interval (95% CI ranging from 1.01 to 1.27. The OR of bone tumor for an increase of 500 gram of birth weight was 1.01 (95% CI 1.00–1.02; p = 0.048 for linear trend. Interestingly, individuals with high birth weight had a greater risk for osteosarcoma (OR = 1.22, 95% CI 1.06–1.40, p = 0.006 than those with normal birth weight. In addition, in the subgroup analysis by geographical region, elevated risk was detected among Europeans (OR = 1.14, 95% CI 1.00–1.29, p = 0.049. The present meta-analysis supported a positive association between high birth weight and bone tumor risk.

  9. Low-protein, high-carbohydrate diet increases glucose uptake and fatty acid synthesis in brown adipose tissue of rats.

    Science.gov (United States)

    Aparecida de França, Suélem; Pavani Dos Santos, Maísa; Nunes Queiroz da Costa, Roger Vinícius; Froelich, Mendalli; Buzelle, Samyra Lopes; Chaves, Valéria Ernestânia; Giordani, Morenna Alana; Pereira, Mayara Peron; Colodel, Edson Moleta; Marlise Balbinotti Andrade, Cláudia; Kawashita, Nair Honda

    2014-04-01

    The aim of this study was to evaluate glucose uptake and the contribution of glucose to fatty acid (FA) synthesis and the glycerol-3-phosphate (G3P) of triacylglycerol synthesis by interscapular brown adipose tissue (IBAT) of low-protein, high-carbohydrate (LPHC) diet-fed rats. LPHC (6% protein; 74% carbohydrate) or control (17% protein; 63% carbohydrate) diets were administered to rats (∼ 100 g) for 15 d. Total FA and G3P synthesis and the synthesis of FA and G3P from glucose were evaluated in vivo by (3)H2O and (14)C-glucose. Sympathetic neural contribution for FA synthesis was evaluated by comparing the synthesis in denervated (7 d before) IBAT with that of the contralateral innervated side. The insulin signaling and β3 adrenergic receptor (β3-AR) contents, as well as others, were determined by Western blot (Student's t test or analysis of variance; P ≤ 0.05). Total FA synthesis in IBAT was 133% higher in the LPHC group and was reduced 85% and 70% by denervation for the LPHC and control groups, respectively. Glucose uptake was 3.5-fold higher in the IBAT of LPHC rats than in that of the control rats, and the contribution of glucose to the total FA synthesis increased by 12% in control rats compared with 18% in LPHC rats. The LPHC diet increased the G3P generation from glucose by 270% and the insulin receptor content and the p-AKT insulin stimulation in IBAT by 120% and reduced the β3-AR content by 50%. The LPHC diet stimulated glucose uptake, both the total rates and the rates derived from glucose-dependent FA and G3P synthesis, by increasing the insulin sensitivity and the sympathetic flux, despite a reduction in the β3-AR content. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. A high-flow humidograph for testing the water uptake by ambient aerosol

    Energy Technology Data Exchange (ETDEWEB)

    Ten Brink, H.M.; Khlystov, A.; Kos, G.P.A. [ECN Fuels Conversion and Environment, Petten (Netherlands); Tuch, T. [Institut of Medical Data Management, Biometrics and Epidemiology, Ludwig-Maximilian University, Muenich (Germany); Roth, C.; Kreyling, W. [Institute for Inhalation Biology, GSF National Research Center for Environment and Health, Neuherberg/Muenich (Germany)

    1999-10-01

    A scanning humidograph, with an air flow rate of 0.5 m{sup 3} s{sup -1} was built to investigate the uptake of water and its effect on sizing, collection and light-scattering of ambient aerosol. The performance of the system was assessed with laboratory particles of ammonium nitrate, ammonium sulfate and sodium chloride which are the major hygroscopic components of ambient aerosol. The increase in size at the deliquescence points, which ideally is a stepwise function of relative humidity, occurs over a range of 3% RH units. This is shown to be an optimum value in a system of such large dimensions. Because of the strong temperature increase of the vapor pressure of ammonium nitrate, its evaporative loss was investigated as a function of heating/drying temperature. The loss of pure test aerosol, with a mass distribution similar to that in the ambient atmosphere, was found to be acceptable for drying temperatures of up to 40C. The sizing of deliquesced aerosol by LAS-X monitors was tested and found to be a complex function of RH. In Berner low pressure impactors growth of hygroscopic aerosol was not observed, not even at an RH approaching saturation. 21 refs.

  11. Uptake of endogenous and exogenous 226Ra by vegetables from soils of a highly radioactive region

    International Nuclear Information System (INIS)

    Lima, V.T.; Penna-Franca, E.

    1988-01-01

    The Pocos de Caldas Plateau is a weathered alkaline igneous intrusion where several radioactive anomalies (U and Th series) exist. Not only the local soils but also the edible vegetables produced in the region can present 226 Ra concentrations up to 10 times higher than those from areas of normal radioactivity. The aim of this work is to evaluate through greenhouse experiments, the uptake of endogenous and exogenous 226 Ra by carrots, brown beans and kale grown from four paired local natural and contaminated farm soils. Simultaneously, sequential selective extractions were performed to estimate the partitioning of 226 Ra among six geochemical fractions. The results showed that concentration ratios (CRs), related to plant dry weight, for endogenous and exogenous 226 Ra in soils, were of the order of 10 -2 -10 -1 and 10 -2 -10 0 respectively. The averages of 226 Ra exchangeable and residual fractions in soils were: 3.2% and 50.2% for endogenous and 15.4% and 6.0% for exogenous radium. The CRs calculated either in relation to total 226 Ra or to the exchangeable fraction in soils showed about the same variability. (author)

  12. Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors

    International Nuclear Information System (INIS)

    Ohara, Kiyoshi; Oki, Akinori; Tanaka, Yumiko Oishi; Onishi, Kayoko; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Satoh, Toyomi; Tsunoda, Hajime; Hata, Masaharu; Sugahara, Shinji; Tokuuye, Koichi; Akine, Yasuyuki; Yoshikawa, Hiroyuki

    2006-01-01

    Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day -1 ) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day -1 (median, 0.021 day -1 ) and late-assessed radioresponse from 0.009 to 0.091 day -1 (median, 0.021 day -1 ), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R 2 = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness

  13. Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Brun, E., E-mail: emmanuel.brun@esrf.fr [European Synchrotron Radiation Facility (ESRF), Grenoble 380000, France and Department of Physics, Ludwig-Maximilians University, Garching 85748 (Germany); Grandl, S.; Sztrókay-Gaul, A.; Gasilov, S. [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Barbone, G. [Department of Physics, Harvard University, Cambridge, Massachusetts 02138 (United States); Mittone, A.; Coan, P. [Department of Physics, Ludwig-Maximilians University, Garching 85748, Germany and Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Bravin, A. [European Synchrotron Radiation Facility (ESRF), Grenoble 380000 (France)

    2014-11-01

    Purpose: Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. Methods: The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure’s possible applications. Results: A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. Conclusions: The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

  14. Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography.

    Science.gov (United States)

    Brun, E; Grandl, S; Sztrókay-Gaul, A; Barbone, G; Mittone, A; Gasilov, S; Bravin, A; Coan, P

    2014-11-01

    Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications. A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

  15. Validating Bioluminescence Imaging as a High-Throughput, Quantitative Modality for Assessing Tumor Burden

    Directory of Open Access Journals (Sweden)

    Zain Paroo

    2004-04-01

    Full Text Available Bioluminescence imaging (BLI is a highly sensitive tool for visualizing tumors, neoplastic development, metastatic spread, and response to therapy. Although BLI has engendered much excitement due to its apparent simplicity and ease of implementation, few rigorous studies have been presented to validate the measurements. Here, we characterize the nature of bioluminescence output from mice bearing subcutaneous luciferase-expressing tumors over a 4-week period. Following intraperitoneal or direct intratumoral administration of luciferin substrate, there was a highly dynamic kinetic profile of light emission. Although bioluminescence was subject to variability, strong correlations (r > .8, p < .001 between caliper measured tumor volumes and peak light signal, area under light signal curve and light emission at specific time points were determined. Moreover, the profile of tumor growth, as monitored with bioluminescence, closely resembled that for caliper measurements. The study shows that despite the dynamic and variable nature of bioluminescence, where appropriate experimental precautions are taken, single time point BLI may be useful for noninvasive, high-throughput, quantitative assessment of tumor burden.

  16. Inactivation of uptake hydrogenase leads to enhanced and sustained hydrogen production with high nitrogenase activity under high light exposure in the cyanobacterium Anabaena siamensis TISTR 8012

    Directory of Open Access Journals (Sweden)

    Khetkorn Wanthanee

    2012-10-01

    Full Text Available Abstract Background Biohydrogen from cyanobacteria has attracted public interest due to its potential as a renewable energy carrier produced from solar energy and water. Anabaena siamensis TISTR 8012, a novel strain isolated from rice paddy field in Thailand, has been identified as a promising cyanobacterial strain for use as a high-yield hydrogen producer attributed to the activities of two enzymes, nitrogenase and bidirectional hydrogenase. One main obstacle for high hydrogen production by A. siamensis is a light-driven hydrogen consumption catalyzed by the uptake hydrogenase. To overcome this and in order to enhance the potential for nitrogenase based hydrogen production, we engineered a hydrogen uptake deficient strain by interrupting hupS encoding the small subunit of the uptake hydrogenase. Results An engineered strain lacking a functional uptake hydrogenase (∆hupS produced about 4-folds more hydrogen than the wild type strain. Moreover, the ∆hupS strain showed long term, sustained hydrogen production under light exposure with 2–3 folds higher nitrogenase activity compared to the wild type. In addition, HupS inactivation had no major effects on cell growth and heterocyst differentiation. Gene expression analysis using RT-PCR indicates that electrons and ATP molecules required for hydrogen production in the ∆hupS strain may be obtained from the electron transport chain associated with the photosynthetic oxidation of water in the vegetative cells. The ∆hupS strain was found to compete well with the wild type up to 50 h in a mixed culture, thereafter the wild type started to grow on the relative expense of the ∆hupS strain. Conclusions Inactivation of hupS is an effective strategy for improving biohydrogen production, in rates and specifically in total yield, in nitrogen-fixing cultures of the cyanobacterium Anabaena siamensis TISTR 8012.

  17. Fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection

    International Nuclear Information System (INIS)

    Som, P.; Atkins, H.L.; Bandoypadhyay, D.

    1980-01-01

    Rapid uptake of F-18 FDG was observed in a variety of transplanted and spontaneous tumors in animals. The tumor uptake reached a peak by 30 min and remained relatively constant up to 60 min, with a very slow wash-out of F-18 activity from the tumor thereafter. Tumor-to-normal tissue and tumor-to-blood ratios ranged from 2.10 to 9.15 and 2.61 to 17.82, respectively, depending on the type of tumor. A scintiscan of a seminoma in a dog showed very high uptake in the viable part and lack of uptake in the necrotic mass. Toxicological studies in mice using 1000 times human tracer dose (HTD) per week for 3 weeks and in dogs using 50 times HTD per week for 3 weeks did not show any evidence of acute or chronic toxicity

  18. Chimeric antigen receptors with human scFvs preferentially induce T cell anti-tumor activity against tumors with high B7H6 expression.

    Science.gov (United States)

    Gacerez, Albert T; Hua, Casey K; Ackerman, Margaret E; Sentman, Charles L

    2018-05-01

    B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display. In this study, we validate the functionality of these human scFvs when formatted into chimeric antigen receptors. The data indicate that T cells expressing these B7H6-specific human scFvs as CARs induced potent anti-tumor activity in vitro and in vivo against tumors expressing high amounts of B7H6. Importantly, these human scFv-based CARs are sensitive to changes in B7H6 expression which may potentially spare non-tumor cells that express B7H6 and provides the foundation for future clinical development.

  19. Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

    Directory of Open Access Journals (Sweden)

    Prat Frederic

    2008-06-01

    Full Text Available Abstract Background Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap. Methods Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm2 for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to in vivo studies on pig esophagi. Results Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases. Conclusion This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.

  20. Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

    Science.gov (United States)

    Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

    2015-01-01

    Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

  1. Intraindividual comparison of F-18-FLT PET and F-18 FET PET in brain tumor patients

    International Nuclear Information System (INIS)

    Kim, Sung Eun; Cheon, G. J.; Cho, Y. S.; Kwak, H. S.; Lee, C. H.; Choi, C. W.; Lim, S. M.

    2003-01-01

    To compare findings on FLT PET with FET PET, we prospectively undertaken FLT, FET and FDG PET in same patient with suspected primary/metastatic and recurrent brain tumors. Seventeen studies in 16 patients (47 8.3 years, M: F 10: 6) with brain tumor (3 for initial diagnosis, 6 for therapeutic response, 6 for detecting recurrence, 1 for diagnosis and recurrence both) were included. Brain tumors were 14 gliomas (6 high- grade 9 low-grade by the WHO classification), 2 metastatic brain tumors and 1 CNS lymphoma. 18F-FDG, FLT and FET PET were performed within two weeks. Attenuation-corrected brain images were acquired 30 minutes after injection of 370-555 MBq FDG, FLT and FET with a dedicated PET scanner (ECAT HR scanner, Siemens-CTI). Maximum SUV (max SUV) and relative uptake defined by FLT and FET accumulation within the tumor in relation to a contralateral control region (max SUV for tumor/ mean SUV for contralateral normal gray matter) were calculated. 26 tumor foci were analyzed. Relative FLT uptake (4.17 2.4, 0.58 to 7.45) was grater than than FET uptake (2.03 1.17, 0.92 to 4.53 (p<0.0006)) and FDG uptake (1.16 0.34, 0.76 to 2.08). Among FLT, FET and FDG uptakes in 20 tumor foci, correlation were poor. the relative FLT uptake of high-grade glioma was higher than low-glioma (6.070.76 vs 3.11 2.15, p=0.002), however, relative FET uptake was not different significantly (2.68 1.51, high-grade vs 1.970.78, low-grade). The correlation between tumor grade (high vs low grade) and relative uptake (FLT and FET) was shown only with relative FLT uptake (r=0.62, p=0.002). The best cut off value of relative FLT uptake between high-grade and low-grade glioma was 4.54 (AUC: 0.89 sensitivity: 100 specificity: 86.7%). Compared with FET uptake, FLT uptake showed much higher contrast and associated with tumor grade. Further study, evaluation of proliferative index of Ki-67 and its relationship with FLT and FET uptake, are ongoing

  2. High-grade soft tissue sarcoma arising in a desmoid tumor: case report and review of the literature.

    Science.gov (United States)

    Bertucci, François; Faure, Marjorie; Ghigna, Maria-Rosa; Chetaille, Bruno; Guiramand, Jérôme; Moureau-Zabotto, Laurence; Sarran, Anthony; Perrot, Delphine

    2015-01-01

    Desmoid tumors are rare benign monoclonal fibroblastic tumors. Their aggressiveness is local with no potential for metastasis or dedifferentiation. Here we report on a 61-year-old patient who presented a locally advanced breast desmoid tumor diagnosed 20 years after post-operative radiotherapy for breast carcinoma. After 2 years of medical treatment, a high-grade undifferentiated pleomorphic soft tissue sarcoma arose within the desmoid tumor. Despite extensive surgery removing both tumors, the patient showed locoregional relapse by the sarcoma, followed by multimetastatic progression, then death 25 months after the surgery. The arising of a soft tissue sarcoma in a desmoid tumor is an exceptional event since our case is the fourth one reported so far in literature. It reinforces the need for timely and accurate diagnosis when a new mass develops in the region of a preexisting desmoid tumor, and more generally when a desmoid tumor modifies its clinical or radiological aspect.

  3. Improving Tumor Uptake and Pharmacokinetics of 64Cu-Labeled Cyclic RGD Peptide Dimers with Gly3 and PEG4 Linkers

    OpenAIRE

    Shi, Jiyun; Kim, Young-Seung; Zhai, Shizhen; Liu, Zhaofei; Chen, Xiaoyuan; Liu, Shuang

    2009-01-01

    Radiolabeled cyclic RGD (Arg-Gly-Asp) peptides represent a new class of radiotracers with potential for the early tumor detection and non-invasive monitoring of tumor metastasis and therapeutic response in cancer patients. This report describes the synthesis of two cyclic RGD peptide dimer conjugates, DOTA-PEG4-E[PEG4-c(RGDfK)]2 (DOTA-3PEG4-dimer: DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and DOTA-G3-E[G3-c(RGDfK)]2 ...

  4. Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.

    NARCIS (Netherlands)

    Brok, M.H.M.G.M. den; Nierkens, S.; Wagenaars, J.A.L.; Ruers, T.J.M.; Schrier, C.C.; Rijke, E.O.; Adema, G.J.

    2012-01-01

    Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic

  5. Androgen receptor status is highly conserved during tumor progression of breast cancer.

    Science.gov (United States)

    Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

    2015-11-09

    highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

  6. Androgen receptor status is highly conserved during tumor progression of breast cancer

    International Nuclear Information System (INIS)

    Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A.; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

    2015-01-01

    With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly

  7. Exposure of tumor-bearing mice to extremely high-frequency electromagnetic radiation modifies the composition of fatty acids in thymocytes and tumor tissue.

    Science.gov (United States)

    Gapeyev, Andrew B; Kulagina, Tatiana P; Aripovsky, Alexander V

    2013-08-01

    To test the participation of fatty acids (FA) in antitumor effects of extremely high-frequency electromagnetic radiation (EHF EMR), the changes in the FA composition in the thymus, liver, blood plasma, muscle tissue, and tumor tissue in mice with Ehrlich solid carcinoma exposed to EHF EMR were studied. Normal and tumor-bearing mice were exposed to EHF EMR with effective parameters (42.2 GHz, 0.1 mW/cm2, 20 min daily during five consecutive days beginning the first day after the inoculation of tumor cells). Fatty acid composition of various organs and tissues of mice were determined using a gas chromatography. It was shown that the exposure of normal mice to EHF EMR or tumor growth significantly increased the content of monounsaturated FA (MUFA) and decreased the content of polyunsaturated FA (PUFA) in all tissues examined. Exposure of tumor-bearing mice to EHF EMR led to the recovery of FA composition in thymocytes to the state that is typical for normal animals. In other tissues of tumor-bearing mice, the exposure to EHF EMR did not induce considerable changes that would be significantly distinguished between disturbances caused by EHF EMR exposure or tumor growth separately. In tumor tissue which is characterized by elevated level of MUFA, the exposure to EHF EMR significantly decreased the summary content of MUFA and increased the summary content of PUFA. The recovery of the FA composition in thymocytes and the modification of the FA composition in the tumor under the influence of EHF EMR on tumor-bearing animals may have crucial importance for elucidating the mechanisms of antitumor effects of the electromagnetic radiation.

  8. Indocyanine green loaded graphene oxide for high-efficient photoacoustic tumor therapy

    Directory of Open Access Journals (Sweden)

    Baoyun Yan

    2016-07-01

    Full Text Available Photoacoustic therapy, using the photoacoustic effect of agents for selectively killing tumor cells, has shown promising for treating tumor. Utilization of high optical absorption probes can help to effectively improve the photoacoustic therapy efficiency. Herein, we report a novel high-absorption photoacoustic probe that is composed of indocyanine green (ICG and graphene oxide (GO, entitled GO-ICG, for photoacoustic therapy. The attached ICG with narrow absorption spectral profile has strong optical absorption in the infrared region. The absorption spectrum of the GO-ICG solution reveals that the GO-ICG particles exhibited a 10-fold higher absorbance at 780nm (its peak absorbance as compared with GO. Importantly, ICG’s fluorescence is quenched by GO via fluorescence resonance energy transfer. As a result, GO-ICG can high-efficiently convert the absorbed light energy to acoustic wave under pulsed laser irradiation. We further demonstrate that GO-ICG can produce stronger photoacoustic wave than the GO and ICG alone. Moreover, we conjugate this contrast agent with integrin αvβ3 mono-clonal antibody to molecularly target the U87-MG human glioblastoma cells for selective tumor cell killing. Finally, our results testify that the photoacoustic therapy efficiency of GO-ICG is higher than the existing photoacoustic therapy agent. Our work demonstrates that GO-ICG is a high-efficiency photoacoustic therapy agent. This novel photoacoustic probe is likely to be an available candidate for tumor therapy.

  9. Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

    NARCIS (Netherlands)

    Oort, van I.M.; Witjes, J.A.; Kok, D.E.G.; Kiemeney, L.A.; Hulsbergen-van de Kaa, C.A.

    2008-01-01

    Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate

  10. VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation

    International Nuclear Information System (INIS)

    Fujisawa, Hiroshi; Nakajima, Nakako Izumi; Sunada, Shigeaki; Lee, Younghyun; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi

    2015-01-01

    High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. ATR inhibitor would be an effective tumor radiosensitizer with carbon ion irradiation. The online version of this article (doi:10.1186/s13014-015-0464-y) contains supplementary material, which is available to authorized users

  11. Magnetic resonance–guided interstitial high-intensity focused ultrasound for brain tumor ablation

    Science.gov (United States)

    MacDonell, Jacquelyn; Patel, Niravkumar; Rubino, Sebastian; Ghoshal, Goutam; Fischer, Gregory; Burdette, E. Clif; Hwang, Roy; Pilitsis, Julie G.

    2018-01-01

    Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors’ interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery. PMID:29385926

  12. Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

    International Nuclear Information System (INIS)

    Fangusaro, Jason

    2012-01-01

    High grade gliomas (HGG) are one of the most common central nervous system (CNS) tumors encountered in adults, but they only represent approximately 8–12% of all pediatric CNS tumors. Historically, pediatric HGG were thought to be similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR) when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic, and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes, and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

  13. Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

    Energy Technology Data Exchange (ETDEWEB)

    Fangusaro, Jason, E-mail: jfangusaro@luriechildrens.org [Pediatric Neuro-Oncology, The Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL (United States)

    2012-08-24

    High grade gliomas (HGG) are one of the most common central nervous system (CNS) tumors encountered in adults, but they only represent approximately 8–12% of all pediatric CNS tumors. Historically, pediatric HGG were thought to be similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR) when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic, and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes, and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

  14. Neuroradiological evaluation of benign extramedullary tumors in the high cervical region and at the foramen magnum

    Energy Technology Data Exchange (ETDEWEB)

    Nishiura, Iwao; Koyama, Tsunemaro; Tanaka, Kimito; Aii, Heihachirou

    1986-06-01

    Twelve cases of benign extramedullary tumors in the high cervical region and at the foramen magnum were experienced during past five years among eighty all spinal and paraspinal tumors. The diagnosis of masses in this region is very difficult because of the variety of clinical course, symptoms and neurological findings as pointed out by many reporters. Also in our cases, 70 % of the patients complained of the deteriorated motor weakness of the upper or lower extremities on admission, though they had noticed the onset of slight neck or occipital pain a few years ago. Neurological examination on admission clearly showed the symptom of myelopathy except in two cases with a tumor at the foramen magnum and C/sub 1/ level. The percentage of positive findings of plain X-rays was 50 %, that of metrizamide myelography was 92 % and that of IV. e. CT and met. e. CT was 100 %. NMR-CT was performed in 2 cases, and in one of them it was useful in confirming the tumor configuration and extension. Five interesting cases were described mainly from the neuroradiological aspects. Finally the differentiation between meningioma and neurinoma was discussed from the aspects of myelogram, CT and NMR-CT. As already pointed out, it is most important not to forget the existence of tumors in this region when one comes across the confused symptoms, afterwards not to overlook the slight positive neurological and neuroradiological findings.

  15. Non-linear relationship between O2 uptake and power output at high intensities of exercise in humans.

    Science.gov (United States)

    Zoladz, J A; Rademaker, A C; Sargeant, A J

    1995-01-01

    1. A slow component to pulmonary oxygen uptake (VO2) is reported during prolonged high power exercise performed at constant power output at, or above, approximately 60% of the maximal oxygen uptake. The magnitude of the slow component is reported to be associated with the intensity of exercise and to be largely accounted for by an increased VO2 across the exercising legs. 2. On the assumption that the control mechanism responsible for the increased VO2 is intensity dependent we hypothesized that it should also be apparent in multi-stage incremental exercise tests with the result that the VO2-power output relationship would be curvilinear. 3. We further hypothesized that the change in the VO2-power output relationship could be related to the hierarchical recruitment of different muscle fibre types with a lower mechanical efficiency. 4. Six subjects each performed five incremental exercise tests, at pedalling rates of 40, 60, 80, 100 and 120 rev min-1, over which range we expected to vary the proportional contribution of different fibre types to the power output. Pulmonary VO2 was determined continuously and arterialized capillary blood was sampled and analysed for blood lactate concentration ([lactate]b). 5. Below the level at which a sustained increase in [lactate]b was observed pulmonary VO2 showed a linear relationship with power output; at high power outputs, however, there was an additional increase in VO2 above that expected from the extrapolation of that linear relationship, leading to a positive curvilinear VO2-power output relationship. 6. No systematic effect on the magnitude or onset of the 'extra' VO2 was found in relation to pedalling rate, which suggests that it is not related to the pattern of motor unit recruitment in any simple way. PMID:8568657

  16. Miniaturized microscope for high throughput screening of tumor spheroids in microfluidic devices

    Science.gov (United States)

    Uranga, Javier; Rodríguez-Pena, Alejandro; Gahigiro, Desiré; Ortiz-de-Solorzano, Carlos

    2018-02-01

    High-throughput in vitro screening of highly physiological three-dimensional cell cultures (3D-HTS) is rapidly gaining importance in preclinical studies, to study the effect of the microenvironment in tumor development, and to evaluate the efficacy of new anticancer drugs. Furthermore, it could also be envisioned the use of 3D-HTS systems in personalized anti-cancer treatment planning, based on tumor organoids or spheroids grown from tumor biopsies or isolated tumor circulating cells. Most commercial, multi-well plate based 3D-HTS systems are large, expensive, and are based on the use of multi-well plates that hardly provide a physiological environment and require the use of large amounts of biological material and reagents. In this paper we present a novel, miniaturized inverted microscope (hereinafter miniscospe), made up of low-cost, mass producible parts, that can be used to monitor the growth of living tumor cell spheroids within customized three-dimensional microfluidic platforms. Our 3D-HTS miniscope combines phase contrast imaging based on oblique back illumination technique with traditional widefield epi-fluorescence imaging, implemented using miniaturized electro-optical parts and gradient-index refraction lenses. This small (3x6x2cm), lightweight device can effectively image overtime the growth of (>200) tumor spheroids in a controlled and reproducible environment. Our miniscope can be used to acquire time-lapse images of cellular living spheroids over the course of several hours and captures their growth before and after drug treatment, to evaluate the effectiveness of the drug.

  17. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    Science.gov (United States)

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  18. Anatomically standardized statistical mapping of 123I-IMP SPECT in brain tumors

    International Nuclear Information System (INIS)

    Shibata, Yasushi; Akimoto, Manabu; Matsushita, Akira; Yamamoto, Tetsuya; Takano, Shingo; Matsumura, Akira

    2010-01-01

    123 I-iodoamphetamine Single Photon Emission Computed Tomography (IMP SPECT) is used to evaluate cerebral blood flow. However, application of IMP SPECT to patients with brain tumors has been rarely reported. Primary central nervous system lymphoma (PCNSL) is a rare tumor that shows delayed IMP uptake. The relatively low spatial resolution of SPECT is a clinical problem in diagnosing brain tumors. We examined anatomically standardized statistical mapping of IMP SPECT in patients with brain lesions. This study included 49 IMP SPECT images for 49 patients with brain lesions: 20 PCNSL, 1 Burkitt's lymphoma, 14 glioma, 4 other tumor, 7 inflammatory disease and 3 without any pathological diagnosis but a clinical diagnosis of PCNSL. After intravenous injection of 222 MBq of 123 I-IMP, early (15 minutes) and delayed (4 hours) images were acquired using a multi-detector SPECT machine. All SPECT data were transferred to a newly developed software program iNeurostat+ (Nihon Medi-physics). SPECT data were anatomically standardized on normal brain images. Regions of increased uptake of IMP were statistically mapped on the tomographic images of normal brain. Eighteen patients showed high uptake in the delayed IMP SPECT images (16 PCNSL, 2 unknown). Other tumor or diseases did not show high uptake of delayed IMP SPECT, so there were no false positives. Four patients with pathologically proven PCNSL showed no uptake in original IMP SPECT. These tumors were too small to detect in IMP SPECT. However, statistical mapping revealed IMP uptake in 18 of 20 pathologically verified PCNSL patients. A heterogeneous IMP uptake was seen in homogenous tumors in MRI. For patients with a hot IMP uptake, statistical mapping showed clearer uptake. IMP SPECT is a sensitive test to diagnose of PCNSL, although it produced false negative results for small posterior fossa tumor. Anatomically standardized statistical mapping is therefore considered to be a useful method for improving the diagnostic

  19. The distribution of FDG at PET examinations constitutes a relative mechanism: significant effects at activity quantification in patients with a high muscular uptake

    International Nuclear Information System (INIS)

    Lindholm, Henry; Johansson, Ove; Jacobsson, Hans; Jonsson, Cathrine

    2012-01-01

    At 18 F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) examinations a high tracer uptake of the skeletal muscles is sometimes encountered which can lead to reduced uptake in pathological lesions. This was evaluated in retrospect in patients being recalled for a repeat examination after reducing the muscular uptake. Ten patients with increased muscular tracer uptake were examined with FDG PET/CT on two occasions with a mean of 6 days. All patients showed at least one pathological lesion with increased tracer uptake. The muscular uptake was reduced at the second examination by informing the patient to refrain from physical activity together with pretreatment with diazepam. The maximum standardized uptake value (SUV max ) of the pathological lesion and SUV mean of certain skeletal muscles, liver, spleen, lungs, blood and certain bone marrow portions were calculated. In all patients, the muscular uptake was reduced to a normal level at visual evaluation as well as at comparison of SUVs with 25 consecutive clinical patients exhibiting a normal FDG distribution (p max increased from 2.4 to 3.7 (54 %) between the examinations (p max to the activity of any of the reference tissues/organs there was no significant difference between the studies. The distribution of FDG constitutes a relative mechanism. This must be especially considered at longitudinal examinations in the same patient at therapy evaluations. In examinations with a somehow distorted general distribution of the activity, it may be more relevant to relate the lesion activity to a reference tissue/organ than relying on SUV assessments. (orig.)

  20. Studies on uptake and distribution of chemotherapeutic agents to malignant tumors of the head and neck in rabbits, 2. /sup 3/H-Adriamycin

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, R. (Gifu Univ. (Japan). Faculty of Medicine)

    1981-09-01

    Experiments were performed to investigate incorporation and distribution of chemotherapeutic agents into malignant tumors of the head and neck by microautoradiographic and electron microscopic-autoradiographic observations of VX2 carcinoma transplanted in the lower genial region of rabbits after injection of /sup 3/H-Adriamycin as a tracer. The following findings were obtained. 1. On microautoradiograms, /sup 3/H-Adriamycin was distributed predominantly in the nucleoplasm, rather than in the cytoplasm, of tumor tissues. 2. At the ultrastructural level, /sup 3/H-Adriamycin was localized in the nuclear membrane and nucleoli within the nucleoplasm and in the rough endoplasmic reticulum and secretory granules within the cytoplasm. 3. These findings seem to indicate that Adriamycin may inhibit the synthesis of DNA and RNA in the nucleoplasm.

  1. Micelle-forming HPMA copolymer conjugates of ritonavir bound via a pH-sensitive spacer with improved cellular uptake designed for enhanced tumor accumulation

    Czech Academy of Sciences Publication Activity Database

    Koziolová, Eva; Machová, Daniela; Pola, Robert; Janoušková, Olga; Chytil, Petr; Laga, Richard; Filippov, Sergey K.; Šubr, Vladimír; Etrych, Tomáš; Pechar, Michal

    2016-01-01

    Roč. 4, č. 47 (2016), s. 7620-7629 ISSN 2050-750X R&D Projects: GA MŠk(CZ) LO1507; GA ČR(CZ) GAP301/12/1254; GA ČR(CZ) GA15-02986S; GA ČR(CZ) GA16-17207S Institutional support: RVO:61389013 Keywords : HPMA copolymer * tumor * micelle Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.543, year: 2016

  2. Glucose uptake and growth of glucose-limited chemostat cultures of Aspergillus niger and a disruptant lacking MstA, a high-affinity glucose transporter

    DEFF Research Database (Denmark)

    Jørgensen, Thomas R; vanKuyk, Patricia A; Poulsen, Bjarne R

    2007-01-01

    This is a study of high-affinity glucose uptake in Aspergillus niger and the effect of disruption of a high-affinity monosaccharide-transporter gene, mstA. The substrate saturation constant (K(s)) of a reference strain was about 15 microM in glucose-limited chemostat culture. Disruption of mst......-affinity uptake system of A. niger. The mstA disruptant and a reference strain were cultivated in glucose-limited chemostat cultures at low, intermediate and high dilution rate (D=0.07 h(-1), 0.14 h(-1) and 0.20 h(-1)). Mycelium harvested from steady-state cultures was subjected to glucose uptake assays...

  3. Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer.

    Science.gov (United States)

    Meiser, Bettina; Price, Melanie A; Butow, Phyllis N; Karatas, Janan; Wilson, Judy; Heiniger, Louise; Baylock, Brandi; Charles, Margaret; McLachlan, Sue-Anne; Phillips, Kelly-Anne

    2013-03-01

    Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.

  4. Changes in medium radioactivity and composition accompany high-affinity uptake of glutamate and aspartate by mouse brain slices

    International Nuclear Information System (INIS)

    Latzkovits, L.; Neidle, A.; Lajtha, A.

    1984-01-01

    In measurements of high affinity transport in tissue slices, the incubation medium is often treated as an ''infinitely large pool''. External substrate concentrations, even at the micromolar level, are assumed to be constant and metabolic interactions between tissue and medium are neglected. In the present report we describe experiments in which glutamic and aspartic acid uptake by mouse brain slices were studied using techniques that could test these assumptions. Cerebral hemispheres were cut into 0.1 mm sections and about 90 mg of tissue incubated in 10 ml of oxygenated medium. After 45 minutes of equilibration, radioactive substrates were added and the concentrations and specific activities of the amino acids and their metabolites in the medium were determined. During the first 10 min following substrate addition, rapid decreases in glutamic and aspartic acid concentrations in the medium were accompanied by large decreases in specific activity caused by the continuous release of these amino acids from the tissue. In addition, extensive conversion of both substrates to glutamine and the preferential accumulation of this metabolite, in the medium, was found. These results demonstrate that metabolism and release occur simultaneously with uptake during transport experiments in vitro and that these processes can take place in specific tissue compartments. It is therefore necessary to measure the tissue and medium concentration levels of amino acids along with their radioactivity in such experiments, since all three processes (transport, metabolism, and compartmentation) are interrelated in the clearance of amino acids from the incubation medium and probably from the extracellular spaces in vivo as well

  5. Examining sex differentials in the uptake and process of HIV testing in three high prevalence districts of India.

    Science.gov (United States)

    Joseph, Saju; Kielmann, Karina; Kudale, Abhay; Sheikh, Kabir; Shinde, Swati; Porter, John; Rangan, Sheela

    2010-03-01

    Sex differentials in the uptake of HIV testing have been reported in a range of settings, however, men's and women's testing patterns are not consistent across these settings, suggesting the need to set sex differentials against gender norms in patient testing behaviour and provider practices. A community-based, cross-sectional survey among 347 people living with HIV in three HIV high prevalence districts of India examined reasons for undergoing an HIV test, location of testing and conditions under which individuals were tested. HIV testing was almost always provider-initiated for men. Men were more likely to be advised to test by a private practitioner and to test in the private sector. Women were more likely to be advised to test by a family member, and to test in the public sector. Men were more likely to receive pre-test information than women, when tested in the private sector. Men were also more likely to receive direct disclosure of their HIV positive status by a health provider, regardless of the sector in which they tested. More women than men were repeatedly tested for HIV, regardless of sector. These sex differentials in the uptake and process of HIV testing are partially explained through differences in public and private sector testing practices. However, they also reflect women's lack of awareness and agency in HIV care seeking and differential treatment by providers. Examining gender dynamics that underpin sex differentials in HIV testing patterns and practices is essential for a realistic assessment of the challenges and implications of scaling-up HIV testing and mainstreaming gender in HIV/AIDS programmes.

  6. Radioiodine therapy in hyperthyroid disease: poorer outcome in patients with high 24 hours radioiodine uptake

    DEFF Research Database (Denmark)

    Kristoffersen, Ulrik Sloth; Hesse, Birger; Rasmussen, Ase Krogh

    2006-01-01

    multinodular goiters (TMG) and 13 toxic adenomas (TA)]. Thyroid status was determined by TSH, fT3 and fT4 levels, and outcome was rendered successful when hyperthyroidism was absent. Relation between low 24 h RIU (below median) or high 24 h RIU (above or equal to median) and outcome was evaluated. RESULTS...

  7. Intraoperative neuronavigation integrated high resolution 3D ultrasound for brainshift and tumor resection control

    Directory of Open Access Journals (Sweden)

    Giovani A.

    2015-06-01

    Full Text Available INTRODUCTION: The link between the neurosurgeon’s knowledge and the scientific improvements made a dramatic change in the field expressed both in impressive drop in the mortality and morbidity rates that were operated in the beginning of the XXth century and in operating with high rates of success cases that were considered inoperable in the past. Neuronavigation systems have been used for many years on surgical orientation purposes especially for small, deep seated lesions where the use of neuronavigation is correlated with smaller corticotomies and with the extended use of transulcal approaches. The major problem of neuronavigation, the brainshift once the dura is opened can be solved either by integrated ultrasound or intraoperative MRI which is out of reach for many neurosurgical departments. METHOD: The procedure of neuronavigation and ultrasonic localization of the tumor is described starting with positioning the patient in the visual field of the neuronavigation integrated 3D ultrasonography system to the control of tumor resection by repeating the ultrasonographic scan in the end of the procedure. DISCUSSION: As demonstrated by many clinical trials on gliomas, the more tumor removed, the better long term control of tumor regrowth and the longer survival with a good quality of life. Of course, no matter how aggressive the surgery, no new deficits are acceptable in the modern era neurosurgery. There are many adjuvant methods for the neurosurgeon to achieve this maximal and safe tumor removal, including the 3T MRI combined with tractography and functional MRI, the intraoperative neuronavigation and neurophysiologic monitoring in both anesthetized and awake patients. The ultrasonography integrated in neuronavigaton comes as a welcomed addition to this adjuvants to help the surgeon achieve the set purpose. CONCLUSION: With the use of this real time imaging device, the common problem of brainshift encountered with the neuronavigation systems

  8. Use of High-Frequency Jet Ventilation for Percutaneous Tumor Ablation

    Energy Technology Data Exchange (ETDEWEB)

    Denys, Alban, E-mail: alban.denys@chuv.ch; Lachenal, Yann; Duran, Rafael [Lausanne University Hospital, Department of Radiology and Interventional Radiology (Switzerland); Chollet-Rivier, Madeleine [Lausanne University Hospital, Department of Anesthesiology (Switzerland); Bize, Pierre [Lausanne University Hospital, Department of Radiology and Interventional Radiology (Switzerland)

    2013-05-02

    PurposeTo report feasibility and potential benefits of high-frequency jet ventilation (HFJV) in tumor ablations techniques in liver, kidney, and lung lesions.MethodsThis prospective study included 51 patients (14 women, mean age 66 years) bearing 66 tumors (56 hepatic, 5 pulmonary, 5 renal tumors) with a median size of 16 ± 8.7 mm, referred for tumor ablation in an intention-to-treat fashion before preoperative anesthesiology visit. Cancellation and complications of HFJV were prospectively recorded. Anesthesia and procedure duration, as well as mean CO{sub 2} capnea, were recorded. When computed tomography guidance was used, 3D spacial coordinates of an anatomical target <2 mm in diameter on 8 slabs of 4 slices of 3.75-mm slice thickness were registered.ResultsHFJV was used in 41 of 51 patients. Of the ten patients who were not candidate for HFJV, two patients had contraindication to HFJV (severe COPD), three had lesions invisible under HFJV requiring deep inspiration apnea for tumor targeting, and five patients could not have HFJV because of unavailability of a trained anesthetic team. No specific complication or hypercapnia related to HFJV were observed despite a mean anesthetic duration of 2 h and ventilation performed in procubitus (n = 4) or lateral decubitus (n = 6). Measured internal target movement was 0.3 mm in x- and y-axis and below the slice thickness of 3.75 mm in the z-axis in 11 patients.ConclusionsHFJV is feasible in 80 % of patients allowing for near immobility of internal organs during liver, kidney, and lung tumor ablation.

  9. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

    2017-01-01

    Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

  10. High carbon dioxide uptake by subtropical forest ecosystems in the East Asian monsoon region

    Science.gov (United States)

    Yu, Guirui; Chen, Zhi; Piao, Shilong; Peng, Changhui; Ciais, Philippe; Wang, Qiufeng; Li, Xuanran; Zhu, Xianjin

    2014-01-01

    Temperate- and high-latitude forests have been shown to contribute a carbon sink in the Northern Hemisphere, but fewer studies have addressed the carbon balance of the subtropical forests. In the present study, we integrated eddy covariance observations established in the 1990s and 2000s to show that East Asian monsoon subtropical forests between 20°N and 40°N represent an average net ecosystem productivity (NEP) of 362 ± 39 g C m−2 yr−1 (mean ± 1 SE). This average forest NEP value is higher than that of Asian tropical and temperate forests and is also higher than that of forests at the same latitudes in Europe–Africa and North America. East Asian monsoon subtropical forests have comparable NEP to that of subtropical forests of the southeastern United States and intensively managed Western European forests. The total NEP of East Asian monsoon subtropical forests was estimated to be 0.72 ± 0.08 Pg C yr−1, which accounts for 8% of the global forest NEP. This result indicates that the role of subtropical forests in the current global carbon cycle cannot be ignored and that the regional distributions of the Northern Hemisphere's terrestrial carbon sinks are needed to be reevaluated. The young stand ages and high nitrogen deposition, coupled with sufficient and synchronous water and heat availability, may be the primary reasons for the high NEP of this region, and further studies are needed to quantify the contribution of each underlying factor. PMID:24639529

  11. Locomotor muscle fatigue does not alter oxygen uptake kinetics during high-intensity exercise

    Directory of Open Access Journals (Sweden)

    James Hopker

    2016-10-01

    Full Text Available The slow component (VO2sc that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre fatigue condition or rest for 33 minutes (control condition according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-second maximal sprints at a fixed pedaling cadence of 90 rev·min-1. Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and VO2max determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue (P = 0.03, the VO2sc was not significantly different between the pre fatigue (464 ± 301 mL·min-1 and the control (556 ± 223 mL·min-1 condition (P = 0.50. Blood lactate response was not significantly different between conditions (P = 0.48 but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition (P < 0.01 suggesting higher muscle recruitment. These results demonstrate experimentally that locomotor muscle fatigue does not significantly alter the VO2 kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the VO2sc is strongly associated with locomotor muscle fatigue.

  12. Locomotor Muscle Fatigue Does Not Alter Oxygen Uptake Kinetics during High-Intensity Exercise.

    Science.gov (United States)

    Hopker, James G; Caporaso, Giuseppe; Azzalin, Andrea; Carpenter, Roger; Marcora, Samuele M

    2016-01-01

    The [Formula: see text] slow component ([Formula: see text]) that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre-fatigue condition) or rest for 33 min (control condition) according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-s maximal sprints at a fixed pedaling cadence of 90 rev·min -1 . Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE) were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and [Formula: see text] determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue ( P = 0.03), the [Formula: see text] was not significantly different between the pre-fatigue (464 ± 301 mL·min -1 ) and the control (556 ± 223 mL·min -1 ) condition ( P = 0.50). Blood lactate response was not significantly different between conditions ( P = 0.48) but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition ( P locomotor muscle fatigue does not significantly alter the [Formula: see text] kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the [Formula: see text] is strongly associated with locomotor muscle fatigue.

  13. Intracellular uptake of 123I-boronophenylalanine-fructose

    International Nuclear Information System (INIS)

    Woo, K. S.; Choi, T. H.; Choi, C. Y.; Jung, W. S.; Lim, S. J.; Lee, S. J.; Lim, S. M.

    1999-01-01

    Boronophenylalanine (BPA) has been used in malignant glioma or melanoma uptake for BNCT. We labeled BPA with 123 I for in vivo quantitation of BPA in BNCT, and tumor imaging with gamma camera. We investigated the amino acid BPA as a boron delivery agent fro BNCT. As the free amino acid, BPA has a limited solubility at physiological pH, which makes it unsuitable for IV or IP injection. Recent studies of the chemistry of BPA have yielded a method of solubilizing BPA at neutral pH using fructose, a common fruit sugar. The use of BPA-fructose has significantly improved high uptake compared to BPA alone in melanoma

  14. Uptake of naturally occurring radioisotopes by vegetation in a region of high radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Mahon, D C; Mathewes, R W [Simon Fraser Univ., Burnaby, British Columbia (Canada)

    1983-05-01

    The accumulation of four naturally occurring radionuclides of the sup(238)U series, uranium, sup(226)Ra, sup(210)Pb and sup(210)Po, in 15 species of native plants was investigated. Of the plants sampled some accumulated, but none concentrated uranium or sup(226)Ra. Grouseberry (Vaccinium scoparium Leiberg) appeared to concentrate sup(210)Pb and sup(210)Po. There were marked seasonal variations in the accumulation of uranium by grass (Calamagrostis rubescens Buckl.), and of sup(210)Pb and sup(210)Po by grass and fireweed (Epilobium angustifolium L.). High positive correlations between soil and vegetation radionuclide content were found for uranium in fireweed and grouseberry in spring, sup(226)Ra in willow (Salix scouleriana L.) in spring, and uranium in fireweed in summer.

  15. High substrate uptake rates empower Vibrio natriegens as production host for industrial biotechnology.

    Science.gov (United States)

    Hoffart, Eugenia; Grenz, Sebastian; Lange, Julian; Nitschel, Robert; Müller, Felix; Schwentner, Andreas; Feith, André; Lenfers-Lücker, Mira; Takors, Ralf; Blombach, Bastian

    2017-09-08

    The productivity of industrial fermentation processes is essentially limited by the biomass specific substrate consumption rate (q S ) of the applied microbial production system. Since q S depends on the growth rate (μ), we highlight the potential of the fastest growing non-pathogenic bacterium, Vibrio natriegens , as novel candidate for future biotechnological processes. V. natriegens grows rapidly in BHIN complex medium with a μ of up to 4.43 h -1 (doubling time of 9.4 min) as well as in minimal medium supplemented with various industrially relevant substrates. Bioreactor cultivations in minimal medium with glucose showed that V. natriegens possesses an exceptionally high q S under aerobic (3.90 ± 0.08 g g -1 h -1 ) and anaerobic (7.81 ± 0.71 g g -1 h -1 ) conditions. Fermentations with resting cells of genetically engineered V. natriegens under anaerobic conditions yielded an overall volumetric productivity of 0.56 ± 0.10 g alanine L -1 min -1 (i.e. 34 g L -1 h -1 ). These inherent properties render V. natriegens a promising new microbial platform for future industrial fermentation processes operating with high productivity. Importance Low conversion rates are one major challenge to realize microbial fermentation processes for the production of commodities operating competitively to existing petrochemical approaches. For this reason, we screened for a novel platform organism possessing superior characteristics to traditionally employed microbial systems. We identified the fast growing Vibrio natriegens which exhibits a versatile metabolism and shows striking growth and conversion rates, as a solid candidate to reach outstanding productivities. Due to these inherent characteristics V. natriegens can speed up common laboratory routines, is suitable for already existing production procedures, and forms an excellent foundation to engineer next generation bioprocesses. Copyright © 2017 American Society for Microbiology.

  16. The Elastin Receptor Complex: a unique matricellular receptor with high anti-tumoral potential

    Directory of Open Access Journals (Sweden)

    Amandine eScandolera

    2016-03-01

    Full Text Available Elastin, one of the longest-lived proteins, confers elasticity to tissues with high mechanical constraints. During aging or pathophysiological conditions such as cancer progression, this insoluble polymer of tropoelastin undergoes an important degradation leading to the release of bioactive elastin-derived peptides (EDP, named elastokines. EDP exhibit several biological functions able to drive tumor development by regulating cell proliferation, invasion, survival, angiogenesis, and matrix metalloproteinase expression in various tumor and stromal cells. Although several receptors have been suggested to bind elastokines (αvβ3 and αvβ5 integrins, galectin-3, their main receptor remains the Elastin Receptor Complex (ERC. This heterotrimer comprises a peripheral subunit, named Elastin Binding Protein (EBP, associated to the Protective Protein/Cathepsin A (PPCA. The latter is bound to a membrane-associated protein called Neuraminidase-1 (Neu-1. The pro-tumoral effects of elastokines have been linked to their binding onto EBP. Additionally, Neu-1 sialidase activity is essential for their signal transduction. Consistently, EDP-EBP interaction and Neu-1 activity emerge as original anti-tumoral targets. Interestingly, besides its direct involvement in cancer progression, the ERC also regulates diabetes outcome and thrombosis, an important risk factor for cancer development and a vascular process highly increased in patients suffering from cancer. In this review, we will describe ERC and elastokines involvement in cancer development suggesting that this unique receptor would be a promising therapeutic target. We will also discuss the pharmacological concepts aiming at blocking its pro-tumoral activities. Finally, its emerging role in cancer-associated complications and pathologies such as diabetes and thrombotic events will be also considered.

  17. Observation on scintigram of bone tumors by color data system

    International Nuclear Information System (INIS)

    Minami, Kyuman

    1982-01-01

    The uptake of RI on bone scintigram was converted with a color data system to a color pattern of 12 colors. The color patterns of bone tumors were analysed in comparison them with those in contralateral part of body. The author observed on color patterns of bone scintigrams in 70 cases of bone tumors, of which 28 cases were malignant, 32 benign and 10 giant cell tumors. Differences of color pattern were found relatively low in tumors of the pelvis, whereas they were high in tumors of the limbs and shoulder. In malignant tumors, differences of the color patterns were marked and wide in range. Applying the color data system to bone scintigram, bone tumors could be objectively observed and the method was very helpful for diagnosis of bone tumors. (author)

  18. Study of thorium uptake by inhabitants of a high background radiation area

    International Nuclear Information System (INIS)

    Melo, D.R.; Lipsztein, J.L.; Juliao, L.M.Q.C.; Lourenco, M.C.; Lauria, D.

    2002-01-01

    Buena, located in the North of Rio de Janeiro, is characterized by its high natural radiation background, due to large deposits of monazite sand. The foodstuffs consumed by the population are basically composed of local products, which contain significant amounts of thorium. The analysis of complete cooked meals have shown an average daily intake of 18 mBq.d -1 of 232 Th and 189 mBq.d -1 of 228 Th. The average urine to feces ratio of 232 Th from samples of volunteers was found equal to 7.5x10 -2 . The comparison of the experimental data with the predicted urine to feces ratios derived using the biokinetic model for thorium described by the ICRP publication 69 and simulating inhalation and ingestion separately, lead to the conclusion that the thorium intake is a combination of inhalation and ingestion. The clearance rate of thorium of monazite in lungs has apparently behaved as Type M compound. Inhalation is the biggest contributor for the committed effective dose due to thorium internal exposure. (author)

  19. High uptake of 2,4,6-trinitrotoluene by vetiver grass - Potential for phytoremediation?

    International Nuclear Information System (INIS)

    Makris, Konstantinos C.; Shakya, Kabindra M.; Datta, Rupali; Sarkar, Dibyendu; Pachanoor, Devanand

    2007-01-01

    2,4,6-Trinitrotoluene (TNT) is a potent mutagen, and a Group C human carcinogen that has been widely used to produce munitions and explosives. Vast areas that have been previously used as ranges, munition burning, and open detonation sites are heavily contaminated with TNT. Conventional remediation activities in such sites are expensive and damaging to the ecosystem. Phytoremediation offers a cost-effective, environment-friendly solution, utilizing plants to extract TNT from contaminated soil. We investigated the potential use of vetiver grass (Vetiveria zizanioides) to effectively remove TNT from contaminated solutions. Vetiver grass plants were grown in hydroponic systems containing 40 mg TNT L -1 for 8 d. Aqueous concentrations of TNT reached the method detection limit (∼1 μg L -1 ) within the 8-d period, demonstrating high affinity of vetiver for TNT, without any visible toxic effects. Results from this preliminary hydroponic study are encouraging, but in need of verification using TNT-contaminated soils. - Vetiver grass demonstrates ability to absorb TNT in aqueous media

  20. Increased cardiac output and maximal oxygen uptake in response to ten sessions of high intensity interval training.

    Science.gov (United States)

    Astorino, Todd A; Edmunds, Ross M; Clark, Amy; King, Leesa; Gallant, Rachael M; Namm, Samantha; Fischer, Anthony; Wood, Kimi A

    2018-01-01

    Increases in maximal oxygen uptake (VO2max) are widely reported in response to completion of high intensity interval training (HIIT), yet the mechanism explaining this result is poorly understood. This study examined changes in VO2max and cardiac output (CO) in response to 10 sessions of low-volume HIIT. Participants included 30 active men and women (mean age and VO2max=22.9±5.4 years and 39.6±5.6 mL/kg/min) who performed HIIT and 30 men and women (age and VO2max=25.7±4.5 years and 40.7±5.2 mL/kg/min) who served as non-exercising controls (CON). High intensity interval training consisted of 6-10 s bouts of cycling per session at 90-110 percent peak power output (PPO) interspersed with 75 s recovery. Before and after training, progressive cycling to exhaustion was completed during which CO, stroke volume (SV), and heart rate (HR) were estimated using thoracic impedance. To confirm VO2max attainment, a verification test was completed after progressive cycling at a work rate equal to 110%PPO. Data demonstrated significant improvements in VO2max (2.71±0.63 L/min to 2.86±0.63 L/min, Psessions of HIIT is due to improvements in oxygen delivery.

  1. Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy?

    Science.gov (United States)

    Akagunduz, Ozlem Ozkaya; Savas, Recep; Yalman, Deniz; Kocacelebi, Kenan; Esassolak, Mustafa

    2015-11-01

    To evaluate the predictive value of adaptive threshold-based metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and maximum lean body mass corrected SUV (SULmax) measured on pretreatment positron emission tomography and computed tomography (PET/CT) imaging in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy. Pretreatment PET/CT of the 62 patients with locally advanced head and neck cancer who were treated consecutively between May 2010 and February 2013 were reviewed retrospectively. The maximum FDG uptake of the primary tumor was defined according to SUVmax and SULmax. Multiple threshold levels between 60% and 10% of the SUVmax and SULmax were tested with intervals of 5% to 10% in order to define the most suitable threshold value for the metabolic activity of each patient's tumor (adaptive threshold). MTV was calculated according to this value. We evaluated the relationship of mean values of MTV, SUVmax and SULmax with treatment response, local recurrence, distant metastasis and disease-related death. Receiver-operating characteristic (ROC) curve analysis was done to obtain optimal predictive cut-off values for MTV and SULmax which were found to have a predictive value. Local recurrence-free (LRFS), disease-free (DFS) and overall survival (OS) were examined according to these cut-offs. Forty six patients had complete response, 15 had partial response, and 1 had stable disease 6 weeks after the completion of treatment. Median follow-up of the entire cohort was 18 months. Of 46 complete responders 10 had local recurrence, and of 16 partial or no responders 10 had local progression. Eighteen patients died. Adaptive threshold-based MTV had significant predictive value for treatment response (p=0.011), local recurrence/progression (p=0.050), and disease-related death (p=0.024). SULmax had a predictive value for local recurrence/progression (p=0.030). ROC curves analysis revealed a cut-off value of 14.00 mL for

  2. Influence of Pathological Nodal Status and Maximal Standardized Uptake Value of the Primary Tumor and Regional Lymph Nodes on Treatment Plans in Patients With Advanced Oral Cavity Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Liao, C.-T.; Wang, H.-M.; Chang, Joseph Tung-Chieh; Lin, C.-Y.; Ng, S.-H.; Huang, S.-F.; Chen, I.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2010-01-01

    Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group. Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose-positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis. Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001). Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients.

  3. RASSF1A promoter is highly methylated in primitive neuroectodermal tumors of the central nervous system.

    Science.gov (United States)

    Inda, María-del-Mar; Castresana, Javier S

    2007-08-01

    Although cancer is rare in children, primary brain tumors constitute the most frequent location of solid tumors in childhood. Primitive neuroectodermal tumors (PNET) of the central nervous system can be divided into infratentorial PNET or medulloblastoma (MB), and supratentorial (sPNET) tumors. Although MB and sPNET are histologically similar, clinical evolution differs, sPNET being more aggressive than MB. Some studies have suggested that MB and sPNET present different molecular genetic aberrations. The RASSF1A (Ras Association Domain Family Protein 1) gene, located at 3p21.3, is highly methylated in multiple primary tumor samples, including neuroblastoma. In order to define whether there are genetic differences in the methylation frequency of RASSF1A between MB and sPNET, we analyzed 32 PNET paraffin-embedded samples (23 MB and 9 sPNET) by methylation specific polymerase chain reaction (MSP). We also analyzed RASSF1A expression by reverse transcription polymerase chain reaction in five PNET cell lines. All PNET cell lines showed lack of RASSF1A expression that was correlated with RASSF1A promoter hypermethylation. RASSF1A methylation was detected in 19 of 21 MB cases (91%) and in five of six sPNET samples (83%). Although the methylation frequency found in MB was slightly higher than in sPNET, no statistical differences were found for the RASSF1A hypermethylation frequency (P > 0.05) presented at MB versus sPNET. Therefore, the inactivation of the RASSF1A gene seems to be an important step in the tumorigenesis of PNET of the central nervous sytem. More studies should be performed in order to determine genetic differences between MB and sPNET.

  4. ⁸⁹Zr-Labeled Versus ¹²⁴I-Labeled αHER2 Fab with Optimized Plasma Half-Life for High-Contrast Tumor Imaging In Vivo.

    Science.gov (United States)

    Mendler, Claudia T; Gehring, Torben; Wester, Hans-Jürgen; Schwaiger, Markus; Skerra, Arne

    2015-07-01

    Immuno-PET imaging of the tumor antigen HER2/neu allows for the noninvasive detection and monitoring of oncogene expression; such detection and monitoring are of prognostic value in patients with breast cancer. Compared with the full-size antibody trastuzumab, smaller protein tracers with more rapid blood clearance permit higher imaging contrast at earlier time points. Antigen-binding fragments (Fabs) of antibodies with moderately prolonged circulation achieved through the genetic fusion with a long, conformationally disordered chain of the natural amino acids Pro, Ala, and Ser (PASylation)-a biologic alternative to chemical conjugation with polyethylene glycol, PEG-offer a promising tracer format with improved pharmacokinetics for in vivo imaging. Recently, the transition metal radionuclide (89)Zr has attracted increasing interest for immuno-PET studies, complementing the conventional halogen radionuclide (124)I. To allow direct comparison of these 2 radioactive labels for the same protein tracer, the recombinant αHER2 Fab fused with 200 Pro, Ala, and Ser (PAS200) residues was either conjugated with (124)I via an iodination reagent or coupled with deferoxamine (Df) and complexed with (89)Zr. After confirmation of the stability of both radioconjugates and quality control in vitro, immuno-PET and biodistribution studies were performed with CD1-Foxn1(nu) mice bearing HER2-positive human tumor xenografts. (89)Zr⋅Df-Fab-PAS200 and (124)I-Fab-PAS200 showed specific tumor uptake of 11 and 2.3 percentage injected dose per gram 24 h after injection, respectively; both led to high tumor-to-blood (3.6 and 4.4, respectively) and tumor-to-muscle (20 and 43, respectively) ratios. With regard to off-target accumulation, overt (124)I activity was seen in the thyroid, as expected, whereas high kidney uptake was evident for (89)Zr; the latter was probably due to glomerular filtration and reabsorption of the protein tracer in proximal tubular cells. Both (89)Zr- and (124)I

  5. Interferon-induced changes in pharmacokinetics and tumor uptake of 111In-labeled antimelanoma antibody 96.5 in melanoma patients

    International Nuclear Information System (INIS)

    Rosenblum, M.G.; Lamki, L.M.; Murray, J.L.; Carlo, D.J.; Gutterman, J.U.

    1988-01-01

    The type I interferons [both partially purified human leukocyte interferon (HuIFN-alpha) and recombinant alpha interferon] and the type II interferons have been shown to increase the expression of tumor-associated antigens in vitro. To determine whether HuIFN-alpha could increase tumor acquisition of the antimelanoma antibody 96.5 in vivo, five patients with metastatic malignant melanoma were treated with HuIFN-alpha at a dose of 3 X 10(6) units daily by im administration. Twenty-four hours after the first dose of HuIFN-alpha, 1 mg of antibody 96.5 labeled with 5 mCi of 111 In was coadministered with 19 mg of unlabeled 96.5. Five patients matched for metastatic site and lesion size who had not received HuIFN-alpha were also given a dose of 5 mCi of radiolabeled 96.5 at the same total antibody dose (20 mg). In patients treated with HuIFN-alpha, there was a statistically significant increase in the plasma half-life of the 111 In label (39.7 +/- 3.3 hr) compared to the untreated control group (29.8 +/- 3.2 hr). In addition, there was an increase in the apparent volume of distribution of the antibody in the HuIFN-alpha group (5.56 +/- 0.67 L) compared to controls (3.15 +/- 0.5 L) suggesting both an increased immediate extravascular distribution of radiolabeled antibody and a decrease in the subsequent rate of clearance of antibody from plasma. These two phenomena result in a 28% decrease in the area under the concentration curve in the HuIFN-alpha-treated group compared to controls. Computer analysis of whole-body scans from patients showed a threefold increase in radiolabeled antibody distributed to tumor relative to blood pool but no change in organ:blood ratios for liver, spleen, bone, or kidney compared to controls

  6. The 'glial' glutamate transporter, EAAT2 (Glt-1) accounts for high affinity glutamate uptake into adult rodent nerve endings.

    Science.gov (United States)

    Suchak, Sachin K; Baloyianni, Nicoletta V; Perkinton, Michael S; Williams, Robert J; Meldrum, Brian S; Rattray, Marcus

    2003-02-01

    The excitatory amino acid transporters (EAAT) removes neurotransmitters glutamate and aspartate from the synaptic cleft. Most CNS glutamate uptake is mediated by EAAT2 into glia, though nerve terminals show evidence for uptake, through an unknown transporter. Reverse-transcriptase PCR identified the expression of EAAT1, EAAT2, EAAT3 and EAAT4 mRNAs in primary cultures of mouse cortical or striatal neurones. We have used synaptosomes and glial plasmalemmal vesicles (GPV) from adult mouse and rat CNS to identify the nerve terminal transporter. Western blotting showed detectable levels of the transporters EAAT1 (GLAST) and EAAT2 (Glt-1) in both synaptosomes and GPVs. Uptake of [3H]D-aspartate or [3H]L-glutamate into these preparations revealed sodium-dependent uptake in GPV and synaptosomes which was inhibited by a range of EAAT blockers: dihydrokainate, serine-o-sulfate, l-trans-2,4-pyrrolidine dicarboxylate (PDC) (+/-)-threo-3-methylglutamate and (2S,4R )-4-methylglutamate. The IC50 values found for these compounds suggested functional expression of the 'glial, transporter, EAAT2 in nerve terminals. Additionally blockade of the majority EAAT2 uptake sites with 100 micro m dihydrokainate, failed to unmask any functional non-EAAT2 uptake sites. The data presented in this study indicate that EAAT2 is the predominant nerve terminal glutamate transporter in the adult rodent CNS.

  7. Effect of high-intensity training versus moderate training on peak oxygen uptake and chronotropic response in heart transplant recipients

    DEFF Research Database (Denmark)

    Dall, C H; Snoer, M; Christensen, S

    2014-01-01

    In heart transplant (HTx) recipients, there has been reluctance to recommend high-intensity interval training (HIIT) due to denervation and chronotropic impairment of the heart. We compared the effects of 12 weeks' HIIT versus continued moderate exercise (CON) on exercise capacity and chronotropic...... response in stable HTx recipients >12 months after transplantation in a randomized crossover trial. The study was completed by 16 HTx recipients (mean age 52 years, 75% males). Baseline peak oxygen uptake (VO2peak ) was 22.9 mL/kg/min. HIIT increased VO2peak by 4.9 ± 2.7 mL/min/kg (17%) and CON by 2.6 ± 2.......2 mL/kg/min (10%) (significantly higher in HIIT; p HIIT, systolic blood pressure decreased significantly (p = 0.037) with no significant change in CON (p = 0.241; between group difference p = 0.027). Peak heart rate (HRpeak ) increased significantly by 4.3 beats per minute (p = 0...

  8. Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report.

    Science.gov (United States)

    Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian

    2018-05-30

    Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.

  9. Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors

    International Nuclear Information System (INIS)

    Glosser, Guila; McManus, Pat; Munzenrider, John; Austin-Seymour, Mary; Fullerton, Barbara; Adams, Judy; Urie, Marcia M.

    1997-01-01

    Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psycho-motor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures

  10. On Statistical Modeling of Sequencing Noise in High Depth Data to Assess Tumor Evolution

    Science.gov (United States)

    Rabadan, Raul; Bhanot, Gyan; Marsilio, Sonia; Chiorazzi, Nicholas; Pasqualucci, Laura; Khiabanian, Hossein

    2017-12-01

    One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate our model with simulated exponentially expanded populations as well as data from cell line and patient sample dilution experiments, demonstrating its utility in prognosticating tumor progression. Our results may have the potential to identify significant mutations that can cause recurrence. These results are relevant in the pretreatment clinical setting to determine appropriate therapy and prepare for potential recurrence pretreatment.

  11. A novel method for monitoring high-risk breast cancer with tumor markers

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1993-01-01

    cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph......BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast...

  12. Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

    Science.gov (United States)

    Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Zhong, Lu; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; He, Zhonggui

    2017-04-01

    Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Thrombocalc: implementation and uptake of personalized postpartum venous thromboembolism risk assessment in a high-throughput obstetric environment.

    Science.gov (United States)

    O'Shaughnessy, Fergal; Donnelly, Jennifer C; Cooley, Sharon M; Deering, Mary; Raman, Ajita; Gannon, Geraldine; Hickey, Jane; Holland, Alan; Hayes, Niamh; Bennett, Kathleen; Ní Áinle, Fionnuala; Cleary, Brian J

    2017-11-01

    Venous thromboembolism risk assessment (VTERA) is recommended in all pregnant and postpartum women. Our objective was to develop, pilot and implement a user-friendly electronic VTERA tool. We developed "Thrombocalc", an electronic VTERA tool using Microsoft EXCEL ™ . Thrombocalc was designed as a score-based tool to facilitate rapid assessment of all women after childbirth. Calculation of a total score estimated risk of venous thromboembolism in line with consensus guidelines. Recommendations for thromboprophylaxis were included in the VTERA output. Implementation was phased. Uptake of the VTERA tool was assessed prospectively by monitoring the proportion of women who gave birth in our institution and had a completed risk assessment. Factors affecting completion and accuracy of risk assessments were also assessed. Thrombocalc was used prospectively to risk-assess 8380 women between September 2014 and December 2015. Compliance with this tool increased dramatically throughout the study period; over 92% of women were risk-assessed in the last quarter of data collection. Compliance was not adversely affected if delivery took place out of working hours [adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI) 0.93-1.14]. Risk assessment was less likely in the case of cesarean deliveries (aOR 0.66, 95% CI 0.60-0.73) and stillborn infants (aOR 0.48, 95% CI 0.29-0.79). Misclassification of risk factors led to approximately 207 (2.5%) inaccurate thromboprophylaxis recommendations. Our electronic, score-based VTERA tool provides a highly effective mechanism for rapid assessment of individual postpartum venous thromboembolism risk in a high-throughput environment. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  14. Application of High-Resolution Magic-Angle Spinning NMR Spectroscopy to Define the Cell Uptake of MRI Contrast Agents

    Science.gov (United States)

    Calabi, Luisella; Alfieri, Goffredo; Biondi, Luca; De Miranda, Mario; Paleari, Lino; Ghelli, Stefano

    2002-06-01

    A new method, based on proton high-resolution magic-angle spinning ( 1H HR-MAS) NMR spectroscopy, has been employed to study the cell uptake of magnetic resonance imaging contrast agents (MRI-CAs). The method was tested on human red blood cells (HRBC) and white blood cells (HWBC) by using three gadolinium complexes, widely used in diagnostics, Gd-BOPTA, Gd-DTPA, and Gd-DOTA, and the analogous complexes obtained by replacing Gd(III) with Dy(III), Nd(III), and Tb(III) (i.e., complexes isostructural to the ones of gadolinium but acting as shift agents). The method is based on the evaluation of the magnetic effects, line broadening, or induced lanthanide shift (LIS) caused by these complexes on NMR signals of intra- and extracellular water. Since magnetic effects are directly linked to permeability, this method is direct. In all the tests, these magnetic effects were detected for the extracellular water signal only, providing a direct proof that these complexes are not able to cross the cell membrane. Line broadening effects (i.e., the use of gadolinium complexes) only allow qualitative evaluations. On the contrary, LIS effects can be measured with high precision and they can be related to the concentration of the paramagnetic species in the cellular compartments. This is possible because the HR-MAS technique provides the complete elimination of bulk magnetic susceptibility (BMS) shift and the differentiation of extra- and intracellular water signals. Thus with this method, the rapid quantification of the MRI-CA amount inside and outside the cells is actually feasible.

  15. Non-FDG PET imaging of brain tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Zemin; GUAN Yihui; ZUO Chuantao; ZHANG Zhengwei; XUE Fangping; LIN Xiangtong

    2007-01-01

    Due to relatively high uptake of glucose in the brain cortex, the use of FDG PET imaging is greatly limited in brain tumor imaging, especially for low-grade gliomas and some metastatic tumours. More and more tracers with higher specificity were developed lately for brain tumor imaging. There are 3 main types of non-FDG PET tracers:amino acid tracers, choline tracers and nucleic acid tracers. These tracers are now widely applied in many aspects of brain tumor imaging. This article summarized the general use of non-FDG PET in different aspects of brain tumor imaging.

  16. Significant suppression of myocardial (18)F-fluorodeoxyglucose uptake using 24-h carbohydrate restriction and a low-carbohydrate, high-fat diet.

    Science.gov (United States)

    Kobayashi, Yasuhiro; Kumita, Shin-ichiro; Fukushima, Yoshimitsu; Ishihara, Keiichi; Suda, Masaya; Sakurai, Minoru

    2013-11-01

    (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a useful tool for evaluating inflammation. Because, myocardial-FDG uptake occurs with diverse physiology, it should be suppressed during evaluation of myocardial inflammation by FDG-PET/CT. Diets inducing fat-based metabolism, such as a low-carbohydrate, high-fat diet (LCHF), are used in uptake-suppression protocols. However, a complete suppression of myocardial-FDG uptake has not been established. Hence, we assessed the efficacy of 24-h carbohydrate restriction along with an LCHF diet compared to that of the conventional protocol in suppressing myocardial-FDG uptake and also compared fat and glucose metabolism between these protocols. Fourteen healthy volunteers agreed to undergo >24-h carbohydrate restriction (glucose, vs. 2.98 [1.76-6.43], p=0.001). Target-to-background ratios [myocardium-to-blood ratio (MBR), myocardium-to-lung ratio (MLR), and myocardium-to-liver ratio (MLvR)] were also significantly lower with the diet-preparation protocol [MBR: 0.75 (0.68-0.84) vs. 1.63 (0.98-4.09), pvs. 4.54 (2.53-12.78), p=0.004; MLvR: 0.48 (0.44-0.56) vs. 1.11 (0.63-2.32), p=0.002]. Only insulin levels were significantly different between the subjects in each protocol group (11.3 [6.2-15.1] vs. 3.9 [2.9-6.2]). Carbohydrate restriction together with an LCHF supplement administered 1h before FDG significantly suppressed myocardial-FDG uptake. FFAs and insulin might not directly affect myocardial-FDG uptake. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  17. Factors affecting gastric uptake in whole body FDG-PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tomemori, Takashi; Kitagawa, Mami; Nakahara, Tadaki; Wu, Jin; Nakagawa, Keiichi; Uno, Kimiichi; Abe, Kinji; Tomiyoshi, Katsumi [Nishidai Clinic Diagnostic Imaging Center, Tokyo (Japan)

    2001-06-01

    Positron emission tomography (PET) using 2-deoxy-2-[{sup 18}F]-fluoro-D-glucose (FDG) is very useful for the detection and staging of tumors. However, FDG is also accumulated in the normal tissues in various degrees. This physiological FDG uptake is often seen in intestine, making confusion with malignant tumor. The aim of this study was to identify factors influencing physiological FDG uptake in the stomach. A total of 136 people who underwent cancer screening or staging of tumors except for gastric cancer using FDG whole-body PET was examined (mean age: 55.6 yrs). All subjects fasted for at least 4 hours before the PET study and were administrated with FDG intravenously (mean FDG dose: 308.9 MBq). Emission images were acquired on a whole-body PET scanner and images were reconstructed without attenuation correction. The intensity of gastric uptake of FDG whole-body PET image was visually classified into 3 grades; grade 2 = the intensity of gastric uptake more than pulmonary uptake, grade 1 = the intensity of gastric uptake equal to or less than pulmonary uptake, grade 0 = no contrast between gastric uptake and background. Twenty-eight subjects (20.6%) were classified into grade 2, 42 subjects (30.9%) were grade 1 and 66 subjects (48.5%) were grade 0. Subjects' age, fasting time, FDG dose, serum glucose level, free fatty acid level and insulin level were not significantly correlated with the intensity of gastric uptake. But the subjects with higher gastric uptake tended to have anti-Helicobactor pylori (H. pylori) antibodies. The rate of having anti-H.pylori antibodies in the grade 2 group is significantly higher than the grade 1 group (85.7% vs. 72.5%, p<0.05), and that of the grade 1 group is significantly higher than the grade 0 group (72.5% vs. 42.2%, p<0.01). Gastric uptake was observed in about half of subjects. Especially, approximately 20% of all showed high gastric uptake, which was associated with H.pylori infection. Therefore, most of the subjects

  18. Factors affecting gastric uptake in whole body FDG-PET imaging

    International Nuclear Information System (INIS)

    Tomemori, Takashi; Kitagawa, Mami; Nakahara, Tadaki; Wu, Jin; Nakagawa, Keiichi; Uno, Kimiichi; Abe, Kinji; Tomiyoshi, Katsumi

    2001-01-01

    Positron emission tomography (PET) using 2-deoxy-2-[ 18 F]-fluoro-D-glucose (FDG) is very useful for the detection and staging of tumors. However, FDG is also accumulated in the normal tissues in various degrees. This physiological FDG uptake is often seen in intestine, making confusion with malignant tumor. The aim of this study was to identify factors influencing physiological FDG uptake in the stomach. A total of 136 people who underwent cancer screening or staging of tumors except for gastric cancer using FDG whole-body PET was examined (mean age: 55.6 yrs). All subjects fasted for at least 4 hours before the PET study and were administrated with FDG intravenously (mean FDG dose: 308.9 MBq). Emission images were acquired on a whole-body PET scanner and images were reconstructed without attenuation correction. The intensity of gastric uptake of FDG whole-body PET image was visually classified into 3 grades; grade 2 = the intensity of gastric uptake more than pulmonary uptake, grade 1 = the intensity of gastric uptake equal to or less than pulmonary uptake, grade 0 = no contrast between gastric uptake and background. Twenty-eight subjects (20.6%) were classified into grade 2, 42 subjects (30.9%) were grade 1 and 66 subjects (48.5%) were grade 0. Subjects' age, fasting time, FDG dose, serum glucose level, free fatty acid level and insulin level were not significantly correlated with the intensity of gastric uptake. But the subjects with higher gastric uptake tended to have anti-Helicobactor pylori (H. pylori) antibodies. The rate of having anti-H.pylori antibodies in the grade 2 group is significantly higher than the grade 1 group (85.7% vs. 72.5%, p<0.05), and that of the grade 1 group is significantly higher than the grade 0 group (72.5% vs. 42.2%, p<0.01). Gastric uptake was observed in about half of subjects. Especially, approximately 20% of all showed high gastric uptake, which was associated with H.pylori infection. Therefore, most of the subjects with high

  19. Newly designed Tc(V)-99m dimercaptosuccinic acid: An agent of high accuracy for the diagnosis of head and neck and soft tissue tumors

    International Nuclear Information System (INIS)

    Endo, K.; Ohta, H.; Sakahara, H.; Nakashima, T.; Masuda, H.; Horiuchi, K.; Yokoyama, A.; Torizuka, K.

    1984-01-01

    Being aware of the ideal nuclear properties of Tc-99m, interest has been focused on the design of (+5) oxidation state Tc-99m dimercaptosuccinic acid (DMSA) as a tumor seeking agent. This Tc(V)-99m DMSA holding a TcO/sup 3-//sub 4/ core, alike PO/sup 3-//sub 4/, with competent characteristics for tumor uptake, had a different distribution behavior from the well-known renal scanning agent; Tc(III)-99m DMSA. Basic studies, carried out in vitro and in vivo with Ehrlich tumor cells or bearing mice, clearly substantiated its great potentiality for clinical use. Therefore, 193 untreated patients with histologically proven diagnosis (132 malignant and 61 benign tumors) were evaluated. In 53 primary head and neck tumor (mainly squamous cell carcinomas and plemorphic adenomas or abscess), its sensitivity and specificity was 78% and 87%, as opposed to Ga-67 citrate of 85% and 51% respectively. In 18 malignant soft tissue tumors, all but one (94%) showed significant uptake of Tc(V)-99m DMSA, while Ga-67 was positive in only 60% of these cases. The specificity of both agents was 74% and 86%, respectively. However in lung and abdominal tumors, lymphomas, melanomas and inflammatory lesions, the sensitivity was poor of less than 40%. Also negative were scans in most thyroid cancers, however, 5 patients with medullary thyroid cancers, were all positive with Tc(V)-99m DMSA and was useful follow patients after surgery. Thus, a different uptake mechanism for this agent could be visualized. The authors conclude that Tc(V)-99m DMSA provided a good basis for its clinical application as a tumor imaging agent, mainly in head and neck squamous cell carcinomas, medullary thyroid cancers and soft tissue tumors

  20. Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

    Science.gov (United States)

    Donnelly, L S; Evans, D G; Wiseman, J; Fox, J; Greenhalgh, R; Affen, J; Juraskova, I; Stavrinos, P; Dawe, S; Cuzick, J; Howell, A

    2014-04-02

    Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

  1. Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

    LENUS (Irish Health Repository)

    Howley, R

    2012-10-15

    Developing targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR\\/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRβ were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.

  2. Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.

    Science.gov (United States)

    van den Bijgaart, Renske J E; Eikelenboom, Dylan C; Hoogenboom, Martijn; Fütterer, Jurgen J; den Brok, Martijn H; Adema, Gosse J

    2017-02-01

    Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4 + and CD8 + T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.

  3. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    International Nuclear Information System (INIS)

    Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

    2009-01-01

    Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

  4. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  5. Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor.

    Directory of Open Access Journals (Sweden)

    Ester Rozenblum

    Full Text Available A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY, and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs/mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found. A large number of focal copy number alterations (FCNAs were detected, including homozygous deletions (HDs targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements. Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis.

  6. Application of lectins to tumor imaging radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kojima, Shuji; Jay, M.

    1986-01-01

    We investigated the in vitro binding of 125 I-lectins to Ehrlich ascites tumor (EAT) cells and in vivo uptake of 125 I-lectins in Ehrlich solid tumor (EST) bearing mice. In in vitro binding assays, phaseolus vulgaris agglutinin (PHA), pisum sativum agglutinin (PSA), and concanavalia agglutinin (Con A) showed a high affinity for EAT cells. The in vivo biodistribution of 125 I-lectins showed 125 I-PSA to be significantly taken up into EST tissues 24 h postinjection. After IV injection of 125 I-PSA, uptake of the radioactivity into the tumor tissues reached a maximum at 6 h, and thereafter decreased. Rapid disappearance of the radioactivity from blood and its excretion into kidney soon after injection of 125 I-PSA were observed. When compared with the biodistribution of 67 Ga-citrate in EST bearing mice 24 h postinjection, tumor to liver (T/B), tumor to muscle (T/M), and tumor to blood (T/B) ratios were superior for 125 I-PSA. At 6 h postinjection, the T/B-ratio of 125 I-PSA was 2.5, and this value may be sufficient to enable discernable diagnostic images. Our results suggest that PSA might be a useful tumor imaging radiopharmaceutical. (orig.)

  7. Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

    International Nuclear Information System (INIS)

    Kim, Jong-Hyuk; Yu, Chi-Ho; Yhee, Ji-Young; Im, Keum-Soon; Kim, Na-Hyun; Sur, Jung-Hyang

    2010-01-01

    Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses. The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although

  8. Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

    Directory of Open Access Journals (Sweden)

    Kim Jong-Hyuk

    2010-05-01

    Full Text Available Abstract Background Human seminoma is classified as classical seminoma (SE and spermatocytic seminoma (SS. Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Methods Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns were classified as SE or SS by immunohistochemistry (IHC using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS program was used for various statistical analyses. Results The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8% and PLAP-/PAS- SSs were 15/23 (61.2%. All SE cases (8/8, 100% were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%, 9 diffuse (9/15, 60%, and 4 intratubular/diffuse (4/15, 26.7% types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. Conclusion In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels

  9. Clearance of the high intestinal 18F-FDG uptake associated with metformin after stopping the drug

    International Nuclear Information System (INIS)

    Oezuelker, Tamer; Oezuelker, Filiz; Oezpacaci, Tevfik; Mert, Meral

    2010-01-01

    This study was done to determine whether interruption of metformin before 18 F-FDG PET/CT imaging could prevent the increased 18 F-FDG uptake in the intestine caused by this drug. Included in the study were 41 patients with known type 2 diabetes mellitus who were referred to our department for evaluation of various neoplastic diseases. Patients underwent two 18 F-FDG PET/CT scans, the first while they were on metformin and the second after they had stopped metformin. They stopped metformin and did not take any other oral antidiabetic medication starting 3 days before the second study and their blood glucose level was regulated with insulin when necessary to keep it within the range 5.55-8.33 mmol/l. FDG uptake was graded visually according to a four-point scale and semiquantitatively by recording the maximum standardized uptake value (SUVmax) in different bowel segments. A paired-samples t-test method was used to determine whether there was a significant difference between SUVmax measurements and visual analysis scores of the metabolic activity of the bowel in the PET/CT scans before and after stopping metformin. Diffuse and intense 18 F-FDG uptake was observed in bowel segments of patients, and the activity in the colon was significantly decreased both visually and semiquantitatively in PET/CT scans performed after patients stopped metformin (p 0.05). Metformin causes an increase in 18 F-FDG uptake in the bowel and stopping metformin before PET/CT study significantly decreased this unwanted uptake, especially in the colon, facilitating the interpretation of images obtained from the abdomen and preventing the obliteration of lesions. (orig.)

  10. The correlation between running economy and maximal oxygen uptake: cross-sectional and longitudinal relationships in highly trained distance runners.

    Science.gov (United States)

    Shaw, Andrew J; Ingham, Stephen A; Atkinson, Greg; Folland, Jonathan P

    2015-01-01

    A positive relationship between running economy and maximal oxygen uptake (V̇O2max) has been postulated in trained athletes, but previous evidence is equivocal and could have been confounded by statistical artefacts. Whether this relationship is preserved in response to running training (changes in running economy and V̇O2max) has yet to be explored. This study examined the relationships of (i) running economy and V̇O2max between runners, and (ii) the changes in running economy and V̇O2max that occur within runners in response to habitual training. 168 trained distance runners (males, n = 98, V̇O2max 73.0 ± 6.3 mL∙kg-1∙min-1; females, n = 70, V̇O2max 65.2 ± 5.9 mL kg-1∙min-1) performed a discontinuous submaximal running test to determine running economy (kcal∙km-1). A continuous incremental treadmill running test to volitional exhaustion was used to determine V̇O2max 54 participants (males, n = 27; females, n = 27) also completed at least one follow up assessment. Partial correlation analysis revealed small positive relationships between running economy and V̇O2max (males r = 0.26, females r = 0.25; Peconomy and V̇O2max in response to habitual training (r = 0.35; Peconomy and V̇O2max in highly trained distance runners. With >85% of the variance in these parameters unexplained by this relationship, these findings reaffirm that running economy and V̇O2max are primarily determined independently.

  11. Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

    2003-07-01

    Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

  12. Comparative Evaluation of Using NOTA and DOTA Derivatives as Bifunctional Chelating Agents in the Preparation of 68Ga-Labeled Porphyrin: Impact on Pharmacokinetics and Tumor Uptake in a Mouse Model.

    Science.gov (United States)

    Guleria, Mohini; Das, Tapas; Amirdhanayagam, Jeyachitra; Sarma, Haladhar D; Dash, Ashutosh

    2018-02-01

    Both NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) derivatives have been used as bifunctional chelating agents (BFCAs) for the preparation of 68 Ga-labeled target-specific agents having potential for positron emission tomography (PET) imaging of cancerous lesions. In the present work, the authors have attempted a comparative pharmacokinetic evaluation between 68 Ga-labeled porphyrins prepared using NOTA and DOTA derivatives as the BFCAs. A symmetrical porphyrin derivative, 5,10,15,20-tetrakis(p-carboxymethyleneoxyphenyl)porphyrin, was synthesized and coupled with two different BFCAs viz. p-NH 2 -benzyl-NOTA and p-NH 2 -benzyl-DOTA. Both the porphyrin-BFCA conjugates were radiolabeled with 68 Ga. A comparative bioevaluation involving pharmacokinetics and tumor affinity was performed in a tumor-bearing small animal model. Gallium-68-labeled porphyrin-amido-benzyl-NOTA and porphyrin-amido-benzyl-DOTA complexes were prepared with high radiochemical purity. Both radiolabeled complexes exhibited almost similar stability in human serum and near-identical tumor affinity and pharmacokinetic behavior in animal studies. The present study demonstrates that the pharmacokinetic behavior of 68 Ga-labeled porphyrin derivatives, prepared using either NOTA or DOTA derivatives as BFCAs, remains almost identical and hence both NOTA and DOTA derivatives could be considered equivalent for developing 68 Ga-based PET agents for imaging of tumorous lesions.

  13. The Spatial Relationship between Apparent Diffusion Coefficient and Standardized Uptake Value of 18F-Fluorodeoxyglucose Has a Crucial Influence on the Numeric Correlation of Both Parameters in PET/MRI of Lung Tumors.

    Science.gov (United States)

    Sauter, Alexander W; Stieltjes, Bram; Weikert, Thomas; Gatidis, Sergios; Wiese, Mark; Klarhöfer, Markus; Wild, Damian; Lardinois, Didier; Bremerich, Jens; Sommer, Gregor

    2017-01-01

    The minimum apparent diffusion coefficient (ADC min ) derived from diffusion-weighted MRI (DW-MRI) and the maximum standardized uptake value (SUV max ) of FDG-PET are markers of aggressiveness in lung cancer. The numeric correlation of the two parameters has been extensively studied, but their spatial interplay is not well understood. After FDG-PET and DW-MRI coregistration, values and location of ADC min - and SUV max -voxels were analyzed. The upper limit of the 95% confidence interval for registration accuracy of sequential PET/MRI was 12 mm, and the mean distance ( D ) between ADC min - and SUV max -voxels was 14.0 mm (average of two readers). Spatial mismatch ( D > 12 mm) between ADC min and SUV max was found in 9/25 patients. A considerable number of mismatch cases (65%) was also seen in a control group that underwent simultaneous PET/MRI. In the entire patient cohort, no statistically significant correlation between SUV max and ADC min was seen, while a moderate negative linear relationship ( r = -0.5) between SUV max and ADC min was observed in tumors with a spatial match ( D ≤ 12 mm). In conclusion, spatial mismatch between ADC min and SUV max is found in a considerable percentage of patients. The spatial connection of the two parameters SUV max and ADC min has a crucial influence on their numeric correlation.

  14. Experience of slowly infused high-iodine-dose contrast computed tomography (SHD) of intracranial tumors

    International Nuclear Information System (INIS)

    Muraoka, Kiyoaki; Numata, Hideharu; Hokama, Yasuo

    1983-01-01

    A study was done on 20 patients with intracranial tumors by means of the slowly infused high-iodine-dose (SHD) contrast-enhancement technique. An intravenous drip infusion of 300 ml of Angiografin was given for three hours. Computerized tomograms were taken 1 hour, (2 hours), and 3 hours after the beginning of the drip infusion. The authors divided the lesions into four groups by analyzing the sequential changes in CT numbers using a histograms or profile of the region of interest. In group I, additional lesions were visible on the SHD scan (one case of metastatic brain tumors from lung cancer). In group 2, lesions were better displayed on the SHD scan due to increased enhancement (17 cases). In group 3, SHD scans showed no change (2 cases of fibrous astrocytoma). In group 4, the enhancement was diminished, but the lesion per se was still clealy identifiable (no case). Finally, in 18 cases out of 20 (90%), an additional or better display of the lesion was detected on SHD enhanced CT. The rational for doing the SHD enhancement is to detect a lesion with a minimally impaired blood-brain barrier by exposing a prolonged high blood-iodine level, and so the scanning is delayed until detectable levels of the contrast medium have accumulated within the vascular-channel pool or extravascular space of the lesion. SHD enhancement is useful: I) for revealing any additional lesion in a metastatic brain tumor; 2) for better displaying an obscure lesion on a usual scan; 3) for differentiating the quality of the lesion (for example, malignancy or cyst formation), and 4) for predicting the prognosis of the lesion. (J.P.N.)

  15. PET and endocrine tumors

    International Nuclear Information System (INIS)

    Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

    2000-01-01

    The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

  16. Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model

    International Nuclear Information System (INIS)

    Yoshimoto, Mitsuyoshi; Kinuya, Seigo; Kawashima, Atsuhiro; Nishii, Ryuichi; Yokoyama, Kunihiko; Kawai, Keiichi

    2006-01-01

    Introduction: Angiogenesis is essential for tumor growth or metastasis. A method involving noninvasive detection of angiogenic activity in vivo would provide diagnostic information regarding antiangiogenic therapy targeting vascular endothelial cells as well as important insight into the role of vascular endothelial growth factor (VEGF) and its receptor (flt-1 and KDR) system in tumor biology. We evaluated radioiodinated VEGF 121 , which displays high binding affinity for KDR, and VEGF 165 , which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model. Methods: VEGF 121 and VEGF 165 were labeled with 125 I by the chloramine-T method. Biodistribution was observed in an LS180 human colon cancer xenograft model. Additionally, autoradiographic imaging and immunohistochemical staining of tumors were performed with 125 I-VEGF 121 . Results: 125 I-VEGF 121 and 125 I-VEGF 165 exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. 125 I-VEGF 121 uptake in tumors was twofold higher than that of 125 I-VEGF 165 (9.12±98 and 4.79±1.08 %ID/g at 2 h, respectively). 125 I-VEGF 121 displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with 125 I-VEGF 165 . 125 I-VEGF 121 accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in 125 I-VEGF 121 tumor accumulation correlated with degree of tumor vascularity. Conclusion: Radioiodinated VEGF 121 is a promising tracer for noninvasive delineation of angiogenesis in vivo

  17. Barriers to uptake among high-risk individuals declining participation in lung cancer screening: a mixed methods analysis of the UK Lung Cancer Screening (UKLS) trial.

    Science.gov (United States)

    Ali, Noor; Lifford, Kate J; Carter, Ben; McRonald, Fiona; Yadegarfar, Ghasem; Baldwin, David R; Weller, David; Hansell, David M; Duffy, Stephen W; Field, John K; Brain, Kate

    2015-07-14

    The current study aimed to identify the barriers to participation among high-risk individuals in the UK Lung Cancer Screening (UKLS) pilot trial. The UKLS pilot trial is a randomised controlled trial of low-dose CT (LDCT) screening that has recruited high-risk people using a population approach in the Cambridge and Liverpool areas. High-risk individuals aged 50-75 years were invited to participate in UKLS. Individuals were excluded if a LDCT scan was performed within the last year, if they were unable to provide consent, or if LDCT screening was unable to be carried out due to coexisting comorbidities. Statistical associations between individual characteristics and UKLS uptake were examined using multivariable regression modelling. In those who completed a non-participation questionnaire (NPQ), thematic analysis of free-text data was undertaken to identify reasons for not taking part, with subsequent exploratory linkage of key themes to risk factors for non-uptake. Comparative data were available from 4061 high-risk individuals who consented to participate in the trial and 2756 who declined participation. Of those declining participation, 748 (27.1%) completed a NPQ. Factors associated with non-uptake included: female gender (OR=0.64, pemotional barriers. Smokers were more likely to report emotional barriers to participation. A profile of risk factors for non-participation in lung screening has emerged, with underlying reasons largely relating to practical and emotional barriers. Strategies for engaging high-risk, hard-to-reach groups are critical for the equitable uptake of a potential future lung cancer screening programme. The UKLS trial was registered with the International Standard Randomised Controlled Trial Register under the reference 78513845. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Use of a combination of CEA and tumor budding to identify high-risk patients with stage II colon cancer.

    Science.gov (United States)

    Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin

    2017-07-24

    High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

  19. Genetic profiles of cervical tumors by high-throughput sequencing for personalized medical care

    International Nuclear Information System (INIS)

    Muller, Etienne; Brault, Baptiste; Holmes, Allyson; Legros, Angelina; Jeannot, Emmanuelle; Campitelli, Maura; Rousselin, Antoine; Goardon, Nicolas; Frébourg, Thierry; Krieger, Sophie; Crouet, Hubert; Nicolas, Alain; Sastre, Xavier; Vaur, Dominique; Castéra, Laurent

    2015-01-01

    Cancer treatment is facing major evolution since the advent of targeted therapies. Building genetic profiles could predict sensitivity or resistance to these therapies and highlight disease-specific abnormalities, supporting personalized patient care. In the context of biomedical research and clinical diagnosis, our laboratory has developed an oncogenic panel comprised of 226 genes and a dedicated bioinformatic pipeline to explore somatic mutations in cervical carcinomas, using high-throughput sequencing. Twenty-nine tumors were sequenced for exons within 226 genes. The automated pipeline used includes a database and a filtration system dedicated to identifying mutations of interest and excluding false positive and germline mutations. One-hundred and seventy-six total mutational events were found among the 29 tumors. Our cervical tumor mutational landscape shows that most mutations are found in PIK3CA (E545K, E542K) and KRAS (G12D, G13D) and others in FBXW7 (R465C, R505G, R479Q). Mutations have also been found in ALK (V1149L, A1266T) and EGFR (T259M). These results showed that 48% of patients display at least one deleterious mutation in genes that have been already targeted by the Food and Drug Administration approved therapies. Considering deleterious mutations, 59% of patients could be eligible for clinical trials. Sequencing hundreds of genes in a clinical context has become feasible, in terms of time and cost. In the near future, such an analysis could be a part of a battery of examinations along the diagnosis and treatment of cancer, helping to detect sensitivity or resistance to targeted therapies and allow advancements towards personalized oncology

  20. Perioperative high dose rate (HDR brachytherapy in unresectable locally advanced pancreatic tumors

    Directory of Open Access Journals (Sweden)

    Brygida Białas

    2011-07-01

    Full Text Available Purpose: The aim of the study was to present an original technique of catheter implantation for perioperative HDR-Ir192 brachytherapy in patients after palliative operations of unresectable locally advanced pancreatic tumors and to estimate the influence of perioperative HDR-Ir192 brachytherapy on pain relief in terminal pancreatic cancer patients. Material and methods: Eight patients with pancreatic tumors located in the head of pancreas underwent palliative operations with the use of HDR-Ir192 brachytherapy. All patients qualified for surgery reported pain of high intensity and had received narcotic painkillers prior to operation. During the last phase of the surgery, the Nucletron® catheters were implanted in patients to prepare them for later perioperative brachytherapy. Since the 6th day after surgery HDR brachytherapy was performed. Before each brachytherapy fraction the location of implants were checked using fluoroscopy. A fractional dose was 5 Gy and a total dose was 20 Gy in the area of radiation. A comparative study of two groups of patients (with and without brachytherapy with stage III pancreatic cancer according to the TNM scale was taken in consideration. Results and Conclusions: The authors claim that the modification of catheter implantation using specially designed cannula, facilitates the process of inserting the catheter into the tumor, shortens the time needed for the procedure, and reduces the risk of complications. Mean survival time was 5.7 months. In the group of performed brachytherapy, the mean survival time was 6.7 months, while in the group of no brachytherapy performed – 4.4 months. In the group of brachytherapy, only one patient increased the dose of painkillers in the last month of his life. Remaining patients took constant doses of medicines. Perioperative HDR-Ir192 brachytherapy could be considered as a practical application of adjuvant therapy for pain relief in patients with an advanced pancreatic cancer.

  1. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of {sup 111}In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    Energy Technology Data Exchange (ETDEWEB)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Reilly, Raymond M. [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network Toronto, Toronto, ON, M5S 3M2 (Canada)], E-mail: raymond.reilly@utoronto.ca

    2008-08-15

    Introduction: Our objective was to define the relationships between tumor uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10{sup 4}, 1.4x10{sup 4}, 4.0x10{sup 4} and 1.0x10{sup 5} IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 {mu}g) or IGFBP-3 (2 or 25 {mu}g) was studied. The relationship between tumor uptake of [{sup 111}In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [{sup 111}In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 {mu}g/ml) in the absence/presence of IGFBP-3 (1 {mu}g/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 {mu}g/ml), was determined. Results: [{sup 111}In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9{+-}0.1 vs. 1.0{+-}0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [{sup 111}In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r{sup 2}=0.99) between the tumor uptake of {sup 111}In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4{+-}0.05 %ID/g for H2N to 2.5{+-}0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC

  2. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of 111In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    International Nuclear Information System (INIS)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle; Reilly, Raymond M.

    2008-01-01

    Introduction: Our objective was to define the relationships between tumor uptake of [ 111 In]-IGF-1 and [ 111 In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [ 111 In]-IGF-1 and [ 111 In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10 4 , 1.4x10 4 , 4.0x10 4 and 1.0x10 5 IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 μg) or IGFBP-3 (2 or 25 μg) was studied. The relationship between tumor uptake of [ 111 In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [ 111 In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 μg/ml) in the absence/presence of IGFBP-3 (1 μg/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 μg/ml), was determined. Results: [ 111 In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9±0.1 vs. 1.0±0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [ 111 In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r 2 =0.99) between the tumor uptake of 111 In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4±0.05 %ID/g for H2N to 2.5±0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC cells to trastuzumab was directly associated with IGF-1R expression, despite co

  3. Characterization of an AtCCX5 gene from Arabidopsis thaliana that involves in high-affinity K+ uptake and Na+ transport in yeast

    International Nuclear Information System (INIS)

    Zhang, Xinxin; Zhang, Min; Takano, Tetsuo; Liu, Shenkui

    2011-01-01

    Highlights: → The AtCCX5 protein coding a putative cation calcium exchanger was characterized. → AtCCX5 expressed in yeast was localized in the plasma membrane and nuclear periphery. → AtCCX5 protein did not show the same transport properties as the CAXs. → AtCCX5 protein involves in mediating high-affinity K + uptake in yeast. → AtCCX5 protein also involves in Na + transport in yeast. -- Abstract: The gene for a putative cation calcium exchanger (CCX) from Arabidopsis thaliana, AtCCX5, was cloned and its function was analyzed in yeast. Green fluorescent protein-tagged AtCCX5 expressed in yeast was localized in the plasma membrane and nuclear periphery. The yeast transformants expressing AtCCX5 were created and their growth in the presence of various cations (K + , Na + , Ca 2+ , Mg 2+ , Fe 2+ , Cu 2+ , Co 2+ , Cd 2+ , Mn 2+ , Ba 2+ , Ni 2+ , Zn 2+ , and Li + ) were analyzed. AtCCX5 expression was found to affect the response to K + and Na + in yeast. The AtCCX5 transformant also showed a little better growth to Zn 2+ . The yeast mutant 9.3 expressing AtCCX5 restored growth of the mutant on medium with low K + (0.5 mM), and also suppressed its Na + sensitivity. Ion uptake experiments showed that AtCCX5 mediated relatively high-affinity K + uptake and was also involved in Na + transport in yeast. Taken together, these findings suggest that the AtCCX5 is a novel transport protein involves in mediating high-affinity K + uptake and Na + transport in yeast.

  4. A high 18F-FDOPA uptake is associated with a slow growth rate in diffuse Grade II-III gliomas.

    Science.gov (United States)

    Isal, Sibel; Gauchotte, Guillaume; Rech, Fabien; Blonski, Marie; Planel, Sophie; Chawki, Mohammad B; Karcher, Gilles; Marie, Pierre-Yves; Taillandier, Luc; Verger, Antoine

    2018-04-01

    In diffuse Grade II-III gliomas, a high 3,4-dihydroxy-6-( 18 F)-fluoro-L-phenylalanine ( 18 F-FDOPA) positron emission tomography (PET) uptake, with a standardized uptake value (SUV max )/contralateral brain tissue ratio greater than 1.8, was previously found to be consistently associated with the presence of an isocitrate dehydrogenase (IDH) mutation, whereas this mutation is typically associated with a better prognosis. This pilot study was aimed to ascertain the prognostic value of this high 18 F-FDOPA uptake in diffuse Grade II-III gliomas with regard to the velocity of diameter expansion (VDE), which represents an established landmark of better prognosis when below 4 mm per year. 20 patients (42 ± 10 years, 10 female) with newly-diagnosed diffuse Grade II-III gliomas (17 with IDH mutation) were retrospectively included. All had a 18 F-FDOPA PET, quantified with SUV max ratio, along with a serial MRI enabling VDE determination. SUV max ratio was above 1.8 in 5 patients (25%) all of whom had a VDE VDE <4 mm/year in the overall population (45 vs 0%, p = 0.04) and also in the subgroup of patients with IDH mutation (45 vs 0%, p = 0.10). This pilot study shows that in diffuse Grade II-III gliomas, a high 18 F-FDOPA uptake would be predictive of low tumour growth, with a different prognostic significance than IDH mutation. Advances in knowledge: 18 F-FDOPA PET in a single session imaging could have prognostic value in initial diagnosis of diffuse Grade II-III gliomas.

  5. Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors.

    Science.gov (United States)

    Colby, Aaron H; Berry, Samantha M; Moran, Ann M; Pasion, Kristine Amber; Liu, Rong; Colson, Yolonda L; Ruiz-Opazo, Nelson; Grinstaff, Mark W; Herrera, Victoria L M

    2017-02-28

    A current challenge in the treatment of peritoneal carcinomatosis is the inability to detect, visualize, and resect small or microscopic tumors of pancreatic, ovarian, or mesothelial origin. In these diseases, the completeness of primary tumor resection is directly correlated with patient survival, and hence, identifying small sub-millimeter tumors (i.e., disseminated disease) is critical. Thus, new imaging techniques and probes are needed to improve cytoreductive surgery and patient outcomes. Highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) are described for use as a visual aid during cytoreductive surgery of pancreatic carcinomatosis. The covalent incorporation of rhodamine into ∼30 nm eNPs increases the fluorescent signal compared to free rhodamine, thereby affording a brighter and more effective probe than would be achieved by a single rhodamine molecule. Using the intraperitoneal route of administration, HFR-eNPs localize to regions of large (∼1 cm), sub-centimeter, and sub-millimeter intraperitoneal tumor in three different animal models, including pancreatic, mesothelioma, and ovarian carcinoma. Tumoral localization of the HFR-eNPs depends on both the material property (i.e., eNP polymer) as well as the surface chemistry (anionic surfactant vs PEGylated noncharged surfactant). In a rat model of pancreatic carcinomatosis, HFR-eNP identification of tumor is validated against gold-standard histopathological analysis to reveal that HFR-eNPs possess high specificity (99%) and sensitivity (92%) for tumors, in particular, sub-centimeter and microscopic sub-millimeter tumors, with an overall accuracy of 95%. Finally, as a proof-of-concept, HFR-eNPs are used to guide the resection of pancreatic tumors in a rat model of peritoneal carcinomatosis.

  6. Ferric reductase genes involved in high-affinity iron uptake are differentially regulated in yeast and hyphae of Candida albicans.

    Science.gov (United States)

    Jeeves, Rose E; Mason, Robert P; Woodacre, Alexandra; Cashmore, Annette M

    2011-09-01

    The pathogenic yeast Candida albicans possesses a reductive iron uptake system which is active in iron-restricted conditions. The sequestration of iron by this mechanism initially requires the reduction of free iron to the soluble ferrous form, which is catalysed by ferric reductase proteins. Reduced iron is then taken up into the cell by a complex of a multicopper oxidase protein and an iron transport protein. Multicopper oxidase proteins require copper to function and so reductive iron and copper uptake are inextricably linked. It has previously been established that Fre10 is the major cell surface ferric reductase in C. albicans and that transcription of FRE10 is regulated in response to iron levels. We demonstrate here that Fre10 is also a cupric reductase and that Fre7 also makes a significant contribution to cell surface ferric and cupric reductase activity. It is also shown, for the first time, that transcription of FRE10 and FRE7 is lower in hyphae compared to yeast and that this leads to a corresponding decrease in cell surface ferric, but not cupric, reductase activity. This demonstrates that the regulation of two virulence determinants, the reductive iron uptake system and the morphological form of C. albicans, are linked. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Malignant phyllodes tumor of the breast with heterologous high-grade angiosarcoma

    Directory of Open Access Journals (Sweden)

    Ghassan Tranesh

    2017-03-01

    Full Text Available Phyllodes tumors (PTs account for <3% of fibroepithelial breast lesions and for 0.3% to 1.0% of primary breast tumors. They occur predominantly in middle-aged women (mean age range, 40–50 years. PTs can be categorized into benign, borderline, and malignant; the first 2 categories are distinguished only by degree of cellular atypia and mitotic activity. Malignant PTs are more frequent among persons of Hispanic ethnicity, especially those born in Central America or South America. Heterologous sarcomatous elements may be present in malignant PTs, predominantly liposarcoma and rarely fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, osteosarcoma, and chondrosarcoma. Breast angiosarcoma (BA is a rare heterologous, sarcomatous element that may arise secondary to malignant PT. We report a 47-year-old woman with no history of previous surgery or radiation therapy who presented to the emergency department with a painful right breast mass. She admittedly noticed the right breast mass for many years; however, recently it increased in size. Mammography and ultrasonography identified a partially cystic mass. Core needle biopsy showed dense hyalinized fibrous tissue with old blood clots, suggestive of infarcted fibroadenoma. The patient received antibiotics and analgesics; however, she reported intractable pain and a worsening skin rash of her right breast. Chest computed tomography and magnetic resonance imaging showed a doubling in mass size, with pectoralis major muscle involvement. Incisional biopsy showed malignant PT with heterologous high-grade angiosarcoma. The diagnosis of angiosarcoma was confirmed through immunoreactivity for CD31, FLI1, and ERG immunostains.

  8. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chih-Chung, E-mail: cchuang@mail.ncku.edu.tw [Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan (China); Chen, Wei-Tsen [Department of Electrical Engineering, Fu Jen Catholic University, New Taipei City 24205, Taiwan (China)

    2014-01-15

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals.

  9. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    International Nuclear Information System (INIS)

    Huang, Chih-Chung; Chen, Wei-Tsen

    2014-01-01

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals

  10. Bridging from Brain to Tumor Imaging: (S-(−- and (R-(+-[18F]Fluspidine for Investigation of Sigma-1 Receptors in Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Mathias Kranz

    2018-03-01

    Full Text Available Sigma-1 receptors (Sig1R are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers (S-(−- and (R-(+-[18F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging. The Sig1R expression in the respective tumors was confirmed by Western blot. Rather low radiotracer uptake was found in heterotopically (subcutaneously implanted tumors. Therefore, a brain tumor model (U87-MG with orthotopic implantation was chosen to investigate the suitability of the two Sig1R radiotracers for brain tumor imaging. High tumor uptake as well as a favorable tumor-to-background ratio was found. These results suggest that Sig1R PET imaging of brain tumors with [18F]fluspidine could be possible. Further studies with this tumor model will be performed to confirm specific binding and the integrity of the blood-brain barrier (BBB.

  11. Clinical evaluation of high-resolution CT, 1. CT diagnosis of liver tumors and its limit

    Energy Technology Data Exchange (ETDEWEB)

    Araki, T [Tokyo Univ. (Japan). Faculty of Medicine

    1980-03-01

    To estimate diagnostic accuracy of CT in liver tumors, CT diagnosis in 120 patients with primary hepatocellular carcinoma was discussed. As a result, primary hepatocellular carcinoma less than 2 cm in diameter could not be visualized by CT. Even tumors between 4 and 8 cm in diameter showed false negative caused by isodense tumors on images of 4 patients. To improve the detectability of liver tumors by CT, the higher resolution of low contrast regions on images are required. As a method to improve qualitative diagnosis of liver tumors, rapid intravenous injection of contrast medium was performed on 42 patients with liver tumors, As a result, images reflecting vascularity of tumors were obtained, and the differential diagnosis was possible to some extent by observing the movement of the contrast. Especially, cavernous hemangioma could be distinguished from hepatocellular carcinoma, because cavernous hemangioma showed specific images and could be diagnosed accurately.

  12. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  13. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

    International Nuclear Information System (INIS)

    Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan; Krebs, Alice; Christian, Sven; Prinz, Florian; Osterland, Marc; Golfier, Sven; Räse, Sebastian; Ansari, Nariman; Esner, Milan; Bickle, Marc; Pampaloni, Francesco; Mattheyer, Christian; Stelzer, Ernst H.; Parczyk, Karsten; Prechtl, Stefan; Steigemann, Patrick

    2014-01-01

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions. - Highlights: • Establishment of a novel method for 3D cell culture based high-content screening. • First reported high

  14. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

    Energy Technology Data Exchange (ETDEWEB)

    Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan; Krebs, Alice; Christian, Sven; Prinz, Florian; Osterland, Marc; Golfier, Sven; Räse, Sebastian [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Ansari, Nariman [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Esner, Milan; Bickle, Marc [Max Planck Institute of Molecular Cell Biology and Genetics, High-Throughput Technology Development Studio (TDS), Dresden (Germany); Pampaloni, Francesco; Mattheyer, Christian; Stelzer, Ernst H. [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Parczyk, Karsten; Prechtl, Stefan [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Steigemann, Patrick, E-mail: Patrick.Steigemann@bayer.com [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany)

    2014-04-15

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions. - Highlights: • Establishment of a novel method for 3D cell culture based high-content screening. • First reported high

  15. Giant cell tumor of the rib: Two cases of F-18 FDG PET/CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hye Lim; Yoo, Le Ryung; Lee, Yeong Joo; Jung, Chan Kwon [Seoul St. Mary' s Hospital, College of MedicineThe Catholic University of Korea, Seoul (Korea, Republic of); Park, Sonya Young Ju [Molecular Imaging Program, Dept. of Radiology, Stanford Hospital and Clinics, Stanford (Korea, Republic of)

    2017-06-15

    We report two cases of giant cell tumor arising from the rib and their F-18 FDG PET/CT findings. The two patients complained of chest wall pain, and large lobulated soft tissue masses with intense FDG uptake were seen on F-18 FDG PET/CT. A malignant tumor such as osteosarcoma or chondrosarcoma was suspected due to the large size of the mass, bony destruction, and intense FDG uptake. En bloc resection was performed and final pathologic results revealed giant cell tumor of the rib. Giant cell tumor of the rib is very rare, and larger lesions with high FDG uptake can be misdiagnosed as an intrathoracic malignancy arising from the rib, pleura, or chest wall.

  16. Comparison of 18F-fluoromethylcholine and 2-deoxy-D-glucose in the distribution of tumor and inflammation

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Furumoto, Shozo; Iwata, Ren; Fukuda, Hiroshi; Kawamura, Kazunori; Ishiwata, Kiichi

    2006-01-01

    The distribution characteristics of 18 F-fluoromethylcholine ( 18 F-choline) in tumor and inflammatory tissue were compared with those of 14 C or 3 H-2-deoxyglucose (2DG) as a substitute for fluorodeoxyglucose (FDG). A solid tumor model of AH109A in the back of Donryu rats and an aseptic inflammation model of turpentine oil injection subcutaneously in rats were used for experiments. Tissue distribution was examined at 5, 30 and 60 min after injection of a mixture of 18 F-choline and 3 H-2DG. Double-tracer high-resolution autoradiographs (ARGs) of tumor and inflammation were obtained using 18 F-choline and 14 C-2DG. Whole body (WB) ARG was performed with 18 F-choline. Tumor uptake of 18 F-choline reached a peak at 30 min, when the tumor to blood ratio was 5.1. Both tumor and inflammation uptake of 2DG were higher than those of 18 F-choline. 18 F-choline uptake by inflammation was lower than that by tumor. The tumor to brain uptake ratio was 5.7 with 18 F-choline and 1.2 with 2DG. In the ARG of inflammation, linear or ring-like structures of 2DG uptake were observed in the wall of the abscess, but were not identified with 18 F-choline. Photomicrography showed that the uptake was limited to granulocytes, macrophages and fibroblasts, consistent with sub-acute or chronic inflammation. 18 F-choline uptake by inflammation was lower than that of 2DG in the tissue distribution study, and 18 F-choline uptake by abscess wall was significantly lower than that of 2DG in the autoradiography study. Our results may suggest the feasibility of 18 F-choline-PET imaging for the differential diagnosis of cancer and chronic inflammation in lung and brain. (author)

  17. Inflammatory myofibroblastic tumor of the mesentery associated with high fever and positive Widal test

    International Nuclear Information System (INIS)

    Chouairy, Camil J.; Bechara, Elie A.; Ghabril, Ramy H.; Gebran, Sleiman J.

    2008-01-01

    Inflammatory myofibroblastic tumor (IMT) is associated in 15-30% of cases with systemic symptomatology , such as prolonged fever, weight loss, elevated erythrocyte sedimentation rate (ESR) , anemia, thrombocytosis and leukocytosis. We report the case of a 4-year-old Lebanese boy who presented with high-grade fever of long duration and a single (unpaired) positive Widal agglutination test. Blood culture was negative. A diagnosis of typhoid fever was made. An abdominal (mesenteric) IMT was incidentally discovered, 30 days after the fever had appeared. After surgery, the fever disappeared immediately, and the ESR returned. We strongly favor the possibility of a false positive Widal test, due to polyclonal increase in serum immunoglobulins, which often occurs in IMT. We also think that IMT might be a mimicker of typhoid fever, both clinically and serologically. Physicians, especially pediatricians practicing in endemic areas, should probably be aware of this mimicry. (author)

  18. Inflammatory myofibroblastic tumor of the mesentery associated with high fever and positive Widal test

    Energy Technology Data Exchange (ETDEWEB)

    Chouairy, Camil J [Dept. of Pathology, Saint George Hospital, Beirut (Lebanon); Bechara, Elie A; Ghabril, Ramy H [Dept. of Pediatrics, Saint George Hospital, Beirut (Lebanon); Gebran, Sleiman J [Dept. of Pediatric Surgery, AlHada Armed Forces Hospital, Taif (Saudi Arabia)

    2008-07-01

    Inflammatory myofibroblastic tumor (IMT) is associated in 15-30% of cases with systemic symptomatology , such as prolonged fever, weight loss, elevated erythrocyte sedimentation rate (ESR) , anemia, thrombocytosis and leukocytosis. We report the case of a 4-year-old Lebanese boy who presented with high-grade fever of long duration and a single (unpaired) positive Widal agglutination test. Blood culture was negative. A diagnosis of typhoid fever was made. An abdominal (mesenteric) IMT was incidentally discovered, 30 days after the fever had appeared. After surgery, the fever disappeared immediately, and the ESR returned. We strongly favor the possibility of a false positive Widal test, due to polyclonal increase in serum immunoglobulins, which often occurs in IMT. We also think that IMT might be a mimicker of typhoid fever, both clinically and serologically. Physicians, especially pediatricians practicing in endemic areas, should probably be aware of this mimicry. (author)

  19. Extraosseous uptake of 99sup(m)technetium methylene diphosphonate

    International Nuclear Information System (INIS)

    Sty, J.R.; Kun, L.; Casper, J.; Babbitt, D.P.

    1980-01-01

    A child with a ganglioneuroblastoma and tumor uptake of 99 sup(m)technetium methylene diphosphate ( 99 sup(m)Tc-MDP) is presented. After surgical removal of an encapsulated tumor and radiation therapy, an interval bone scan demonstrated the same presurgical abnormality. Awareness of abnormal uptake of 99 sup(m)Tc-MDP in irradiated renal tissue prevents interpreting radiation nephritis as recurrent tumor. (orig.) [de

  20. High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Willis, Callen [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Banerjee, Debarshi [Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Mitchell, Jason [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Hernandez, Sonia L. [Department of Surgery, University of Chicago, Chicago, Illinois (United States); Hei, Tom [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Kadenhe-Chiweshe, Angela [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Yamashiro, Darrell J. [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (United States); Connolly, Eileen P., E-mail: epc2116@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States)

    2016-04-01

    Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

  1. Bleomycin treatment of brain tumors: an evaluation

    DEFF Research Database (Denmark)

    Linnert, Mette; Gehl, Julie

    2009-01-01

    Bleomycin has been used in the treatment of brain tumors for over 30 years. Currently, we are evaluating electrochemotherapy (the use of electric pulses to enhance uptake of bleomycin) for patients with secondary brain tumors. We, therefore, reviewed the literature with specific reference...... fever, headaches, nausea and vomiting, lethargy, and peritumoral edema. Out of 189 patients treated from 1973 to 2007, only five patients (3%) had severe and six patients (3%) had moderate adverse effects. One death was directly related to this treatment, where very high doses were used. Two patients...

  2. Gastroenteropancreatic neuroendocrine tumors (GEP-NETS)

    International Nuclear Information System (INIS)

    Vargas Martinez, Cristian Camilo; Castano Llano, Rodrigo

    2010-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) are rare neoplasms which can occur anywhere in the gastrointestinal tract. Their particular characteristics include uptake of silver salts, neuroendocrine cell marker expression and hormonal secretory granules. Depending on their size, anatomical location and upon whether or not metastasis has occurred, these tumors can show different clinical patterns and have different prognoses. Early diagnosis is essential for treating these lesions and improving the patients' prognoses, but it requires a high degree of suspicion and confirmation by special testing. Surgical treatment is the first choice, but other medical therapy can be helpful for patients who have unresectable disease. This review presents the most relevant aspects of classification, morphology, methods of locating tumors, diagnosis and treatment of GEP-NETS. It presents only the Colombian experience in the epidemiology and management of these tumors.

  3. High-dose inhaled salbutamol has no acute effects on aerobic capacity or oxygen uptake kinetics in healthy trained men

    DEFF Research Database (Denmark)

    Elers, J; Mørkeberg, Jakob; Jansen, T

    2012-01-01

    enrolled nine healthy well-trained men in a randomized, blinded, placebo-controlled crossover study. Subjects were randomized to inhalation of 40 puffs of 0.2 mg salbutamol or two placebo tablets and performed an incremental test to exhaustion and three submaximal tests at 75% of peak power to determine...... oxygen uptake kinetics. During the incremental test, there were no effects of inhaled salbutamol on VO(2max) in absolute or relative terms, and no effect on peak power and lactate threshold. During the submaximal test, we found no effects on the time constant, time delay, the mean response time or O(2...

  4. Plasma uric acid and tumor volume are highly predictive of outcome in nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy

    International Nuclear Information System (INIS)

    Lin, Hui; Lin, Huan-Xin; Ge, Nan; Wang, Hong-Zhi; Sun, Rui; Hu, Wei-Han

    2013-01-01

    The combined predictive value of plasma uric acid and primary tumor volume in nasopharyngeal carcinoma (NPC) patients receiving intensity modulated radiation therapy (IMRT) has not yet been determined. In this retrospective study, plasma uric acid level was measured after treatment in 130 histologically-proven NPC patients treated with IMRT. Tumor volume was calculated from treatment planning CT scans. Overall (OS), progression-free (PFS) and distant metastasis-free (DMFS) survival were compared using Kaplan-Meier analysis and the log rank test, and Cox multivariate and univariate regression models were created. Patients with a small tumor volume (<27 mL) had a significantly better DMFS, PFS and OS than patients with a large tumor volume. Patients with a high post-treatment plasma uric acid level (>301 μmol/L) had a better DMFS, PFS and OS than patients with a low post-treatment plasma uric acid level. Patients with a small tumor volume and high post-treatment plasma uric acid level had a favorable prognosis compared to patients with a large tumor volume and low post-treatment plasma uric acid level (7-year overall OS, 100% vs. 48.7%, P <0.001 and PFS, 100% vs. 69.5%, P <0.001). Post-treatment plasma uric acid level and pre-treatment tumor volume have predictive value for outcome in NPC patients receiving IMRT. NPC patients with a large tumor volume and low post-treatment plasma uric acid level may benefit from additional aggressive treatment after IMRT

  5. Threefold Increase in PrEP Uptake Over Time with High Adherence Among Young Men Who Have Sex With Men in Chicago.

    Science.gov (United States)

    Morgan, Ethan; Moran, Kevin; Ryan, Daniel T; Mustanski, Brian; Newcomb, Michael E

    2018-05-04

    The goal of this work is to better understand utilization and uptake of pre-exposure prophylaxis (PrEP) among young men who have sex with men (YMSM) and transgender women (TGW). We assessed trends and correlates of PrEP use and adherence across three time points of longitudinal data collection among 885 YMSM and TGW (aged 16-29) from the RADAR cohort in Chicago, 2015-2017. Past 6-month PrEP use increased across three visits: from 6.6 to 17.5%. In multivariable models, past 6-month PrEP use was significantly associated with participation in condomless sex, having more sexual partners, and older age. At least three-quarters of current PrEP users reported being ≥ 90% adherent to PrEP medication across all visits. Past 6-month PrEP use increased over time with those who participated in high-risk HIV behaviors also those most likely to have taken PrEP. As PrEP uptake continues to rise, more research will be needed to understand predictors of PrEP usage, as well as patterns of sexual behavior change following uptake.

  6. High affinity (3H) β-Alanine uptake by scar margins of ferric chloride-induced epileptogenic foci in rat isocortex

    International Nuclear Information System (INIS)

    Robitaille, Y.; Sherwin, A.

    1984-01-01

    Cortical astrocytes of normal mammalian brain are endowed with a high affinity uptake system for β-Alanine which is competitively inhibited by gamma aminobutyric acid (GABA), a neurotransmitter strongly implicated in epileptogenesis. The authors evaluated ( 3 H) β-Alanine uptake by reactive astrocytes proliferating within scar of epileptogenic foci induced in rat motor cortex by microinjections of 100 mM ferric chloride. Following in vitro incubation of scar tissue with ( 3 H) β-Alanine, ultrastructural morphometry of grain patterns at 5, 30 and 120 days post injection revealed early and significant grain count increases over astroglial processes, predominantly those related to perivascular glial end-feet. Astrocytic cell body and endothelial cell counts showed a more gradual and stepwise increase. Similar data were obtained by comparing visual and edited mean astrocytic grain counts. These results suggest that the enhanced uptake of reactive astrocytes may reflect a marked decrease of inhibitory GABAergic neurons within ferric chloride-induced scars. 7 figures, 1 table

  7. Evaluating the extent of cell death in 3D high frequency ultrasound by registration with whole-mount tumor histopathology

    International Nuclear Information System (INIS)

    Vlad, Roxana M.; Kolios, Michael C.; Moseley, Joanne L.; Czarnota, Gregory J.; Brock, Kristy K.

    2010-01-01

    Purpose: High frequency ultrasound imaging, 10-30 MHz, has the capability to assess tumor response to radiotherapy in mouse tumors as early as 24 h after treatment administration. The advantage of this technique is that the image contrast is generated by changes in the physical properties of dying cells. Therefore, a subject can be imaged before and multiple times during the treatment without the requirement of injecting specialized contrast agents. This study is motivated by a need to provide metrics of comparison between the volume and localization of cell death, assessed from histology, with the volume and localization of cell death surrogate, assessed as regions with increased echogeneity from ultrasound images. Methods: The mice were exposed to radiation doses of 2, 4, and 8 Gy. Ultrasound images were collected from each tumor before and 24 h after exposure to radiation using a broadband 25 MHz center frequency transducer. After radiotherapy, tumors exhibited hyperechoic regions in ultrasound images that corresponded to areas of cell death in histology. The ultrasound and histological images were rigidly registered. The tumors and regions of cell death were manually outlined on histological images. Similarly, the tumors and hyperechoic regions were outlined on the ultrasound images. Each set of contours was converted to a volumetric mesh in order to compare the volumes and the localization of cell death in histological and ultrasound images. Results: A shrinkage factor of 17±2% was calculated from the difference in the tumor volumes evaluated from histological and ultrasound images. This was used to correct the tumor and cell death volumes assessed from histology. After this correction, the average absolute difference between the volume of cell death assessed from ultrasound and histological images was 11±14% and the volume overlap was 70±12%. Conclusions: The method provided metrics of comparison between the volume of cell death assessed from histology and

  8. The high affinity K+ transporter AtHAK5 plays a physiological role in planta at very low K+ concentrations and provides a caesium uptake pathway in Arabidopsis.

    Science.gov (United States)

    Qi, Zhi; Hampton, Corrina R; Shin, Ryoung; Barkla, Bronwyn J; White, Philip J; Schachtman, Daniel P

    2008-01-01

    Caesium (Cs(+)) is a potentially toxic mineral element that is released into the environment and taken up by plants. Although Cs(+) is chemically similar to potassium (K(+)), and much is known about K(+) transport mechanisms, it is not clear through which K(+) transport mechanisms Cs(+) is taken up by plant roots. In this study, the role of AtHAK5 in high affinity K(+) and Cs(+) uptake was characterized. It is demonstrated that AtHAK5 is localized to the plasma membrane under conditions of K(+) deprivation, when it is expressed. Growth analysis showed that AtHAK5 plays a role during severe K(+) deprivation. Under K(+)-deficient conditions in the presence of Cs(+), Arabidopsis seedlings lacking AtHAK5 had increased inhibition of root growth and lower Cs(+) accumulation, and significantly higher leaf chlorophyll concentrations than wild type. These data indicate that, in addition to transporting K(+) in planta, AtHAK5 also transports Cs(+). Further experiments showed that AtHAK5 mediated Cs(+) uptake into yeast cells and that, although the K(+) deficiency-induced expression of AtHAK5 was inhibited by low concentrations of NH(4)(+) in planta, Cs(+) uptake by yeast was stimulated by low concentrations of NH(4)(+). Interestingly, the growth of the Arabidopsis atakt1-1 mutant was more sensitive to Cs(+) than the wild type. This may be explained, in part, by increased expression of AtHAK5 in the atakt1-1 mutant. It is concluded that AtHAK5 is a root plasma membrane uptake mechanism for K(+) and Cs(+) under conditions of low K(+) availability.

  9. Imaging of intraperitoneal tumors with technetium-99m GSA

    International Nuclear Information System (INIS)

    Yao, Zhengsheng; Zhang, Meili; Sakahara, Harumi; Saga, Tsuneo; Nakamoto, Yuji; Sato, Noriko; Zhao, Songji; Konishi, Junji; Arano, Yasushi

    1998-01-01

    99m Tc labeled galactosyl serum albumin (GSA) has been used clinically as a receptor-binding agent for the assessment of liver function. The aim of this study was to investigate the usefulness of 99m Tc-GSA in intraperitoneal (i.p.) tumor imaging. A tumor model was established by i.p. inoculating nude mice with human ovarian cancer cell SHIN-3, or colon cancer cell LS180. Radiolabels were i.p. injected into the tumor-bearing mice and the biodistribution of radioactivity was examined. After administration, 99m Tc-GSA rapidly accumulated in the tumor. The tumor uptake was 5.82-8.46% ID/g from 30 min to 6 h after the injection. Radioactivity in the blood was very low, less than 0.3% ID/g, resulting in high tumor-to-blood ratio. Tumors could be clearly seen by scintigraphic imaging. Accumulation of i.p.-injected 99m Tc labeled human serum albumin (HSA) in i.p. tumors was similar to that of 99m Tc-GSA, but radioactivity of 99m Tc-HSA in the circulation was high, resulting in a significantly lower tumor-to-blood ratio. In conclusion, 99m Tc-GSA, when i.p. injected, accumulated in i.p. tumors and cleared from circulation rapidly, which would make it useful for the imaging of i.p. tumors. (author)

  10. In vitro and in vivo evaluations of a radioiodinated thymidine phosphorylase inhibitor as a tumor diagnostic agent for angiogenic enzyme imaging

    International Nuclear Information System (INIS)

    Akizawa, Hiromichi; Zhao, Songji; Takahashi, Masayuki; Nishijima, Ken-ichi; Kuge, Yuji; Tamaki, Nagara; Seki, Koh-ichi; Ohkura, Kazue

    2010-01-01

    Introduction: The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis, tumor invasiveness and activation of antitumor agents. We evaluated radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ([ 125 I]IIMU) having high TP-inhibitory potency as the new radiotracer for SPECT targeting of TP expression in tumors. Methods: The characteristics of the radioiodinated TP inhibitor IIMU were determined by evaluating the uptake by tumor cells in vitro and by biodistribution studies in vivo. The distribution of the radiotracer and the extent of TP-specific uptake by tumors were evaluated by a counting method in tumor-bearing mice. Results: The in vitro uptake of radiolabeled IIMU by A431 cells along with high TP expressions was attributed to the binding of the radiotracer to its target enzyme, i.e., TP. In vivo distribution of the radiotracer in A431 tumor-bearing mice revealed tumor/blood and tumor/muscle activity uptake ratios of 36 and 106, respectively, at 3 h after the radiotracer injection. On using low TP-expressing tumors and TP blocking studies as controls, minor TP-specific accumulation of the radiotracer was detected in these studies. Conclusion: According to the binding of radioiodinated IIMU to the angiogenic enzyme TP, it can be concluded that radioiodinated IIMU might be suitable as a SPECT tracer for tumor imaging.

  11. Sensitive and selective tumor imaging with novel and highly activatable fluorescence probes

    International Nuclear Information System (INIS)

    Urano, Yasuteru

    2008-01-01

    Selective and sensitive tumor imaging in vivo is one of the most requested methodologies in medical sciences. Although several imaging modalities have been developed including positron emission tomography (PET) and magnetic resonance (MR) imaging for the detection of tumors, none of these modalities can activate the signals upon being accumulated or uptaken to tumor sites. Among these modalities, only optical fluorescence imaging has a marked advantage, that is, their signals can be dramatically increased upon detecting some biological features. In this short review, I will introduce some recent strategies for activatable optical fluorescence imaging of tumors, and discuss their advantages over other modalities. (author)

  12. Precipitation reactions caused by nitrogen uptake during service at high temperatures of a niobium stabilised austenitic stainless steel

    International Nuclear Information System (INIS)

    Erneman, J.; Schwind, M.; Liu, P.; Nilsson, J.-O.; Andren, H.-O.; Aagren, J.

    2004-01-01

    Precipitation phenomena in type 347 austenitic stainless steels have been investigated after long-term heat treatment and creep in air at 700 and 800 deg. C. Nitrogen uptake was observed during long-term creep testing at 800 deg. C. No such effect was observed at 700 deg. C although times up to about 70,000 h were used. The major phases precipitated after long time exposure at 800 deg. C were primary Nb(C,N), Z-phase, Cr 2 N and M 23 C 6 , while primary Nb(C,N), secondary Nb(C,N) and σ-phase were the major phases at 700 deg. C. Z-phase precipitated in both intragranular and intergranular form at 800 deg. C. Large precipitates exhibiting a core/rim structure showed a rim of Z-phase surrounding undissolved primary Nb(C,N). The microstructural evolution during creep deformation in air at 800 deg. C was modelled thermodynamically. The model satisfactorily predicts nitrogen uptake and the essential features of the evolution of the microstructure with time. The precipitation sequence could be qualitatively described, although it was not possible to model the formation of all precipitates

  13. Endocrine function following high dose proton therapy for tumors of the upper clivus

    Energy Technology Data Exchange (ETDEWEB)

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  14. Endocrine function following high dose proton therapy for tumors of the upper clivus

    International Nuclear Information System (INIS)

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.

    1988-01-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement

  15. Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

    International Nuclear Information System (INIS)

    Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

    2008-01-01

    Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

  16. High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures.

    Science.gov (United States)

    Penfornis, Patrice; Cai, David Z; Harris, Michael R; Walker, Ryan; Licini, David; Fernandes, Joseph D A; Orr, Griffin; Koganti, Tejaswi; Hicks, Chindo; Induru, Spandana; Meyer, Mark S; Khokha, Rama; Barr, Jennifer; Pochampally, Radhika R

    2014-08-01

    Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49f(hi) /CD90(lo) cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49f(hi) /CD90(lo) cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Synthesis, uptake mechanism characterization and biological evaluation of {sup 18}F labeled fluoroalkyl phenylalanine analogs as potential PET imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Wang Limin [Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 (United States); Qu Wenchao; Lieberman, Brian P.; Ploessl, Karl [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Kung, Hank F., E-mail: kunghf@gmail.co [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)

    2011-01-15

    Introduction: Amino acids based tracers represent a promising class of tumor metabolic imaging agents with successful clinical applications. Two new phenylalanine derivatives, p-(2-[{sup 18}F]fluoroethyl)-L-phenylalanine (FEP, [{sup 18}F]2) and p-(3-[{sup 18}F]fluoropropyl)-L-phenylalanine (FPP, [{sup 18}F]3) were synthesized and evaluated in comparison to clinically utilized O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine (FET, [{sup 18}F]1). Methods: FEP ([{sup 18}F]2) and FPP ([{sup 18}F]3) were successfully synthesized by a rapid and efficient two-step nucleophilic fluorination of tosylate precursors and deprotection reaction. In vitro cell uptake studies were carried out in 9L glioma cells. In vivo studies, 9L tumor xenografts were implanted in Fisher 344 rats. Results: FEP ([{sup 18}F]2) and FPP ([{sup 18}F]3) could be efficiently labeled within 90 min with good enantiomeric purity (>95%), good yield (11-37%) and high specific activity (21-69 GBq/{mu}mol). Cell uptake studies showed FEP had higher uptake than FPP as well as reference ligand FET ([{sup 18}F]1). Uptake mechanism studies suggested that FEP is a selective substrate for system L and prefers its subtype LAT1. In vivo biodistribution studies demonstrated FEP had specific accumulation in tumor cells and tumor to background ratio reached 1.45 at 60 min. Small animal positron emission tomography (PET) imaging studies showed FEP was comparable to FET for imaging rats bearing 9L tumor model. FEP had high uptake in 9L tumor compared to surrounding tissue and was quickly excreted through urinary tract. Conclusion: Biological evaluations indicate that FEP ([{sup 18}F]2) is a potential useful tracer for tumor imaging with PET.

  18. Thallium-201 scintigraphy for bone and soft tissue tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tokuumi, Yuji; Tsuchiya, Hiroyuki; Sunayama, Chiaki; Matsuda, Eizo; Asada, Naohiro; Taki, Junichi; Sumiya, Hisashi; Miyauchi, Tsutomu; Tomita, Katsuro [Kanazawa Univ. (Japan). School of Medicine

    1995-05-01

    This study was undertaken to assess the usefulness of thallium-201 scintigraphy in bone and soft tissue tumors. Pre-therapy scintigraphy was undertaken in a total of 136 patients with histologically confirmed diagnosis, consisting of 74 with malignant bone and soft tissue tumors, 39 with benign ones, 12 with diseases analogous to tumors, and 11 others. Thallium activity was graded on a scale of 0-4: 0=background activity, 1=equivocal activity, 2=definitive activity, but less than myocardium, 3=definite activity equal to myocardium, and 4=activity greater than myocardium. In the group of malignant tumors, thallium-201 uptake was found in 80%, although it was low for chondrosarcoma (2/8) and malignant Schwannoma (one/3). The group of benign tumors, however, showed it in only 41%, being restricted to those with giant cell tumors, chondroblastoma, fibromatosis, and osteoid osteoma. Thallium-201 uptake was also found in all 8 patients with metastatic tumors. In 23 patients undergoing thallium imaging before and after chemotherapy, scintigraphic findings revealed a high correlation with histopathological findings. Thus, thallium-201 scintigraphy may be potentially used to distinguish malignant from benign bone and soft tissue tumors, except for a few histopathological cases, as well as to determine loco-regional metastases and response to chemotherapy. (N.K.).

  19. IMPROVED TUMOR CELL KILLING BY TRAIL REQUIRES SELECTIVE AND HIGH AFFINITY RECEPTOR ACTIVATION

    NARCIS (Netherlands)

    Szegezdi, Eva; van der Sloot, Almer M.; Alessandro, Natoni; Mahalingam, Devalingam; Cool, Robbert H.; Munoz, Ines G.; Montoya, Guillermo; Quax, Wim J.; Luis Serrano, Steven de Jong; Samali, Afshin; Wallach, D; Kovalenko, A; Feldman, M

    2011-01-01

    Apoptosis can be activated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a wide range of tumor cells, but not in non-transformed cells. TRAIL interaction with receptors DR4 or DR5 induces apoptosis, whereas DcR1, DcR2 and osteoprotegerin are decoy receptors for TRAIL. TRAIL

  20. High Prevalence of Vitamin D Deficiency in Patients with Bone Tumors.

    Science.gov (United States)

    Horas, Konstantin; Maier, Gerrit; Jakob, Franz; Maus, Uwe; Kurth, Andreas; Jakuscheit, Axel; Rudert, Maximilian; Holzapfel, Boris Michael

    2017-09-14

    The aim of this study was to evaluate the prevalence of vitamin D deficiency in patients with different types of bone tumors and to elucidate whether or not there are differences in prediagnostic vitamin D levels in patients with malignant compared to benign bone tumors. Prediagnostic serum 25(OH)D levels of 105 consecutive patients that presented with bone tumors and tumor-like lesions to two Orthopedic Level I University Centers in Germany between 2011 and 2016 were measured on admission. We found an alarming and widespread rate of vitamin D deficiency in patients with bone tumors. Specifically, 83% of all patients had low vitamin D levels with a mean 25(OH)D level of 19.82 ng/ml. Notably, patients diagnosed with malignant bone tumors had significantly lower vitamin D levels compared to patients with benign bone lesions (p = 0.0008). In conclusion, it is essential to assess vitamin D levels in patients with tumors involving bone. In addition, there might be an association between vitamin D deficiency and the onset or course of primary malignant bone tumors.

  1. Distribution and ultrastructure of neurons in opossum piriform cortex displaying immunoreactivity to GABA and GAD and high-affinity tritiated GABA uptake

    International Nuclear Information System (INIS)

    Haberly, L.B.; Hansen, D.J.; Feig, S.L.; Presto, S.

    1987-01-01

    GABAergic neurons have been identified in the piriform cortex of the opossum at light and electron microscopic levels by immunocytochemical localization of GABA and the GABA-synthesizing enzyme glutamic acid decarboxylase and by autoradiographic visualization of high-affinity 3 H-GABA uptake. Four major neuron populations have been distinguished on the basis of soma size, shape, and segregation at specific depths and locations: large horizontal cells in layer Ia of the anterior piriform cortex, small globular cells with thin dendrites concentrated in layers Ib and II of the posterior piriform cortex, and multipolar and fusiform cells concentrated in the deep part of layer III in anterior and posterior parts of the piriform cortex and the subjacent endopiriform nucleus. All four populations were well visualized with both antisera, but the large layer Ia horizontal cells displayed only very light 3 H-GABA uptake, thus suggesting a lack of local axon collaterals or lack of high-affinity GABA uptake sites. The large, ultrastructurally distinctive somata of layer Ia horizontal cells receive a very small number of symmetrical synapses; the thin, axonlike dendrites of small globular cells are exclusively postsynaptic and receive large numbers of both symmetrical and asymmetrical synapses, in contrast to somata which receive a small number of both types; and the deep multipolar and fusiform cells receive a highly variable number of symmetrical and asymmetrical synapses on somata and proximal dendrites. Labeled puncta of axon terminal dimensions were found in large numbers in the neuropil surrounding pyramidal cell somata in layer II and in the endopiriform nucleus. Moderately large numbers of labeled puncta were found in layer I at the depth of pyramidal cell apical dendrites with greater numbers in layer Ia at the depth of distal apical segments than in layer Ib

  2. Platelet Proteome and Tumor Dormancy: Can Platelets Content Serve as Predictive Biomarkers for Exit of Tumors from Dormancy?

    Energy Technology Data Exchange (ETDEWEB)

    Almog, Nava, E-mail: nava.almog@tufts.edu; Klement, Giannoula Lakka, E-mail: nava.almog@tufts.edu [Center of Cancer Systems Biology, Caritas St. Elizabeth' s Medical Center, Tufts University School of Medicine, Boston, MA (United States)

    2010-05-11

    Although tumor dormancy is highly prevalent, the underling mechanisms are still mostly unknown. It is unclear which lesions will progress and become a disseminated cancer, and which will remain dormant and asymptomatic. Yet, an improved ability to predict progression would open the possibility of timely treatment and improvement in outcomes. We have recently described the ability of platelets to selectively uptake angiogenesis regulators very early in tumor growth, and proposed their use as an early marker of malignancy. In this review we will summarize current knowledge about these processes and will discuss the possibility of using platelet content to predict presence of occult tumors.

  3. High FDG uptake areas on pre-radiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for locally advanced oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Calais, Jeremie; Lemarignier, Charles; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital, Nuclear Medicine Department, Rouen (France); University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Dubray, Bernard [University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France); Nkhali, Lamyaa; Thureau, Sebastien; Modzelewski, Romain; Gardin, Isabelle [Henri Becquerel Cancer Center and Rouen University Hospital, Nuclear Medicine Department, Rouen (France); University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France); Di Fiore, Frederic [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Rouen University Hospital, Department of Oncology, Henri Becquerel Cancer Center, IRON, Rouen (France); Michel, Pierre [Rouen University Hospital, Department of Gastroenterology, Rouen (France)

    2015-05-01

    The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[{sup 18}F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUV{sub max}) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance. The study included 98 consecutive patients with LAOC treated by chemoradiotherapy (CRT). All patients underwent FDG PET/CT at initial staging and during systematic follow-up in a single institution. FDG PET/CT acquisitions were coregistered on the initial CT scan. Various subvolumes within the initial tumour (30, 40, 50, 60, 70, 80 and 90 % SUV{sub max} thresholds) and in the subsequent local recurrence (LR, 40 and 90 % SUV{sub max} thresholds) were pasted on the initial CT scan and compared[Dice, Jaccard, overlap fraction (OF), common volume/baseline volume, common volume/recurrent volume]. Thirty-five patients had LR. The initial metabolic tumour volume was significantly higher in LR tumours than in the locally controlled tumours (mean 25.4 vs 14.2 cc; p = 0.002). The subvolumes delineated on initial PET/CT with a 30-60 % SUV{sub max} threshold were in good agreement with the recurrent volume at 40 % SUV{sub max} (OF = 0.60-0.80). The subvolumes delineated on initial PET/CT with a 30-60 % SUV{sub max} threshold were in good to excellent agreement with the core volume (90 % SUV{sub max}) of the relapse (common volume/recurrent volume and OF indices 0.61-0.89). High FDG uptake on pretreatment PET/CT identifies tumour subvolumes that are at greater risk of recurrence after CRT in

  4. Uptake and adherence of a self-directed internet-based mental health intervention with tailored e-mail reminders in senior high schools in Norway.

    Science.gov (United States)

    Lillevoll, Kjersti R; Vangberg, Hans Christian B; Griffiths, Kathleen M; Waterloo, Knut; Eisemann, Martin R

    2014-01-21

    Internet-based cognitive behavioural therapy (ICBT) is a promising approach to the prevention and reduction of depressive symptoms among adolescents. This study aimed to evaluate the feasibility and efficacy of disseminating a self-directed internet-based mental health intervention (MoodGYM) in senior high schools. It also sought to investigate possible effects of tailored and weekly e-mail reminders on initial uptake and adherence to the intervention. A baseline survey was conducted in four senior high schools in two Norwegian municipalities (n = 1337). 52.8% (707/1337) of the students consented to further participation in the trial and were randomly allocated to one of three MoodGYM intervention groups (tailored weekly e-mail reminder (n = 175), standardized weekly e-mail reminder (n = 176 ) or no e-mail reminder (n = 175)) or a waitlist control group (n = 180). We tested for effects of the intervention on depression and self-esteem using multivariate analysis of variance, effects of tailored e-mail and self-reported current need of help on initial uptake of the intervention using logistic regression and the effect of weekly e-mails on adherence using ordinal regression. There was substantial non-participation from the intervention, with only 8.5% (45/527) participants logging on to MoodGYM, and few proceeding beyond the first part of the programme. No significant effect on depression or self-esteem was found among the sample as a whole or among participants with elevated depression scores at baseline. Having a higher average grade in senior high school predicted initial uptake of the intervention, but tailored e-mail and self-reported current need of help did not. Weekly e-mail prompts did not predict adherence. The main reasons for non-use reported were lack of time/forgetting about it and doubt about the usefulness of the program. Overall, disseminating a self-directed internet-based intervention to a school population proved difficult despite steps taken to

  5. Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure inhibit prostate tumor growth in TRAMP mice

    Czech Academy of Sciences Publication Activity Database

    Mikyšková, Romana; Indrová, Marie; Štěpánek, Ivan; Kanchev, Ivan; Bieblová, Jana; Vošahlíková, Š.; Moserová, I.; Truxová, I.; Fučíková, J.; Bartunkova, J.; Spisek, R.; Sedláček, Radislav; Reiniš, Milan

    2017-01-01

    Roč. 6, č. 12 (2017), č. článku e1362528. ISSN 2162-402X R&D Projects: GA MŠk(CZ) LM2015040; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk ED2.1.00/19.0395; GA ČR GA15-24769S Institutional support: RVO:68378050 Keywords : dendritic cells * docetaxel * high hydrostatic pressure * immunotherapy * prostate cancer Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Immunology Impact factor: 7.719, year: 2016

  6. Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment.

    Science.gov (United States)

    Pan, Changqie; Liu, Yuqing; Zhou, Minyu; Wang, Wensheng; Shi, Min; Xing, Malcolm; Liao, Wangjun

    2018-01-01

    A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@ IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical ( 1 H nuclear magnetic resonance) and physical (morphology and super-magnetic) characterization, FA-DOX@IONPs were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that FA-DOX@IONPs had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles (DOX@IONPs), and caused cellular apoptosis. The FA-DOX@IONP-mediated cellular uptake and intracellular internalization were clarified by fluorescence microscopy. FA-DOX@IONPs plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer.

  7. Awake craniotomy, electrophysiologic mapping, and tumor resection with high-field intraoperative MRI.

    Science.gov (United States)

    Parney, Ian F; Goerss, Stephan J; McGee, Kiaran; Huston, John; Perkins, William J; Meyer, Frederic B

    2010-05-01

    Awake craniotomy and electrophysiologic mapping (EPM) is an established technique to facilitate the resection of near eloquent cortex. Intraoperative magnetic resonance imaging (iMRI) is increasingly used to aid in the resection of intracranial lesions. Standard draping protocols in high-field iMRI units make awake craniotomies challenging, and only two groups have previously reported combined EPM and high-field iMRI. We present an illustrative case describing a simple technique for combining awake craniotomy and EPM with high-field iMRI. A movable platter is used to transfer the patient from the operating table to a transport trolley and into the adjacent MRI and still maintaining the patient's surgical position. This system allows excess drapes to be removed, facilitating awake craniotomy. A 57-year-old right-handed man presented with new onset seizures. Magnetic resonance imaging demonstrated a large left temporal mass. The patient underwent an awake, left frontotemporal craniotomy. The EPM demonstrated a single critical area for speech in his inferior frontal gyrus. After an initial tumor debulking, the scalp flap was loosely approximated, the wound was covered with additional drapes, and the excess surrounding drapes were trimmed. An iMRI was obtained. The image-guidance system was re-registered and the patient was redraped. Additional resection was performed, allowing extensive removal of what proved to be an anaplastic astrocytoma. The patient tolerated this well without any new neurological deficits. Standard protocols for positioning and draping in high-field iMRI units make awake craniotomies problematic. This straightforward technique for combined awake EPM and iMRI may facilitate safe removal of large lesions in eloquent cortex. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17 α-methylestradiol in normal and tumor-bearing rats

    International Nuclear Information System (INIS)

    Feenstra, A.; Vaalburg, W.; Nolten, G.M.J.; Reiffers, S.; Talma, A.G.; Wiegman, T.; van der Molen, H.D.; Woldring, M.G.

    1983-01-01

    Tritiated 17α-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17α-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (K/sub d/ = 1.96 x 10 -10 M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 h after injection. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23 to 30% of the uptake in the uterus. Tritiated 17α-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that a 17 α-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical

  9. Characterization of 68Zn uptake, translocation, and accumulation into developing grains and young leaves of high Zn-density rice genotype*

    Science.gov (United States)

    Wu, Chun-yong; Feng, Ying; Shohag, Md. Jahidul Islam; Lu, Ling-li; Wei, Yan-yan; Gao, Chong; Yang, Xiao-e

    2011-01-01

    Zinc (Zn) is an essential micronutrient for humans, but Zn deficiency has become serious as equally as iron (Fe) and vitamin A deficiencies nowadays. Selection and breeding of high Zn-density crops is a suitable, cost-effective, and sustainable way to improve human health. However, the mechanism of high Zn density in rice grain is not fully understood, especially how Zn transports from soil to grains. Hydroponics experiments were carried out to compare Zn uptake and distribution in two different Zn-density rice genotypes using stable isotope technique. At seedling stage, IR68144 showed higher 68Zn uptake and transport rate to the shoot for the short-term, but no significant difference was observed in both genotypes for the long-term. Zn in xylem sap of IR68144 was consistently higher, and IR68144 exhibited higher Zn absorption ratio than IR64 at sufficient (2.0 µmol/L) or surplus (8.0 µmol/L) Zn supply level. IR64 and IR68144 showed similar patterns of 68Zn accumulation in new leaves at seedling stage and in developing grains at ripening stage, whereas 68Zn in new leaves and grains of IR68144 was consistently higher. These results suggested that a rapid root-to-shoot translocation and enhanced xylem loading capacity may be the crucial processes for high Zn density in rice grains. PMID:21528496

  10. [The development of novel tumor targeting delivery strategy].

    Science.gov (United States)

    Gao, Hui-le; Jiang, Xin-guo

    2016-02-01

    Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor

  11. Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology

    Science.gov (United States)

    Che, James; Yu, Victor; Dhar, Manjima; Renier, Corinne; Matsumoto, Melissa; Heirich, Kyra; Garon, Edward B.; Goldman, Jonathan; Rao, Jianyu; Sledge, George W.; Pegram, Mark D.; Sheth, Shruti; Jeffrey, Stefanie S.; Kulkarni, Rajan P.; Sollier, Elodie; Di Carlo, Dino

    2016-01-01

    Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells. PMID:26863573

  12. Cellular uptake of magnetite nanoparticles enhanced by NdFeB magnets in staggered arrangement

    International Nuclear Information System (INIS)

    Lu, Yi-Ching; Chang, Fan-Yu; Tu, Shu-Ju; Chen, Jyh-Ping; Ma, Yunn-Hwa

    2017-01-01

    Magnetic force may greatly enhance uptake of magnetic nanoparticles (MNPs) by cultured cells; however, the effects of non-uniformity of magnetic field/ magnetic gradient on MNP internalization in culture has not been elucidated. Cellular uptake of polyacrylic acid coated-MNP by LN229 cells was measured with cylindrical NdFeB magnets arranged in a staggered pattern. The magnetic field generated by placing a magnet underneath (H-field) elicited a homogenous distribution of MNPs on the cells in culture; whereas the field without magnet underneath (L-field) resulted in MNP distribution along the edge of the wells. Cell-associated MNP (MNP cell ) appeared to be magnetic field- and concentration-dependent. In H-field, MNP cell reached plateau within one hour of exposure to MNP with only one-min application of the magnetic force in the beginning of incubation; continuous presence of the magnet for 2 h did not further increase MNP cell , suggesting that magnetic force-induced uptake may be primarily contributed to enhanced MNP sedimentation. Although MNP distribution was much inhomogeneous in L-field, averaged MNP cell in the L-field may reach as high as 80% of that in H-field during 1–6 h incubation, suggesting high capacity of MNP internalization. In addition, no significant difference was observed in MNP cell analyzed by flow cytometry with the application of H-field of staggered plate vs. filled magnet plate. Therefore, biological variation may dominate MNP internalization even under relatively uniformed magnetic field; whereas non-uniformed magnetic field may serve as a model for tumor targeting with MNPs in vivo. - Graphical abstract: Averaged MNP uptake by glioma cells in the low and non-uniformed magnetic field reached as high as 80% of that in uniformed magnetic field, which is probably due to both heterogeneous distributions of MNPs in the non-uniformed magnetic field and high capacity of the MNP uptake by these cells. - Highlights: • Enhanced sedimentation

  13. Cellular uptake of magnetite nanoparticles enhanced by NdFeB magnets in staggered arrangement

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yi-Ching; Chang, Fan-Yu [Department of Physiology and Pharmacology & Healthy Aging Research Center, Guishan, Taoyuan City 33302, Taiwan, ROC (China); Tu, Shu-Ju [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Guishan, Taoyuan City 33302, Taiwan, ROC (China); Chen, Jyh-Ping [Department of Chemical and Materials Engineering, Chang Gung University, Guishan, Taoyuan City 33302, Taiwan, ROC (China); Ma, Yunn-Hwa, E-mail: yhma@mail.cgu.edu.tw [Department of Physiology and Pharmacology & Healthy Aging Research Center, Guishan, Taoyuan City 33302, Taiwan, ROC (China); Department of Neurology, Chang Gung Memorial Hospital, Guishan, Taoyuan City 33305, Taiwan, ROC (China)

    2017-04-01

    Magnetic force may greatly enhance uptake of magnetic nanoparticles (MNPs) by cultured cells; however, the effects of non-uniformity of magnetic field/ magnetic gradient on MNP internalization in culture has not been elucidated. Cellular uptake of polyacrylic acid coated-MNP by LN229 cells was measured with cylindrical NdFeB magnets arranged in a staggered pattern. The magnetic field generated by placing a magnet underneath (H-field) elicited a homogenous distribution of MNPs on the cells in culture; whereas the field without magnet underneath (L-field) resulted in MNP distribution along the edge of the wells. Cell-associated MNP (MNP{sub cell}) appeared to be magnetic field- and concentration-dependent. In H-field, MNP{sub cell} reached plateau within one hour of exposure to MNP with only one-min application of the magnetic force in the beginning of incubation; continuous presence of the magnet for 2 h did not further increase MNP{sub cell}, suggesting that magnetic force-induced uptake may be primarily contributed to enhanced MNP sedimentation. Although MNP distribution was much inhomogeneous in L-field, averaged MNP{sub cell} in the L-field may reach as high as 80% of that in H-field during 1–6 h incubation, suggesting high capacity of MNP internalization. In addition, no significant difference was observed in MNP{sub cell} analyzed by flow cytometry with the application of H-field of staggered plate vs. filled magnet plate. Therefore, biological variation may dominate MNP internalization even under relatively uniformed magnetic field; whereas non-uniformed magnetic field may serve as a model for tumor targeting with MNPs in vivo. - Graphical abstract: Averaged MNP uptake by glioma cells in the low and non-uniformed magnetic field reached as high as 80% of that in uniformed magnetic field, which is probably due to both heterogeneous distributions of MNPs in the non-uniformed magnetic field and high capacity of the MNP uptake by these cells. - Highlights:

  14. High Stromal Carbonic Anhydrase IX Expression Is Associated With Decreased Survival in p16-Negative Head-and-Neck Tumors

    International Nuclear Information System (INIS)

    Brockton, Nigel; Dort, Joseph; Lau, Harold; Hao, Desiree; Brar, Sony; Klimowicz, Alexander; Petrillo, Stephanie; Diaz, Roman; Doll, Corinne; Magliocco, Anthony

    2011-01-01

    Purpose: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. Methods and Materials: Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). Results: High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. Conclusions: This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.

  15. High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Xiao Y

    2015-02-01

    Full Text Available Yunbin Xiao,1,* Zuan Tao Lin,2,* Yanmei Chen,1 He Wang,1 Ya Li Deng,2 D Elizabeth Le,3 Jianguo Bin,1 Meiyu Li,1 Yulin Liao,1 Yili Liu,1 Gangbiao Jiang,2 Jianping Bin1 1State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People’s Republic of China; 3Cardiovascular Division, Oregon Health and Science University, Portland, OR, USA *These authors contributed equally to this work Abstract: Magnetic resonance imaging (MRI contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors. Keywords: superparamagnetic

  16. Conventional-Dose versus High-Dose Chemotherapy for Relapsed Germ Cell Tumors

    Directory of Open Access Journals (Sweden)

    Deaglan J. McHugh

    2018-01-01

    Full Text Available The majority of metastatic germ cell tumors (GCTs are cured with cisplatin-based chemotherapy, but 20–30% of patients will relapse after first-line chemotherapy and require additional salvage strategies. The two major salvage approaches in this scenario are high-dose chemotherapy (HDCT with autologous stem cell transplant (ASCT or conventional-dose chemotherapy (CDCT. Both CDCT and HDCT have curative potential in the management of relapsed/refractory GCT. However, due to a lack of conclusive randomized trials, it remains unknown whether sequential HDCT or CDCT represents the optimal initial salvage approach, with practice varying between tertiary institutions. This represents the most pressing question remaining for defining GCT treatment standards and optimizing outcomes. The authors review prognostic factors in the initial salvage setting as well as the major studies assessing the efficacy of CDCT, HDCT, or both, describing the strengths and weaknesses that formed the rationale behind the ongoing international phase III “TIGER” trial.

  17. Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center.

    Science.gov (United States)

    Brown, Desmond A; Himes, Benjamin T; Major, Brittny T; Mundell, Benjamin F; Kumar, Ravi; Kall, Bruce; Meyer, Fredric B; Link, Michael J; Pollock, Bruce E; Atkinson, John D; Van Gompel, Jamie J; Marsh, W Richard; Lanzino, Giuseppe; Bydon, Mohamad; Parney, Ian F

    2018-01-01

    To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates. All adult patients undergoing neurosurgical intervention for an intracranial neoplastic lesion between January 1, 2009, and December 31, 2013, were included. Cases were categorized as biopsy, extra-axial/skull base, intra-axial, or transsphenoidal. Complications were categorized as neurologic, medical, wound, mortality, or none and compared for patients managed by a chief resident vs a consultant neurosurgeon. A total of 6277 neurosurgical procedures for intracranial neoplasms were performed. After excluding radiosurgical procedures and pediatric patients, 4151 adult patients who underwent 4423 procedures were available for analysis. Complications were infrequent, with overall rates of 9.8% (435 of 4423 procedures), 1.7% (73 of 4423), and 1.4% (63 of 4423) for neurologic, medical, and wound complications, respectively. The rate of perioperative mortality was 0.3% (14 of 4423 procedures). Case performance and management by a chief resident did not negatively impact outcome. In our large-volume brain tumor practice, rates of complications were low, and management of cases by chief residents in a semiautonomous manner did not negatively impact surgical outcomes. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  18. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

    2015-07-01

    Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene

  19. Functional High-Intensity Circuit Training Improves Body Composition, Peak Oxygen Uptake, Strength, and Alters Certain Dimensions of Quality of Life in Overweight Women.

    Science.gov (United States)

    Sperlich, Billy; Wallmann-Sperlich, Birgit; Zinner, Christoph; Von Stauffenberg, Valerie; Losert, Helena; Holmberg, Hans-Christer

    2017-01-01

    The effects of circuit-like functional high-intensity training (Circuit HIIT ) alone or in combination with high-volume low-intensity exercise (Circuit combined ) on selected cardio-respiratory and metabolic parameters, body composition, functional strength and the quality of life of overweight women were compared. In this single-center, two-armed randomized, controlled study, overweight women performed 9-weeks (3 sessions·wk -1 ) of either Circuit HIIT ( n = 11), or Circuit combined ( n = 8). Peak oxygen uptake and perception of physical pain were increased to a greater extent ( p body mass, body-mass-index, waist-to-hip ratio, fat mass, and enhanced fat-free mass; decreased ratings of perceived exertion during submaximal treadmill running; improved the numbers of push-ups, burpees, one-legged squats, and 30-s skipping performed, as well as the height of counter-movement jumps; and improved physical and social functioning, role of physical limitations, vitality, role of emotional limitations, and mental health to a similar extent (all p training can be employed to improve body composition, selected variables of functional strength, and certain dimensions of quality of life in overweight women. However, Circuit HIIT improves peak oxygen uptake to a greater extent, but with more perception of pain, whereas Circuit combined results in better perception of general health.

  20. The influence of P-glycoprotein expression and its inhibitors on the distribution of doxorubicin in breast tumors

    International Nuclear Information System (INIS)

    Patel, Krupa J; Tannock, Ian F

    2009-01-01

    Anti-cancer drugs access solid tumors via blood vessels, and must penetrate tumor tissue to reach all cancer cells. Previous studies have demonstrated steep gradients of decreasing doxorubicin fluorescence with increasing distance from blood vessels, such that many tumor cells are not exposed to drug. Studies using multilayered cell cultures show that increased P-glycoprotein (PgP) is associated with better penetration of doxorubicin, while PgP inhibitors decrease drug penetration in tumor tissue. Here we evaluate the effect of PgP expression on doxorubicin distribution in vivo. Mice bearing tumor sublines with either high or low expression of PgP were treated with doxorubicin, with or without pre-treatment with the PgP inhibitors verapamil or PSC 833. The distribution of doxorubicin in relation to tumor blood vessels was quantified using immunofluorescence. Our results indicate greater uptake of doxorubicin by cells near blood vessels in wild type as compared to PgP-overexpressing tumors, and pre-treatment with verapamil or PSC 833 increased uptake in PgP-overexpressing tumors. However, there were steeper gradients of decreasing doxorubicin fluorescence in wild-type tumors compared to PgP overexpressing tumors, and treatment of PgP overexpressing tumors with PgP inhibitors led to steeper gradients and greater heterogeneity in the distribution of doxorubicin. PgP inhibitors increase uptake of doxorubicin in cells close to blood vessels, have little effect on drug uptake into cells at intermediate distances, and might have a paradoxical effect to decrease doxorubicin uptake into distal cells. This effect probably contributes to the limited success of PgP inhibitors in clinical trials

  1. MFH Mimic in Breast: A High-Grade Malignant Phyllodes Tumor

    Directory of Open Access Journals (Sweden)

    A. L. Hemalatha

    2012-01-01

    Full Text Available Malignant phyllodes tumor is usually diagnosed by the presence of benign duct-like epithelium and malignant mesenchymal tissue. In addition to the usual fibrosarcomatous features, the mesenchymal component may show areas resembling osteogenic sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, malignant mesenchymoma, and, very rarely, malignant fibrous histiocytoma. We present one such rare case of malignant phyllodes tumor with malignant fibrous histiocytoma-like stromal differentiation.

  2. A novel Tc-99m and fluorescence-labeled arginine-arginine-leucine-containing peptide as a multimodal tumor imaging agent in a murine tumor model.

    Science.gov (United States)

    Kim, Myoung Hyoun; Kim, Seul-Gi; Kim, Dae-Weung

    2018-06-15

    We developed a Tc-99m and TAMRA-labeled peptide, Tc-99m arginine-arginine-leucine (RRL) peptide (TAMRA-GHEG-ECG-RRL), to target tumor cells and evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-RRL as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-RRL was synthesized using Fmoc solid-phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC-3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-RRL complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC-3 cells incubated with TAMRA-GHEG-ECG-RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc-99m TAMRA-GHEG-ECG-RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tc-99m TAMRA-GHEG-ECG-RRL has potential as a dual-modality tumor imaging agent. Copyright © 2018 John Wiley & Sons, Ltd.

  3. Synthesis and evaluation of Tc-99m and fluorescence-labeled elastin-derived peptide, VAPG for multimodal tumor imaging in murine tumor model.

    Science.gov (United States)

    Kim, Myoung Hyoun; Kim, Chang Guhn; Kim, Seul-Gi; Kim, Dae-Weung

    2017-12-01

    We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-VAPG to target tumor cells and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-VAPG was synthesized by using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-VAPG with Tc-99m was done by using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with SW620 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry by using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-VAPG complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-VAPG determined by saturation binding was 16.8 ± 3.6 nM. Confocal microscopy images of SW620 cells incubated with TAMRA-GHEG-ECG-VAPG showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of VAPG. Specific uptake of Tc-99m TAMRA-GHEG-ECG-VAPG was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumor cells. Tc-99m TAMRA-GHEG-ECG-VAPG has potential as a dual-modality tumor imaging agent. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions

    Directory of Open Access Journals (Sweden)

    Lingling Han

    2015-01-01

    Full Text Available This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA- induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4, AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase (ACC, and uncoupling protein 3 (UCP3 were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9 and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM, P<0.05 and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min, P<0.05. The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (all P<0.05, but those in the 10−9 and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (all P<0.05. In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation.

  5. High air-sea CO 2 uptake rates in nearshore and shelf areas of Southern Greenland: Temporal and spatial variability

    DEFF Research Database (Denmark)

    Rysgaard, Søren; Mortensen, J.; Juul-Pedersen, T.

    2012-01-01

    significant correlation between average annual gross primary production and annual air-sea flux during 2005-2010, which suggests that regulation of pCO 2 in the fjord is more complex. Despite three confined periods with supersaturated pCO 2 conditions in surface waters during 2005-2010, Godthåbsfjord can......The present study is based on hourly samplings of wind speed, monthly sampling sessions of temperature, salinity, dissolved inorganic carbon, alkalinity, nutrients, primary productivity and vertical export in the outer sill region (station GF3) of a sub-arctic SW Greenland fjord (Godthåbsfjord......) through 2005-2010. Air-sea CO 2 fluxes varied at GF3 from c. -20gCm -2month -1 (uptake from the atmosphere) to 25gCm -2month -1 (release to the atmosphere) during 2005-10. The average annual air-sea CO 2 flux of -83 to -108gCm -2yr -1 was within the range of the local gross annual primary productivity...

  6. Methionine Uptake and Required Radiation Dose to Control Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Toshihiko, E-mail: tiuchi@chiba-cc.jp [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hatano, Kazuo [Division of Radiation Oncology, Tokyo Bay Advanced Imaging and Radiation Oncology Clinic, Makuhari, Chiba (Japan); Uchino, Yoshio [Division of Nuclear Medicine, Chiba Ryogo Center, Chiba (Japan); Itami, Makiko [Division of Surgical Pathology, Chiba Cancer Center, Chiba (Japan); Hasegawa, Yuzo; Kawasaki, Koichiro; Sakaida, Tsukasa [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hara, Ryusuke [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan)

    2015-09-01

    Purpose: The purpose of this study was to retrospectively assess the feasibility of radiation therapy planning for glioblastoma multiforme (GBM) based on the use of methionine (MET) positron emission tomography (PET), and the correlation among MET uptake, radiation dose, and tumor control. Methods and Materials: Twenty-two patients with GBM who underwent MET-PET prior to radiation therapy were enrolled. MET uptake in 30 regions of interest (ROIs) from 22 GBMs, biologically effective doses (BEDs) for the ROIs and their ratios (MET uptake:BED) were compared in terms of whether the ROIs were controlled for >12 months. Results: MET uptake was significantly correlated with tumor control (odds ratio [OR], 10.0; P=.005); however, there was a higher level of correlation between MET uptake:BED ratio and tumor control (OR, 40.0; P<.0001). These data indicated that the required BEDs for controlling the ROIs could be predicted in terms of MET uptake; BED could be calculated as [34.0 × MET uptake] Gy from the optimal threshold of the MET uptake:BED ratio for tumor control. Conclusions: Target delineation based on MET-PET was demonstrated to be feasible for radiation therapy treatment planning. MET-PET could not only provide precise visualization of infiltrating tumor cells but also predict the required radiation doses to control target regions.

  7. Advantage of highly immunoreactive monoclonal antibodies in radioimmunoscintigraphy for tumor detection, (1)

    International Nuclear Information System (INIS)

    Yokoyama, Kunihiko

    1988-01-01

    Immunoreactivity (IR) is the fraction of a monoclonal antibody (MoAb) preparation capable of binding to an excess of a specific antigen. One of the most important requirements for successful radioimmunoscintigraphy is to use a highly immunoreactive MoAb. To assess the effect of an antibody IR on biodistribution, a fast and simple purification method has been developed using a high performance liquid chromatography (HPLC) system equipped with a hydroxylapatite (HA) column. The column was eluted at ambient temperature with 0.12 M sodium phosphate buffer (pH 6.8). With this system, the F ab fragments from the MoAb 96.5 against the human melanoma associated p97 antigen were separated into two well-resolved peaks at retention times of 6 and 16 min. FEM-XII cells (human skin melanoma cell line) were used in a cell binding assay (CBA) to determine the maximal percent IR and the affinity constant of each HA-HPLC peak. The second peak from an 125 I-F ab 96.5 showed approximately two times greater maximal binding than did the first peak, whereas the affinity constant for the two was the same. This indicated that the F ab 96.5 preparations used in this study were a mixture of more active and less active components. Moreover, prior to the HA-HPLC experiments, these preparations were analyzed with a gel filtration HPLC showing a single molecular weight peak. This suggested that the HA-HPLC separation was not based on molecular weight differences although the separation mechanism of HA has not yet been fully understood. Thereby, it is concluded that the HA-HPLC is a powerful tool to purify MoAbs into the higher immunoreactive fraction which has a potential advantage in tumor targeting. (author)

  8. Classification of brain tumor extracts by high resolution ¹H MRS using partial least squares discriminant analysis

    Directory of Open Access Journals (Sweden)

    A.V. Faria

    2011-02-01

    Full Text Available High resolution proton nuclear magnetic resonance spectroscopy (¹H MRS can be used to detect biochemical changes in vitro caused by distinct pathologies. It can reveal distinct metabolic profiles of brain tumors although the accurate analysis and classification of different spectra remains a challenge. In this study, the pattern recognition method partial least squares discriminant analysis (PLS-DA was used to classify 11.7 T ¹H MRS spectra of brain tissue extracts from patients with brain tumors into four classes (high-grade neuroglial, low-grade neuroglial, non-neuroglial, and metastasis and a group of control brain tissue. PLS-DA revealed 9 metabolites as the most important in group differentiation: γ-aminobutyric acid, acetoacetate, alanine, creatine, glutamate/glutamine, glycine, myo-inositol, N-acetylaspartate, and choline compounds. Leave-one-out cross-validation showed that PLS-DA was efficient in group characterization. The metabolic patterns detected can be explained on the basis of previous multimodal studies of tumor metabolism and are consistent with neoplastic cell abnormalities possibly related to high turnover, resistance to apoptosis, osmotic stress and tumor tendency to use alternative energetic pathways such as glycolysis and ketogenesis.

  9. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

    Science.gov (United States)

    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  10. ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Haiyan; Kamkaew, Anyanee; Jiang, Dawei; Yang, Yunan [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); England, Christopher G.; Hernandez, Reinier; Graves, Stephen A.; Barnhart, Todd E. [University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); Majewski, Rebecca L. [University of Wisconsin-Madison, Department of Biomedical Engineering, Madison, WI (United States); Cai, Weibo [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin-Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2016-11-15

    Overexpression of CD146 in solid tumors has been linked to disease progression, invasion, and metastasis. We describe the generation of a {sup 64}Cu-labeled CD146-specific antibody and its use for quantitative immunoPET imaging of CD146 expression in six lung cancer models. The anti-CD146 antibody (YY146) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with {sup 64}Cu. CD146 expression was evaluated in six human lung cancer cell lines (A549, NCI-H358, NCI-H522, HCC4006, H23, and NCI-H460) by flow cytometry and quantitative western blot studies. The biodistribution and tumor uptake of {sup 64}Cu-NOTA-YY146 was assessed by sequential PET imaging in athymic nude mice bearing subcutaneous lung cancer xenografts. The correlation between CD146 expression and tumor uptake of {sup 64}Cu-NOTA-YY146 was evaluated by graphical software while ex vivo biodistribution and immunohistochemistry studies were performed to validate the accuracy of PET data and spatial expression of CD146. Flow cytometry and western blot studies showed similar findings with H460 and H23 cells showing high levels of expression of CD146. Small differences in CD146 expression levels were found among A549, H4006, H522, and H358 cells. Tumor uptake of {sup 64}Cu-NOTA-YY146 was highest in CD146-expressing H460 and H23 tumors, peaking at 20.1 ± 2.86 and 11.6 ± 2.34 %ID/g at 48 h after injection (n = 4). Tumor uptake was lowest in the H522 model (4.1 ± 0.98 %ID/g at 48 h after injection; n = 4), while H4006, A549 and H358 exhibited similar uptake of {sup 64}Cu-NOTA-YY146. A positive correlation was found between tumor uptake of {sup 64}Cu-NOTA-YY146 (%ID/g) and relative CD146 expression (r {sup 2} = 0.98, p < 0.01). Ex vivo biodistribution confirmed the accuracy of the PET data. The strong correlation between tumor uptake of {sup 64}Cu-NOTA-YY146 and CD146 expression demonstrates the potential use of this radiotracer for imaging tumors that elicit varying levels of CD146

  11. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models.

    Science.gov (United States)

    Zhang, Libo; Vines, Douglass C; Scollard, Deborah A; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain

    2017-01-01

    Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68 Ga-DOTA-TATE uptake and 177 Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68 Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68 Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177 Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro , NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131 I-MIBG therapy, low 123 I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68 Ga-DOTA-TATE uptake and antitumor efficacy of 177 Lu-DOTA-TATE. 68 Ga-DOTA-TATE PET is superior to 123 I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177 Lu-DOTA-TATE therapy.

  12. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

    Directory of Open Access Journals (Sweden)

    Libo Zhang

    2017-01-01

    Full Text Available Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2 expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15 compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2. Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal, tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET, a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy.

  13. High-level expression of podoplanin in benign and malignant soft tissue tumors: immunohistochemical and quantitative real-time RT-PCR analysis.

    Science.gov (United States)

    Xu, Yongjun; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tetsuo; Ariizumi, Takashi; Li, Guidong; Umezu, Hajime; Endo, Naoto

    2011-03-01

    Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells. D2-40 is a commercially available mouse monoclonal antibody which binds to an epitope on human podoplanin. D2-40 immunoreactivity is therefore highly sensitive and specific for lymphatic endothelium. Recent investigations have shown widespread applications of immunohistochemical staining with D2-40 in evaluating podoplanin expression as an immunohistochemical marker for diagnosis and prognosis in various tumors. To determine whether the podoplanin (D2-40) antibody may be useful for the diagnosis of soft tissue tumors, 125 cases, including 4 kinds of benign tumors, 15 kinds of malignant tumors and 3 kinds of tumor-like lesions were immunostained using the D2-40 antibody. Total RNA was extracted from frozen tumor tissue obtained from 41 corresponding soft tissue tumor patients and 12 kinds of soft tissue tumor cell lines. Quantitative real-time PCR reactions were performed. Immunohistochemical and quantitative real-time RT-PCR analyses demonstrated the expression of the podoplanin protein and mRNA in the majority of benign and malignant soft tissue tumors and tumor-like lesions examined, with the exception of alveolar soft part sarcoma, embryonal and alveolar rhabdomyosarcoma, extraskeletal Ewing's sarcoma/peripheral primitive neuro-ectodermal tumor and lipoma, which were completely negative for podoplanin. Since it is widely and highly expressed in nearly all kinds of soft tissue tumors, especially in spindle cell sarcoma, myxoid type soft tissue tumors and soft tissue tumors of the nervous system, podoplanin is considered to have little value in the differential diagnosis of soft tissue tumors.

  14. BPA and BSH accumulation in experimental tumors

    International Nuclear Information System (INIS)

    Patel, H.; Sedgwick, E.M.

    2000-01-01

    The accumulation of boronated compounds into tumors is a critical component to the success of BNCT. To date, great variability has been demonstrated in the tumor:blood ratio achieved in samples both from different patients and within samples taken from the same patient. The factors that probably influence the level of uptake include the vascular perfusion within the tumor, the permeability of these vessels and the viability of the tumor cells themselves. These experiments were designed to measure these various factors in different experimental tumor models and to relate these measurements to the uptake of both BPA (Boronophenylalanine) and BSH (Sodiumborocaptate). They demonstrate that within different tumors there can be wide variations in the vascular parameters. In addition, the viability of the tumor cells may also be an important determinant of tumor uptake. (author)

  15. Tumor cytotoxicity by endothelial cells. Impairment of the mitochondrial system for glutathione uptake in mouse B16 melanoma cells that survive after in vitro interaction with the hepatic sinusoidal endothelium.

    Science.gov (United States)

    Ortega, Angel L; Carretero, Julian; Obrador, Elena; Gambini, Juan; Asensi, Miguel; Rodilla, Vicente; Estrela, José M

    2003-04-18

    High GSH content associates with high metastatic activity in B16-F10 melanoma cells cultured to low density (LD B16M). GSH homeostasis was investigated in LD B16M cells that survive after adhesion to the hepatic sinusoidal endothelium (HSE). Invasive B16M (iB16M) cells were isolated using anti-Met-72 monoclonal antibodies and flow cytometry-coupled cell sorting. HSE-derived NO and H(2)O(2) caused GSH depletion and a decrease in gamma-glutamylcysteine synthetase activity in iB16M cells. Overexpression of gamma-glutamylcysteine synthetase heavy and light subunits led to a rapid recovery of cytosolic GSH, whereas mitochondrial GSH (mtGSH) further decreased during the first 18 h of culture. NO and H(2)O(2) damaged the mitochondrial system for GSH uptake (rates in iB16M were approximately 75% lower than in LD B16M cells). iB16M cells also showed a decreased activity of mitochondrial complexes II, III, and IV, less O(2) consumption, lower ATP levels, higher O(2) and H(2)O(2) production, and lower mitochondrial membrane potential. In vitro growing iB16M cells maintained high viability (>98%) and repaired HSE-induced mitochondrial damages within 48 h. However, iB16M cells with low mtGSH levels were highly susceptible to TNF-alpha-induced oxidative stress and death. Therefore depletion of mtGSH levels may represent a critical target to challenge survival of invasive cancer cells.

  16. False-positive 111In-pentetreotide Uptake in Gastritis

    International Nuclear Information System (INIS)

    Usmani, Sharjeel; Alshammari, Alshaima

    2013-01-01

    111 In-pentetreotide [ 111 In-octreoscan] is the most widely used radiolabeled somatostatin analog for evaluating neuroendocrine tumor overexpression of somatostatin receptors. False-positives studies of somatostatin receptor scintigraphy have been reported and often the cause is unexplained but assumed to be due to high number of somatostatin receptors in other pathologies. Causes of false-positives include visualization of the gallbladder, nasal mucosa and pulmonary hilar areas in respiratory infections, thyroid abnormalities, accessory spleens, recent Cerebrovascular accidents (CVA's) and activity at the site of a recent surgical incision. In infection or inflammation the cause of false-positive uptake is probably the result of tracer binding by somatostatin receptors on the inflammatory leukocytes. In this case report, we report, a 44-year-old male patient with false-positive 111 In-pentetreotide uptake due to gastritis

  17. Proton magnetic resonance spectroscopy in the distinction of high-grade cerebral gliomas from single metastatic brain tumors

    International Nuclear Information System (INIS)

    Server, Andres; Schellhorn, Till; Haakonsen, Monika; Nakstad, Per H.; Josefsen, Roger; Kulle, Bettina; Maehlen, Jan; Kumar, Theresa; Gadmar, Oeystein; Langberg, Carl W.

    2010-01-01

    Background: Brain metastases and primary high-grade gliomas, including glioblastomas multiforme (GBM) and anaplastic astrocytomas (AA), may be indistinguishable by conventional magnetic resonance (MR) imaging. Identification of these tumors may have therapeutic consequences. Purpose: To assess the value of MR spectroscopy (MRS) using short and intermediate echo time (TE) in differentiating solitary brain metastases and high-grade gliomas on the basis of differences in metabolite ratios in the intratumoral and peritumoral region. Material and Methods: We performed MR imaging and MRS in 73 patients with histologically verified intraaxial brain tumors: 53 patients with high-grade gliomas (34 GBM and 19 AA) and 20 patients with metastatic brain tumors. The metabolite ratios of Cho/Cr, Cho/NAA, and NAA/Cr at intermediate TE and the presence of lipids at short TE were assessed from spectral maps in the tumoral core, peritumoral edema, and contralateral normal-appearing white matter. The differences in the metabolite ratios between high-grade gliomas/GBM/AA and metastases were analyzed statistically. Cutoff values of Cho/Cr, Cho/NAA, and NAA/Cr ratios in the peritumoral edema, as well as Cho/Cr and NAA/Cr ratios in the tumoral core for distinguishing high-grade gliomas/GBM/AA from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Significant differences were noted in the peritumoral Cho/Cr, Cho/NAA, and NAA/ Cr ratios between high-grade gliomas/GBM/AA and metastases. ROC analysis demonstrated a cutoff value of 1.24 for peritumoral Cho/Cr ratio to provide sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 100%, 88.9%, 80.0%, and 100%, respectively, for discrimination between high-grade gliomas and metastases. By using a cutoff value of 1.11 for peritumoral Cho/NAA ratio, the sensitivity was 100%, the specificity was 91.1%, the PPV was 83.3%, and the NPV was 100%. Conclusion: The results of this

  18. Octreotide Uptake in Parathyroid Adenoma

    Directory of Open Access Journals (Sweden)

    Seyhan Karaçavuş

    2012-08-01

    Full Text Available The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive parathyroid tumors. (MIRT 2012;21:77-79

  19. Early prediction of 90Sr and 137Cs content in edible parts of crops and selection of plants with high uptake ability

    International Nuclear Information System (INIS)

    Zhao Wenhu; Xu Shiming; Hou Lanxin; Shang Zhaorong

    1995-10-01

    The uptake characteristics to 90 Sr and 137 Cs of nine kinds of crops, including spring wheat, rice, soybean, vegetables etc., were studied from seedling to maturity. The change of 90 Sr content per unit of dry weight can be classified into two types--the 90 Sr content kept in the same level during the whole growing season and kept increasing with the growing period until it came to the maximum point at the time of maturity. 90 Sr and 137 Cs in the aerial part of plants were mainly distributed in leaves, but the amounts in seeds and fruits were less. The content of 90 Sr decreased but the content of 137 Cs increased from young to old leaves. So it could be concluded that early prediction of the radioactive content of edible parts according to the content of young leaves was possible. Selection of 169 species in 18 families of plants with high uptake ability of 90 Sr and 137 Cs, which grow in Qinshan region near a nuclear power plant and in Beijing region, is also reported. (8 refs., 6 figs., 16 tabs.)

  20. The effects of high-Dk rigid contact lens center thickness, material permeability, and blinking on the oxygen uptake of the human cornea.

    Science.gov (United States)

    Gardner, Hope Patterson; Fink, Barbara A; Mitchell, Lynn G; Hill, Richard M

    2005-06-01

    The human corneal oxygen uptake responses associated with the static (nonblinking) and dynamic (blinking) wear of five rigid gas-permeable materials with high oxygen permeabilities were determined for three different center thicknesses and compared with the responses for the normal open eye and severe hypoxic stress (static wear of polymethylmethacrylate). Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode during two sessions with each