WorldWideScience

Sample records for cancer imaging agents

  1. The preparation and characterization of peptide's lung cancer imaging agent

    International Nuclear Information System (INIS)

    Liu Jianfeng; Chu Liping; Wang Yan; Wang Yueying; Liu Jinjian; Wu Hongying

    2010-01-01

    Objective: To screen in vivo lung cancer specific binding seven peptides by T7 phage display peptide library, so as to prepare peptide's lung cancer early diagnostic agent. Methods: Use phage display in vivo technology, the 7-peptide phage that binding the lung cancer specifically was obtained, then the DNA sequence was measured and the seven peptide was synthesized. After labeled by 125 I, the seven peptide was injected into mice via vein and the distribution was observed. Results: One peptide was obtained by four rounds screening, and the peptide can bind lung cancer tissue specifically. Two hours after injection get the best imaging of lung cancer, metabolism of peptide in mice is fast, the distribution in vivo is decrease six hours and almost disappear 20 hours after injection. Conclusion: The peptide can image and diagnose lung cancer better. (authors)

  2. Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents

    Science.gov (United States)

    2009-09-01

    both Gd groups for MR imaging and cytotoxic moieties can be used as a unique biocompatible platform for theranostic applications in breast cancer ...TITLE: Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents PRINCIPAL INVESTIGATOR: Dmitri Artemov, Ph.D...AUG 2009 - 4. TITLE AND SUBTITLE Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents 5a. CONTRACT

  3. Metal ion cage complexes as imaging agents for cancer cells

    International Nuclear Information System (INIS)

    Di Bartolo, N.; Smith, S.; Sargeson, A.

    2000-01-01

    Full text: Cage ligands are very attractive for use in radiolabelling antibodies. Their synthesis is based around Co(III) octahedral co-ordination chemistry and they may be easily derivatised for attachment to antibodies. They are known to form kinetically inert metal complexes. Copper-64 (t 1/2 = 12.7 h) has been identified as having potential value in diagnostic and therapeutic application. Its positron annihilation radiation is useful for PET imaging, while its beta (E max 578 keV, 37.2 %) emissions may also be suitable for therapy. In the current study, the new hexa-aza-cryptand, 1 -N-(4-amino-benzyl)-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]eicosane- 1,8-diamine, or SarAr, has been synthesised specifically for radiolabelling antibodies with 64 Cu and a kit formulation has been produced. The resulting radiolabelled immunoconjugate ( 64 Cu-SarArB-72.3) was injected into nude mice bearing LS174t colorectal carcinoma. Clearance of 64 CuSarAr-B72.3 from the liver and kidneys was typical of a whole IgG antibody. Tumour localisation was comparable to similar radiolabelled immunoconjugates (38± 5 % ID/g at 48 hours). Biodistribution studies of 123 I- and 111 In- radiolabelled B72.3 were conducted in the same animal model. MIRDOSE 3 was used to compare target to non-target dose of their analogous therapeutic counterparts ( 90 Y and 131 I respectively) with 64 Cu-SarAr-B72.3. Total body dose for 64 Cu-SarAr-B72.3 was significantly lower (0.09 rad/mCi) than analogous products ( 131 I-B72.3, 2.64 rad/mCi; 90 Y- B72.3, 2.387 rad/mCi) while still providing enough dose to small tumours to be potentially therapeutic. In order to assess therapeutic effect of 64 Cu, a biological study was conducted over a 12 month period. Nude mice bearing tumours between 3.5 - 5.5 mm in length were injected with various doses (0, 10, 20, 30, 40 MBq) of 64 Cu-SarAr-B72.3. Animals were regularly monitored for tumour size, animal mass, behavioural and physical abnormalities (e.g. movement / gait

  4. Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents.

    Science.gov (United States)

    Gao, Yong; Hernandez, Christopher; Yuan, Hai-Xia; Lilly, Jacob; Kota, Pavan; Zhou, Haoyan; Wu, Hanping; Exner, Agata A

    2017-10-01

    Ultrasound is frequently utilized in diagnosis of gynecologic malignancies such as ovarian cancer. Because epithelial ovarian cancer (EOC) is often characterized by overexpression of cancer antigen 125 (CA-125), ultrasound contrast agents able to target this molecular signature could be a promising complementary strategy. In this work, we demonstrate application of CA-125-targeted echogenic lipid and surfactant-stabilized nanobubbles imaged with standard clinical contrast harmonic ultrasound for imaging of CA-125 positive OVCAR-3 tumors in mice. Surface functionalization of the nanobubbles with a CA-125 antibody achieved rapid significantly (P CA-125 negative SKOV-3 tumors. Targeted nanobubbles also exhibited increased tumor retention and prolonged echogenicity compared to untargeted nanobubbles. Data suggest that ultrasound molecular imaging using CA-125 antibody-conjugated nanobubbles may contribute to improved diagnosis of EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Development of Lipid-Based Nanoparticles for In Vivo Targeted Delivery of Imaging Agents into Breast Cancer Cells

    Science.gov (United States)

    2009-10-01

    targeted therapy. Targeted delivery of a combined imaging and therapy agent to cancer cells is an avenue to develop a new generation of effective and...ligands for targeting HER-2/neu on breast cancer cells . In near future we will test these nanoparticles with SK-BR-3 (HER-2/neu+) and MDA-MD-468 (HER-2/neu-) breast cancer cell lines.

  6. Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer

    Science.gov (United States)

    Sundaram, Karthik M.

    Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynecologic malignant tumors. Diagnosis of epithelial ovarian cancer (EOC) presents two main challenges. The first challenge is detecting low volume (prolactin receptor (PRLR) - a cell surface tyrosine kinase receptor that is over-expressed in moderate to high levels on > 98% of epithelial ovarian cancers. Upon binding of native ligands to PRLR, the ligand:PRLR complex is internalized by cells. By conjugating gadolinium-chelates, molecules normally used as contrast agents diagnostically, to human placental lactogen (hPL), a native ligand of PRLR, we show that MRI becomes highly sensitive and specific for detecting PRLR (+) tumors in a nude mouse model of EOC. We further establish the adaptability of this approach for fluorescence-based imaging techniques using an hPL conjugated Cy5.5 dye. We conclude that molecular imaging of PRLR with hPL-conjugated imaging agents can address the current challenges that limit EOC diagnosis.

  7. Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging, and Transgene Delivery

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    2017-05-01

    Full Text Available Despite advances in technology, the formidable challenge of treating cancer, especially if advanced, still remains with no significant improvement in survival rates, even with the most common forms of cancer. Oncolytic viral therapies have shown great promise for the treatment of various cancers, with the possible advantages of stronger treatment efficacy compared to conventional therapy due to higher tumor selectivity, and less toxicity. They are able to preferentially and selectively propagate in cancer cells, consequently destroying tumor tissue mainly via cell lysis, while leaving non-cancerous tissues unharmed. Several wild-type and genetically engineered vaccinia virus (VACV strains have been tested in both preclinical and clinical trials with promising results. Greater understanding and advancements in molecular biology have enabled the generation of genetically engineered oncolytic viruses for safer and more efficacious treatment, including arming VACVs with cytokines and immunostimulatory molecules, anti-angiogenic agents, and enzyme prodrug therapy, in addition to combining VACVs with conventional external and systemic radiotherapy, chemotherapy, immunotherapy, and other virus strains. Furthermore, novel oncolytic vaccinia virus strains have been generated that express reporter genes for the tracking and imaging of viral therapy and monitoring of therapeutic response. Further study is needed to unlock VACVs’ full potential as part of the future of cancer therapy.

  8. Development of novel epidermal growth receptor-based radiopharmaceuticals: Imaging agents for breast cancer

    International Nuclear Information System (INIS)

    Van Brocklin, Henry F.

    2001-01-01

    The goal of this research was to develop epidermal growth factor receptor (EGFR) nuclear medicine breast cancer imaging agents. Our approach was to synthesize small molecule inhibitors of the EGFR tyrosine kinase (tk) suitable for labeling with single photon or positron-emitting radioisotopes and evaluate the imaging potential of these new molecules.We have synthesized and fully characterized 22 quinazoline compounds. All compounds inhibit EGFR tk phosphorylation activity in the nanomolar range. All compounds tested exhibited specificity for the EGFR tk versus the ErbB2 and ErbB4 tyrosine kinases. A radiometric binding assay using an iodine-125 labeled quinazoline was developed to determine the affinity of the quinazolines for the EGFR tk ATP binding site. The affinities ranged from 0.4-51 nM. The octanol/water partition coefficients (Log P; lipophilicity) of the new compounds ranged from 2.2-5.5. Six compounds have been labeled with fluorine-18. Biodistribution in EGFR overexpressing tumor bearing mice demonstrated tumor uptake but highlighted delivery and metabolism issues. The 2-fluoro quinazoline was not metabolized in an in vitro hepatocyte study. From this work a breadth of agent characteristics was created establishing the foundation for future research toward the optimal EGFR imaging agent

  9. Nanoparticle Contrast Agents for Enhanced Microwave Imaging and Thermal Treatment of Breast Cancer

    Science.gov (United States)

    2010-10-01

    Sahakian, J. H. Booske, and S. C. Hagness, “Toward carbon-nanotube-based theranostic agents for microwave detection and treatment of breast cancer ... theranostic agents for microwave detection and treatment of breast cancer : Enhanced dielectric and heating response of tissue-mimicking materials...NO. 8, AUGUST 2010 1831 Toward Carbon-Nanotube-Based Theranostic Agents for Microwave Detection and Treatment of Breast Cancer : Enhanced Dielectric

  10. Biodegradable polymer based theranostic agents for photoacoustic imaging and cancer therapy

    Science.gov (United States)

    Wang, Yan J.; Strohm, Eric M.; Kolios, Michael C.

    2016-03-01

    In this study, multifunctional theranostic agents for photoacoustic (PA), ultrasound (US), fluorescent imaging, and for therapeutic drug delivery were developed and tested. These agents consisted of a shell made from a biodegradable Poly(lactide-co-glycolic acid) (PLGA) polymer, loaded with perfluorohexane (PFH) liquid and gold nanoparticles (GNPs) in the core, and lipophilic carbocyanines fluorescent dye DiD and therapeutic drug Paclitaxel (PAC) in the shell. Their multifunctional capacity was investigated in an in vitro study. The PLGA/PFH/DiD-GNPs particles were synthesized by a double emulsion technique. The average PLGA particle diameter was 560 nm, with 50 nm diameter silica-coated gold nano-spheres in the shell. MCF7 human breast cancer cells were incubated with PLGA/PFH/DiDGNPs for 24 hours. Fluorescent and PA images were recorded using a fluorescent/PA microscope using a 1000 MHz transducer and a 532 nm pulsed laser. For the particle vaporization and drug delivery test, MCF7 cells were incubated with the PLGA/PFH-GNPs-PAC or PLGA/PFH-GNPs particles for 6, 12 and 24 hours. The effects of particle vaporization and drug delivery inside the cells were examined by irradiating the cells with a laser fluence of 100 mJ/cm2, and cell viability quantified using the MTT assay. The PA images of MCF7 cells containing PLGA/PFH/DiD-GNPs were spatially coincident with the fluorescent images, and confirmed particle uptake. After exposure to the PLGA/PFHGNP- PAC for 6, 12 and 24 hours, the cell survival rate was 43%, 38%, and 36% respectively compared with the control group, confirming drug delivery and release inside the cells. Upon vaporization, cell viability decreased to 20%. The particles show potential as imaging agents and drug delivery vehicles.

  11. Estrogen receptor targeted contrast agents for molecular magnetic resonance imaging of breast cancer hormonal status

    Directory of Open Access Journals (Sweden)

    Adi ePais

    2016-04-01

    Full Text Available The estrogen receptor α (ER is over expressed in most breast cancers and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer, as well as in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging effects of two novel ER- targeted contrast agents (CAs based on pyridine-tetra-acetate-Gd(III chelate conjugated to 17β-estradiol (EPTA-Gd or to tamoxifen (TPTA-Gd. The experiments were conducted in solution, in human breast cancer cells and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen like agonistic activity, enhancing cell proliferation, as well as up-regulating cMyc oncogene and down-regulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors’ ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also

  12. Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells.

    Science.gov (United States)

    Geninatti Crich, S; Cadenazzi, M; Lanzardo, S; Conti, L; Ruiu, R; Alberti, D; Cavallo, F; Cutrin, J C; Aime, S

    2015-04-21

    In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml(-1) (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.

  13. Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.

    Science.gov (United States)

    Sundaram, Karthik M; Zhang, Yilin; Mitra, Anirban K; Kouadio, Jean-Louis K; Gwin, Katja; Kossiakoff, Anthony A; Roman, Brian B; Lengyel, Ernst; Piccirilli, Joseph A

    2017-04-01

    Poor prognosis of ovarian cancer, the deadliest of the gynecologic malignancies, reflects major limitations associated with detection and diagnosis. Current methods lack high sensitivity to detect small tumors and high specificity to distinguish malignant from benign tissue, both impeding diagnosis of early and metastatic cancer stages and leading to costly and invasive surgeries. Tissue microarray analysis revealed that >98% of ovarian cancers express the prolactin receptor (PRLR), forming the basis of a new molecular imaging strategy. We fused human placental lactogen (hPL), a specific and tight binding PRLR ligand, to magnetic resonance imaging (gadolinium) and near-infrared fluorescence imaging agents. Both in tissue culture and in mouse models, these imaging bioconjugates underwent selective internalization into ovarian cancer cells via PRLR-mediated endocytosis. Compared with current clinical MRI techniques, this targeted approach yielded both enhanced signal-to-noise ratio from accumulation of signal via selective internalization and improved specificity conferred by PRLR upregulation in malignant ovarian cancer. These features endow PRLR-targeted imaging with the potential to transform ovarian cancer detection. Cancer Res; 77(7); 1684-96. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Spectroscopic Photoacoustic Molecular Imaging of Breast Cancer using a B7-H3-targeted ICG Contrast Agent.

    Science.gov (United States)

    Wilson, Katheryne E; Bachawal, Sunitha V; Abou-Elkacem, Lotfi; Jensen, Kristen; Machtaler, Steven; Tian, Lu; Willmann, Jürgen K

    2017-01-01

    Purpose: Breast cancer imaging methods lack diagnostic accuracy, in particular for patients with dense breast tissue, and improved techniques are critically needed. The purpose of this study was to evaluate antibody-indocyanine green (ICG) conjugates, which undergo dynamic absorption spectrum shifts after cellular endocytosis and degradation, and spectroscopic photoacoustic (sPA) imaging to differentiate normal breast tissue from breast cancer by imaging B7-H3, a novel breast cancer associated molecular target. Methods: Quantitative immunohistochemical staining of endothelial and epithelial B7-H3 expression was assessed in 279 human breast tissue samples, including normal (n=53), benign lesions (11 subtypes, n=129), and breast cancers (4 subtypes, n=97). After absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control-ICG (Iso-ICG) were characterized, sPA imaging in a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was performed and compared to imaging of control conditions [B7-H3-ICG in tumor negative animals (n=60), Iso-ICG (n=30), blocking B7-H3+B7-H3-ICG (n=20), and free ICG (n=20)] and validated with ex vivo histological analysis. Results: Immunostaining showed differential B7-H3 expression on both the endothelium and tumor epithelium in human breast cancer with an area under the ROC curve of 0.93 to differentiate breast cancer vs non-cancer. Combined in vitro/in vivo imaging showed that sPA allowed specific B7-H3-ICG detection down to the 13 nM concentration and differentiation from Iso-ICG. sPA molecular imaging of B7-H3-ICG showed a 3.01-fold (Pbreast cancer. Leveraging antibody-ICG contrast agents and their dynamic optical absorption spectra allows for highly specific sPA imaging of breast cancer.

  15. In Vivo 3T Magnetic Resonance Imaging Using a Biologically Specific Contrast Agent for Prostate Cancer: A Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Christopher Brian Abraham

    2017-01-01

    Full Text Available We characterized in vivo a functional superparamagnetic iron-oxide magnetic resonance contrast agent that shortens the T2 relaxation time in magnetic resonance imaging (MRI of prostate cancer xenografts. The agent was developed by conjugating Molday ION™ carboxyl-6 (MIC6, with a deimmunized mouse monoclonal antibody (muJ591 targeting prostate-specific membrane antigen (PSMA. This functional contrast agent could be used as a noninvasive method to detect prostate cancer cells that are PSMA positive and more readily differentiate them from surrounding tissues for treatment. The functional contrast agent was injected intravenously into mice and its effect was compared to both MIC6 (without conjugated antibody and phosphate-buffered saline (PBS injection controls. MR imaging was performed on a clinical 3T MRI scanner using a multiecho spin echo (MESE sequence to obtain T2 relaxation time values. Inductively coupled plasma atomic emission spectroscopy was used to confirm an increase in elemental iron in injected mice tumours relative to controls. Histological examination of H&E stained tissues showed normal morphology of the tissues collected.

  16. Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer

    Directory of Open Access Journals (Sweden)

    Emily S Day

    2010-06-01

    Full Text Available Emily S Day, Lissett R Bickford, John H Slater, Nicholas S Riggall, Rebekah A Drezek, Jennifer L WestDepartment of Bioengineering, Rice University, Houston, TX, USAAbstract: The goal of this study was to develop near-infrared (NIR resonant gold-gold sulfide nanoparticles (GGS-NPs as dual contrast and therapeutic agents for cancer management via multiphoton microscopy followed by higher intensity photoablation. We demonstrate that GGS-NPs exposed to a pulsed, NIR laser exhibit two-photon induced photoluminescence that can be utilized to visualize cancerous cells in vitro. When conjugated with anti-HER2 antibodies, these nanoparticles specifically bind SK-BR-3 breast carcinoma cells that overexpress the HER2 receptor, enabling the cells to be imaged via multiphoton microscopy with an incident laser power of 1 mW. Higher excitation power (50 mW could be employed to induce thermal damage to the cancerous cells, producing extensive membrane blebbing within seconds leading to cell death. GGS-NPs are ideal multifunctional agents for cancer management because they offer the ability to pinpoint precise treatment sites and perform subsequent thermal ablation in a single setting.Keywords: cancer, nanomedicine, multiphoton microscopy, photoluminescence, photothermal therapy, theranostics

  17. Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

    KAUST Repository

    Hajjar, Dina

    2017-06-13

    Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia\\'s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

  18. Imaging efficacy of a targeted imaging agent for fluorescence endoscopy

    Science.gov (United States)

    Healey, A. J.; Bendiksen, R.; Attramadal, T.; Bjerke, R.; Waagene, S.; Hvoslef, A. M.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. A significant unmet clinical need exists in the area of screening for earlier and more accurate diagnosis and treatment. We have identified a fluorescence imaging agent targeted to an early stage molecular marker for colorectal cancer. The agent is administered intravenously and imaged in a far red imaging channel as an adjunct to white light endoscopy. There is experimental evidence of preclinical proof of mechanism for the agent. In order to assess potential clinical efficacy, imaging was performed with a prototype fluorescence endoscope system designed to produce clinically relevant images. A clinical laparoscope system was modified for fluorescence imaging. The system was optimised for sensitivity. Images were recorded at settings matching those expected with a clinical endoscope implementation (at video frame rate operation). The animal model was comprised of a HCT-15 xenograft tumour expressing the target at concentration levels expected in early stage colorectal cancer. Tumours were grown subcutaneously. The imaging agent was administered intravenously at a dose of 50nmol/kg body weight. The animals were killed 2 hours post administration and prepared for imaging. A 3-4mm diameter, 1.6mm thick slice of viable tumour was placed over the opened colon and imaged with the laparoscope system. A receiver operator characteristic analysis was applied to imaging results. An area under the curve of 0.98 and a sensitivity of 87% [73, 96] and specificity of 100% [93, 100] were obtained.

  19. Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging.

    Science.gov (United States)

    Lee, Haerim; Lee, Eunhye; Kim, Do Kyung; Jang, Nam Kyu; Jeong, Yong Yeon; Jon, Sangyong

    2006-06-07

    We report the fabrication and characterization of antifouling polymer-coated magnetic nanoparticles as nanoprobes for magnetic resonance (MR) contrast agents. Magnetite superparamagnetic iron oxide nanoparticles (SPION) were coated with the protein- or cell-resistant polymer, poly(TMSMA-r-PEGMA), to generate stable, protein-resistant MR probes. Coated magnetic nanoparticles synthesized using two different preparation methods (in situ and stepwise, respectively) were both well dispersed in PBS buffer at a variety of pH conditions (pH 1-10). In addition, dynamic light scattering data revealed that their sizes were not altered even after 24 h of incubation in 10% serum containing cell culture medium, indicative of a lack of protein adsorption on their surfaces. When the antibiofouling polymer-coated SPION were incubated with macrophage cells, uptake was significantly lower in comparison to that of the popular contrast agent, Feridex I.V., suggesting that the polymer-coated SPION can be long-circulated in plasma by escaping from uptake by the reticular endothelial system (RES) such as macrophages. Indeed, when the coated SPION were administered to tumor xenograft mice by intravenous injection, the tumor could be detected in T2-weighted MR images within 1 h as a result of the accumulation of the nanomagnets within the tumor site. Although the poly(TMSMA-r-PEGMA)-coated SPION do not have any targeting ligands on their surface, they are potentially useful for cancer diagnosis in vivo.

  20. Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer.

    Science.gov (United States)

    Eyvazzadeh, Nazila; Shakeri-Zadeh, Ali; Fekrazad, Reza; Amini, Elahe; Ghaznavi, Habib; Kamran Kamrava, S

    2017-09-01

    Because of their great scientific and technological potentials, iron oxide nanoparticles (IONPs) have been the focus of extensive investigations in biomedicine over the past decade. Additionally, the surface plasmon resonance effect of gold nanoparticles (AuNPs) makes them a good candidate for photothermal therapy applications. The unique properties of both IONPs (magnetic) and AuNPs (surface plasmon resonance) may lead to the development of a multi-modal nanoplatform to be used as a magnetic resonance imaging (MRI) contrast agent and as a nanoheater for photothermal therapy. Herein, core-shell gold-coated IONPs (Au@IONPs) were synthesized and investigated as an MRI contrast agent and as a light-responsive agent for cancer photothermal therapy.The synthesized Au@IONPs were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. The transverse relaxivity (r 2 ) of the Au@IONPs was measured using a 3-T clinical MRI scanner. Through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of the Au@IONs was examined on a KB cell line, derived from the epidermal carcinoma of a human mouth. Moreover, the photothermal effects of Au@IONPs in the presence of a laser beam (λ = 808 nm; 6.3 W/cm 2 ; 5 min) were studied.The results show that the Au@IONPs are spherical with a hydrodynamic size of 33 nm. A transverse relaxivity of 95 mM -1  S -1 was measured for the synthesized Au@IONPs. It is evident from the MTT results that no significant cytotoxicity in KB cells occurs with Au@IONPs. Additionally, no significant cell damage induced by the laser is observed. Following the photothermal treatment using Au@IONPs, approximately 70% cell death is achieved. It is found that cell lethality depended strongly on incubation period and the Au@IONP concentration.The data highlight the potential of Au@IONPs as a dual-function MRI contrast agent and

  1. Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

    Science.gov (United States)

    Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David; Thurber, Greg M

    2018-04-26

    Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

  2. Infectious Agents and Cancer

    African Journals Online (AJOL)

    Human papilloma virus (HPV) -. I. Adult T-cell leukaemia/ lymphoma. Hepatoccllular carcinoma. Hepatocellular carcinoma. Cervical cancer, other anogenital cancers, laryngeal / cancer, oral cavity cancers. Oncorna virus - Lymphomas, leukaemia. Human herpes virus type 8 - Kaposi's sarcoma, primary effusion lymphoma.

  3. Developments Toward Diagnostic Breast Cancer Imaging Using Near-Infrared Optical Measurements and Fluorescent Contrast Agents1

    Directory of Open Access Journals (Sweden)

    Daniel J. Hawrysz

    2000-09-01

    Full Text Available The use of near-infrared (NIR light to interrogate deep tissues has enormous potential for molecular-based imaging when coupled with NIR excitable dyes. More than a decade has now passed since the initial proposals for NIR optical tomography for breast cancer screening using time-dependent measurements of light propagation in the breast. Much accomplishment in the development of optical mammography has been demonstrated, most recently in the application of time-domain, frequency-domain, and continuous-wave measurements that depend on endogenous contrast owing to angiogenesis and increased hemoglobin absorbance for contrast. Although exciting and promising, the necessity of angiogenesis-mediated absorption contrast for diagnostic optical mammography minimizes the potential for using NIR techniques to assess sentinel lymph node staging, metastatic spread, and multifocality of breast disease, among other applications. In this review, we summarize the progress made in the development of optical mammography, and focus on the emerging work underway in the use of diagnostic contrast agents for the molecular-based, diagnostic imaging of breast.

  4. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p ultrasound imaging was significantly (p ultrasound imaging in hens with OVCA were positively correlated with increased (p therapeutics. © The Author(s) 2014.

  5. In vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

    Science.gov (United States)

    2016-11-01

    algorithms have been developed to de- convolute the individual chromophore PA images. Five dyes (IRDye800CW, AlexaFluor750, Cy7-NHS- ester, Cy7...specific biomarker. Thi the PA signal spectrum of endogenous or exogenous dye components and algorithms have been developed to de-convolve the... incubated in a 4 µM solution of the TMIA in PBS, washed thrice in PBS by centrifugation and resuspension, and Fig. 5. Sensitivity of IRDye800CW using

  6. Highly biocompatible TiO2:Gd3+ nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging

    Science.gov (United States)

    Chandran, Parwathy; Sasidharan, Abhilash; Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2011-10-01

    We report the development of a novel magnetic nano-contrast agent (nano-CA) based on Gd3+ doped amorphous TiO2 of size ~25 nm, exhibiting enhanced longitudinal relaxivity (r1) and magnetic resonance (MR) contrasting together with excellent biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T clinical MR imaging system revealed that the amorphous phase of doped titania has the highest r1 relaxivity which is ~2.5 fold higher than the commercially used CA Magnevist™. The crystalline (anatase) samples formed by air annealing at 250 °C and 500 °C showed significant reduction in r1 values and MR contrast, which is attributed to the loss of proton-exchange contribution from the adsorbed water and atomic re-arrangement of Gd3+ ions in the crystalline host lattice. Nanotoxicity studies including cell viability, plasma membrane integrity, reactive oxygen stress and expression of pro-inflammatory cytokines, performed on human primary endothelial cells (HUVEC), human blood derived peripheral blood mononuclear cells (PBMC) and nasopharyngeal epidermoid carcinoma (KB) cell line showed excellent biocompatibility up to relatively higher doses of 200 μg ml-1. The potential of this nano-CA to cause hemolysis, platelet aggregation and plasma coagulation were studied using human peripheral blood samples and found no adverse effects, illustrating the possibility of the safe intravenous administration of these agents for human applications. Furthermore, the ability of these agents to specifically detect cancer cells by targeting molecular receptors on the cell membrane was demonstrated on folate receptor (FR) positive oral carcinoma (KB) cells, where the folic acid conjugated nano-CA showed receptor specific accumulation on cell membrane while leaving the normal fibroblast cells (L929) unstained. This study reveals that the Gd3+ doped amorphous TiO2 nanoparticles having enhanced magnetic resonance contrast and high biocompatibility is a promising candidate for

  7. Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-01-01

    Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  8. Interleukin 16- (IL-16- Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Animesh Barua

    2015-01-01

    Full Text Available Limited resolution of transvaginal ultrasound (TVUS scanning is a significant barrier to early detection of ovarian cancer (OVCA. Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16 by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P<0.05 and late stages (P<0.001. Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  9. Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI

    International Nuclear Information System (INIS)

    Jafari, Atefeh; Shayesteh, Saber Farjami; Salouti, Mojtaba; Heidari, Zahra; Rajabi, Ahmad Bitarafan; Boustani, Komail; Nahardani, Ali

    2015-01-01

    The targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent may facilitate their accumulation in cancer cells and enhance the sensitivity of MR imaging. In this study, SPIONs coated with dextran (DSPIONs) were conjugated with bombesin (BBN) to produce a targeting contrast agent for detection of breast cancer using MRI. X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analyses indicated the formation of dextran-coated superparamagnetic iron oxide nanoparticles with an average size of 6.0 ± 0.5 nm. Fourier transform infrared spectroscopy confirmed the conjugation of the BBN with the DSPIONs. A stability study proved the high optical stability of DSPION–BBN in human blood serum. DSPION–BBN biocompatibility was confirmed by cytotoxicity evaluation. A binding study showed the targeting ability of DSPION–BBN to bind to T47D breast cancer cells overexpressing gastrin-releasing peptide (GRP) receptors. T 2 -weighted and T 2 *-weighted color map MR images were acquired. The MRI study indicated that the DSPION–BBN possessed good diagnostic ability as a GRP-specific contrast agent, with appropriate signal reduction in T 2 *-weighted color map MR images in mice with breast tumors. (paper)

  10. Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI

    Science.gov (United States)

    Jafari, Atefeh; Salouti, Mojtaba; Farjami Shayesteh, Saber; Heidari, Zahra; Bitarafan Rajabi, Ahmad; Boustani, Komail; Nahardani, Ali

    2015-02-01

    The targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent may facilitate their accumulation in cancer cells and enhance the sensitivity of MR imaging. In this study, SPIONs coated with dextran (DSPIONs) were conjugated with bombesin (BBN) to produce a targeting contrast agent for detection of breast cancer using MRI. X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analyses indicated the formation of dextran-coated superparamagnetic iron oxide nanoparticles with an average size of 6.0 ± 0.5 nm. Fourier transform infrared spectroscopy confirmed the conjugation of the BBN with the DSPIONs. A stability study proved the high optical stability of DSPION-BBN in human blood serum. DSPION-BBN biocompatibility was confirmed by cytotoxicity evaluation. A binding study showed the targeting ability of DSPION-BBN to bind to T47D breast cancer cells overexpressing gastrin-releasing peptide (GRP) receptors. T2-weighted and T2*-weighted color map MR images were acquired. The MRI study indicated that the DSPION-BBN possessed good diagnostic ability as a GRP-specific contrast agent, with appropriate signal reduction in T2*-weighted color map MR images in mice with breast tumors.

  11. Preclinical imaging and translational animal models of cancer for accelerated clinical implementation of nanotechnologies and macromolecular agents.

    Science.gov (United States)

    De Souza, Raquel; Spence, Tara; Huang, Huang; Allen, Christine

    2015-12-10

    The majority of animal models of cancer have performed poorly in terms of predicting clinical performance of new therapeutics, which are most often first evaluated in patients with advanced, metastatic disease. The development and use of metastatic models of cancer may enhance clinical translatability of preclinical studies focused on the development of nanotechnology-based drug delivery systems and macromolecular therapeutics, potentially accelerating their clinical implementation. It is recognized that the development and use of such models are not without challenge. Preclinical imaging tools offer a solution by allowing temporal and spatial characterization of metastatic lesions. This paper provides a review of imaging methods applicable for evaluation of novel therapeutics in clinically relevant models of advanced cancer. An overview of currently utilized models of oncology in small animals is followed by image-based development and characterization of visceral metastatic cancer models. Examples of imaging tools employed for metastatic lesion detection, evaluation of anti-tumor and anti-metastatic potential and biodistribution of novel therapies, as well as the co-development and/or use of imageable surrogates of response, are also discussed. While the focus is on development of macromolecular and nanotechnology-based therapeutics, examples with small molecules are included in some cases to illustrate concepts and approaches that can be applied in the assessment of nanotechnologies or macromolecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Tc-99m imaging agents

    International Nuclear Information System (INIS)

    Weininger, J.; Trumper, J.

    1984-01-01

    A wide range of pharmaceuticals for labeling with Tc-99m, developed by the Soreq Radiopharmaceuticals Department, is described. Details of the production and quality control of 13 kits are given, as well as the range of results required for consistently high quality imaging agents

  13. LUGOL'S IODINE CHROMOENDOSCOPY VERSUS NARROW BAND IMAGE ENHANCED ENDOSCOPY FOR THE DETECTION OF ESOPHAGEAL CANCER IN PATIENTS WITH STENOSIS SECONDARY TO CAUSTIC/CORROSIVE AGENT INGESTION.

    Science.gov (United States)

    Pennachi, Caterina Maria Pia Simoni; Moura, Diogo Turiani Hourneaux de; Amorim, Renato Bastos Pimenta; Guedes, Hugo Gonçalo; Kumbhari, Vivek; Moura, Eduardo Guimarães Hourneaux de

    2017-01-01

    The diagnosis of corrosion cancer should be suspected in patients with corrosive ingestion if after a latent period of negligible symptoms there is development of dysphagia, or poor response to dilatation, or if respiratory symptoms develop in an otherwise stable patient of esophageal stenosis. Narrow Band Imaging detects superficial squamous cell carcinoma more frequently than white-light imaging, and has significantly higher sensitivity and accuracy compared with white-light. To determinate the clinical applicability of Narrow Band Imaging versus Lugol´s solution chromendoscopy for detection of early esophageal cancer in patients with caustic/corrosive agent stenosis. Thirty-eight patients, aged between 28-84 were enrolled and examined by both Narrow Band Imaging and Lugol´s solution chromendoscopy. A 4.9mm diameter endoscope was used facilitating examination of a stenotic area without dilation. Narrow Band Imaging was performed and any lesion detected was marked for later biopsy. Then, Lugol´s solution chromoendoscopy was performed and biopsies were taken at suspicious areas. Patients who had abnormal findings at the routine, Narrow Band Imaging or Lugol´s solution chromoscopy exam had their stenotic ring biopsied. We detected nine suspicious lesions with Narrow Band Imaging and 14 with Lugol´s solution chromendoscopy. The sensitivity and specificity of the Narrow Band Imaging was 100% and 80.6%, and with Lugol´s chromoscopy 100% and 66.67%, respectively. Five (13%) suspicious lesions were detected both with Narrow Band Imaging and Lugol's chromoscopy, two (40%) of these lesions were confirmed carcinoma on histopathological examination. Narrow Band Imaging is an applicable option to detect and evaluate cancer in patients with caustic /corrosive stenosis compared to the Lugol´s solution chromoscopy.

  14. Excess of Radiation Burden for Young Testicular Cancer Patients using Automatic Exposure Control and Contrast Agent on Whole-body Computed Tomography Imaging.

    Science.gov (United States)

    Niiniviita, Hannele; Kulmala, Jarmo; Pölönen, Tuukka; Määttänen, Heli; Järvinen, Hannu; Salminen, Eeva

    2017-06-01

    The aim of the study was to assess patient dose from whole-body computed tomography (CT) in association with patient size, automatic exposure control (AEC) and intravenous (IV) contrast agent. Sixty-five testicular cancer patients (mean age 28 years) underwent altogether 279 whole-body CT scans from April 2000 to April 2011. The mean number of repeated examinations was 4.3. The GE LightSpeed 16 equipped with AEC and the Siemens Plus 4 CT scanners were used for imaging. Whole-body scans were performed with (216) and without (63) IV contrast. The ImPACT software was used to determine the effective and organ doses. Patient doses were independent (p agent caused significantly higher (13% Plus 4, 35% LightSpeed 16) exposure than non-contrast imaging (p agent and careful set-up of the AEC modulation parameters is recommended to avoid excessive radiation exposure on the whole-body CT imaging of young patients.

  15. Ultrasound Molecular Imaging of the Breast Cancer Neovasculature using Engineered Fibronectin Scaffold Ligands: A Novel Class of Targeted Contrast Ultrasound Agent.

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Wilson, Katheryne E; Johnson, Sadie M; Chowdhury, Sayan M; Bachawal, Sunitha; Hackel, Benjamin J; Tian, Lu; Willmann, Jürgen K

    2016-01-01

    Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10(th) type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (Pbreast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (Pbreast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI.

  16. Innovative agents in cancer prevention.

    Science.gov (United States)

    Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

    2005-01-01

    There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

  17. Targeted nanotechnology for cancer imaging.

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B; Karathanasis, Efstathios

    2014-09-30

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Targeted Nanotechnology for Cancer Imaging

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  19. The synthesis of a D-glucosamine contrast agent, Gd-DTPA-DG, and its application in cancer molecular imaging with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Wei [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000 (China); Chen Yue, E-mail: chenyue5523@126.com [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000 (China); Guo Dajing [Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010 (China); Huang Zhanwen; Cai Liang [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000 (China); He Ling [West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China)

    2011-09-15

    Objective: The purpose of this study is to describe the synthesis of Gadolinium-diethylenetriamine pentaacetic acid-deoxyglucosamine (Gd-DTPA-DG) which is a D-glucosamine metabolic MR imaging contrast agent. We will also discuss its use in a pilot MRI study using a xenograft mouse model of human adenocarcinoma. Methods: This novel contrast agent was specifically studied because of its ability to 'target' metabolically active tumor tissues. In this study Gd-DTPA-DG is used to investigate how tumor tissues would react to a dose of 0.2 mmol Gd/kg over a 120 min exposure in a xenograft mouse model. These experiments used athymic mice implanted with human pulmonary adenocarcinoma (A549) as demonstrated by dynamic MRI. Alternately, another contrast agent that is not specific for targeting, Gd-DTPA, was used as the control at a similar dose of gadolinium. Efficacy of the targeted contrast agent was assessed by measuring relaxation rate in vitro and signal intensity (SI) in vivo. Statistical differences were calculated using one-way analysis of variance. Results: The synthesized Gd-DTPA-DG was shown to improve the contrast of tumor tissue in this model. Gd-DTPA-DG was also shown to have a similar pharmacokinetic rate but generated a higher relaxation rate in tumor tissues relative to the control contrast Gd-DTPA. In comparison to the pre-contrast imaging, the SI of tumor tissue in the experimental group was shown to be significantly increased at 15 min after injection of Gd-DTPA-DG (p < 0.001). The enhanced signal intensity spread from the edge of the tumor to the center and seemed to strengthen the idea that MRI performance would be useful in different tumor tissues. Conclusion: This preliminary study shows that this new chelated contrast agent, Gd-DTPA-DG, can be specifically targeted to accumulation in tumor tissue as compared to normal tissues. This targeted paramagnetic contrast agent has potential for specific cancer molecular imaging with MRI.

  20. Optical imaging for monitoring tumor oxygenation response after initiation of single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Shigeto Ueda

    Full Text Available PURPOSE: Optical imaging techniques for measuring tissue hemoglobin concentration have been recently accepted as a way to assess tumor vascularity and oxygenation. We investigated the correlation between early optical response to single-agent bevacizumab and treatment outcome. METHODS: Seven patients with advanced or metastatic breast cancer were treated with single-agent bevacizumab followed by addition of weekly paclitaxel. Optical imaging of patient's breasts was performed to measure tumor total hemoglobin concentration (tHb and oxygen saturation (stO2 at baseline and on days 1, 3, 6, 8, and 13 after the first infusion of bevacizumab. To assess early metabolic response, 2-deoxy-2-(18F-fluoro-D-glucose (FDG positron emission tomography/computed tomography (PET/CT, 18F-fluoromisonidazole (FMISO-PET/CT, and magnetic resonance imaging were performed at baseline and after two cycles of the regimen. RESULTS: Seven patients were grouped as responders (n = 4 and nonresponders (n = 3 on the basis of metabolic response measured by FDG-PET/CT. The responders showed remarkable tumor shrinkage and low accumulations of FMISO tracer relative to those of the nonresponders at the completion of two cycles of chemotherapy. Tumors of both groups showed remarkable attenuation of mean tHb as early as day 1 after therapy initiation. The nonresponders had lower baseline stO2 levels compared with adjacent breast tissue stO2 levels along with a pattern of steadily low stO2 levels during the observation window. On the other hand, the responders appeared to sustain high stO2 levels with temporal fluctuation. CONCLUSIONS: Low tumor stO2 level after single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.

  1. Targeted deletion of the ara operon of Salmonella typhimurium enhances L-arabinose accumulation and drives PBAD-promoted expression of anti-cancer toxins and imaging agents.

    Science.gov (United States)

    Hong, Hyun; Lim, Daejin; Kim, Geun-Joong; Park, Seung-Hwan; Sik Kim, Hyeon; Hong, Yeongjin; Choy, Hyon E; Min, Jung-Joon

    2014-01-01

    Tumor-specific expression of antitumor drugs can be achieved using attenuated Salmonella typhimurium harboring the PBAD promoter, which is induced by L-arabinose. However, L-arabinose does not accumulate because it is metabolized to D-xylulose-5-P by enzymes encoded by the ara operon in Salmonellae. To address this problem, we developed an engineered strain of S. typhimurium in which the ara operon is deleted. Linear DNA transformation was performed using λ red recombinase to exchange the ara operon with linear DNA carrying an antibiotic-resistance gene with homology to regions adjacent to the ara operon. The ara operon-deleted strain and its parental strain were transformed with a plasmid encoding Renilla luciferase variant 8 (RLuc8) or cytolysin A (clyA) under the control of the PBAD promoter. Luciferase assays demonstrated that RLuc8 expression was 49-fold higher in the ara operon-deleted S. typhimurium than in the parental strain after the addition of L-arabinose. In vivo bioluminescence imaging showed that the tumor tissue targeted by the ara operon-deleted Salmonella had a stronger imaging signal (~30-fold) than that targeted by the parental strain. Mice with murine colon cancer (CT26) that had been injected with the ara operon-deleted S. typhimurium expressing clyA showed significant tumor suppression. The present report demonstrates that deletion of the ara operon of S. typhimurium enhances L-arabinose accumulation and thereby drives PBAD-promoted expression of cytotoxic agents and imaging agents. This is a promising approach for tumor therapy and imaging.

  2. Photoacoustic imaging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Xuanjin Yang

    2017-07-01

    Full Text Available Photoacoustic imaging (PAI, also known as optoacoustic imaging, is a rapidly growing imaging modality with potential in medical diagnosis and therapy monitoring. This paper focuses on the techniques of prostate PAI and its potential applications in prostate cancer detection. Transurethral light delivery combined with transrectal ultrasound detection overcomes light scattering in the surrounding tissue and provides optimal photoacoustic signals while minimizing invasiveness. While label-free PAI based on endogenous contrast has promising potential for prostate cancer detection, exogenous contrast agents can further enhance the sensitivity and specificity of prostate cancer PAI. Further in vivo studies are required in order to achieve the translation of prostate PAI to clinical implementation. The minimal invasiveness, relatively low cost, high specificity and sensitivity, and real-time imaging capability are valuable advantages of PAI that may improve the current prostate cancer management in clinic.

  3. Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles

    Directory of Open Access Journals (Sweden)

    Cheng CC

    2013-04-01

    Full Text Available Chun-Chia Cheng,1,2,* Chiung-Fang Huang,3,4,* Ai-Sheng Ho,5 Cheng-Liang Peng,6 Chun-Chao Chang,7,8 Fu-Der Mai,1,9 Ling-Yun Chen,10 Tsai-Yueh Luo,2 Jungshan Chang1,11,121Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, 2Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 3School of Dental Technology, Taipei Medical University, Taipei, 4Division of Family and Operative Dentistry, Department of Dentistry, Taipei Medical University Hospital, Taipei, 5Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, 6Institute of Biomedical Engineering, National Taiwan University, Taipei, 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, 8Department of Internal Medicine, Taipei Medical University, Taipei, 9Department of Biochemistry, Taipei Medical University, Taipei, 10Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 11Neuroscience Research Center, Taipei Medical University Hospital, Taipei, 12Research Center for Biomedical Implants and Microsurgery Devices, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workAbstract: Increased expression of cellular membrane bound glucose-regulated protein 78 (GRP78 is considered to be one of the biomarkers for gastric cancers. Therefore, peptides or molecules with specific recognition to GRP78 can act as a guiding probe to direct conjugated imaging agents to localized cancers. Based on this rationale, GRP78-guided polymeric micelles were designed and manufactured for nuclear imaging detection of tumors. Thiolated GRP78 binding peptide (GRP78BP was first labeled with maleimide-terminated poly(ethylene glycol–poly(ε-caprolactone and then mixed with diethylenetriaminepentaacetic acid (DTPA-linked poly(ethylene glycol–poly(ε-caprolactone to form DTPA/GRP78BP-conjugated micelles. The coupling efficiency of micelles with

  4. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  5. Cancer Stratification by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Justus Weber

    2015-03-01

    Full Text Available The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2. Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter, as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers.

  6. Development of Novel Technetium-99m-Labeled Steroids as Estrogen-Responsive Breast Cancer Imaging Agents

    Science.gov (United States)

    2007-06-01

    bipyridine derivatives with model azides (benzyl azide). Again the reactions go well to give the expected 1,4- disubstituted triazoles . In this case, the...as breast, endometrial and ovarian cancer, and osteoporosis, chemical modulation of the ER- regulated pathways is a critical clinical objective. Recent...20-tetraene-3,17β-diols as ERα-Hormone Binding Domain Ligands: Effect of the Methoxy Group on Receptor Binding and Uterotrophic Growth . J. Med. Chem

  7. Contrast Agent in Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Vu-Quang, Hieu

    2015-01-01

    Nanoparticles have been employed as contrast agent in magnetic resonance imaging (MRI) in order to improve sensitivity and accuracy in diagnosis. In addition, these contrast agents are potentially combined with other therapeutic compounds or near infrared bio-imaging (NIR) fluorophores to obtain...... theranostic or dual imaging purposes, respectively. There were two main types of MRI contrast agent that were synthesized during this PhD project including fluorine containing nanoparticles and magnetic nanoparticles. In regard of fluorine containing nanoparticles, there were two types contrast agent...... that were synthesized in project I and II. In project I, Poly (lactic-co-glycolic acid)-block-poly (ethylene glycol)-Folate Pefluorooctyl Bromide/Indocyanine green/ Doxorubicin (PLGA-PEG-Folate PFOB/ICG/Dox) has been formulated for the dual imaging NIR and 19F MRI as well as in the combination of Dox...

  8. Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer

    International Nuclear Information System (INIS)

    Gao, Mingzhang; Wang, Min; Miller, Kathy D.; Zheng, Qi-Huang

    2012-01-01

    Carbon-11-labeled chromen-4-one derivatives were synthesized as new potential PET agents for imaging of DNA repair enzyme DNA-dependent protein kinase (DNA-PK) in cancer. The target tracers, X-[ 11 C]methoxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; [ 11 C]4a–d), were prepared from their corresponding precursors, X-hydroxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; 5a–d), with [ 11 C]CH 3 OTf through O-[ 11 C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a C-18 Sep-Pak Plus cartridge. The radiochemical yields decay corrected to end of bombardment (EOB), from [ 11 C]CO 2 , were 40–60%. The specific activity at end of synthesis (EOS) was 185–370 GBq/μmol. - Highlights: ► New chromen-4-one derivatives were synthesized. ► New carbon-11-labeled chromen-4-one derivatives were synthesized. ► Simple solid-phase extraction (SPE) method was employed in radiosynthesis.

  9. Sanguinarine: A Novel Agent Against Prostate Cancer

    National Research Council Canada - National Science Library

    Ahmad, Nihal

    2007-01-01

    ..., has been shown to possess anti-microbial, antioxidant and anti-inflammatory properties. Our earlier studies suggested that sanguinarine may be developed as an agent for the management of prostate cancer...

  10. Sanguinarine: A Novel Agent Against Prostate Cancer

    National Research Council Canada - National Science Library

    Ahmad, Nihal

    2008-01-01

    ..., has been shown to possess anti-microbial, antioxidant and anti-inflammatory properties. Our earlier studies suggested that sanguinarine may be developed as an agent for the management of prostate cancer...

  11. Utility of a prototype liposomal contrast agent for x-ray imaging of breast cancer: a proof of concept using micro-CT in small animals

    Science.gov (United States)

    Badea, C. T.; Samei, E.; Ghaghada, K.; Saunders, R.; Yuan, H.; Qi, Y.; Hedlund, L. W.; Mukundan, S.

    2008-03-01

    Imaging tumor angiogenesis in small animals is extremely challenging due to the size of the tumor vessels. Consequently, both dedicated small animal imaging systems and specialized intravascular contrast agents are required. The goal of this study was to investigate the use of a liposomal contrast agent for high-resolution micro-CT imaging of breast tumors in small animals. A liposomal blood pool agent encapsulating iodine with a concentration of 65.5 mg/ml was used with a Duke Center for In Vivo Microscopy (CIVM) prototype micro-computed tomography (micro-CT) system to image the R3230AC mammary carcinoma implanted in rats. The animals were injected with equivalent volume doses (0.02 ml/kg) of contrast agent. Micro-CT with the liposomal blood pool contrast agent ensured a signal difference between the blood and the muscle higher than 450 HU allowing the visualization of the tumors 3D vascular architecture in exquisite detail at 100-micron resolution. The micro-CT data correlated well with the histological examination of tumor tissue. We also studied the ability to detect vascular enhancement with limited angle based reconstruction, i.e. tomosynthesis. Tumor volumes and their regional vascular percentage were estimated. This imaging approach could be used to better understand tumor angiogenesis and be the basis for evaluating anti-angiogenic therapies.

  12. Ultrasound imaging beyond the vasculature with new generation contrast agents.

    Science.gov (United States)

    Perera, Reshani H; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan; Exner, Agata A

    2015-01-01

    Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 µm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer. © 2015 Wiley Periodicals, Inc.

  13. Nanogels as imaging agents for modalities spanning the electromagnetic spectrum.

    Science.gov (United States)

    Chan, Minnie; Almutairi, Adah

    2016-01-21

    In the past few decades, advances in imaging equipment and protocols have expanded the role of imaging in in vivo diagnosis and disease management, especially in cancer. Traditional imaging agents have rapid clearance and low specificity for disease detection. To improve accuracy in disease identification, localization and assessment, novel nanomaterials are frequently explored as imaging agents to achieve high detection specificity and sensitivity. A promising material for this purpose are hydrogel nanoparticles, whose high hydrophilicity, biocompatibility, and tunable size in the nanometer range make them ideal for imaging. These nanogels (10 to 200 nm) can circumvent uptake by the reticuloendothelial system, allowing longer circulation times than small molecules. In addition, their size/surface properties can be further tailored to optimize their pharmacokinetics for imaging of a particular disease. Herein, we provide a comprehensive review of nanogels as imaging agents in various modalities with sources of signal spanning the electromagnetic spectrum, including MRI, NIR, UV-vis, and PET. Many materials and formulation methods will be reviewed to highlight the versatility of nanogels as imaging agents.

  14. New agents for cancer chemoprevention.

    Science.gov (United States)

    Kelloff, G J; Boone, C W; Crowell, J A; Steele, V E; Lubet, R A; Doody, L A; Malone, W F; Hawk, E T; Sigman, C C

    1996-01-01

    Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid], calcium, Beta carotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylornithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs. Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin

  15. Multimodal nanoparticle imaging agents: design and applications

    Science.gov (United States)

    Burke, Benjamin P.; Cawthorne, Christopher; Archibald, Stephen J.

    2017-10-01

    Molecular imaging, where the location of molecules or nanoscale constructs can be tracked in the body to report on disease or biochemical processes, is rapidly expanding to include combined modality or multimodal imaging. No single imaging technique can offer the optimum combination of properties (e.g. resolution, sensitivity, cost, availability). The rapid technological advances in hardware to scan patients, and software to process and fuse images, are pushing the boundaries of novel medical imaging approaches, and hand-in-hand with this is the requirement for advanced and specific multimodal imaging agents. These agents can be detected using a selection from radioisotope, magnetic resonance and optical imaging, among others. Nanoparticles offer great scope in this area as they lend themselves, via facile modification procedures, to act as multifunctional constructs. They have relevance as therapeutics and drug delivery agents that can be tracked by molecular imaging techniques with the particular development of applications in optically guided surgery and as radiosensitizers. There has been a huge amount of research work to produce nanoconstructs for imaging, and the parameters for successful clinical translation and validation of therapeutic applications are now becoming much better understood. It is an exciting time of progress for these agents as their potential is closer to being realized with translation into the clinic. The coming 5-10 years will be critical, as we will see if the predicted improvement in clinical outcomes becomes a reality. Some of the latest advances in combination modality agents are selected and the progression pathway to clinical trials analysed. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  16. Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.

    Science.gov (United States)

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U S; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-18

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  17. Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging

    Science.gov (United States)

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U. S.; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-01

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  18. Innovation in cancer imaging.

    Science.gov (United States)

    Debergh, I; Vanhove, C; Ceelen, W

    2012-01-01

    Cancer is rapidly becoming the worldwide leading cause of premature death. Iconographic techniques have traditionally provided information on tumor anatomy. The recent introduction of functional and molecular imaging techniques allows probing tumor physiology and biology in addition to mere anatomical description. In addition to the research implications, these novel imaging techniques offer early response assessment and target visualization which, in the era of personalized medicine, may offer significant advances in cancer therapy. Here, we provide an overview of the most important developments in cancer imaging, with a focus on the clinical applications. Copyright © 2012 S. Karger AG, Basel.

  19. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto

    2012-01-01

    that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... an important tool in the development of liposomal drugs. However, advanced imaging systems now provide new possibilities for non-invasive monitoring of liposome biodistribution in humans. Thus, advances in imaging and developments in liposome radiolabeling techniques allow us to enter a new arena where we...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...

  20. Contrast Agent in Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Vu-Quang, Hieu

    2015-01-01

    cancer cells for cancer diagnosis in MRI. F127-Folate coated SPION were stable in various types of suspension medium for over six months. They could specifically target folate receptor of cancer cells in vitro and in vivo thus enhancing the contrast in MRI T2/T2* weighted images. These are preliminary...... for chemotherapy. The nanoparticles were 150 nm in size with spherical shape, which contained PFOB in the inner core and Dox and ICG in the polymeric shell. More importantly, they could target folate receptor expressing cancer cells, which provide positive in vitro and in vivo NIR and 19F MRI results. In project...

  1. Imaging in oral cancers

    Directory of Open Access Journals (Sweden)

    Supreeta Arya

    2012-01-01

    Full Text Available Oral cavity squamous cell cancers form a significant percentage of the cancers seen in India. While clinical examination allows direct visualization, it cannot evaluate deep extension of disease. Cross-sectional imaging has become the cornerstone in the pretreatment evaluation of these cancers and provides accurate information about the extent and depth of disease that can help decide the appropriate management strategy and indicate prognosis. Early cancers are treated with a single modality, either surgery or radiotherapy while advanced cancers are offered a combination of surgery, radiotherapy and chemotherapy. Imaging can decide resectability, help plan the precise extent of resection, and indicate whether organ conservation therapy should be offered. Quality of life issues necessitate preservation of form and function and pretreatment imaging helps plan appropriate reconstruction and counsel patients regarding lifestyle changes. Oral cavity has several subsites and the focus of the review is squamous cancers of the gingivobuccal region, oral tongue and retromolar trigone as these are most frequently encountered in the subcontinent. References for this review were identified by searching Medline and PubMed databases. Only articles published in English language literature were selected. This review aims to familiarize the radiologist with the relevant anatomy of the oral cavity, discuss the specific issues that influence prognosis and management at the above subsites, the optimal imaging methods, the role of imaging in accurately staging these cancers and in influencing management. A checklist for reporting will emphasize the information to be conveyed by the radiologist.

  2. Biocompatible astaxanthin as novel contrast agent for biomedical imaging.

    Science.gov (United States)

    Nguyen, Van Phuc; Park, Suhyun; Oh, Junghwan; Wook Kang, Hyun

    2017-08-01

    Photoacoustic imaging (PAI) is a hybrid imaging modality with high resolution and sensitivity that can be beneficial for cancer staging. Due to insufficient endogenous photoacoustic (PA) contrast, the development of exogenous agents is critical in targeting cancerous tumors. The current study demonstrates the feasibility of marine-oriented material, astaxanthin, as a biocompatible PA contrast agent. Both silicon tubing phantoms and ex vivo bladder tissues are tested at various concentrations (up to 5 mg/ml) of astaxanthin to quantitatively explore variations in PA responses. A Q-switched Nd : YAG laser (λ = 532 nm) in conjunction with a 5 MHz ultrasound transducer is employed to generate and acquire PA signals from the samples. The phantom results presented that the PA signal amplitudes increase linearly with the astaxanthin concentrations (threshold detection = 0.31 mg/ml). The tissue injected with astaxanthin yields up to 16-fold higher PA signals, compared with that with saline. Due to distribution of the injected astaxanthin, PAI can image the margin of astaxanthin boles as well as quantify their volume in 3D reconstruction. Further investigations on selective tumor targeting are required to validate astaxanthin as a potential biocompatible contrast agent for PAI-assisted bladder cancer detection. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Karadjian, V.

    1987-01-01

    The origine of nuclear magnetic resonance signal is reminded and different ways for contrast enhancement in magnetic resonance imaging are presented, especially, modifications of tissus relaxation times. Investigations have focused on development of agents incorporating either paramagnetic ions or stable free radicals. Pharmacological and toxicological aspects are developed. The diagnostic potential of these substances is illustrated by the example of gadolinium complexes [fr

  4. Imaging of kidney cancer

    International Nuclear Information System (INIS)

    Guermazi, A.

    2006-01-01

    This is one of the first books to deal specifically with diagnostic imaging of the entire spectrum of kidney cancers. Both new and conventional imaging modalities are fully considered. After an introductory chapter on the histopathological classification of kidney cancers, the advantages and disadvantages of the various imaging modalities used in the diagnosis and assessment of disease extension are documented. Subsequent chapters offer an exhaustive description of the radiological features of the different histological subtypes of kidney cancer, with radiological and histological illustrations and tables. The latest innovations in interventional and minimally invasive procedures are also well covered. The book benefits from carefully chosen and technically excellent images. Each of the 24 chapters is written by an internationally acclaimed expert, making this book the most current and complete treatment of the subject available. It should be of great interest to radiologists, oncologists, and urologists. (orig.)

  5. Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.

    Science.gov (United States)

    Ashton, Jeffrey R; Clark, Darin P; Moding, Everett J; Ghaghada, Ketan; Kirsch, David G; West, Jennifer L; Badea, Cristian T

    2014-01-01

    To provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT. Primary lung tumors were generated in LSL-Kras(G12D); p53(FL/FL) mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed-two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues. Dual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R(2) = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements. Dual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex

  6. Radiolabeled cyclic arginine-glycine-aspartic (RGD)-conjugated iron oxide nanoparticles as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer

    Science.gov (United States)

    Deng, Shengming; Zhang, Wei; Zhang, Bin; Hong, Ruoyu; Chen, Qing; Dong, Jiajia; Chen, Yinyiin; Chen, Zhiqiang; Wu, Yiwei

    2015-01-01

    Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) modified with a novel cyclic arginine-glycine-aspartate (RGD) peptide were made and radiolabeled as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer. The probe was tested both in vitro and in vivo to determine its receptor targeting efficacy and feasibility for SPECT and MRI. The radiochemical syntheses of 125I-cRGD-USPIO were accomplished with a radiochemical purity of 96.05 ± 0.33 %. High radiochemical stability was found in fresh human serum and in phosphate-buffered saline. The average hydrodynamic size of 125I-cRGD-USPIO determined by dynamic light scattering was 51.3 nm. Results of in vitro experiments verified the specificity of the radiolabeled nanoparticles to tumor cells. Preliminary biodistribution studies of 125I-radiolabeled cRGD-USPIO in Bcap37-bearing nude mice showed that it had long circulation half-life, high tumor uptake, and high initial blood retention with moderate liver uptake. In vivo tumor targeting and uptake of the radiolabeled nanoparticles in mice model were visualized by SPECT and MRI collected at different time points. Our results strongly indicated that the 125I-cRGD-USPIO could be used as a promising bifunctional radiotracer for early clinical tumor detection with high sensitivity and high spatial resolution by SPECT and MRI.

  7. Magnetic resonance imaging with hyperpolarized agents: methods and applications

    Science.gov (United States)

    Adamson, Erin B.; Ludwig, Kai D.; Mummy, David G.; Fain, Sean B.

    2017-07-01

    In the past decade, hyperpolarized (HP) contrast agents have been under active development for MRI applications to address the twin challenges of functional and quantitative imaging. Both HP helium (3He) and xenon (129Xe) gases have reached the stage where they are under study in clinical research. HP 129Xe, in particular, is poised for larger scale clinical research to investigate asthma, chronic obstructive pulmonary disease, and fibrotic lung diseases. With advances in polarizer technology and unique capabilities for imaging of 129Xe gas exchange into lung tissue and blood, HP 129Xe MRI is attracting new attention. In parallel, HP 13C and 15N MRI methods have steadily advanced in a wide range of pre-clinical research applications for imaging metabolism in various cancers and cardiac disease. The HP [1-13C] pyruvate MRI technique, in particular, has undergone phase I trials in prostate cancer and is poised for investigational new drug trials at multiple institutions in cancer and cardiac applications. This review treats the methodology behind both HP gases and HP 13C and 15N liquid state agents. Gas and liquid phase HP agents share similar technologies for achieving non-equilibrium polarization outside the field of the MRI scanner, strategies for image data acquisition, and translational challenges in moving from pre-clinical to clinical research. To cover the wide array of methods and applications, this review is organized by numerical section into (1) a brief introduction, (2) the physical and biological properties of the most common polarized agents with a brief summary of applications and methods of polarization, (3) methods for image acquisition and reconstruction specific to improving data acquisition efficiency for HP MRI, (4) the main physical properties that enable unique measures of physiology or metabolic pathways, followed by a more detailed review of the literature describing the use of HP agents to study: (5) metabolic pathways in cancer and cardiac

  8. Imaging and prostate cancer

    International Nuclear Information System (INIS)

    Schwartz, Lawrence H.

    1996-01-01

    The use of imaging in evaluating patients with prostate cancer is highly dependent upon the purpose of the evaluation. Ultrasound, Computed Tomography, Magnetic Resonance Imaging, TC-99m Bone Scanning, and Positron Emission Tomography may all be utilized for imaging in prostate cancer. The utility of each of these modalities depends upon the intended purpose: for instance, screening, staging, or evaluating for progression of disease in patients with prostate cancer. Transrectal ultrasound is performed by placing a 5MHz to 7.5 MHz transducer in the rectum and imaging the prostate in the coronal and sagittal planes. Prostate cancer generally appears as an area of diminished echogenocity in the peripheral zone of the prostate gland. However, up to 24% of prostate cancers are isoechoic and cannot be well distinguished from the remainder of the peripheral zone. In addition, the incidence of malignancy in a lesion judged to be suspicious on ultrasound is between 20% and 25%. Therefore, while ultrasound is the least expensive of the three cross sectional imaging modalities, its relatively low specificity precludes it from being used as a screening examination. Investigators have also looked at the ability of ultrasound to evaluate the presence and extent of extracapsular spread of prostate cancer. The RDOG (Radiology Diagnostic Oncology Group) multi-institutional cooperative trial reported a disappointing overall accuracy of ultrasound of 58% for staging prostate cancer. The accuracy was somewhat higher 63%, for patients with advanced disease. The other cross-sectional imaging modalities available for imaging the prostate include Computed Tomography and Magnetic Resonance Imaging. Computed Tomography is useful as an 'anatomic' imaging technique to detect lymph node enlargement. It is not sensitive in detecting microscopic nodal involvement with tumor, or tumor in non-enlarged pelvic lymph nodes. The primary prostate neoplasm is generally the same attenuation as the normal

  9. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging.

    Science.gov (United States)

    Haedicke, Katja; Brand, Christian; Omar, Murad; Ntziachristos, Vasilis; Reiner, Thomas; Grimm, Jan

    2017-06-01

    Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher ® (BHQ) dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to α v β 3 -integrin expressing glioblastoma cell spheroids in vitro . The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo . Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  10. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Katja Haedicke

    2017-06-01

    Full Text Available Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher® (BHQ dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to αvβ3-integrin expressing glioblastoma cell spheroids in vitro. The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo. Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  11. Breast cancer imaging devices.

    Science.gov (United States)

    Moadel, Renee M

    2011-05-01

    Conventional mammography is a screening procedure constrained by low specificity in the detection of breast cancer. Approximately 40% of women undergoing mammography screening have dense breast tissue, and conventional mammographic imaging has a sensitivity range of only 50%-85% for malignant lesions. Magnetic resonance imaging (MRI) is now recommended for breast cancer screening in high-risk patients. However, approximately 15% of patients cannot tolerate MRI. These are the clinical situations in which positron emission mammography (PEM) and breast-specific gamma (BSG) camera systems fulfill a need for primary breast cancer imaging. Because breast cancer is the most common malignancy and the second most common cause of cancer death among women, many nuclear medicine imaging techniques are essential in the evaluation and therapy of patients with this disease. Nuclear medicine surgical techniques consist of sentinel lymph node localization and the use of radiolabeled seeds for intraoperative localization of nonpalpable breast cancers. The Food and Drug Administration (FDA) has approved the PEM Flex Solo II scanner, which has the capability for stereotactic biopsy, with an array of pixelated lutetium yttrium orthosilicate (LYSO) crystals, position-sensitive photomultiplier tubes (PS-PMT), and a spatial resolution of 2.4 mm. Clear PEM is a scanner in development with cerium-doped LYSO (LYSO:Ce) crystals, multipixel avalanche photodiodes, depth of interaction measurement with a resolution of 1.3 mm. The Dilon 6800 Gamma Camera is a BSG device approved by the FDA with stereotactic biopsy guidance capability, a pixelated array of sodium iodide crystals, PS-PMTs, and an extrinsic spatial resolution of 6 mm at 3 cm from the camera. GE has just received clearance from the FDA for a molecular breast imaging camera, the Discovery NM 750 b, with pixelated cadmium zinc telluride crystals, semiconductor photoelements and an extrinsic resolution of 3.5 mm at 3 cm. The Society of

  12. Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner

    Directory of Open Access Journals (Sweden)

    Taylor RM

    2012-08-01

    Full Text Available Robert M Taylor,1,2 Laurel O Sillerud1,31Department of Biochemistry and Molecular Biology, 2New Mexico Cancer Nanoscience and Microsystems Training Center, 3UNM Cancer Center, University of New Mexico, Albuquerque, NM, USABackground and methods: Problems with the clinical management of prostate cancer include the lack of both specific detection and efficient therapeutic intervention. We report the encapsulation of superparamagnetic iron platinum nanoparticles (SIPPs and paclitaxel in a mixture of polyethyleneglycolated, fluorescent, and biotin-functionalized phospholipids to create multifunctional SIPP-PTX micelles (SPMs that were conjugated to an antibody against prostate-specific membrane antigen (PSMA for the specific targeting, magnetic resonance imaging (MRI, and treatment of human prostate cancer xenografts in mice.Results: SPMs were 45.4 ± 24.9 nm in diameter and composed of 160.7 ± 22.9 µg/mL iron, 247.0 ± 33.4 µg/mL platinum, and 702.6 ± 206.0 µg/mL paclitaxel. Drug release measurements showed that, at 37°C, half of the paclitaxel was released in 30.2 hours in serum and two times faster in saline. Binding assays suggested that PSMA-targeted SPMs specifically bound to C4-2 human prostate cancer cells in vitro and released paclitaxel into the cells. In vitro, paclitaxel was 2.2 and 1.6 times more cytotoxic than SPMs to C4-2 cells at 24 and 48 hours of incubation, respectively. After 72 hours of incubation, paclitaxel and SPMs were equally cytotoxic. SPMs had MRI transverse relaxivities of 389 ± 15.5 Hz/mM iron, and SIPP micelles with and without drug caused MRI contrast enhancement in vivo.Conclusion: Only PSMA-targeted SPMs and paclitaxel significantly prevented growth of C4-2 prostate cancer xenografts in nude mice. Furthermore, mice injected with PSMA-targeted SPMs showed significantly more paclitaxel and platinum in tumors, compared with nontargeted SPM-injected and paclitaxel-injected mice.Keywords: iron platinum, MRI

  13. Perfluorocarbon Nanoparticles: Evolution of a Multimodality and Multifunctional Imaging Agent

    Directory of Open Access Journals (Sweden)

    Patrick M. Winter

    2014-01-01

    Full Text Available Perfluorocarbon nanoparticles offer a biologically inert, highly stable, and nontoxic platform that can be specifically designed to accomplish a range of molecular imaging and drug delivery functions in vivo. The particle surface can be decorated with targeting ligands to direct the agent to a variety of biomarkers that are associated with diseases such as cancer, cardiovascular disease, obesity, and thrombosis. The surface can also carry a high payload of imaging agents, ranging from paramagnetic metals for MRI, radionuclides for nuclear imaging, iodine for CT, and florescent tags for histology, allowing high sensitivity mapping of cellular receptors that may be expressed at very low levels in the body. In addition to these diagnostic imaging applications, the particles can be engineered to carry highly potent drugs and specifically deposit them into cell populations that display biosignatures of a variety of diseases. The highly flexible and robust nature of this combined molecular imaging and drug delivery vehicle has been exploited in a variety of animal models to demonstrate its potential impact on the care and treatment of patients suffering from some of the most debilitating diseases.

  14. Comparative biodistribution of imaging agents for in vivo molecular profiling of disseminated prostate cancer in mice bearing prostate cancer xenografts: focus on 111In- and 125I-labeled anti-HER2 humanized monoclonal trastuzumab and ABY-025 Affibody

    International Nuclear Information System (INIS)

    Malmberg, Jennie; Sandström, Mattias; Wester, Kenneth; Tolmachev, Vladimir; Orlova, Anna

    2011-01-01

    Introduction: Human epidermal growth factor receptor type 2 (HER2) overexpression supports proliferation of androgen-independent prostate cancer (PC). Radionuclide molecular imaging of HER2 expression in disseminated PC would aid in the selection of patients who are likely responders to HER2 targeting therapy. In this study, we evaluated whether ABY-025 Affibody molecule, a small (∼ 7-kDa) HER2-binding scaffold protein, produces superior tumor-to-nontumor ratios compared with those obtained through the use of radiolabeled humanized anti-HER2 antibody, trastuzumab. The influence of 111 In vs. 125 I radiolabel was evaluated for both tracers. Methods: ABY-025 was labeled with 111 In using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelator, site-specifically coupled to the C-terminus via the maleimido derivative. Trastuzumab was labeled with 111 In using a CHX-A″ diethylene triamine pentaacetic acid (DTPA) chelator. An indirect radioiodination with [ 125 I]-N-succinimidyl-para-iodobenzoate was used for both targeting proteins. Biodistribution of all labeled targeting proteins was evaluated in mice bearing DU-145 PC xenografts. Results: The use of residualizing 111 In-label facilitated better tumor uptake and better tumor-to-nontumor ratios for both targeting agents. [ 111 In]-ABY-025 provided tumor uptake of 7.1±0.8% injected dose per gram of tissue (% ID/g) and tumor-to-blood ratio of 47±13 already at 6 h postinjection. The maximum tumor-to-nontumor ratios with [ 111 In]-CHX-DTPA-trastuzumab were achieved at 72 h postinjection, whereas tumor uptake was 11±4% ID/g and tumor-to-blood ratio was 18±7. The biodistribution data were confirmed with gamma-camera imaging. Conclusions: Radiolabeled ABY-025 Affibody molecule provides higher contrast in imaging of HER2-expressing PC xenografts than radiolabeled trastuzumab. Residualizing radiometal label for ABY-025 provides better contrast in imaging of HER2-expressing PC xenografts than nonresidualizing

  15. Cardiac image segmentation for contrast agent videodensitometry.

    Science.gov (United States)

    Mischi, Massimo; Kalker, Antonius A C M; Korsten, Hendrikus H M

    2005-02-01

    Indicator dilution techniques are widely used in the intensive care unit and operating room for cardiac parameter measurements. However, the invasiveness of current techniques represents a limitation for their clinical use. The development of stable ultrasound contrast agents allows new applications of the indicator dilution method. Ultrasound contrast agent dilutions permit an echographic noninvasive measurement of cardiac output, ejection fraction, and blood volumes. The indicator dilution curves are measured by videodensitometry of specific regions of interest and processed for the cardiac parameter assessment. Therefore, the major indicator dilution imaging issue is the detection of proper contrast videodensitometry regions that maximize the signal-to-noise ratio of the measured indicator dilution curves. This paper presents an automatic contour detection algorithm for indicator dilution videodensitometry. The algorithm consists of a radial filter combined with an outlier correction. It maximizes the region of interest by excluding cardiac structures that act as interference to the videodensitometric analysis. It is fast, projection independent, and allows the simultaneous detection of multiple contours in real time. The system is compared to manual contour definition on both echographic and magnetic resonance images.

  16. Fluoroquinolones as imaging agents for bacterial infection.

    Science.gov (United States)

    Naqvi, Syed Ali Raza; Drlica, Karl

    2017-10-31

    Diagnosis of deep-seated bacterial infection is difficult, as neither standard anatomical imaging nor radiolabeled, autologous leukocytes distinguish sterile inflammation from infection. Two recent imaging efforts are receiving attention: (1) radioactive derivatives of sorbitol show good specificity with Gram-negative bacterial infections, and (2) success in combining anatomical and functional imaging for cancer diagnosis has rekindled interest in 99m Tc-fluoroquinolone-based imaging. With the latter, computed tomography (CT) would be combined with single-photon-emission-computed tomography (SPECT) to detect 99m Tc-fluoroquinolone-bacterial interactions. The present minireview provides a framework for advancing fluoroquinolone-based imaging by identifying gaps in our understanding of the process. One issue is the reliance of 99m Tc labeling on the reduction of sodium pertechnetate, which can lead to colloid formation and loss of specificity. Specificity problems may be reduced by altering the quinolone structure (for example, switching from ciprofloxacin to sitafloxacin). Another issue is the uncharacterized nature of 99m Tc-ciprofloxacin binding to, or sequestration in, bacteria: specific interactions with DNA gyrase, an intracellular fluoroquinolone target, are unlikely. Labeling with 68 Ga rather than 99m Tc enables detection by positron emission tomography, but with similar biological uncertainties. Replacing the C6-F of the fluoroquinolone with 18 F provides an alternative to pertechnetate and gallium that may lead to imaging based on drug interactions with gyrase. Gyrase-based imaging requires knowledge of fluoroquinolone action, which we update. We conclude that quinolone-based probes show promise for the diagnosis of infection, but improvements in specificity and sensitivity are needed. These improvements include the optimization of the quinolone structure; such chemistry efforts can be accelerated by refining microbiological assays.

  17. In vitro and in vivo evaluation of anti-nucleolin-targeted magnetic PLGA nanoparticles loaded with doxorubicin as a theranostic agent for enhanced targeted cancer imaging and therapy.

    Science.gov (United States)

    Mosafer, Jafar; Abnous, Khalil; Tafaghodi, Mohsen; Mokhtarzadeh, Ahad; Ramezani, Mohammad

    2017-04-01

    A superparamagnetic iron oxide nanoparticles (SPIONs)/doxorubicin (Dox) co-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeted with AS1411 aptamer (Apt) against murine C26 colon carcinoma cells is successfully developed via a modified multiple emulsion solvent evaporation method for theranostic purposes. The mean size of SPIO/Dox-NPs (NPs) was 130nm with a narrow particle size distribution and Dox loading of 3.0%. The SPIO loading of 16.0% and acceptable magnetic properties are obtained and analyzed using thermogravimetric and vibration simple magnetometer analysis, respectively. The best release profile from NPs was observed in PBS at pH 7.4, in which very low burst release was observed. Nucleolin is a targeting ligand to facilitate anti-tumor delivery of AS1411-targeted NPs. The Apt conjugation to NPs (Apt-NPs) enhanced cellular uptake of Dox in C26 cancer cells. Apt-NPs enhance the cytotoxicity effect of Dox followed by a significantly higher tumor inhibition and prolonged animal survival in mice bearing C26 colon carcinoma xenografts. Furthermore, Apt-NPs enhance the contrast of magnetic resonance images in tumor site. Altogether, these Apt-NPs could be considered as a powerful tumor-targeted delivery system for their potential as dual therapeutic and diagnostic applications in cancers. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling.

    Science.gov (United States)

    Young, Jennifer D; Abbate, Vincenzo; Imberti, Cinzia; Meszaros, Levente K; Ma, Michelle T; Terry, Samantha Y A; Hider, Robert C; Mullen, Greg E; Blower, Philip J

    2017-08-01

    The clinical impact and accessibility of 68 Ga tracers for the prostate-specific membrane antigen (PSMA) and other targets would be greatly enhanced by the availability of a simple, 1-step kit-based labeling process. Radiopharmacy staff are accustomed to such procedures in the daily preparation of 99m Tc radiopharmaceuticals. Currently, chelating agents used in 68 Ga radiopharmaceuticals do not meet this ideal. The aim of this study was to develop and evaluate preclinically a 68 Ga radiotracer for imaging PSMA expression that could be radiolabeled simply by addition of 68 Ga generator eluate to a cold kit. Methods: A conjugate of a tris(hydroxypyridinone) (THP) chelator with the established urea-based PSMA inhibitor was synthesized and radiolabeled with 68 Ga by adding generator eluate directly to a vial containing the cold precursors THP-PSMA and sodium bicarbonate, with no further manipulation. It was analyzed after 5 min by instant thin-layer chromatography and high-performance liquid chromatography. The product was subjected to in vitro studies to determine PSMA affinity using PSMA-expressing DU145-PSMA cells, with their nonexpressing analog DU145 as a control. In vivo PET imaging and ex vivo biodistribution studies were performed in mice bearing xenografts of the same cell lines, comparing 68 Ga-THP-PSMA with 68 Ga-HBED-CC-PSMA. Results: Radiolabeling was complete (>95%) within 5 min at room temperature, showing a single radioactive species by high-performance liquid chromatography that was stable in human serum for more than 6 h and showed specific binding to PSMA-expressing cells (concentration giving 50% inhibition of 361 ± 60 nM). In vivo PET imaging showed specific uptake in PSMA-expressing tumors, reaching 5.6 ± 1.2 percentage injected dose per cubic centimeter at 40-60 min and rapid clearance from blood to kidney and bladder. The tumor uptake, biodistribution, and pharmacokinetics were not significantly different from those of 68 Ga

  19. Oral contrast agents in abdominal MR imaging

    International Nuclear Information System (INIS)

    Heuck, A.F.; Schhidbauer, E.; Allgayer, B.

    1991-01-01

    This paper compares Gd-DTPA, FE 2+ SO 4 , and Fe 2 Cl 3 -EDTA solutions as oral contrast agents in abdominal/pelvic MR imaging. MR imaging was performed at 1.5 T in 62 patients with tumors or inflammatory disorders of the abdomen and pelvis and in 28 normal volunteers. After precontrast imaging, an oral contrast medium was administered. Thirty subjects received 700-1,200 mL of a Gd-DTPA solution (1.0 mM; 15 g of mannitol per liter), 30 ingested the same amount of 5.0 mM Fe 2+ SO 4 , and 30 received Fe 2 Cl 3 -EDTA solution. The postcontrast study included T1- and T2-weighted spin-echo sequences and T1- and T2*-weighted gradient-echo sequences. Bowel peristalsis was reduced with intravenous application of Buscopan. Gd-DTPA, Fe 2+ SO 4 solution, and Fe 2 Cl 3 -EDTA solution provided homogeneous hyperintense signal intensity and high contrast of stomach and duodenum in all sequences, with significantly improved delineation of pathologic structures and abdominal organs in 78% of cases. Best contrast was achieved in T1-weighted sequences

  20. Overview of mechanisms of cancer chemopreventive agents

    International Nuclear Information System (INIS)

    De Flora, Silvio; Ferguson, Lynnette R.

    2005-01-01

    Epidemiological data provide evidence that it is possible to prevent cancer and other chronic diseases, some of which share common pathogenetic mechanisms, such as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is avoidance of exposure to recognized risk factors. As complementary strategies, it is possible to render the organism more resistant to mutagens/carcinogens and/or to inhibit progression of the disease by administering chemopreventive agents. In a primary prevention setting, addressed to apparently healthy individuals, it is possible to inhibit mutation and cancer initiation by triggering protective mechanisms either in the extracellular environment or inside cells, e.g., by modifying transmembrane transport, modulating metabolism, blocking reactive species, inhibiting cell replication, maintaining DNA structure, modulating DNA metabolism and repair, and controlling gene expression. Tumor promotion can be counteracted by inhibiting genotoxic effects, favoring antioxidant and anti-inflammatory activity, inhibiting proteases and cell proliferation, inducing cell differentiation, modulating apoptosis and signal transduction pathways, and protecting intercellular communications. In a secondary prevention setting, when a premalignant lesion has been detected, it is possible to inhibit tumor progression via the same mechanisms, and in addition by affecting the hormonal status and the immune system in various ways, and by inhibiting tumor angiogenesis. Although tertiary prevention, addressed to cancer patients after therapy, is outside the classical definition of chemoprevention, it exploits similar mechanisms. It is also possible to affect cell-adhesion molecules, to activate antimetastasis genes, and to inhibit proteases involved in basement membrane degradation

  1. OVULATION INDUCTION AGENTS AND OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Barbara Požlep

    2001-10-01

    Full Text Available Background. Ovarian cancer is the most frequentcause of death among gynecologic malignancies. Epidemiologicaldata show that environmental, hormonal and geneticfactors are etiologically significant. Beside the already knownrisk factors, ovulation induction agents have been reported asrisk factors in literature since 1986. Over the last two decades,ovulation induction agents have been widely used in variousassisted reproduction techniques (ART. This study focusedon the question whether in patients receiving ovulation inductionagents the risk for developing pathologic processes onthe ovaries was higher than in those not receiving them, andwhether they were related to the dose and type of ovulationinduction agent.Methods. In a prospective study 380 subjects were enrolled.The study group consisted of 280 women who had undergonean ART procedure three or more times. The control group consistedof 120 infertile women, never included in an ART procedure.All the enrolled subjects underwent the same examinations:a detailed gynecological history was taken, pelvic examinationand vaginal ultrasound were performed, and a bloodsample for tumour marker CA 125 determination was taken.Statistical analysis was done using Chi-square test, t test andlogistic regression.Results. Ultrasound examination revealed pathology on thegenital tract in 136 women in the study group and in 60 womenin the control group. Differences in the incidence of ovarian,tubal and uterine pathology were not statistically significant.The analysis of the medical records showed that the incidenceof ovarian pathology was significantly higher in thestudy than in the control group (p < 0.05. We found no correlationbetween the incidence of ovarian pathology and typeor dose of ovulation induction agent. Increased CA 125 levelswere found in 12 women. In none of the women neither malignantnor borderline malignant disease was found.Conclusions. Although the analysis of the data from medicalhistory showed

  2. Pharmacokinetics of 3-[{sup 125}I]iodo-{alpha}-methyl-L-tyrosine, a tumor imaging agent, after probenecid loading in mice implanted with colon cancer DLD-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Syuichi [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Division of Health Science, Graduate School of Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 9200-942 (Japan); Shikano, Naoto [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan)], E-mail: sikano@ipu.ac.jp; Kotani, Takashi; Ogura, Masato [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Nishii, Ryuichi [Research Institute, Shiga Medical Center, 5-4-30 Moriyama, Moriyama-City, Shiga 524-8524 (Japan); Yoshimoto, Mitsuyoshi [Division of Health Science, Graduate School of Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 9200-942 (Japan); Yamaguchi, Naoto [Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Iwamura, Yukio [Center for Humanities and Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kubota, Nobuo; Ishikawa, Nobuyoshi [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kawai, Keiichi [Division of Health Science, Graduate School of Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 9200-942 (Japan)

    2007-11-15

    Introduction: In order to improve tumor imaging, changes in the pharmacokinetics of 3-[{sup 123}I]iodo-{alpha}-methyl-L-tyrosine ([{sup 123}I]IMT), an artificial amino acid that exhibits high tumor accumulation, after probenecid (PBC) loading was studied in mice implanted with colon cancer DLD-1 cells using {sup 125}I-labeled IMT ([{sup 125}I]IMT). Methods: DLD-1-implanted KSN-slc nude male mice received 740 kBq of [{sup 125}I]IMT via the tail vein at 5 min after 50 mg/kg body weight PBC loading, and autoradiography was performed at 5, 15 and 30 min after injection. Male ddY mice then received 670 kBq of [{sup 125}I]IMT and 50 mg/kg 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH) or p-aminohippurate (PAH) via the tail vein, and kidney autoradiography was performed at 5 min after injection. In vitro inhibition study was then performed based on the accumulation mechanisms of [{sup 125}I]IMT in DLD-1, using 1 mM L-tyrosine, BCH, {alpha}-(methylamino)-isobutyric acid, N-benzoyl-{beta}-alanine, PBC, PAH, 2,4-dinitrophenol and sodium azide. Both Na{sup +}-dependent and Na{sup +}-independent uptake were investigated. Results: Higher tumor accumulation in PBC-loaded DLD-1-implanted mice was seen when compared to control mice. PAH and BCH, respectively, reduced renal accumulation in the tubule segment-2 (S2)-like and S1-like regions. We confirmed that [{sup 125}I]IMT transport is predominantly mediated by L-type amino acid transporter-1 in DLD-1 cells. Conclusions: [{sup 125}I]IMT uptake is mediated by organic anion and amino acid transporters in the kidney. Organic anion transporter inhibitors may yield better tumor images with good tumor/normal tissue radioactivity ratios if adequate administration plans are developed.

  3. Cancer nanomedicine: from drug delivery to imaging.

    Science.gov (United States)

    Chow, Edward Kai-Hua; Ho, Dean

    2013-12-18

    Nanotechnology-based chemotherapeutics and imaging agents represent a new era of "cancer nanomedicine" working to deliver versatile payloads with favorable pharmacokinetics and capitalize on molecular and cellular targeting for enhanced specificity, efficacy, and safety. Despite the versatility of many nanomedicine-based platforms, translating new drug or imaging agents to the clinic is costly and often hampered by regulatory hurdles. Therefore, translating cancer nanomedicine may largely be application-defined, where materials are adapted only toward specific indications where their properties confer unique advantages. This strategy may also realize therapies that can optimize clinical impact through combinatorial nanomedicine. In this review, we discuss how particular materials lend themselves to specific applications, the progress to date in clinical translation of nanomedicine, and promising approaches that may catalyze clinical acceptance of nano.

  4. Imaging Mouse Models of Cancer.

    Science.gov (United States)

    Lyons, Scott Keith

    2015-01-01

    Mouse models of cancer have proven to be an indispensable resource in furthering both our basic knowledge of cancer biology and the translation of new cancer treatments and imaging approaches into the clinic. As mouse models have developed and improved in their ability to model many diverse aspects of the human disease, so too has the need for robust imaging approaches to measure key biological parameters noninvasively. The aim of this review is to provide a brief overview of the various imaging approaches available to researchers today for imaging preclinical cancer models, highlighting their relative strengths and weaknesses. The very nature of modeling cancer in the mouse is also changing, and brief mention will be made on how imaging can maximize the utility of these new, accurate, and genetically versatile models.

  5. Imaging in early phase childhood cancer trials

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, Peter C. [Children' s Hospital of Philadelphia, Division of Clinical Pharmacology and Therapeutics, Philadelphia, PA (United States)

    2009-02-15

    Advances made in the treatment of childhood malignancies during the last four decades have resulted in overall cure rates of approximately 80%, but progress has slowed significantly during the last 10 years, underscoring the need for more effective and less toxic agents. Current research is focused on development of molecularly targeted agents, an era ushered in with the discovery of imatinib mesylate for the treatment of chronic myelogenous leukemia. Since imatinib's introduction into the clinic, an increasing number of tyrosine kinase inhibitors have been developed and entered into clinical trials and practice. Parallel to the initial advances made in molecularly targeted agents has been the development of a spectrum of novel imaging modalities. Future goals for imaging in childhood cancer research thus include (1) patient identification based on target identification or other biologic characteristics of the tumor, (2) assessing pharmacokinetic-pharmacodynamic (PK-PD) effects, and (3) predictive value with an early indication of patient benefit. Development and application of novel imaging modalities for children with cancer can serve to streamline development of molecularly targeted agents. (orig.)

  6. Magnetic Resonance Imaging Contrast Agents: A Review of Literature

    Directory of Open Access Journals (Sweden)

    Zahra Sahraei

    2015-10-01

    Full Text Available  Magnetic Resonance Imaging (MRI contrast agents most commonly agents used in diagnosing different diseases. Several agents have been ever introduced with different peculiar characteristics. They vary in potency, adverse reaction and other specification, so it is important to select the proper agent in different situations. We conducted a systematic literature search in MEDLINE/PUBMED, Web of Science (ISI, Scopus,Google Scholar by using keywords "gadolinium" and "MRI contrast Medias", "Gadofosvest", "Gadobenate" and "Gadoxetate". The most frequent contrast media agents made based on gadolinium (Gd. These are divided into two categories based on the structure of their chelating parts, linear agents and macrocyclic agents. All characteristics of contrast media factors, including efficiency, kinetic properties, stability, side effects and the rate of resolution are directly related to the structure of chelating part of that formulation.In vitro data has shown that the macrocyclic compounds are the most stable Gd-CA as they do not bind to serum proteins, they all possess similar and relatively low relaxivity and the prevalence of Nephrogenic Systemic Fibrosis (NSF has decreased by increasing the use of macrocyclic agents in recent years. No cases of NSF have been recorded after the administration of any of the high-relaxivity protein interacting agents, the vascular imaging agent gadofosveset trisodium (Ablavar, the hepatic imaging agent gadoxetate meglumine (Eovist, and the multipurpose agent gadobenate dimeglumine (MultiHance. In pregnancy and lactating women, stable macrocyclic agent is recommended.

  7. Synthesis and stability test of radiogadolinium(III-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer

    Directory of Open Access Journals (Sweden)

    Hardiani Rahmania

    2015-01-01

    Full Text Available Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obtain better sensitivity, specificity and depiction localization of the disease. In this study, we developed a new molecular imaging agent, radiogadolinium(III-DOTA-PAMAM G3.0-trastuzumab in the form of 147Gd-DOTA-PAMAM G3.0-trastuzumab, that can be both target-specific radiopharmaceutical in SPECT as well as targeted contrast agent in MRI for the purpose of diagnosis of HER-2 positive breast cancer. 147Gd radionuclide emits γ-rays that can be used in SPECT modality, but because of technical constraint, 147Gd radionuclide was simulated by its radioisotope, 153Gd. Gd-DOTA complex has also been known as good MRI contrast agent. PAMAM G3.0 is useful to concentrate Gd-DOTA compelexes in large quantities, thus minimizing the number of trastuzumab molecules used. Trastuzumab is human monoclonal antibody that can spesifically interact with HER-2. Synthesis of radiogadolinium(III-DOTA-PAMAM G3.0-trastuzumab was initiated by conjugating DOTA NHS ester ligand with PAMAM G3.0 dendrimer. The DOTA-PAMAM G3.0 produced was conjugated to trastuzumab molecule and labeled with 153Gd. Characterization DOTA-PAMAM G3.0-trastuzumab immunoconjugate was performed using HPLC system equipped with SEC. The formation of immunoconjugate was indicated by the shorter retention time (6.82 min compared to that of trastuzumab (7.06 min. Radiochemical purity of radiogadolinium(III-DOTA-PAMAM G3.0-trastuzumab was >99% after purification process by PD-10 desalting column. Radiogadolinium(III-DOTA-PAMAM G3.0-trastuzumab compound was stable at room temperature and at 2–8 0C as indicated by its radiochemical purity 97.6 ± 0.5%–99.1 ± 0.5% after 144 h storage.

  8. Nuclear medicine for imaging of epithelial ovarian cancer.

    Science.gov (United States)

    Abedi, Seyed Mohammad; Mardanshahi, Alireza; Shahhosseini, Roza; Hosseinimehr, Seyed Jalal

    2016-05-01

    Cancer is one of the leading causes of mortality worldwide. Usually, the diagnosis of cancer at an early stage is important to facilitate proper treatment and survival. Nuclear medicine has been successfully used in the diagnosis, staging, therapy and monitoring of cancers. Single-photon emission computed tomography and PET-based companion imaging agents are in development for use as a companion diagnostic tool for patients with ovarian cancer. The present review discusses the basic and clinical studies related to the use of radiopharmaceuticals in the diagnosis and management of ovarian cancer, focusing on their utility and comparing them with other imaging techniques such as computed tomography and MRI.

  9. Quantitative Image Informatics for Cancer Research (QIICR) | Informatics Technology for Cancer Research (ITCR)

    Science.gov (United States)

    Imaging has enormous untapped potential to improve cancer research through software to extract and process morphometric and functional biomarkers. In the era of non-cytotoxic treatment agents, multi- modality image-guided ablative therapies and rapidly evolving computational resources, quantitative imaging software can be transformative in enabling minimally invasive, objective and reproducible evaluation of cancer treatment response. Post-processing algorithms are integral to high-throughput analysis and fine- grained differentiation of multiple molecular targets.

  10. Aspirin as a Chemopreventive Agent for Cancer: a New Hope?

    Directory of Open Access Journals (Sweden)

    Isnatin Miladiyah

    2016-01-01

    Full Text Available Introduction: inflammation has been shown to play a major role in the pathogenesis of cancer. Inflammatory process activates the immune system through pro-inflammatory mediators and subsequent triggers transformation into malignant cells. Some tumors or cancers has been associated with chronic infections, such as hepatitis B and C viruses (hepatocellular carcinoma, human papilloma virus (cervical cancer, Helicobacter pylori (gastric cancer and lymphoma, and prostatitis (prostate cancer. A considerable study have investigated the benefits of aspirin for the prevention and treatment of cancer or tumors. Objectives: This paper aims to describe the relationship between inflammation and cancer incidence, so that use of aspirin as an anti-inflammatory agent is a rational choice in the treatment and prevention of cancer. Conclusion: Aspirin potential for chemoprevention of various types of cancer. Considering the high risk of side effects of aspirin, aspirin is not intended as a routine therapy to prevent the occurrence of cancer.

  11. Radiological imaging of rectal cancer

    Directory of Open Access Journals (Sweden)

    Lidija Lincender-Cvijetić

    2012-11-01

    Full Text Available This article discusses the possibilities of diagnosing abdominal imaging in patients with rectal cancer, detecting lesions and assessing the stage of the lesions, in order to select the appropriate therapy. Before the introduction of imaging technologies, the diagnosis of colorectal pathology was based on conventional methods of inspecting intestines with a barium enema, with either a single or double contrast barium enema. Following the development of endoscopic methods and the wide use of colonoscopy, colonoscopy became the method of choice for diagnosing colorectal diseases. The improvement of Computerized Tomography (CT and Magnetic Resonance Imaging (MRI, gave us new possibilities for diagnosing colorectal cancer. For rectal cancer, trans-rectal US (TRUS or endo-anal US (EAUS have a significant role. For staging rectal cancer, the Multi Slice Computed Tomography (MSCT is not the method of choice, but Magnetic Resonance Imaging (MRI is preferred when it comes to monitoring the rectum. Therole of the MRI in the T staging of rectal cancer is crucial in preoperative assessment of: thickness – the width of the tumor, the extramural invasion, the circumference of resection margin (CRM, andthe assessment of the inclusion of mesorectal fascia. For successful execution of surgical techniques, good diagnostic imaging of the cancer is necessary in order to have a low level of recurrence. According to medical studies, the sensitivity of FDG-PET in diagnosing metastatic nodals is low, but for now it is not recommended in routine diagnosis of metastatic colorectal carcinoma.

  12. Improved radionuclide bone imaging agent injection needle withdrawal method can improve image quality

    International Nuclear Information System (INIS)

    Qin Yongmei; Wang Laihao; Zhao Lihua; Guo Xiaogang; Kong Qingfeng

    2009-01-01

    Objective: To investigate the improvement of radionuclide bone imaging agent injection needle withdrawal method on whole body bone scan image quality. Methods: Elbow vein injection syringe needle directly into the bone imaging agent in the routine group of 117 cases, with a cotton swab needle injection method for the rapid pull out the needle puncture point pressing, pressing moment. Improvement of 117 cases of needle injection method to put two needles into the skin swabs and blood vessels, pull out the needle while pressing two or more entry point 5min. After 2 hours underwent whole body bone SPECT imaging plane. Results: The conventional group at the injection site imaging agents uptake rate was 16.24%, improved group was 2.56%. Conclusion: The modified bone imaging agent injection needle withdrawal method, injection-site imaging agent uptake were significantly decreased whole body bone imaging can improve image quality. (authors)

  13. Modified natural nanoparticles as contrast agents for medical imaging

    NARCIS (Netherlands)

    Cormode, David P.; Jarzyna, Peter A.; Mulder, Willem J. M.; Fayad, Zahi A.

    2010-01-01

    The development of novel and effective contrast agents is one of the drivers of the ongoing improvement in medical imaging. Many of the new agents reported are nanoparticle-based. There are a variety of natural nanoparticles known, e.g. lipoproteins, viruses or ferritin. Natural nanoparticles have

  14. Contrast agents for photoacoustic and thermoacoustic imaging: a review.

    Science.gov (United States)

    Wu, Dan; Huang, Lin; Jiang, Max S; Jiang, Huabei

    2014-12-18

    Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

  15. Contrast Agents for Photoacoustic and Thermoacoustic Imaging: A Review

    Directory of Open Access Journals (Sweden)

    Dan Wu

    2014-12-01

    Full Text Available Photoacoustic imaging (PAI and thermoacoustic imaging (TAI are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

  16. A dual function theranostic agent for near-infrared photoacoustic imaging and photothermal therapy

    Science.gov (United States)

    Upputuri, Paul Kumar; Huang, Shuo; Wang, Mingfeng; Pramanik, Manojit

    2016-03-01

    Theranostic, defined as combining diagnostic and therapeutic agents, has attracted more attention in biomedical application. It is essential to monitor diseased tissue before treatment. Photothermal therapy (PTT) is a promising treatment of cancer tissue due to minimal invasion, unharmful to normal tissue and high efficiency. Photoacoustic tomography (PAT) is a hybrid nonionizing biomedical imaging modality that combines rich optical contrast and high ultrasonic resolution in a single imaging modality. The near infra-red (NIR) wavelengths, usually used in PAT, can provide deep penetration at the expense of reduced contrast, as the blood absorption drops in the NIR range. Exogenous contrast agents with strong absorption in the NIR wavelength range can enhance the photoacoustic imaging contrast as well as imaging depth. Most theranostic agents incorporating PAT and PTT are inorganic nanomaterials that suffer from poor biocompatibility and biodegradability. Herein, we present an benzo[1,2-c;4,5-c'] bis[1,2,5] thiadiazole (BBT), based theranostic agent which not only acts as photoacoustic contrast agent but also a photothermal therapy agent. Experiments were performed on animal blood and organic nanoparticles embedded in a chicken breast tissue using PAT imaging system at ~803 nm wavelengths. Almost ten time contrast enhancement was observed from the nanoparticle in suspension. More than 6.5 time PA signal enhancement was observed in tissue at 3 cm depth. HeLa cell lines was used to test photothermal effect showing 90% cells were killed after 10 min laser irradiation. Our results indicate that the BBT - based naoparticles are promising theranostic agents for PAT imaging and cancer treatment by photothermal therapy.

  17. Sanguinarine: A Novel Agent Against Prostate Cancer

    National Research Council Canada - National Science Library

    Ahmad, Nihal

    2005-01-01

    .... Therefore, the search for novel agents and approaches for the treatment of CaP continues. Natural plant-based products have shown promise as anticancer agents. Sanguinarine (13-methyl[ 1,3]benzodioxolo[5,6-c]- 1,3-dioxolo[4,5-i]phenanthridinium...

  18. Evaluation of potential gastrointestinal contrast agents for echoplanar MR imaging

    International Nuclear Information System (INIS)

    Reimer, P.; Schmitt, F.; Ladebeck, R.; Graessner, J.; Schaffer, B.

    1993-01-01

    The purpose of this study was to investigate approved aqueous gastrointestinal contrast agents for use in abdominal EPI. Conventional and echoplanar MR imaging experiments were performed with 1.0 Tesla whole body systems. Phantom measurements of Gastrografin, barium sulfate suspension, oral gadopentetate dimeglumine, water, and saline were performed. Signal intensity (SI) of aqueous oral barium sulfate and iodine based CT contrast agents was lower on conventional spin-echo (SE), Flash, and Turbo-Flush images than on EP images. The contrast agents exhibited higher SI on T2-weighted SE PE images and TI-time dependence on inversion recovery EP-images. The barium sulfate suspension was administered in volunteers to obtain information about bowel lumen enhancement and susceptibility artifacts. Oral administration of the aqueous barium sulfate suspension increased bowel lumen signal and reduced susceptibility artifacts. (orig.)

  19. Lung cancer imaging

    CERN Document Server

    Ravenel, James G

    2013-01-01

    This book provides a guide to the diagnosis, staging and overview of the management of lung cancer relevant to practicing radiologists so that they can better understand the decision making issues and provide more useful communication to treating physicians.

  20. Targeted nanodiamonds as phenotype-specific photoacoustic contrast agents for breast cancer.

    Science.gov (United States)

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Cheng, Kun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M Laird

    2015-03-01

    The aim is to develop irradiated nanodiamonds (INDs) as a molecularly targeted contrast agent for high-resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. The surface of acid treated radiation-damaged nanodiamonds was grafted with PEG to improve its stability and circulation time in blood, followed by conjugation to an anti-HER2 peptide with a final nanoparticle size of approximately 92 nm. Immunocompetent mice bearing orthotopic HER2-positive or negative tumors were administered INDs and PA imaged using an 820-nm near-infrared laser. PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 h. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are nontoxic. PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high-resolution (sub-mm) and phenotype-specific monitoring of cancer growth.

  1. In vitro evaluation of the L-peptide modified magnetic lipid nanoparticles as targeted magnetic resonance imaging contrast agent for the nasopharyngeal cancer.

    Science.gov (United States)

    Chen, Yung-Chu; Min, Chia-Na; Wu, Han-Chung; Lin, Chin-Tarng; Hsieh, Wen-Yuan

    2013-11-01

    The purpose of this study was to analyze the encapsulation of superparamagnetic iron oxide nanoparticles (SPION) by the lipid nanoparticle conjugated with the 12-mer peptides (RLLDTNRPLLPY, L-peptide), and the delivery of this complex into living cells. The lipid nanoparticles employed in this work were highly hydrophilic, stable, and contained poly(ethylene-glycol) for conjugation to the bioactive L-peptide. The particle sizes of two different magnetic lipid nanoparticles, L-peptide modified (LML) and non-L-peptide modified (ML), were both around 170 nm with a narrow range of size disparity. The transversal relaxivity, r2, for both LML and ML nanoparticles were found to be significantly higher than the longitudinal relaxivity r1 (r2/r1 > 20). The in vitro tumor cell targeting efficacy of the LML nanoparticles were evaluated and compared to the ML nanoparticles, upon observing cellular uptake of magnetic lipid nanoparticles by the nasopharyngeal carcinoma cells, which express cell surface specific protein for the L-peptide binding revealed. In the Prussian blue staining experiment, cells incubated with LML nanoparticles indicated much higher intracellular iron density than cells incubated with only the ML and SPION nanoparticles. In addition, the MTT assay showed the negligible cell cytotoxicity for LML, ML and SPION nanoparticles. The MR imaging studies demonstrate the better T2-weighted images for the LML-nanoparticle-loaded nasopharyngeal carcinoma cells than the ML- and SPION-loaded cells.

  2. Targeted delivery of cancer-specific multimodal contrast agents for intraoperative detection of tumor boundaries and therapeutic margins

    Science.gov (United States)

    Xu, Ronald X.; Xu, Jeff S.; Huang, Jiwei; Tweedle, Michael F.; Schmidt, Carl; Povoski, Stephen P.; Martin, Edward W.

    2010-02-01

    Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative information that supports critical decision-making in the operating room. Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72 antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies. Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms, LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model. Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative detection of tumor boundaries and therapeutic margins.

  3. 64Cu loaded liposomes as positron emission tomography imaging agents

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Binderup, Tina; Rasmussen, Palle

    2011-01-01

    We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper...

  4. Advanced Contrast Agents for Multimodal Biomedical Imaging Based on Nanotechnology.

    Science.gov (United States)

    Calle, Daniel; Ballesteros, Paloma; Cerdán, Sebastián

    2018-01-01

    Clinical imaging modalities have reached a prominent role in medical diagnosis and patient management in the last decades. Different image methodologies as Positron Emission Tomography, Single Photon Emission Tomography, X-Rays, or Magnetic Resonance Imaging are in continuous evolution to satisfy the increasing demands of current medical diagnosis. Progress in these methodologies has been favored by the parallel development of increasingly more powerful contrast agents. These are molecules that enhance the intrinsic contrast of the images in the tissues where they accumulate, revealing noninvasively the presence of characteristic molecular targets or differential physiopathological microenvironments. The contrast agent field is currently moving to improve the performance of these molecules by incorporating the advantages that modern nanotechnology offers. These include, mainly, the possibilities to combine imaging and therapeutic capabilities over the same theranostic platform or improve the targeting efficiency in vivo by molecular engineering of the nanostructures. In this review, we provide an introduction to multimodal imaging methods in biomedicine, the sub-nanometric imaging agents previously used and the development of advanced multimodal and theranostic imaging agents based in nanotechnology. We conclude providing some illustrative examples from our own laboratories, including recent progress in theranostic formulations of magnetoliposomes containing ω-3 poly-unsaturated fatty acids to treat inflammatory diseases, or the use of stealth liposomes engineered with a pH-sensitive nanovalve to release their cargo specifically in the acidic extracellular pH microenvironment of tumors.

  5. Targeting SR-BI for cancer diagnostics, imaging and therapy

    Directory of Open Access Journals (Sweden)

    Maneesha Amrita Rajora

    2016-09-01

    Full Text Available Scavenger receptor class B type I (SR-BI plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumours and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents. This brief review highlights these key developments in SR-BI-targeted cancer therapies and imaging probes. Special attention is given to the exploration of high density lipoprotein nanomimetic platforms that take advantage of upregulated SR-BI expression to facilitate targeted drug-delivery and cancer diagnostics, and promising future directions in the development of these agents.

  6. Lung cancer and angiogenesis imaging using synchrotron radiation

    International Nuclear Information System (INIS)

    Liu Xiaoxia; Zhao Jun; Xu, Lisa X; Sun Jianqi; Gu Xiang; Liu Ping; Xiao Tiqiao

    2010-01-01

    Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue. The effect of the object-detector distance and the energy level on the phase-contrast difference was investigated and found to be in good agreement with the theory of in-line phase-contrast imaging. Moreover, 3D image reconstruction of lung tumor angiogenesis was obtained for the first time using a contrast agent, demonstrating the feasibility of micro-angiography with synchrotron radiation for imaging tumor angiogenesis deep inside the body.

  7. Using Nanoparticles in Medicine for Liver Cancer Imaging

    Directory of Open Access Journals (Sweden)

    Farideh Farokhi Moghadam

    2017-07-01

    Full Text Available One of the most important types of liver cancer is hepatocellular carcinoma (HCC. HCC is the fifth most common cancer, and its correct diagnosis is very important. For the quick diagnosis of HCC, the use of nanoparticles is helpful. The major applications of nanoparticles are in medicine for organ imaging. Two methods of liver imaging are X-ray computed tomography (CT and magnetic resonance imaging (MRI. In this review, we attempt to summarize some of the contrast agents used in imaging such as superparamagnetic iron oxide nanoparticles (SPIONs and iron oxide nanoparticles (IONPs, various types of enhanced MRI for the liver, and nanoparticles like gold (AuNPs, which is used to develop novel CT imaging agents.

  8. Clinical photoacoustic imaging of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Valluru, Keerthi S.; Willmann, Juergen K. [Dept. of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford (United States)

    2016-08-15

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  9. Gadolinium-based contrast agents in pediatric magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gale, Eric M.; Caravan, Peter [Massachusetts General Hospital, Harvard Medical School, Department of Radiology, The Martinos Center for Biomedical Imaging, Boston, MA (United States); Rao, Anil G. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); McDonald, Robert J. [College of Medicine, Mayo Clinic, Department of Radiology, Rochester, MN (United States); Winfeld, Matthew [University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (United States); Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Pediatric Radiology, Cincinnati, OH (United States); Gee, Michael S. [MassGeneral Hospital for Children, Harvard Medical School, Division of Pediatric Imaging, Department of Radiology, Boston, MA (United States)

    2017-05-15

    Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available. (orig.)

  10. Gadolinium-based contrast agents in pediatric magnetic resonance imaging

    International Nuclear Information System (INIS)

    Gale, Eric M.; Caravan, Peter; Rao, Anil G.; McDonald, Robert J.; Winfeld, Matthew; Fleck, Robert J.; Gee, Michael S.

    2017-01-01

    Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available. (orig.)

  11. The clinical use of contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bydder, G.M.

    1987-01-01

    Interest in the use of external agents to increase tissue contrasts has come from many sources dating back to the earliest work in NMR, to animal studies and to the widespread use of contrast agents in conventional radiological practice. The first clinical magnetic resonance images were published in 1980 and in the following year a brief account of the use of the paramagnetic agents in human volunteers was established. It was apparent relatively early in the development of magnetic resonance imaging (MRI) that a high level of soft tissue contrast was available de novo and the need for externally administered agents might therefore be small. This observation was tempered by the fact that separation of tumour from oedema was frequently better with contrast enhanced CT X-ray than with unenhanced MRI and that of a contrast agent might therefore be needed for MRI. At the end of 1983 the first parenteral agent gadoliminum diethylene triamine pentaacetic acid (Gd-DTPA) was used in volunteers and clinical studies began in 1984. At the present time only molecular O/sub 2/, oral iron compounds and Gd-DTPA are in clinical use although there are a number of other agents which have been used in animals and some of these may become available for clinical use in the foreseeable future

  12. Mesoscopic and macroscopic optoacoustic imaging of cancer.

    Science.gov (United States)

    Taruttis, Adrian; van Dam, Gooitzen M; Ntziachristos, Vasilis

    2015-04-15

    Optoacoustic imaging combines the rich contrast of optical methods with the resolution of ultrasound imaging. It can therefore deliver optical visualization of cancer far deeper in tissue than optical microscopy and other conventional optical imaging methods. Technological progress and novel contrast media have resulted in optoacoustic imaging being propagated to basic cancer research and in clinical translation projects. We briefly review recent technological advances, showcase the ability to resolve unique cancer biomarkers based on spectral features at different imaging scales, and highlight the imaging performance achieved in preclinical and clinical imaging applications. . ©2015 American Association for Cancer Research.

  13. Multimodal Imaging Nanoparticles Derived from Hyaluronic Acid for Integrated Preoperative and Intraoperative Cancer Imaging

    Directory of Open Access Journals (Sweden)

    William M. Payne

    2017-01-01

    Full Text Available Surgical resection remains the most promising treatment strategy for many types of cancer. Residual malignant tissue after surgery, a consequence in part due to positive margins, contributes to high mortality and disease recurrence. In this study, multimodal contrast agents for integrated preoperative magnetic resonance imaging (MRI and intraoperative fluorescence image-guided surgery (FIGS are developed. Self-assembled multimodal imaging nanoparticles (SAMINs were developed as a mixed micelle formulation using amphiphilic HA polymers functionalized with either GdDTPA for T1 contrast-enhanced MRI or Cy7.5, a near infrared fluorophore. To evaluate the relationship between MR and fluorescence signal from SAMINs, we employed simulated surgical phantoms that are routinely used to evaluate the depth at which near infrared (NIR imaging agents can be detected by FIGS. Finally, imaging agent efficacy was evaluated in a human breast tumor xenograft model in nude mice, which demonstrated contrast in both fluorescence and magnetic resonance imaging.

  14. Gold nanoparticles as a contrast agent for in vivo tumor imaging with photoacoustic tomography

    International Nuclear Information System (INIS)

    Zhang, Q; Jiang, H; Iwakuma, N; Grobmyer, S R; Sharma, P; Moudgil, B M; Wu, C; McNeill, J

    2009-01-01

    Photoacoustic tomography (PAT) is a rapidly emerging non-invasive imaging technology that integrates the merits of high optical contrast with high ultrasound resolution. The ability to quantitatively and non-invasively image nanoparticles has important implications for the development of nanoparticles as in vivo cancer diagnostic and therapeutic agents. In this study, the ability of systemically administered poly(ethylene glycol)-coated (PEGylated) gold nanoparticles as a contrast agent for in vivo tumor imaging with PAT has been evaluated. We demonstrate that gold nanoparticles (20 and 50 nm) have high photoacoustic contrast as compared to mouse tissue ex vivo. Gold nanoparticles can be visualized in mice in vivo following subcutaneous administration using PAT. Following intravenous administration of PEGylated gold nanoparticles to tumor-bearing mice, accumulation of gold nanoparticles in tumors can be effectively imaged with PAT. With gold nanoparticles as a contrast agent, PAT has important potential applications in the image guided therapy of superficial tumors such as breast cancer, melanoma and Merkel cell carcinoma.

  15. Detection of apoptosis in cancer cell lines using Surface Plasmon Resonance imaging

    NARCIS (Netherlands)

    Stojanović, I.; van Hal, Y.; van der Velden, T.J.G.; Schasfoort, Richardus B.M.; Terstappen, Leonardus Wendelinus Mathias Marie

    2016-01-01

    Induction of apoptosis in cancer cells by therapeutic agents is an important event to detect the potential effectiveness of therapies. Here we explore the potential of Surface Plasmon Resonance imaging (SPRi) to assess apoptosis in cancer cells exposed to therapeutic agents by measuring the

  16. A brief account of nanoparticle contrast agents for photoacoustic imaging

    OpenAIRE

    Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V.; Lanza, Gregory M.

    2013-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be view...

  17. Electric and magnetic properties of contrast agents for thermoacoustic imaging

    Science.gov (United States)

    Ogunlade, Olumide; Beard, Paul

    2014-03-01

    The endogenous contrast in thermoacoustic imaging is due to the water and ionic content in tissue. This results in poor tissue speci city between high water content tissues. As a result, exogenous contrast agents have been employed to improve tissue speci city and also increase the SNR. An investigation into the sources of contrast produced by several exogenous contrast agents is described. These include three gadolinium based MRI contrast agents, iron oxide particles, single wall carbon nanotubes, saline and sucrose solutions. Both the dielectric and magnetic properties of contrast agents at 3GHz have been measured using microwave resonant cavities. The DC conductivity of the contrast agents were also measured. It is shown that the measured increase in dielectric contrast, relative to water, is due to dipole rotational loss of polar non electrolytes, ionic loss of electrolytes or a combination of both. It is shown that for the same dielectric contrast, electrolytes make better thermoacoustic contrast agents than non-electrolytes, for thermoacoustic imaging.

  18. Mesoscopic and Macroscopic Optoacoustic Imaging of Cancer

    NARCIS (Netherlands)

    Taruttis, Adrian; van Dam, Gooitzen M.; Ntziachristos, Vasilis

    2015-01-01

    Optoacoustic imaging combines the rich contrast of optical methods with the resolution of ultrasound imaging. It can therefore deliver optical visualization of cancer far deeper in tissue than optical microscopy and other conventional optical imaging methods. Technological progress and novel

  19. A brief account of nanoparticle contrast agents for photoacoustic imaging.

    Science.gov (United States)

    Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V; Lanza, Gregory M

    2013-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds. Copyright © 2013 Wiley Periodicals, Inc.

  20. Multifunctional gold nanostars for molecular imaging and cancer therapy

    OpenAIRE

    Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew M.; Register, Janna K.; Vo-Dinh, Tuan

    2015-01-01

    Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL), and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enab...

  1. Environmental carcinogenic agents and cancer prevention. Risk assessment and management

    International Nuclear Information System (INIS)

    Tsugane, Shoichiro

    2013-01-01

    Many agents in our environment have been established as being carcinogenic, and in most cases, the carcinogenic properties of these agents were identified because of high-dose occupational or accidental exposure. Risk characterization, taking into account the dose-response relationship, and exposure assessment are essential for risk assessment and subsequent cancer prevention. Based on scientific risk assessment, risk management should be conducted practically by considering the economic, social, political, and other technical issues and by balancing the risks and benefits. Asbestos and environmental tobacco smoke are typical examples of established carcinogenic agents in the general environment, contributing to low-dose exposure. Further epidemiological studies are required to investigate the carcinogenicity of low-dose exposure to known carcinogenic agents such as arsenic and cadmium through dietary intake, radiation via medical and natural exposure, and air pollution due to diesel exhaust. In contrast, occupational chemical exposure to 1,2-dichloropropane and/or dichloromethane, whose carcinogenicity had not been established, was suggested to cause cholangiocarcinoma among workers involved in offset color proof-printing only after a rare situation of high-dose exposure was unveiled. Continuous monitoring of unusual cancer occurrences in target populations such as workers in occupational and regional settings as well as exposure reduction to suspected carcinogenic agents to levels as low as reasonably achievable is essential for reducing the risk of cancer due to environmental carcinogens. (author)

  2. PET imaging in breast cancer

    International Nuclear Information System (INIS)

    Bombardieri, E.; Crippa, F.

    2001-01-01

    The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18 F has the advantages of the a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complete other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. These statements are coming from the examination of more than 2000 breast cancer detection

  3. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate

    DEFF Research Database (Denmark)

    Nelson, Sarah J; Kurhanewicz, John; Vigneron, Daniel B

    2013-01-01

    This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-¹³C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-f...

  4. Hypofractionated Radiotherapy as Local Hemostatic Agent in Advanced Cancer

    Science.gov (United States)

    Rasool, Malik Tariq; Manzoor, Najmi Arshad; Mustafa, Syed Arshad; Maqbool, Lone Mohammad; Afroz, Fir

    2011-01-01

    Purpose: Tumor bleeding continues to remain a challenge in an oncological setting, and radiotherapy has been studied as a local hemostatic agent. We studied the role of local radiotherapy in controlling bleeding at our center. Materials and Methods: We reviewed 25 treated cases (cancer urinary bladder: 12, lung cancer: 5, cervical cancer: 4, uterine cancer: 1, rectal cancer: 2, schwanoma: 1) at our center from March 2008 to December 2010. All patients had either an advanced or recurrent disease. Radiotherapy schedule was either 20 Gray in 5 fractions or 15 Gray in 5 fractions and was delivered with Cobalt 60. Results and Conclusion: Of 25 patients, 22 (88%) responded, and there was complete cessation of bleeding. Both 15 Gray and 20 Gray dose schedule had equal efficacy. Treatment was well tolerated without any intermission. Radiotherapy is a safe and effective option in controlling tumor bleeding. PMID:22346046

  5. Evaluation of the Efficacy of Targeted Imaging Agents

    Science.gov (United States)

    Graham, Michael M.; Weber, Wolfgang A.

    2016-01-01

    This paper presents our adaptation of Fryback and Thornbury’s hierarchical scheme for modeling the efficacy of diagnostic imaging systems. The original scheme was designed to evaluate new medical imaging systems but is less successful when applied to evaluate new radiopharmaceuticals. The proposed adaptation, which is specifically directed toward evaluating targeted imaging agents, has 6 levels: in vitro characterization, in vivo animal studies, initial human studies, impact on clinical care (change in management), impact on patient outcome, and societal efficacy. These levels, particularly the first four, implicitly define the sequence of studies needed to move an agent from the radiochemistry synthesis laboratory to the clinic. Completion of level 4 (impact on clinical care) should be sufficient for initial approval and reimbursement. We hope that the adapted scheme will help streamline the process and assist in bringing new targeted radiopharmaceuticals to approval over the next few years. PMID:26769867

  6. Diagnostic imaging of lung cancer with In-111-MDEGD

    International Nuclear Information System (INIS)

    Nakajima, Susumu; Hayashi, Hideo; Maeda, Tomio

    1987-01-01

    Indium-111-mono DTPA-ethyleneglycol Ga deuterporphyrin (In-111-MDEGD) is a new tumor imaging agent in lung cancer. The agent has been studied with golden hamsters bearing adenocarcinoma, C57 black mice bearing Lewis lung adenocarcinoma, and nude mice bearing human lung adenocarcinoma xerografts. It has been revealed that the tumor-to-lung, tumor-to-kidney, and tumor-to-blood ratios are higher for In-111-MDEGD than for Ga-67 citrate widely used in imaging tumors, and that the agent is not accumulated in inflammatory lesions. The results were encouraging enough to start clinical diagnostic trials in lung cancer. In this paper, an overview of In-111-MDEGD, along with its preliminary data, is given. (Namekawa, K.)

  7. Transrectal ultrasound imaging and prostate cancer

    NARCIS (Netherlands)

    Goossen, Tjerk; Wijkstra, Hessel

    2003-01-01

    Prostate cancer is one of the most important causes of death from cancer in men. Ultrasound imaging is frequently used in the diagnosis of prostate cancer. This paper presents an overview of currently available ultrasound imaging techniques. The underlying principles and methods are discussed

  8. Magnetic nanoparticles as contrast agents for molecular imaging in medicine

    Science.gov (United States)

    O'Donnell, Matthew

    2018-05-01

    For over twenty years, superparamagnetic nanoparticles have been developed for a number of medical applications ranging from bioseparations, magnetic drug targeting, hyperthermia and imaging. Recent studies have shown that they can be functionalized for in vivo biological targeting, potentially enabling nanoagents for molecular imaging and site-localized drug delivery. Here we review several imaging technologies developed using functionalized superparamagnetic iron oxide nanoparticles (SPIONs) as targeted molecular agents. Several imaging modalities have exploited the large induced magnetic moment of SPIONs to create local mechanical force. Magnetic force microscopy can probe nanoparticle uptake in single cells. For in vivo applications, magnetomotive modulation of primary images in ultrasound (US), photoacoustics (PA), and optical coherence tomography (OCT) can help identify very small concentrations of nanoagents while simultaneously suppressing intrinsic background signals from tissue.

  9. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

    Directory of Open Access Journals (Sweden)

    D’Hollander A

    2016-08-01

    Full Text Available Antoine D’Hollander,1–3 Evelien Mathieu,1,4 Hilde Jans,1 Greetje Vande Velde,2,3 Tim Stakenborg,1 Pol Van Dorpe,1,4 Uwe Himmelreich,2,3 Liesbet Lagae1,4 1Department of Life Science Technology, Imec, 2Department of Imaging and Pathology, Faculty of Medicine, Biomedical MRI Unit, 3Faculty of Medicine, Molecular Small Animal Imaging Center (MoSAIC, 4Department of Physics, Faculty of Sciences, Laboratory of Solid State Physics and Magnetism, KU Leuven, Leuven, Belgium Abstract: The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS, realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3. Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. Keywords: SERS, gold nanostars, cancer imaging, Raman active

  10. Image guided prostate cancer treatments

    Energy Technology Data Exchange (ETDEWEB)

    Bard, Robert L. [Bard Cancer Center, Biofoundation for Angiogenesis Research and Development, New York, NY (United States); Fuetterer, Jurgen J. [Radboud Univ. Nijmegen, Medical Centre (Netherlands). Dept. of Radiology; Sperling, Dan (ed.) [Sperling Prostate Center, Alpha 3TMRI, New York, NY (United States)

    2014-07-01

    Systematic overview of the application of ultrasound and MRI in the diagnosis and treatment of diseases of the lower urinary tract. Detailed information on image-guided therapies, including focused ultrasound, photodynamic therapy, and microwave and laser ablation. Numerous high-quality illustrations based on high-end equipment. Represents the state of the art in Non Invasive Imaging and Minimally Invasive Ablation Treatment (MIAT). Image-Guided Prostate Cancer Treatments is a comprehensive reference and practical guide on the technology and application of ultrasound and MRI in the male pelvis, with special attention to the prostate. The book is organized into three main sections, the first of which is devoted to general aspects of imaging and image-guided treatments. The second section provides a systematic overview of the application of ultrasound and MRI to the diagnosis and treatment of diseases of the lower urinary tract. Performance of the ultrasound and MRI studies is explained, and the normal and abnormal pathological anatomy is reviewed. Correlation with the ultrasound in the same plane is provided to assist in understanding the MRI sequences. Biopsy and interventional procedures, ultrasound-MRI fusion techniques, and image-guided therapies, including focused ultrasound, photodynamic therapy, microwave and laser ablation, are all fully covered. The third section focuses on securing treatment effectiveness and the use of follow-up imaging to ensure therapeutic success and detect tumor recurrence at an early stage, which is vital given that prompt focal treatment of recurrence is very successful. Here, particular attention is paid to the role of Doppler ultrasound and DCE-MRI technologies. This book, containing a wealth of high-quality illustrations based on high-end equipment, will acquaint beginners with the basics of prostate ultrasound and MRI, while more advanced practitioners will learn new skills, means of avoiding pitfalls, and ways of effectively

  11. Ad-PUMA sensitizes ovarian cancer cells to chemotherapeutic agents.

    Science.gov (United States)

    Luan, Q-C; Sun, Y-R; Han, P; Chen, Y

    2015-12-01

    Ovarian cancer accounted for the first cause of death in female reproductive system tumor even with the operation and chemotherapy. We sought to evaluate the therapeutic potential of p53 up-regulated modulator of apoptosis (PUMA) in ovarian cancer. An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents, was used to treat two different ovarian cancer cell lines. The mechanism of PUMA-mediated growth suppression and apoptosis was investigated by analysis of caspase-9 activation and the change of mitochondrial membrane potential (Δψm). The exogenous PUMA was expressed 6 h after Ad-PUMA infection, which increased the chemosensitivity of the cancer cells and decreased the IC50 of chemotherapeutic agents compared with uninfected cells. The apoptotic percentage of OVCAR-3 and SKOV3 increased greatly compared with Taxol or Cisplatin alone. There was shear zone in caspase-9 and Δψm decrease after Ad-PUMA infection which suggested apoptosis started in mitochondrial mediated pathway. PUMA plays a role in suppressing tumor growth and sensitizing ovarian cancer cells to anticancer drugs and may be a promising tool for cancer biotherapy.

  12. Examining multi-component DNA-templated nanostructures as imaging agents

    Science.gov (United States)

    Jaganathan, Hamsa

    2011-12-01

    Magnetic resonance imaging (MRI) is the leading non-invasive tool for disease imaging and diagnosis. Although MRI exhibits high spatial resolution for anatomical features, the contrast resolution is low. Imaging agents serve as an aid to distinguish different types of tissues within images. Gadolinium chelates, which are considered first generation designs, can be toxic to health, while ultra-small, superparamagnetic nanoparticles (NPs) have low tissue-targeting efficiency and rapid bio-distribution, resulting to an inadequate detection of the MRI signal and enhancement of image contrast. In order to improve the utility of MRI agents, the challenge in composition and structure needs to be addressed. One-dimensional (1D), superparamagnetic nanostructures have been reported to enhance magnetic and in vivo properties and therefore has a potential to improve contrast enhancement in MRI images. In this dissertation, the structure of 1D, multi-component NP chains, scaffolded on DNA, were pre-clinically examined as potential MRI agents. First, research was focused on characterizing and understanding the mechanism of proton relaxation for DNA-templated NP chains using nuclear magnetic resonance (NMR) spectrometry. Proton relaxation and transverse relaxivity were higher in multi-component NP chains compared to disperse NPs, indicating the arrangement of NPs on a 1D structure improved proton relaxation sensitivity. Second, in vitro evaluation for potential issues in toxicity and contrast efficiency in tissue environments using a 3 Tesla clinical MRI scanner was performed. Cell uptake of DNA-templated NP chains was enhanced after encapsulating the nanostructure with layers of polyelectrolytes and targeting ligands. Compared to dispersed NPs, DNA-templated NP chains improved MRI contrast in both the epithelial basement membrane and colon cancer tumors scaffolds. The last part of the project was focused on developing a novel MRI agent that detects changes in DNA methylation

  13. Ions doped melanin nanoparticle as a multiple imaging agent.

    Science.gov (United States)

    Ha, Shin-Woo; Cho, Hee-Sang; Yoon, Young Il; Jang, Moon-Sun; Hong, Kwan Soo; Hui, Emmanuel; Lee, Jung Hee; Yoon, Tae-Jong

    2017-10-10

    Multimodal nanomaterials are useful for providing enhanced diagnostic information simultaneously for a variety of in vivo imaging methods. According to our research findings, these multimodal nanomaterials offer promising applications for cancer therapy. Melanin nanoparticles can be used as a platform imaging material and they can be simply produced by complexation with various imaging active ions. They are capable of specifically targeting epidermal growth factor receptor (EGFR)-expressing cancer cells by being anchored with a specific antibody. Ion-doped melanin nanoparticles were found to have high bioavailability with long-term stability in solution, without any cytotoxicity in both in vitro and in vivo systems. By combining different imaging modalities with melanin particles, we can use the complexes to obtain faster diagnoses by computed tomography deep-body imaging and greater detailed pathological diagnostic information by magnetic resonance imaging. The ion-doped melanin nanoparticles also have applications for radio-diagnostic treatment and radio imaging-guided surgery, warranting further proof of concept experimental.

  14. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

    Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

  15. In vivo imaging agents: an international market report

    International Nuclear Information System (INIS)

    1990-01-01

    The purpose of this study is to provide a global perspective of the in vivo imaging agents business to market planning executives who are working for companies that develop, produce and distribute various types of in vivo imaging agents. Others that could find this study useful include investment bankers, regulatory and governmental authorities and purchasers of these products. The study attempts to diligently provide market data by type for important geographic markets - Western Europe, the U.S.A., and Japan. A competitive intelligence section which discusses companies involved in these markets constitutes the last part of this study. These profiles are not intended to extensively evaluate each company's marketing strengths or strategies but to provide a general idea of the market presence and prospects. A combination of primary and secondary research is used for all findings. (author)

  16. Synthesis of serotonin transporter imaging agent [125I] ADAM

    International Nuclear Information System (INIS)

    Lu Chunxiong; Wu Chunying; Jiang Quanfu; Chen Zhengping; Zhang Tongxing; Li Xiaoming; Wang Songpei

    2005-01-01

    The synthesis of serotonin transporter imaging agent [ 125 I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine([ 125 I] ADAM) was reported. The chemical structure of the labeling precursor 5-(tributyl-stannyl)-2-((2-((dimethylamino)methyl)phenyl)thio)phenylamine and all its intermediates were verified by IR, 1 HNMR and MS. The radioiodinated compound was prepared using iododestannylation reaction by hydrogen peroxide. Final radiochemical purity was above 95% determined by TLC. (authors)

  17. Selective anti-cancer agents as anti-aging drugs.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2013-12-01

    Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are involved in both cancer and aging). In cancer, intrinsic and acquired resistance, tumor heterogeneity, adaptation, and genetic instability of cancer cells all hinder cancer-directed therapy. But for anti-aging applications, these hurdles are irrelevant. For example, since anti-aging interventions should be aimed at normal postmitotic cells, no selection for resistance is expected. At low doses, certain agents may decelerate aging and age-related diseases. Importantly, deceleration of aging can in turn postpone cancer, which is an age-related disease.

  18. Novel agents in the management of lung cancer.

    LENUS (Irish Health Repository)

    Kennedy, B

    2012-01-31

    Lung cancer is the leading cause of cancer death worldwide. Survival remains poor as approximately 80% of cases present with advanced stage disease. However, new treatments are emerging which offer hope to patients with advanced disease. Insights into cell biology have identified numerous intracellular and extracellular peptides that are pivotal in cancer cell signalling. Disrupting the function of these peptides inhibits intracellular signal transduction and diminishes uncontrolled proliferation, resistance to apoptosis and tumour angiogenesis. The most widely studied signalling pathway is the Epidermal Growth Factor (EGF) pathway. EGF signalling can be disrupted at numerous points. Blockade of the cell surface receptor is achieved by the monoclonal antibody cetuximab; intracellular tyrosine kinase activity is inhibited by erlotinib. Vascular Endothelial Growth Factor (VEGF) regulates another pathway important for tumour growth. Inhibition of VEGF impairs angiogenesis and disrupts metastatic spread. Bevacizumab is a monoclonal antibody that binds to VEGF and blocks interaction with its cell surface receptor. Clinical trials have demonstrated that disruption of these signalling pathways can improve survival in advanced lung cancer. New compounds including folate antimetabolites such as pemetrexed, proteasome inhibitors such as bortezomib, modified glutathione analogues such as TLK286, and other agents such as epothilones and other small molecules are currently being evaluated in patients with lung cancer. As more and more signalling peptides are targeted for manipulation, it is hoped that a new era is dawning in the treatment of advanced stage lung cancer. This review will focus on emerging new therapies in the management of lung cancer.

  19. MR imaging of prostate cancer

    International Nuclear Information System (INIS)

    Heuck, A.; Scheidler, J.; Sommer, B.; Graser, A.; Mueller-Lisse, U.G.; Massmann, J.

    2003-01-01

    Accurate diagnosis and staging of prostate cancer (PC) is developing into an important health care issue in light of the high incidence of PC and the improvements in stage-adapted therapy. The purpose of this paper is to provide an overview on the current role of MR imaging and MR spectroscopy in the diagnosis and staging of PC.Material and methods Pertinent literature was searched and evaluated to collect information on current clinical indications, study techniques, diagnostic value, and limitations of magnetic resonance imaging and spectroscopy. Major indications for MR imaging of patients with supected PC are to define tumor location before biopsy when clinical or TRUS findings are inconclusive, and to provide accurate staging of histologically proven PC to ascertain effective therapy. Current MR imaging techniques for the evaluation of PC include multiplanar high-resolution T2-weighted FSE and T1-weighted SE sequences using combined endorectal and phased-array coils. Using these techniques, the reported accuracy of MR imaging for the diagnosis of extracapsular tumor extension ranges between 82 and 88% with sensitivities between 80 and 95%, and specificities between 82 and 93%. Typical MR findings of PC in different stages of disease, as well as diagnostic problems, such as chronic prostatitis, biopsy-related hemorrhage and therapy-related changes of prostatic tissue are discussed. In addition, the current perspectives and limitations of MR spectroscopy in PC are summarized. Current MR imaging techniques provide important diagnostic information in the pretherapeutic workup of PC including a high staging accuracy, and is superior to TRUS. (orig.) [de

  20. Leukemia after therapy with alkylating agents for childhood cancer

    International Nuclear Information System (INIS)

    Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.

    1987-01-01

    The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents

  1. Ultrasound contrast agent imaging : Real-time imaging of the superharmonics

    NARCIS (Netherlands)

    Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M.D.; De Jong, N.; Vos, H.J.

    2015-01-01

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher

  2. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    Science.gov (United States)

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G.-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-06-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.

  3. [Molecular mechanism regulating effect of anti-cancer agents].

    Science.gov (United States)

    Saya, Hideyuki

    2009-01-01

    Faithful genome duplication is achieved by accurate coordination between DNA replication and chromosome segregation. Abnormalities occurring in this process are checked by biochemical signal transduction pathways, called checkpoints, which ensure the orderly progression of events in the cell cycle. Checkpoints prevent transition into subsequent phases until all processes in the previous phase are completed. Defects in cell cycle checkpoints result in gene mutations, chromosome damage, and aneuploidy, all of which contribute to tumorigenesis. However, it has recently been uncovered that the impairment of checkpoint function is the major reason why DNA damaging anti-cancer agents can selectively kill cancer cells. Given that G1 and G2 checkpoint functions are generally impaired in cancer cells, cells with DNA damage are unable to maintain G2 arrest and eventually die as they enter mitosis. This process is known as mitotic catastrophe.

  4. Resveratrol as an anti-cancer agent: A review.

    Science.gov (United States)

    Rauf, Abdur; Imran, Muhammad; Butt, Masood Sadiq; Nadeem, Muhammad; Peters, Dennis G; Mubarak, Mohammad S

    2016-12-21

    Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemopreventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.

  5. Promising oncolytic agents for metastatic breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Cody JJ

    2015-06-01

    Full Text Available James J Cody,1 Douglas R Hurst2 1ImQuest BioSciences, Frederick, MD, 2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: New therapies for metastatic breast cancer patients are urgently needed. The long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. In addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. Oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. A number of different viruses have been used to develop oncolytic agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia virus, measles virus, reovirus, and others. In general, clinical trials for several cancers have demonstrated excellent safety records and evidence of efficacy. However, the impressive tumor responses often observed in preclinical studies have yet to be realized in the clinic. In order for the promise of oncolytic virotherapy to be fully realized for breast cancer patients, effectiveness must be demonstrated in metastatic disease. This review provides a summary of oncolytic virotherapy strategies being developed to target metastatic breast cancer. Keywords: oncolytic virus, virotherapy, breast cancer, metastasis 

  6. Quinone-fused porphyrins as contrast agents for photoacoustic imaging

    KAUST Repository

    Banala, Srinivas

    2017-06-27

    Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents with high absorption coefficients in the optical window for tissue imaging, i.e. the near infrared (NIR) range between 680 and 950 nm. We herein report the photoacoustic properties of quinone-fused porphyrins inserted with different transition metals as new highly promising candidates. These dyes exhibit intense NIR absorption, a lack of fluorescence emission, and PA sensitivity in concentrations below 3 nmol mL. In this context, the highest PA signal was obtained with a Zn(ii) inserted dye. Furthermore, this dye was stable in blood serum and free thiol solution and exhibited negligible cell toxicity. Additionally, the Zn(ii) probe could be detected with an up to 3.2 fold higher PA intensity compared to the clinically most commonly used PA agent, ICG. Thus, further exploration of the \\'quinone-fusing\\' approach to other chromophores may be an efficient way to generate highly potent PA agents that do not fluoresce and shift their absorption into the NIR range.

  7. Lung cancer mutations and use of targeted agents in Hispanics.

    Science.gov (United States)

    Cress, W Douglas; Chiappori, Alberto; Santiago, Pedro; Muñoz-Antonia, Teresita

    2014-01-01

    Hispanic/Latinos (H/L) are expected to grow to over 24% of the USA population by 2050 and lung cancer is the number one cause of cancer death among H/L men. Due to the information that is becoming available via genetic testing, lung cancer molecular profiling is allowing for increasing application of personalized lung cancer therapies. However, to benefit the most people, development of these therapies and genetic tests must include research on as many racial and ethnic groups as possible. The purpose of this review is to bring attention to the fact that the mutations driving lung cancer in H/Ls differ in frequency and nature relative to the non-Hispanic White (WNH) majority that dominate current databases and participate in clinical trials that test new therapies. Clinical trials using new agents targeting genetic alterations (driver mutations) in lung cancer have demonstrated significant improvements in patient outcomes (for example, gefitinib, erlotinib or crizotinib for lung adenocarcinomas harboring EGFR mutations or EML4-ALK fusions, respectively). The nature and frequencies of some lung cancer driver mutations have been shown to be considerably different among racial and ethnic groups. This is particularly true for H/Ls. For example, several reports suggest a dramatic shift in the mutation pattern from predominantly KRAS in a WNH population to predominantly EGFR in multiple H/L populations. However, these studies are limited, and the effects of racial and ethnic differences on the incidence of mutations in lung cancer remain incompletely understood. This review serves as a call to address this problem.

  8. AAZTA: an ideal chelating agent for the development of {sup 44}Sc PET imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Gabor; Szikra, Dezso; Trencsenyi, Gyoergy [Scanomed Ltd., Debrecen (Hungary); University of Debrecen, Medical Imaging Clinic (Hungary); Fekete, Aniko [University of Debrecen, Medical Imaging Clinic (Hungary); Garai, Ildiko [Scanomed Ltd., Debrecen (Hungary); Giani, Arianna M.; Negri, Roberto [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); Masciocchi, Norberto [Dipartimento di Scienza e Alta Tecnologia e To.Sca.Lab, Universita degli Studi dell' Insubria, Como (Italy); Maiocchi, Alessandro; Uggeri, Fulvio [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Toth, Imre [Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary); Aime, Silvio [Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Universita degli Studi di Torino (Italy); Giovenzana, Giovanni B. [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); CAGE Chemicals srl, Novara (Italy); Baranyai, Zsolt [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary)

    2017-02-13

    Unprecedented fast and efficient complexation of Sc{sup III} was demonstrated with the chelating agent AAZTA (AAZTA=1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)] amino-6-methylperhydro-1,4-d iazepine) under mild experimental conditions. The robustness of the {sup 44}Sc(AAZTA){sup -} chelate and conjugated biomolecules thereof is further shown by in vivo PET imaging in healthy and tumor mice models. The new results pave the way towards development of efficient Sc-based radiopharmaceuticals using the AAZTA chelator. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Evaluation of Tl-201 SPECT imaging findings in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sinem Ozyurt

    2015-07-01

    Full Text Available Objectives: To compare with histopathological findings the findings of prostate cancer imaging by SPECT method using Tl-201 as a tumor seeking agent. Methods: The study comprised 59 patients (age range 51-79 years, mean age 65.3 ± 6.8 years who were planned to have transrectal ultrasonography (TRUS-guided biopsies due to suspicion of prostate cancer between April 2011 and September 2011. Early planar, late planar and SPECT images were obtained for all patients. Scintigraphic evaluation was made in relation to uptake presence and patterns in the visual assessment and to Tumor/Background (T/Bg ratios for both planar and SPECT images in the quantitative assessment. Histopathological findings were compatible with benign etiology in 36 (61% patients and malign etiology in 23 (39% patients. Additionally, comparisons were made to evaluate the relationships between uptake patterns,total PSA values and Gleason scores. Results: A statistically significant difference was found between the benign and malignant groups in terms of uptake in planar and SPECT images and T/Bg ratios and PSA values. No statistically significant difference was found between uptake patterns of planar and SPECT images and Gleason scores in the malignant group. Conclusions: SPECT images were superior to planar images in the comparative assessment. Tl-201 SPECT imaging can provide an additional contribution to clinical practice in the diagnosis of prostate cancer and it can be used in selected patients.

  10. Liver nodules. MR imaging using extracellular gadolinium agent

    International Nuclear Information System (INIS)

    Yoshimitsu, Kengo; Honda, Hiroshi

    2009-01-01

    Extracellular gadolinium (Gd)-containing contrast medium, including gadopentetate dimeglumine (Gd-DTPA), has been playing a main role in the diagnostic MR imaging of the liver. Its significance is two-fold: assessment of the degree of neovascularity or angiogenesis in its early dynamic phase, and that of bulk of interstitium in its equilibrium phase. With the advent of gadolinium ethoxybenzyl diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), which can be used as a dynamic study agent by bolus injection in addition to its original use as a tissue-specific agent, some possibility has been suggested that extracellular Gd agent would be no longer available in the near future in the field of liver MR imaging. Neovascularity or arterial supply of a lesion may well be assessed by Gd-EOB-DTPA, when carefully selected pulse sequence and well designed injection protocol are used, as well as by Gd-DTPA. However, the pertinent assessment of interstitium or stroma can never be achieved by Gd-EOB-DTPA or any other contrast medium present. The interstitium of neoplasm, typically called as stromal fibrosis, is generated through the interaction between the neoplasm per se and its host, and its clinicopathological significance related to disease prognosis has well been established in some disease entities. Extracellular Gd agent is the only contrast medium that can provide information regarding the tumor stroma in a simple, easy, safe and non-invasive fashion, when properly used. This review article discusses, dynamic MR imaging features of representative liver diseases, including several recent topics. From technical point of view, 3D gradient-echo sequence with fat suppression should be used for dynamic studies along with tailored injection protocol using autoinjector and saline flush. Vascularity of hepatocellular carcinoma (HCC) can now be properly assessed by dynamic MR with approximately 90% concordance with CT during hepatic arteriography. Portal phase images can be used to

  11. Urinary bladder cancer: role of MR imaging.

    Science.gov (United States)

    Verma, Sadhna; Rajesh, Arumugam; Prasad, Srinivasa R; Gaitonde, Krishnanath; Lall, Chandana G; Mouraviev, Vladimir; Aeron, Gunjan; Bracken, Robert B; Sandrasegaran, Kumaresan

    2012-01-01

    Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. © RSNA, 2012.

  12. Promising oncolytic agents for metastatic breast cancer treatment

    Science.gov (United States)

    Cody, James J; Hurst, Douglas R

    2015-01-01

    New therapies for metastatic breast cancer patients are urgently needed. The long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. In addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. Oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. A number of different viruses have been used to develop oncolytic agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia virus, measles virus, reovirus, and others. In general, clinical trials for several cancers have demonstrated excellent safety records and evidence of efficacy. However, the impressive tumor responses often observed in preclinical studies have yet to be realized in the clinic. In order for the promise of oncolytic virotherapy to be fully realized for breast cancer patients, effectiveness must be demonstrated in metastatic disease. This review provides a summary of oncolytic virotherapy strategies being developed to target metastatic breast cancer. PMID:27512671

  13. Targeted Nanodiamonds as Phenotype Specific Photoacoustic Contrast Agents for Breast Cancer

    Science.gov (United States)

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Cheng, Kun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M. Laird

    2015-01-01

    Aim The aim is to develop irradiated nanodiamonds (INDs) as a molecularly-targeted contrast agent for high resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. Materials & Methods The surface of acid treated radiation-damaged nanodiamonds was grafted with polyethylene glycol (PEG) to improve its stability and circulation time in blood, followed by conjugation to an anti-Human epidermal growth factor receptor-2 (HER2) peptide (KCCYSL) with a final nanoparticle size of ca. 92 nm. Immunocompetent mice bearing orthotopic HER2 positive or negative tumors were administered INDs and PA imaged using an 820-nm near infrared laser. Results PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 hours. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are non-toxic. Conclusions PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high resolution (sub-mm) and phenotype specific monitoring of cancer growth. PMID:25723091

  14. Innovative Treatments for Cancer:. The Impact of Delivering siRNAs, Chemotherapies, and Preventative Agents Using Nanoformulations

    Science.gov (United States)

    Hook, Sara S.; Farrell, Dorothy; Hinkal, George W.; Ptak, Krzystzof; Grodzinski, Piotr; Panaro, Nicholas J.

    2013-09-01

    A multi-disciplinary approach to research epitomized by the emerging field of cancer nanotechnology can catalyze scientific developments and enable clinical translation beyond what we currently utilize. Engineers, chemists, and physical scientists are teaming up with cancer biologists and clinical oncologists to attack the vast array of cancer malignancies using materials at the nanoscale. We discuss how nanoformulations are enabling the targeted, efficient, delivery of not only genetic therapies such silencing RNAs, but also conventional cytotoxic agents and small molecules which results in decreased systemic toxicity and improved therapeutic index. As preventative approaches, there are various imaging agents and devices are being developed for screening purposes as well as new formulations of sunscreens, neutraceuticals, and cancer vaccines. The goal then of incorporating nanotechnology into clinical applications is to achieve new and more effective ways of diagnosing, treating, and preventing cancer to ultimately change the lives of patients worldwide.

  15. Images of gastric cancer stages

    International Nuclear Information System (INIS)

    Castro Aragon, I.M.

    1999-01-01

    The present work has the objective to review the importance of the images in the preoperating stage of the gastric cancer. It has been emphasized in the modalities of transabdominal ultrasound as much as endoscopic and TAC since they are most valuable in the stage. Certainly the importance of conventional radiology (gastroduodenal series) is also valuable in the stage of the tumor, specially in considering the depth of the same one. In order to make this overhaul, the recent bibliography was consulted but, specially the published one by Japaneses since they follow a classification and methodology different from the used one in most of the countries that belong to the World-wide Organization of the Health. They made an overhaul of approximately 200 cases of patients who have been diagnosed and treated in the Center of Detection of Gastric Cancer of Cartago. In each case review the file, radiological, sonographic and pathological studies, and the cases were chosen that better illustrated the exposed subjects. (Author) [es

  16. Imaging in Vivo Extracellular pH with a Single Paramagnetic Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agent

    Directory of Open Access Journals (Sweden)

    Guanshu Liu

    2012-01-01

    Full Text Available The measurement of extracellular pH (pHe has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance imaging (MRI contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST was designed to measure tumor pHe throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb3+-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, 10-o-aminoanilide (Yb-DO3A-oAA suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pHe measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer.

  17. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    Science.gov (United States)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  18. Magnetic susceptibility imaging with a nonionic contrast agent

    International Nuclear Information System (INIS)

    Cacheris, W.; Rocklage, S.M.; Quay, S.; Dow, W.; Love, D.; Worah, D.; Lim, K.

    1988-01-01

    The magnetic susceptibility mechanism for MR imaging contrast enhancement has the advantage of providing useful information, such as cerebral blood flow, without crossing the blood-brain barrier. In this paper the authors report the use of a highly effective, relatively nontoxic chelate as a magnetic susceptibility agent. Dy-DTPA-bis(methylamide) (Dy-DTPA-BMA) has an extremely low acute toxicity (LD-50, intravenous, mice ∼ 40 mmol/kg). Doses of 1 mmol/kg and 2 mmol/kg Dy-DTPA-BMA lowered the initial signal intensity 63% to 57%, respectively. The utility of this technique in detecting areas of reduced blood flow within the brain was demonstrated by imaging a rabbit with a cerebral perfusion deficit

  19. DNA as sensors and imaging agents for metal ions.

    Science.gov (United States)

    Xiang, Yu; Lu, Yi

    2014-02-17

    Increasing interest in detecting metal ions in many chemical and biomedical fields has created demands for developing sensors and imaging agents for metal ions with high sensitivity and selectivity. This review covers recent progress in DNA-based sensors and imaging agents for metal ions. Through both combinatorial selection and rational design, a number of metal-ion-dependent DNAzymes and metal-ion-binding DNA structures that can selectively recognize specific metal ions have been obtained. By attachment of these DNA molecules with signal reporters such as fluorophores, chromophores, electrochemical tags, and Raman tags, a number of DNA-based sensors for both diamagnetic and paramagnetic metal ions have been developed for fluorescent, colorimetric, electrochemical, and surface Raman detection. These sensors are highly sensitive (with a detection limit down to 11 ppt) and selective (with selectivity up to millions-fold) toward specific metal ions. In addition, through further development to simplify the operation, such as the use of "dipstick tests", portable fluorometers, computer-readable disks, and widely available glucose meters, these sensors have been applied for on-site and real-time environmental monitoring and point-of-care medical diagnostics. The use of these sensors for in situ cellular imaging has also been reported. The generality of the combinatorial selection to obtain DNAzymes for almost any metal ion in any oxidation state and the ease of modification of the DNA with different signal reporters make DNA an emerging and promising class of molecules for metal-ion sensing and imaging in many fields of applications.

  20. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Hao Hong

    2008-01-01

    Full Text Available Carcinoembryonic antigen (CEA, highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET] have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”.

  1. Aspirin as a chemoprevention agent for colorectal cancer.

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-11-01

    Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

  2. Molecular Imaging of Proteases in Cancer

    Directory of Open Access Journals (Sweden)

    Yunan Yang

    2009-01-01

    Full Text Available Proteases play important roles during tumor angiogenesis, invasion, and metastasis. Various molecular imaging techniques have been employed for protease imaging: optical (both fluorescence and bioluminescence, magnetic resonance imaging (MRI, single-photon emission computed tomography (SPECT, and positron emission tomography (PET. In this review, we will summarize the current status of imaging proteases in cancer with these techniques. Optical imaging of proteases, in particular with fluorescence, is the most intensively validated and many of the imaging probes are already commercially available. It is generally agreed that the use of activatable probes is the most accurate and appropriate means for measuring protease activity. Molecular imaging of proteases with other techniques (i.e. MRI, SPECT, and PET has not been well-documented in the literature which certainly deserves much future effort. Optical imaging and molecular MRI of protease activity has very limited potential for clinical investigation. PET/SPECT imaging is suitable for clinical investigation; however the optimal probes for PET/SPECT imaging of proteases in cancer have yet to be developed. Successful development of protease imaging probes with optimal in vivo stability, tumor targeting efficacy, and desirable pharmacokinetics for clinical translation will eventually improve cancer patient management. Not limited to cancer, these protease-targeted imaging probes will also have broad applications in other diseases such as arthritis, atherosclerosis, and myocardial infarction.

  3. Multiparametric magnetic resonance imaging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Sandeep S Hedgire

    2012-01-01

    Full Text Available In India, prostate cancer has an incidence rate of 3.9 per 100,000 men and is responsible for 9% of cancer-related mortality. It is the only malignancy that is diagnosed with an apparently blind technique, i.e., transrectal sextant biopsy. With increasing numbers of high-Tesla magnetic resonance imaging (MRI equipment being installed in India, the radiologist needs to be cognizant about endorectal MRI and multiparametric imaging for prostate cancer. In this review article, we aim to highlight the utility of multiparamteric MRI in prostate cancer. It plays a crucial role, mainly in initial staging, restaging, and post-treatment follow-up.

  4. Optical Imaging in Breast Cancer Diagnosis: The Next Evolution

    Directory of Open Access Journals (Sweden)

    Michel Herranz

    2012-01-01

    Full Text Available Breast cancer is one of the most common cancers among the population of the Western world. Diagnostic methods include mammography, ultrasound, and magnetic resonance; meanwhile, nuclear medicine techniques have a secondary role, being useful in regional assessment and therapy followup. Optical imaging is a very promising imaging technique that uses near-infrared light to assess optical properties of tissues and is expected to play an important role in breast cancer detection. Optical breast imaging can be performed by intrinsic breast tissue contrast alone (hemoglobin, water, and lipid content or with the use of exogenous fluorescent probes that target specific molecules for breast cancer. Major advantages of optical imaging are that it does not use any radioactive components, very high sensitivity, relatively inexpensive, easily accessible, and the potential to be combined in a multimodal approach with other technologies such as mammography, ultrasound, MRI, and positron emission tomography. Moreover, optical imaging agents could, potentially, be used as “theranostics,” combining the process of diagnosis and therapy.

  5. Nicotinic α4β2 receptor imaging agents

    International Nuclear Information System (INIS)

    Pichika, Rama; Easwaramoorthy, Balasubramaniam; Collins, Daphne; Christian, Bradley T.; Shi, Bingzhi; Narayanan, Tanjore K.; Potkin, Steven G.; Mukherjee, Jogeshwar

    2006-01-01

    The α4β2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using 3 H-cytisine exhibited a K i =0.50 nM for the α4β2 sites. The radiosynthesis of 2- 18 F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ( 18 F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/μmol. In vitro autoradiography in rat brain slices indicated selective binding of 18 F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for 18 F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 μM nicotine in these brain regions. Positron emission tomography imaging study of 18 F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of 18 F-nifene indicates promise as a PET imaging agent and thus needs further evaluation

  6. Shape Effects in Nanoparticle-Based Imaging Agents

    Science.gov (United States)

    Culver, Kayla Shani Brook

    At the nanoscale, material properties become highly size and shape dependent. These properties can be manipulated and exploited for a variety of biomedical applications, including sensing, drug delivery, diagnostics, and imaging. In particular, nanoparticles of different materials, sizes and shapes have been developed as high-performance contrast agents for optical, electron, and medical imaging. In this thesis, I focus on gold nanoparticles because they are widely used as contrast agents in multiple types of imaging modalities. Additionally, the surface of gold can be readily functionalized with ligands and the structure of the particles can be manipulated to modulate their performance as imaging agents. The properties of nanoparticles can generate contrast directly. For example, the light scattering properties of gold particles can be visualized in optical microscopy, the high electron density of gold produces contrast in electron microscopy, and the x-ray absorption properties of gold can be detected in medical x-ray and computed tomography imaging. Alternatively, the properties of the nanomaterial can be exploited to modulate the signal produced by other molecules that are bound to the particle surface. The light emission of molecular fluorophores can be quenched or dramatically increased by coupling to the optical field enhancements of gold nanoparticles, and the performance of gadolinium (Gd(III))-based magnetic resonance imaging (MRI) contrast agents can be increased by coupling to the rotational motion of nanoparticles. In this dissertation, I focus specifically on how the structure of star-shaped gold particles (nanostars) can be exploited as single-particle optical probes and to dramatically enhance the relaxivity of Gd(III) bound to the surface. Differential interference contrast (DIC) is a type of wide-field diffraction-limited optical microscopy that is commonly used by biologists to image cells without labels. Here, I demonstrate the DIC can be used

  7. A biomimetic Au@BSA-DTA nanocomposites-based contrast agent for computed tomography imaging.

    Science.gov (United States)

    Zhao, Wenjing; Wang, Zhiming; Chen, Lina; Huang, Chusen; Huang, Yuankui; Jia, Nengqin

    2017-09-01

    Early detection of cancer is increasingly important for being considered to increase the survival rate in the treatment process. The past decades years have witnessed the great progress in the biological detection application of gold nanoparticles. Herein, we reported a facile one-pot synthesis process to obtain gold nanoparticles (Au@BSA) with bovine serum albumin (BSA) as a biotemplate following with conjugation of diatrizoic acid (DTA) for a potential X-ray computed tomography (CT) imaging contrast agent (Au@BSA-DTA). The as-prepared biomimetic material was characterized systematically by several techniques. It was shown that the prepared biomaterial is colloid stable under the tested range of pH and temperature. The cell cytotoxicity assay, hemolytic assay and cell morphology observation showed that Au@BSA-DTA has good biocompatibility and hemocompatibility at a concentration of Au even up to 80μg/mL. Besides, the biomimetic material Au@BSA-DTA with double radiodense elements of Au and iodine displayed much stronger CT imaging effect compared with the traditional small molecule contrast agents, which paves the potential clinical application in cancer early diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Advances in imaging diagnosis of liver cancer

    Directory of Open Access Journals (Sweden)

    ZHANG Chunyu

    2017-07-01

    Full Text Available Liver biopsy is the gold standard for the diagnosis of primary liver cancer, but it is an invasive examination. At present, imaging has become the preferred method for the diagnosis of liver cancer. This article summarizes new imaging methods and techniques for the diagnosis and evaluation of primary liver cancer, including contrast-enhanced ultrasound, CT perfusion imaging, diffusion-weighted imaging-intravoxel incoherent motion, IDEAL IQ sequence, dynamic contrast-enhanced MRI, and hepatocyte-specific contrast-enhanced imaging, and points out that diagnostic imaging can not only evaluate the degree of tumor differentiation, blood supply and perfusion, and invasiveness of lesions, but also predict the prognosis and evaluate liver function. Therefore, it can provide a reference for clinical diagnosis and treatment.

  9. Positrons as imaging agents and probes in nanotechnology

    International Nuclear Information System (INIS)

    Smith, Suzanne V

    2009-01-01

    Positron emission tomography (PET) tracks a positron emitting radiopharmaceutical injected into the body and generates a 3-dimensional image of its location. Introduced in the early 70s, it has now developed into a powerful medical diagnostic tool for routine clinical use as well as in drug development. Unrivalled as a highly sensitive, specific and non-invasive imaging tool, PET unfortunately lacks the resolution of Computer Tomography (CT) and Magnetic Resonance Imaging (MRI). As the resolution of PET depends significantly on the energy of the positron incorporated in the radiopharmaceutical and its interaction with its surrounding tissue, there is growing interest in expanding our understanding of how positrons interact at the atomic and molecular level. A better understanding of these interactions will contribute to improving the resolution of PET and assist in the design of better imaging agents. Positrons are also used in Positron Annihilation Lifetime Spectroscopy (PALS) to determine electron density and or presence and incidence of micro- and mesopores (0.1 to 10 nm) in materials. The control of porosity in engineered materials is crucial for applications such as controlled release or air and water resistant films. Equally important to the design of nano and microtechnologies, is our understanding of the microenvironments within these pores and on surfaces. Hence as radiopharmaceuticals are designed to track disease, nuclear probes (radioactive molecules) are synthesized to investigate the chemical properties within these pores. This article will give a brief overview of the present role of positrons in imaging as well as explore its potential to contribute in the engineering of new materials to the marketplace.

  10. Radiolabeled Zn-DPA as a potential infection imaging agent

    International Nuclear Information System (INIS)

    Liu Xinrong; Cheng Dengfeng; Gray, Brian D.; Wang Yuzhen; Akalin, Ali; Rusckowski, Mary; Pak, Koon Y.; Hnatowich, Donald J.

    2012-01-01

    Introduction: A zinc-dipicolylamine analog (Zn-DPA) conjugated with a fluorophore (PSVue®794) has been shown to image bacterial infections in mice. However, radiolabeled Zn-DPA has not previously been considered for nuclear imaging of infection. Methods: Both 111 In-labeled DOTA-biotin and Zn-DPA-biotin were combined using streptavidin (SA) as a noncovalent linker. Mice injected intramuscularly with Streptococcus pyogenes (infection model) or with lipopolysaccharide (LPS) (inflammation model) were coinjected intravenously with 6 μg of DPA as PSVue794 and as 111 In-DOTA-biotin/SA/biotin-Zn-DPA. Periodic fluorescent and SPECT (single photon emission computed tomography)/CT (computed tomography) images were acquired, and biodistributions were obtained at 22 h. Results: Histological examination confirmed the validity of both the infection and inflammation animal models. Both the whole-body optical and nuclear images showed obvious accumulations in the target thigh in both models at all time points. At 22 h, the average target thigh accumulation of 111 In was 1.66%ID/g (S.D. 0.15) in the infection mice compared to 0.58%ID/g (S.D. 0.07) in the inflammation mice (P 111 In target/normal thigh ratio was 2.8 fold higher in the infection animals compared to the inflammation animals. Conclusions: These preliminary results show that Zn-DPA within streptavidin targets S. pyogenes-infected mice similarly to its free fluorescent analogue. The significantly higher accumulation in the live bacterial infection thigh compared to that of the LPS-induced inflammation thigh suggests that Zn-DPA may be a promising imaging agent to distinguish between bacterial infections and sterile inflammations.

  11. Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

    Science.gov (United States)

    Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

    2009-01-01

    Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

  12. Cellular Imaging | Center for Cancer Research

    Science.gov (United States)

    Innovative imaging methods developed and refined within CCR revealed atomic-level structures of biological molecules and unveiled dynamic views of a cell’s interior that are driving the design of new treatments and diagnostics for cancer.

  13. Diagnostic performance of power doppler and ultrasound contrast agents in early imaging-based diagnosis of organ-confined prostate cancer: Is it possible to spare cores with contrast-guided biopsy?

    Energy Technology Data Exchange (ETDEWEB)

    Delgado Oliva, F., E-mail: frandelgol@hotmail.com; Arlandis Guzman, S.; Bonillo García, M.; Broseta Rico, E.; Boronat Tormo, F.

    2016-10-15

    Objectives: To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS. Material and methods: A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4–20 ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS-targeted (SonoVue) 2-core biopsies. Results: Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3 ± 7.01 years (95% CI, 63.75–64.70); mean total PSA was 8.9 ± 3.61 ng/mL (95% CI, 8.67–9.13) and the mean prostate volume was 56.2 ± 29 cc (95% CI, 54.2–58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16

  14. Tracers and contrast agents in cardiovascular imaging: present and future

    International Nuclear Information System (INIS)

    Marmion, M.; Deutsch, E.

    1996-01-01

    This brief article addresses the current status and future potential of nuclear medicine, X-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR) imaging in the diagnosis of cardiovascular diseases. The currently perceived advantages and disadvantages, as well as the possible future roles, of each of the modalities with regard to the evaluation of coronary artery disease are delineated. The certain advent of Mr and US myocardial contrast agents, combined with the inexorable pressures of health care reform, will alter the future usage patterns of all four modalities. Future debates about which modality should be used in which clinical situation will be based not on 'anatomy vs function', nor on the issues of cost effectiveness and patient outcomes

  15. Exploiting Cancer Metal Metabolism using Anti-Cancer Metal-Binding Agents.

    Science.gov (United States)

    Merlot, Angelica M; Kalinowski, Danuta S; Kovacevic, Zaklina; Jansson, Patric J; Sahni, Sumit; Huang, Michael L; Lane, Darius L; Lok, Hiu; Richardson, Des R

    2017-07-05

    Metals are vital cellular elements necessary for multiple indispensable biological processes of living organisms, including energy transduction and cell proliferation. Interestingly, alterations in metal levels and also changes in the expression of proteins involved in metal metabolism have been demonstrated in a variety of cancers. Considering this and the important role of metals for cell growth, the development of drugs that sequester metals have become an attractive target for the development of novel anti-cancer agents. Interest in this field has surged with the design and development of new generations of chelators of the thiosemicarbazone class. These ligands have shown potent anti-cancer and anti-metastatic activity in vitro and in vivo. Due to their efficacy and safe toxicological assessment, some of these agents have recently entered multi-center clinical trials as therapeutics for advanced and resistant tumors. This review highlights the role, and changes in homeostasis, of metals in cancer and emphasizes the pre-clinical development and clinical assessment of metal ion-binding agents, namely, thiosemicarbazones, as anti-tumor agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Kit for preparing a technetium-99m myocardial imaging agent

    International Nuclear Information System (INIS)

    Woulfe, S.R.; Deutsch, E.A.; Dyszlewski, M.; Neumann, W.L.

    1992-01-01

    This patent describes a kit for preparing a technetium 99m myocardial imaging agent. It comprises a first vial containing a lyophilized pyrogen free, sterile mixture of an effective reducing agent and a first ligand having the following general formula: wherein the R 1 groups may be the same or different and are selected from the group consisting of hydrogen, hydroxy, C 1 - C 5 alkyl, C 1 - C 5 alkyl substituted by hydroxyl, ether, ester, amide, ketone, aldehyde and nitrile; the R 2 groups may be the same or different and are selected from the group consisting of hydrogen, hydroxy, C 1 - C 5 alkyl, C 1 - C 5 alkyl substituted by hydroxyl, ether, ester, amide, ketone, aldehyde, and nitrile; the X and Y groups may be the same or different and are selected from the group consisting of oxygen and sulfur; and n is equal to 1 or 2; and a second vial containing a lyophilized pyrogen free, sterile protected salt of a phosphine ligand

  17. Imaging biomarker roadmap for cancer studies

    NARCIS (Netherlands)

    O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

  18. Imaging strategy in differentiated thyroid cancer

    NARCIS (Netherlands)

    Phan, Thi Thanh Ha

    2007-01-01

    This thesis focuses on clinical dilemmas, which the clinician faces in the management of patients with differentiated thyroid cancer (DTC) with a specific emphasis on the role of current and new diagnostic imaging. Thyroid cancer is a rare disease, but it is the most common endocrine malignancy of

  19. Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

    Science.gov (United States)

    Mahajan, A; Goh, V; Basu, S; Vaish, R; Weeks, A J; Thakur, M H; Cook, G J

    2015-10-01

    Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure-function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [(18)F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed "theranostics". Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  20. Near-infrared Au nanorods in photodynamic therapy, hyperthermia agents, and near-infrared optical imaging

    Science.gov (United States)

    Kuo, Wen-Shuo; Chang, Chich-Neng; Chang, Yi-Ting; Yang, Meng-Heng; Chien, Yi-Hsin; Chen, Shean-Jen; Yeh, Chen-Sheng

    2011-03-01

    The development of multifunctional nanomaterials is currently a topic of interest in the field of nanotechnology. Integrated systems that incorporate therapeutics, molecular targeting, and diagnostic imaging capabilities are considered to be the next generation of multifunctional nanomedicine. In this work, we present the first example of using Au nanorods simultaneously serving not only as photodynamic and photothermal agents to destroy A549 malignant cells but also as optical contrast agents simultaneously to monitor cellular image. Au nanorods were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and hyperthermia. With the combination of PDT and hyperthermia proved to be efficiently killing cancer cells as compared to PDT or hyperthermia treatment alone and enhanced the effectiveness of photodestruction. Moreover, Au nanorods conjugated with ICG displayed high chemical stability and simultaneously acted as a promising cellular image probe. As a result, the preparation of Au nanorods conjugated with photosensitizers as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

  1. Diagnostic Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kemal Kara

    2012-12-01

    Full Text Available Lung cancer is the most common cause of cancer related death in men and women. It is frequently seen among men than in women and male-female ratio is 1.5:1. Common epidemiological factors that increase risk of lung cancer is smoking. Early age to start smoking, high number of smoking cigarettes per a day and depth of inhalation increase risk of lung cancer. 25% of patients with lung cancer are nonsmokers that passively exposed to cigarette smoke. Occupational exposure to substances such as asbestos, arsenic, nickel, beryllium, mustard gas increases the risk of lung cancer. The well defined risk factor is exposure to asbestos. In addition advanced age, diffuse pulmonary fibrosis, chronic obstructive pulmonary disease (COPD and genetic predisposition are the risk factors that increases lung cancer. [TAF Prev Med Bull 2012; 11(6.000: 749-756

  2. Highly specific spectroscopic photoacoustic molecular imaging of dynamic optical absorption shifts of an antibody-ICG contrast agent (Conference Presentation)

    Science.gov (United States)

    Wilson, Katheryne E.; Bachawal, Sunitha; Abou-Elkacem, Lotfi; Jensen, Kristen C.; Machtaler, Steven; Tian, Lu; Willmann, Juergen K.

    2017-03-01

    Improved techniques for breast cancer screening are critically needed as current methods lack diagnostic accuracy. Using spectroscopic photoacoustic (sPA) molecular imaging with a priori knowledge of optical absorption spectra allows suppression of endogenous background signal, increasing the overall sensitivity and specificity of the modality to exogenous contrast agents. Here, sPA imaging was used to monitor antibody-indocyanine green (ICG) conjugates as they undergo optical absorption spectrum shifts after cellular endocytosis and degradation to allow differentiation between normal murine mammary glands from breast cancer by enhancing molecular imaging signal from target (B7-H3)-bound antibody-ICG. First, B7-H3 was shown to have highly specific (AUC of 0.93) expression on both vascular endothelium and tumor stroma in malignant lesions through quantitative immunohistochemical staining of B7-H3 on 279 human samples (normal (n=53), benign lesions (11 subtypes, n=182), breast cancers (4 subtypes, n=97)), making B7-H3 a promising target for sPA imaging. Second, absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control (Iso-ICG) were characterized through in vitro and in vivo experiments. Finally, a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was imaged, and sPA imaging in found a 3.01 (IQR 2.63, 3.38, Pcontrast agents, which have dynamic optical absorption spectra representative of molecular interactions, allows for highly specific sPA imaging of murine breast cancer.

  3. Nanobodies As Novel Agents for Targeting Angiogenesis in Solid Cancers

    Directory of Open Access Journals (Sweden)

    Roghaye Arezumand

    2017-12-01

    Full Text Available Solid cancers are dependent on angiogenesis for sustenance. The FDA approval of Bevacizumab in 2004 inspired many scientists to develop more inhibitors of angiogenesis. Although several monoclonal antibodies (mAbs are being administered to successfully combat various pathologies, the complexity and large size of mAbs seem to narrow the therapeutic applications. To improve the performance of cancer therapeutics, including those blocking tumor angiogenesis, attractive strategies such as miniaturization of the antibodies have been introduced. Nanobodies (Nbs, small single-domain antigen-binding antibody fragments, are becoming promising therapeutic and diagnostic proteins in oncology due to their favorable unique structural and functional properties. This review focuses on the potential and state of the art of Nbs to inhibit the angiogenic process for therapy and the use of labeled Nbs for non-invasive in vivo imaging of the tumors.

  4. Antimicrobial Peptides as Infection Imaging Agents: Better Than Radiolabeled Antibiotics

    Directory of Open Access Journals (Sweden)

    Muammad Saeed Akhtar

    2012-01-01

    Full Text Available Nuclear medicine imaging techniques offer whole body imaging for localization of number and site of infective foci inspite of limitation of spatial resolution. The innate human immune system contains a large member of important elements including antimicrobial peptides to combat any form of infection. However, development of antibiotics against bacteria progressed rapidly and gained popularity over antimicrobial peptides but even powerful antimicrobials failed to reduce morbidity and mortality due to emergence of mutant strains of bacteria resulting in antimicrobial resistance. Differentiation between infection and inflammation using radiolabeled compounds with nuclear medicine techniques has always been a dilemma which is still to be resolved. Starting from nonspecific tracers to specific radiolabeled tracers, the question is still unanswered. Specific radiolabeled tracers included antibiotics and antimicrobial peptides which bind directly to the bacteria for efficient localization with advanced nuclear medicine equipments. However, there are merits and demerits attributed to each. In the current paper, radiolabeled antibiotics and radiolabeled peptides for infection localization have been discussed starting with the background of primitive nonspecific tracers. Radiolabeled antimicrobial peptides have certain merits compared with labeled antibiotics which make them superior agents for localization of infective focus.

  5. [Preserving one's self-image despite cancer].

    Science.gov (United States)

    Caltagirone, Aury

    2014-03-01

    Cancer and the side effects of the treatments affect a patient's self-image. The assistance of a personal image consultant and socio-aesthetician can help the patient restore their appearance and become more accepting of themselves. It enables them to be more at ease in their relationships with others and reinforces self-esteem.

  6. Tc-99m labeled Sparfloxacin: A specific infection imaging agent

    International Nuclear Information System (INIS)

    Singh, A.K.; Verma, J.; Bhatnagar, A.; Ali, A.

    2003-01-01

    lesions as well as lesions with infection because of hypervascularity. However, rapid wash out of tracer was noted from sterile inflammatory lesions, while progressive concentration of radiotracer was seen in the lesions with infection. Delayed scans done at two hours post-injection revealed a four fold increase radio tracer concentration at the sites of infection as compared to the sites of sterile inflammation. Based on the results of this preliminary study it was concluded that Tc- 99m Sparfloxacin specifically concentrates in infection in animal models and could potentially be a specific bacterial infection-imaging agent. (author)

  7. T-oligo as an anticancer agent in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wojdyla, Luke; Stone, Amanda L. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Sethakorn, Nan [Department of Medicine, University of Chicago, Chicago, IL (United States); Uppada, Srijayaprakash B.; Devito, Joseph T. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Bissonnette, Marc [Department of Medicine, University of Chicago, Chicago, IL (United States); Puri, Neelu, E-mail: neelupur@uic.edu [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States)

    2014-04-04

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.

  8. T-oligo as an anticancer agent in colorectal cancer

    International Nuclear Information System (INIS)

    Wojdyla, Luke; Stone, Amanda L.; Sethakorn, Nan; Uppada, Srijayaprakash B.; Devito, Joseph T.; Bissonnette, Marc; Puri, Neelu

    2014-01-01

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC

  9. Quantitative Molecular Imaging with a Single Gd-Based Contrast Agent Reveals Specific Tumor Binding and Retention in Vivo.

    Science.gov (United States)

    Johansen, Mette L; Gao, Ying; Hutnick, Melanie A; Craig, Sonya E L; Pokorski, Jonathan K; Flask, Chris A; Brady-Kalnay, Susann M

    2017-06-06

    Magnetic resonance imaging (MRI) has become an indispensable tool in the diagnosis and treatment of many diseases, especially cancer. However, the poor sensitivity of MRI relative to other imaging modalities, such as PET, has hindered the development and clinical use of molecular MRI contrast agents that could provide vital diagnostic information by specifically locating a molecular target altered in the disease process. This work describes the specific and sustained in vivo binding and retention of a protein tyrosine phosphatase mu (PTPμ)-targeted, molecular magnetic resonance (MR) contrast agent with a single gadolinium (Gd) chelate using a quantitative MRI T 1 mapping technique in glioma xenografts. Quantitative T 1 mapping is an imaging method used to measure the longitudinal relaxation time, the T 1 relaxation time, of protons in a magnetic field after excitation by a radiofrequency pulse. T 1 relaxation times can in turn be used to calculate the concentration of a gadolinium-containing contrast agent in a region of interest, thereby allowing the retention or clearance of an agent to be quantified. In this context, retention is a measure of molecular contrast agent binding. Using conventional peptide chemistry, a PTPμ-targeted peptide was linked to a chelator that had been conjugated to a lysine residue. Following complexation with Gd, this PTPμ-targeted molecular contrast agent containing a single Gd ion showed significant tumor enhancement and a sustained increase in Gd concentration in both heterotopic and orthotopic tumors using dynamic quantitative MRI. This single Gd-containing PTPμ agent was more effective than our previous version with three Gd ions. Differences between nonspecific and specific agents, due to specific tumor binding, can be determined within the first 30 min after agent administration by examining clearance rates. This more facile chemistry, when combined with quantitative MR techniques, allows for widespread adoption by academic

  10. (18)F-labelled metomidate analogues as adrenocortical imaging agents.

    Science.gov (United States)

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Långström, Bengt

    2009-05-01

    Two- and one-step syntheses of (18)F-labelled analogues of metomidate, such as 2-[(18)F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[(18)F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[(18)F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[(18)F]fluoroethyl 4-methylbenzenesulfonate or 3-[(18)F]fluoropropyl 4-methylbenzenesulfonate. These were used as (18)F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46+/-3% and 79+/-30%, respectively. Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  11. Employing image processing techniques for cancer detection using microarray images.

    Science.gov (United States)

    Dehghan Khalilabad, Nastaran; Hassanpour, Hamid

    2017-02-01

    Microarray technology is a powerful genomic tool for simultaneously studying and analyzing the behavior of thousands of genes. The analysis of images obtained from this technology plays a critical role in the detection and treatment of diseases. The aim of the current study is to develop an automated system for analyzing data from microarray images in order to detect cancerous cases. The proposed system consists of three main phases, namely image processing, data mining, and the detection of the disease. The image processing phase performs operations such as refining image rotation, gridding (locating genes) and extracting raw data from images the data mining includes normalizing the extracted data and selecting the more effective genes. Finally, via the extracted data, cancerous cell is recognized. To evaluate the performance of the proposed system, microarray database is employed which includes Breast cancer, Myeloid Leukemia and Lymphomas from the Stanford Microarray Database. The results indicate that the proposed system is able to identify the type of cancer from the data set with an accuracy of 95.45%, 94.11%, and 100%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Magnetic Iron Oxide Nanoparticles for Multimodal Imaging and Therapy of Cancer

    Directory of Open Access Journals (Sweden)

    In-Kyu Park

    2013-07-01

    Full Text Available Superparamagnetic iron oxide nanoparticles (SPION have emerged as an MRI contrast agent for tumor imaging due to their efficacy and safety. Their utility has been proven in clinical applications with a series of marketed SPION-based contrast agents. Extensive research has been performed to study various strategies that could improve SPION by tailoring the surface chemistry and by applying additional therapeutic functionality. Research into the dual-modal contrast uses of SPION has developed because these applications can save time and effort by reducing the number of imaging sessions. In addition to multimodal strategies, efforts have been made to develop multifunctional nanoparticles that carry both diagnostic and therapeutic cargos specifically for cancer. This review provides an overview of recent advances in multimodality imaging agents and focuses on iron oxide based nanoparticles and their theranostic applications for cancer. Furthermore, we discuss the physiochemical properties and compare different synthesis methods of SPION for the development of multimodal contrast agents.

  13. Head and neck cancer imaging. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Hermans, Robert (ed.) [University Hospital, Leuven (Belgium). Dept. of Radiology

    2012-07-01

    Imaging is crucial in the multidisciplinary approach to head and neck cancer management. The rapid technological development of recent years makes it necessary for all members of the multidisciplinary team to understand the potential applications, limitations, and advantages of existing and evolving imaging technologies. It is equally important that the radiologist has sufficient clinical background knowledge to understand the clinical significance of imaging findings. This book provides an overview of the findings obtained using different imaging techniques during the evaluation of head and neck neoplasms, both before and after therapy. All anatomic areas in the head and neck are covered, and the impact of imaging on patient management is discussed in detail. The authors are recognized experts in the field, and numerous high-quality images are included. This second edition provides information on the latest imaging developments in this area, including the application of PET-CT and diffusion-weighted magnetic resonance imaging.

  14. MR and optical imaging of early micrometastases in lymph nodes: triple labeling with nano-sized agents yielding distinct signals.

    Science.gov (United States)

    Kosaka, Nobuyuki; Bernardo, Marcelino; Mitsunaga, Makoto; Choyke, Peter L; Kobayashi, Hisataka

    2012-01-01

    Few imaging methods are available for depicting in vivo cancer cell migration within the lymphatic system. Detection of such early micrometastases requires extremely high target to background. In this study, we dual-labeled human breast cancer cells (MDA-MB468) with a small particle of iron oxide (SPIO) and a quantum dot (QD), and tracked these cells in the lymphatic system in mice using in vivo MRI and optical imaging. A generation-6 gadolinium-dendrimer-based MRI contrast agent (Gd-G6) was employed for visualizing regional lymphatic channels and nodes. Since Gd-G6 shortened T(1) leading to high signal, whereas SPIO-labeled cancer cells greatly lowered signal, a small number of cells were simultaneously visualized within the draining lymphatic basins. One million dual-labeled cancer cells were subcutaneously injected into the paws of mice 24 h prior to imaging. Then whole body images were acquired pre- and post-intracutaneous injection of Gd-G6 with 3D-T(1) w-FFE and balanced-FFE sequences for cancer cell tracking and MR lymphangiography. In vivo MRI clearly visualized labeled cancer cells migrating from the paw to the axillary lymph nodes using draining lymphatics. In vivo optical imaging using a fluorescence surgical microscope demonstrated tiny cancer cell clusters in the axillary lymph node with high spatial resolution. Thus, using a combination of MRI and optical imaging, it is possible to depict macro- and early micrometastases within the lymphatic system. This platform offers a versatile research tool for investigating and treating lymphatic metastases in animal models. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

    Science.gov (United States)

    Shi, Changhong; Wu, Jason Boyang; Pan, Dongfeng

    2016-05-01

    A class of near-infrared fluorescence (NIRF) heptamethine cyanine dyes that are taken up and accumulated specifically in cancer cells without chemical conjugation have recently emerged as promising tools for tumor imaging and targeting. In addition to their fluorescence and nuclear imaging-based tumor-imaging properties, these dyes can be developed as drug carriers to safely deliver chemotherapy drugs to tumors. They can also be used as effective agents for photodynamic therapy with remarkable tumoricidal activity via photodependent cytotoxic activity. The preferential uptake of dyes into cancer but not normal cells is co-operatively mediated by the prevailing activation of a group of organic anion-transporting polypeptides on cancer cell membranes, as well as tumor hypoxia and increased mitochondrial membrane potential in cancer cells. Such mechanistic explorations have greatly advanced the current application and future development of NIRF dyes and their derivatives as anticancer theranostic agents. This review summarizes current knowledge and emerging advances in NIRF dyes, including molecular characterization, photophysical properties, multimodal development and uptake mechanisms, and their growing potential for preclinical and clinical use.

  16. Imaging in Colorectal Cancer: Progress and Challenges for the Clinicians

    Directory of Open Access Journals (Sweden)

    Eric Van Cutsem

    2016-08-01

    Full Text Available The use of imaging in colorectal cancer (CRC has significantly evolved over the last twenty years, establishing important roles in surveillance, diagnosis, staging, treatment selection and follow up. The range of modalities has broadened with the development of novel tracer and contrast agents, and the fusion of technologies such as positron emission tomography (PET and computed tomography (CT. Traditionally, the most widely used modality for assessing treatment response in metastasised colon and rectal tumours is CT, combined with use of the RECIST guidelines. However, a growing body of evidence suggests that tumour size does not always adequately correlate with clinical outcomes. Magnetic resonance imaging (MRI is a more versatile technique and dynamic contrast-enhanced (DCE-MRI and diffusion-weighted (DW-MRI may be used to evaluate biological and functional effects of treatment. Integrated fluorodeoxyglucose (FDG-PET/CT combines metabolic and anatomical imaging to improve sensitivity and specificity of tumour detection, and a number of studies have demonstrated improved diagnostic accuracy of this modality in a variety of tumour types, including CRC. These developments have enabled the progression of treatment strategies in rectal cancer and improved the detection of hepatic metastatic disease, yet are not without their limitations. These include technical, economical and logistical challenges, along with a lack of robust evidence for standardisation and formal guidance. In order to successfully apply these novel imaging techniques and utilise their benefit to provide truly personalised cancer care, advances need to be clinically realised in a routine and robust manner.

  17. Imaging Prostate Cancer Microenvironment by Collagen Hybridization

    Science.gov (United States)

    2015-10-01

    Description of Goals: The overall goal is to have a fully validated probe ready for human administration and to file a FDA Investigational New Drug (IND...Level of Funding: $249,274 Description of Goals: The goal is to develop a new nicotinic receptor-based PET agent that enables imaging of...drug carriers optimized for local nanoparticle-based chemotherapy. (B) To test imaging after local and systemic administration . New Title: PSMA

  18. Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy

    International Nuclear Information System (INIS)

    Bai, Ling-Yu; Yang, Xiao-Quan; An, Jie; Zhang, Lin; Zhao, Kai; Qin, Meng-Yao; Fang, Bi-Yun; Li, Cheng; Xuan, Yang; Zhang, Xiao-Shuai; Zhao, Yuan-Di; Ma, Zhi-Ya

    2015-01-01

    Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T 2 -weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy. (paper)

  19. Optical imaging for breast cancer prescreening

    Directory of Open Access Journals (Sweden)

    Godavarty A

    2015-07-01

    Full Text Available Anuradha Godavarty,1 Suset Rodriguez,1 Young-Jin Jung,2 Stephanie Gonzalez1 1Optical Imaging Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL, USA; 2Department of Radiological Science, Dongseo University, Busan, South Korea Abstract: Breast cancer prescreening is carried out prior to the gold standard screening using X-ray mammography and/or ultrasound. Prescreening is typically carried out using clinical breast examination (CBE or self-breast examinations (SBEs. Since CBE and SBE have high false-positive rates, there is a need for a low-cost, noninvasive, non-radiative, and portable imaging modality that can be used as a prescreening tool to complement CBE/SBE. This review focuses on the various hand-held optical imaging devices that have been developed and applied toward early-stage breast cancer detection or as a prescreening tool via phantom, in vivo, and breast cancer imaging studies. Apart from the various optical devices developed by different research groups, a wide-field fiber-free near-infrared optical scanner has been developed for transillumination-based breast imaging in our Optical Imaging Laboratory. Preliminary in vivo studies on normal breast tissues, with absorption-contrasted targets placed in the intramammary fold, detected targets as deep as 8.8 cm. Future work involves in vivo imaging studies on breast cancer subjects and comparison with the gold standard X-ray mammography approach. Keywords: diffuse optical imaging, near-infrared, hand-held devices, breast cancer, prescreening, early detection 

  20. National Cancer Institute Formulary: A Public-Private Partnership Providing Investigators Access to Investigational Anticancer Agents.

    Science.gov (United States)

    Cristofaro, J V; Ansher, S S; Zwiebel, J A; Ivy, P; Conley, B; Abrams, J S; Doroshow, J H

    2017-05-01

    As part of the White House Cancer Moonshot Initiative, the National Cancer Institute (NCI) has developed a drug formulary to provide investigational anticancer agents to the extramural research community. This article describes how the NCI Formulary functions, how researchers may apply for access to drugs in the formulary, and the NCI's initial goals for formulary participation. Approved investigators may apply for access to formulary agents at: https://nciformulary.cancer.gov. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  1. Fusion Imaging in the Diagnosis of Cancer

    International Nuclear Information System (INIS)

    Maldonado, A.; Gonzalez Alenda, J.

    2007-01-01

    Early diagnosis is one of the most important aids in the fight against cancer. Of the tests available in Medicine, anatomic imaging techniques such as Computed Tomography (CT)and Magnetic Resonance Imaging (MRI) have been the ones used for many years. the emergence of Positron Emission Tomography (PET) more than a decade ago was a major breakthrough in the early diagnosis of malignant lesions, as it was based on tumor metabolism and not on anatomy. The merger of both techniques into one thanks to PET-CT cameras has made this technology the most important tool in the management of cancer patients. (Author)

  2. Optical Coherence Tomography in Cancer Imaging

    Science.gov (United States)

    Nam, Ahhyun Stephanie; Vakoc, Benjamin; Blauvelt, David; Chico-Calero, Isabel

    Investigations into the biology of cancer and novel cancer therapies rely on preclinical mouse models and traditional histological endpoints. Drawbacks of this approach include a limit in the number of time points for evaluation and an increased number of animals per study. This has motivated the use of intravital microscopy, which can provide longitudinal imaging of critical tumor parameters. Here, the capabilities of OCT as an intravital microscopy of the tumor microenvironment are summarized, and the state of OCT adoption into cancer research is summarized.

  3. Nanotechnology for sensing, imaging, and treating cancer.

    Science.gov (United States)

    Panchapakesan, Balaji; Wickstrom, Eric

    2007-04-01

    Nanotechnology encompasses the creation and use of materials, devices, and systems at the level of atoms, molecules, and supramolecular structures. Nanotechnology for cancer consists of three main areas: (1) nanodetectors for sensing proteins and cancer cells, (2) nanoparticle or nanovector formulations for high-contrast imaging, and (3) nanotechnology-based drug delivery and therapeutic formulations. Although there are tremendous challenges facing nanotechnologists, nanotechnology, if properly integrated with established cancer research, can make laboratory-to-clinic transfer of technology successful, which can result in breakthrough potential for patient care.

  4. Nanoplatforms for magnetic resonance imaging of cancer

    International Nuclear Information System (INIS)

    Cywinska, M. A.; Grudzinski, I. P.; Cieszanowski, A.; Bystrzejewski, M.; Poplawska, M.

    2011-01-01

    The application of biomedical nanotechnology in magnetic resonance imaging (MRI) is expect to have a major impact leading to the development of new contrast drug candidates on the nanoscale (1 - 100 nm) that are able to react with specific biological targets at a molecular level. One of the major challenges in this regard is the construction of nanomaterials, especially used in molecular MRI diagnostics of cancer in vivo, specialized antitumor drug delivery or real-time evaluation of the efficacy of the implemented cancer treatment. In this paper, we tried to gain further insights into current trends of nanomedicine, with special focus on preclinical MRI studies in translation cancer research. (authors)

  5. STTARR: a radiation treatment and multi-modal imaging facility for fast tracking novel agent development in small animal models

    International Nuclear Information System (INIS)

    Yeung, Ivan; McKee, Trevor; Jaffray, David; Hill, Richard

    2014-01-01

    Small animal models play a pivotal role in the pipeline development of novel agents and strategies in personalized cancer therapy. The Spatio-Temporal Targeting and Amplification of Radiation Response Program (STTARR) consists of an animal imaging and precision radiation facility designed to provide innovative biologic imaging and targeted radiation treatment strategies in small animals. The design is to mirror the imaging and radiation treatment facility in a modern cancer center. The STTARR features imaging equipment of small animal scale including CT, MRI, PET, SPECT, Optical devices as well as image guided irradiators. The fleet of imaging and irradiation equipment provides a platform for identification of biological targets of the specific molecular pathways that influence both tumor progression and a patient's response to radiation therapy. Examples will be given in the utilization of the imaging facilities for development in novel approaches in cancer therapy including a PET-FAZA study for hypoxia measurement in a pancreatic adenocarcinoma xenograft model. In addition, the cone-beam image guided small animal irradiator developed at our institute will also be described. The animal platform (couch) provides motion in 3 dimensions to position the animal to the isocentre of the beam. A pair of rotational arms supporting the X-ray/detector pair enables acquisition of cone-beam images of the animal which give rise to image guided precision of 0.5 mm. The irradiation energy ranges from 50 to 225 kVp at a dose rate from 10-400 cGy/min. The gantry is able to direct X-ray beam of different directions to give conformal radiation treatment to the animal. A dedicated treatment planning system is able to perform treatment planning and provide commonly used clinical metrics in the animal treatment plan. Examples will be given to highlight the use of the image guided irradiator for research of drug/irradiation regimen in animal models. (author)

  6. Image-Guided Cancer Nanomedicine

    OpenAIRE

    Dong-Hyun Kim

    2018-01-01

    Multifunctional nanoparticles with superior imaging properties and therapeutic effects have been extensively developed for the nanomedicine. However, tumor-intrinsic barriers and tumor heterogeneity have resulted in low in vivo therapeutic efficacy. The poor in vivo targeting efficiency in passive and active targeting of nano-therapeutics along with the toxicity of nanoparticles has been a major problem in nanomedicine. Recently, image-guided nanomedicine, which can deliver nanoparticles loca...

  7. Imaging applications of nanotechnology in cancer.

    Science.gov (United States)

    Gunasekera, U Ayanthi; Pankhurst, Quentin A; Douek, Michael

    2009-09-01

    Consider a single agent capable of diagnosing cancer, treating it simultaneously and monitoring response to treatment. Particles of this agent would seek cancer cells accurately and destroy them without harming normal surrounding cells. Science fiction or reality? Nanotechnology and nanomedicine are rapidly growing fields that encompass the creation of materials and devices at atomic, molecular and supramolecular level, for potential clinical use. Advances in nanotechnology are bringing us closer to the development of dual and multi-functional nanoparticles that are challenging the traditional distinction between diagnostic and treatment agents. Examples include contrast agents capable of delivering targeted drugs to specific epithelial receptors. This opens the way for targeted chemotherapy which could minimise systemic side-effects, avoid damage to benign tissues and also reduce the therapeutic treatment dose of a drug required. Most of the current research is still at the pre-clinical stage, with very few instances of bench to bedside research. In order to encourage more translational research, a fundamental change is required to consider the current clinical challenges and then look at ways in which nanotechnology can address these.

  8. Development of New Contrast Agents for Imaging Function and Metabolism by Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Alexandra Carvalho

    2017-07-01

    Full Text Available Liposomes are interesting nanosystems with a wide range of medical application. One particular application is their ability to enhance contrast in magnetic resonance images; when properly loaded with magnetic/superparamagnetic nanoparticles, this means to act as contrast agents. The design of liposomes loaded with magnetic particles, magnetoliposomes, presents a large number of possibilities depending on the application from image function to metabolism. More interesting is its double function application as theranostics (diagnostics and therapy. The synthesis, characterization, and possible medical applications of two types of magnetoliposomes are reviewed. Their performance will be compared, in particular, their efficiency as contrast agents for magnetic resonance imaging, measured by their relaxivities r 1 and r 2 relating to their particular composition. One of the magnetoliposomes had 1,2-diacyl-sn-glycero-3-phosphocholine (soy as the main phospholipid component, with and without cholesterol, varying its phospholipid to cholesterol molar ratios. The other formulation is a long-circulating liposome composed of 1,2-diacyl-sn-glycero-3-phosphocholine (egg, cholesterol, and 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine- N -[methoxy(polyethylene glycol-2000]. Both nanosystems were loaded with superparamagnetic iron oxide nanoparticles with different sizes and coatings.

  9. Early-life exposures to infectious agents and later cancer development.

    Science.gov (United States)

    Vedham, Vidya; Verma, Mukesh; Mahabir, Somdat

    2015-12-01

    There is a growing understanding that several infectious agents are acquired in early life and this is the reason why available vaccines target the new born, infants, and adolescents. Infectious agents are associated with cancer development and it is estimated that about 20% of the world's cancer burden is attributed to infectious agents. There is a growing evidence that certain infectious agents acquired in early life can give rise to cancer development, but estimates of the cancer burden from this early-life acquisition is unknown. In this article, we have selected five cancers (cervical, liver, Burkitt's lymphoma-leukemia, nasopharyngeal carcinoma, and adult T-cell leukemia-lymphoma) and examine their links to infectious agents (HPV, HBV, HCV, EBV, and HTLV-1) acquired in early life. For these agents, the acquisition in early life is from mother-to-child transmission, perinatal contact (with genital tract secretions, amniotic fluids, blood, and breast milk), saliva, sexual intercourse, and blood transfusion. We also discuss prevention strategies, address future directions, and propose mechanisms of action after a long latency period from the time of acquisition of the infectious agent in early life to cancer development. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.

  10. Technetium-99m isonitrile complex as a potential myocardial imaging agent

    International Nuclear Information System (INIS)

    Khalil, M.N.; Hubner, P.J.B.; Thornback, J.; Early, M.Y; Berry, J.M.; Morton, D.B.

    1985-01-01

    99 Tcsup(m)-tertiary butyl isonitrile (BIN) was assessed as a myocardial imaging agent in 4 dogs with normal hearts and three with experimentally induced myocardial infarction. Results are presented showing normal cardiac images, the detection of antero-apical infarcts, plasma clearance curves and tissue distribution in various organs. It is suggested that 99 Tcsup(m)-BIN has a potential role as a myocardial imaging agent in man. (U.K.)

  11. Prospective of 68Ga Radionuclide Contribution to the Development of Imaging Agents for Infection and Inflammation

    Science.gov (United States)

    2018-01-01

    During the last decade, the utilization of 68Ga for the development of imaging agents has increased considerably with the leading position in the oncology. The imaging of infection and inflammation is lagging despite strong unmet medical needs. This review presents the potential routes for the development of 68Ga-based agents for the imaging and quantification of infection and inflammation in various diseases and connection of the diagnosis to the treatment for the individualized patient management. PMID:29531507

  12. Optical imaging of cancer and cell death

    NARCIS (Netherlands)

    Xie, Bangwen

    2013-01-01

    The aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and cell death. In this thesis, we mainly focus on optical imaging and its application, both at microscopic

  13. Ultrasound Imaging Methods for Breast Cancer Detection

    NARCIS (Netherlands)

    Ozmen, N.

    2014-01-01

    The main focus of this thesis is on modeling acoustic wavefield propagation and implementing imaging algorithms for breast cancer detection using ultrasound. As a starting point, we use an integral equation formulation, which can be used to solve both the forward and inverse problems. This thesis

  14. Polymeric nanomedicine for cancer MR imaging and drug delivery.

    Science.gov (United States)

    Khemtong, Chalermchai; Kessinger, Chase W; Gao, Jinming

    2009-06-28

    Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (nanoscopic therapeutic and diagnostic systems have been translated into clinical practice. In this feature article, we will provide an up-to-date review on the development and biomedical applications of nanocomposite materials for cancer diagnosis and therapy. An overview of each functional component, i.e. polymer carriers, MR imaging agents, and therapeutic drugs, will be presented. Integration of different functional components will be illustrated in several highlighted examples to demonstrate the synergy of the multifunctional nanomedicine design.

  15. Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

    International Nuclear Information System (INIS)

    Tanaka, Mamoru; Kamiya, Takeshi; Joh, Takashi; Kataoka, Hiromi; Yano, Shigenobu; Ohi, Hiromi; Kawamoto, Keisuke; Shibahara, Takashi; Mizoshita, Tsutomu; Mori, Yoshinori; Tanida, Satoshi

    2013-01-01

    Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients. We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl 2 (L)] and [PdCl 2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl 2 (L)] and [PdCl 2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo. CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl 2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl 2 (L)] induced DNA double-strand breaks. These results indicate that [PdCl 2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications

  16. Paired-agent imaging for resection during surgery (PAIRS) of head and neck squamous cell carcinomas (Conference Presentation)

    Science.gov (United States)

    Samkoe, Kimberley S.; Tichauer, Kenneth M.; Chen, Eunice; Gunn, Jason R.; Hoopes, P. Jack; Wells, Wendy A.; Hasan, Tayyaba; Pogue, Brian W.

    2016-03-01

    Ninety percent of patients with head and neck squamous cell carcinomas (HNSCC) have overexpression of epidermal growth factor receptor (EGFR), which is correlated with poor prognosis. Complete surgical resection of HNSCC tumors has a large impact on patient survival, where detection of tumor at or close to surgical margins increases the risk of death at 5-years by 90%. In addition, large surgical margins can greatly increase the morbidity experienced by the patient due to functional and cosmetic damage of oral and facial structures. Single fluorescence targeting agents are often used for tumor detection in in vivo pre-clinical imaging; however, the arising signal is qualitative at best because it is a complex mixture of vascular perfusion, vascular leakage, inhibited lymphatic clearance, and receptor binding. In vivo ratiometric receptor concentration imaging (RCI) allows quantification of receptor expression (hence identification of cancerous tissue) by utilizing co-administered paired-agents consisting of a targeted agent and non-targeted perfusion agent to reference the plasma delivery and leakage. A panel of HNSCC tumors with varying levels of EGFR expression (SCC-15 >SCC-25 > SCC-09) have been imaged using ABY-029, a clinically relevant anti-EGFR affibody labeled with IRDye 800CW, and affibody control imaging agent labeled with IRDye 680RD. RCI maps of in vivo tissue have been created and are spatially correlated with EGFR and CD31 immunohistochemistry and basic H and E staining. The RCI threshold parameters for distinguishing tumor from normal tissues (skin and muscle) and the accuracy of margin detection in these tumors will be presented. RCI surgical resection will be further developed using a novel multi-channel, gated fluorescence-guided surgery (FGS) imaging system that is capable of performing RCI in normal room light.

  17. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  18. Quinones derived from plant secondary metabolites as anti-cancer agents.

    Science.gov (United States)

    Lu, Jin-Jian; Bao, Jiao-Lin; Wu, Guo-Sheng; Xu, Wen-Shan; Huang, Ming-Qing; Chen, Xiu-Ping; Wang, Yi-Tao

    2013-03-01

    Quinones are plant-derived secondary metabolites that present some anti-proliferation and anti-metastasis effects in various cancer types both in vitro and in vivo. This review focuses on the anti-cancer prospects of plant-derived quinones, namely, aloe-emodin, juglone, β-lapachol, plumbagin, shikonin, and thymoquinone. We intend to summarize their anti-cancer effects and investigate the mechanism of actions to promote the research and development of anti-cancer agents from quinones.

  19. Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

    Science.gov (United States)

    Yi, Xiaomin; Wang, Fuli; Qin, Weijun; Yang, Xiaojian; Yuan, Jianlin

    2014-01-01

    Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized. PMID:24648733

  20. Towards safety of oral anti-cancer agents, the need to educate our pharmacists

    Directory of Open Access Journals (Sweden)

    Sanaa Saeed Mekdad

    2017-01-01

    Full Text Available Introduction: The global prevalence of cancer is rising. Use of oral anticancer medications has expanded exponentially. Knowledge about these medications as well as safe handling guidelines has not kept abreast with the rapidity these medications are applied in clinical practice. They pose serious hazards on all personal involved in handling these medications as well as on patients and their caregivers. We addressed the gaps in knowledge and safe handling of oral anticancer agents among pharmacists in institutional based cancer care. Materials and Methods: We used a 41 item questionnaire to explore three domains, pharmacists’ knowledge, safe handling practice and confidence and self-improving strategies towards these agents among pharmacists in multicentre specialized cancer care. Results: Participants included 120 pharmacists dedicated to handle and dispense oral anticancer agents. About 20% of Pharmacists have adequate knowledge about oral anticancer agents. Less than 50% apply safe handling principles adequately. Only a quarter are confident in educating cancer patients and their caregivers about Oral Anti-Cancer Agents. Conclusions: Pharmacists’ knowledge about Oral Anticancer agents needs to be improved. Safe handling and dispensing practice of these medications should be optimized. Pharmacists’ confidence towards educating patients and their caregiver needs to be addressed. Enhancing safety of oral anticancer agents should be a priority. Involving all key players, research and quality improving projects are needed to improve all aspects of the safety of oral anticancer agents.

  1. Polymer-Based Materials in Cancer Treatment: From Therapeutic Carrier and Ultrasound Contrast Agent to Theranostic Applications.

    Science.gov (United States)

    Methachan, Boriphat; Thanapprapasr, Kamolrat

    2017-01-01

    The emergence of theranostics with ultrasound technology is a promising development, as it opens pathways to providing more effective treatments for cancer. Advancements in ultrasound imaging would give a more detailed and accurate image for better diagnosis and treatment planning. Polymeric ultrasound contrast agents (UCAs) are appealing because they are stable and easily modified for active targeting. In addition, a better therapy could be achieved in conjunction with advancements in UCAs. The active targeting not only makes the precise imaging possible, but also leads to targeted delivery of active components to specific local treatment sites. A polymeric nanocarrier with surface bioconjugation is the key to prolonging the bioavailability of the encapsulated drugs or genes and the capacity to target the specific tumor site. Using ultrasound with other imaging modalities will open more precise and better ways for diagnosis and therapy and bring us a step closer to personalized medicine. This review focuses on polymer-based materials of UCAs, multimodal imaging agents and therapeutic carriers that have been currently explored for their theranostic applications involving ultrasound for cancer diagnosis and treatment. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  2. Functional MR Imaging in Gynecologic Cancer.

    Science.gov (United States)

    deSouza, Nandita M; Rockall, Andrea; Freeman, Susan

    2016-02-01

    Dynamic-contrast enhanced (DCE) and diffusion-weighted (DW) MR imaging are invaluable in the detection, staging, and characterization of uterine and ovarian malignancies, for monitoring treatment response, and for identifying disease recurrence. When used as adjuncts to morphologic T2-weighted (T2-W) MR imaging, these techniques improve accuracy of disease detection and staging. DW-MR imaging is preferred because of its ease of implementation and lack of need for an extrinsic contrast agent. MR spectroscopy is difficult to implement in the clinical workflow and lacks both sensitivity and specificity. If used quantitatively in multicenter clinical trials, standardization of DCE- and DW-MR imaging techniques and rigorous quality assurance is mandatory. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents.

    Science.gov (United States)

    Rand, Danielle; Uchida, Masaki; Douglas, Trevor; Rose-Petruck, Christoph

    2014-09-22

    Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based "nanobubble" contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size.

  4. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    Energy Technology Data Exchange (ETDEWEB)

    Peruzzini, D.; Viti, J. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Tortoli, P. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Verweij, M. D. [Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands); Jong, N. de; Vos, H. J., E-mail: h.vos@erasmusmc.nl [Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands)

    2015-10-28

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. “superharmonic” imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which ‘signal’ denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

  5. Theranostic liposomes as a bimodal carrier for magnetic resonance imaging contrast agent and photosensitizer.

    Science.gov (United States)

    Skupin-Mrugalska, Paulina; Sobotta, Lukasz; Warowicka, Alicja; Wereszczynska, Beata; Zalewski, Tomasz; Gierlich, Piotr; Jarek, Marcin; Nowaczyk, Grzegorz; Kempka, Marek; Gapinski, Jacek; Jurga, Stefan; Mielcarek, Jadwiga

    2018-03-01

    The present study is focused on the development of liposomes bearing gadolinium chelate (GdLip) providing two functionalities for magnetic resonance imaging (MRI) and photodynamic therapy of cancer. A lipid derivative of gadolinium(III) diethylenetriamine pentaacetic acid salt (GdDTPA1) was inserted in the liposomal membrane and served as MRI contrast agent whereas a zinc phthalocyanine (ZnPc) was used as a model photosensitizer. In addition to conventional liposomes, pegylated lipids were used for the preparation of "stealth" liposomes. The characterization of different GdLip formulations involved evaluation of the liposomes size by nanoparticle tracking analysis, thermal phase behavior by differential scanning calorimetry and ZnPc-mediated singlet oxygen production. Furthermore, relaxivity measurements were performed as well as cytotoxicity and photodynamic activity against cancerous and normal cell lines was studied. Size and thermal behavior were only slightly influenced by GdLip composition, however it distinctly affected singlet oxygen production of ZnPc-loaded GdLip. The quantum yields of singlet oxygen generation by zinc phthalocyanine incorporated in GdLip containing cationic or/and pegylated lipids were smaller than those obtained for non-pegylated carriers with l-α-phosphatidylglycerol. In general, all formulations of GdLip, irrespectively of composition, were characterized by relaxivities higher than those of commercially used contrast agents (e.g. Magnevist®). NMR study has shown that the incorporation of ZnPc into the formulations of GdLip increases the relaxation parameters r 1 and r 2 , compared to the values for the non-loaded vesicles. GdDTPA1 did not influence the photodynamic activity of ZnPc against HeLa cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. TRAIL: A Novel Therapeutic Agent for Prostate Cancer

    National Research Council Canada - National Science Library

    Li, Honglin

    2004-01-01

    This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

  7. TRAIL: A Novel Therapeutic Agent for Prostate Cancer

    National Research Council Canada - National Science Library

    Li, Honglin

    2002-01-01

    This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

  8. TRAIL: A Novel Therapeutic Agent for Prostate Cancer

    National Research Council Canada - National Science Library

    Li, Honglin

    2003-01-01

    This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

  9. Melanin-Based Contrast Agents for Biomedical Optoacoustic Imaging and Theranostic Applications.

    Science.gov (United States)

    Longo, Dario Livio; Stefania, Rachele; Aime, Silvio; Oraevsky, Alexander

    2017-08-07

    Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting resulting ultrasound waves. This technique takes advantage of the spectroscopic approach to molecular imaging, and delivers high-resolution images in the depth of tissue. Resolution of the optoacoustic imaging is scalable, so that biomedical systems from cellular organelles to large organs can be visualized and, more importantly, characterized based on their optical absorption coefficient, which is proportional to the concentration of absorbing chromophores. Optoacoustic imaging was shown to be useful in both preclinical research using small animal models and in clinical applications. Applications in the field of molecular imaging offer abundant opportunities for the development of highly specific and effective contrast agents for quantitative optoacoustic imaging. Recent efforts are being made in the direction of nontoxic biodegradable contrast agents (such as nanoparticles made of melanin) that are potentially applicable in clinical optoacoustic imaging. In order to increase the efficiency and specificity of contrast agents and probes, they need to be made smart and capable of controlled accumulation in the target cells. This review was written in recognition of the potential breakthroughs in medical optoacoustic imaging that can be enabled by efficient and nontoxic melanin-based optoacoustic contrast agents.

  10. Upconversion nanoparticles and their composite nanostructures for biomedical imaging and cancer therapy

    Science.gov (United States)

    Cheng, Liang; Wang, Chao; Liu, Zhuang

    2012-12-01

    Upconversion nanoparticles (UCNPs), particularly lanthanide-doped nanocrystals, which emit high energy photons under excitation by the near-infrared (NIR) light, have found potential applications in many different fields, including biomedicine. Compared with traditional down-conversion fluorescence imaging, the NIR light excited upconversion luminescence (UCL) imaging relying on UCNPs exhibits improved tissue penetration depth, higher photochemical stability, and is free of auto-fluorescence background, which promises biomedical imaging with high sensitivity. On the other hand, the unique upconversion process of UCNPs may be utilized to activate photosensitive therapeutic agents for applications in cancer treatment. Moreover, the integration of UCNPs with other functional nanostructures could result in the obtained nanocomposites having highly enriched functionalities, useful in imaging-guided cancer therapies. This review article will focus on the biomedical imaging and cancer therapy applications of UCNPs and their nanocomposites, and discuss recent advances and future prospects in this emerging field.

  11. Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0238 TITLE: Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer PRINCIPAL...of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Oxygen-rich environments can create pro- mutagenic DNA lesions such as 8-oxoguanine (8-oxo-G) that can be misreplicated during translesion DNA synthesis

  12. Development of the MASCC Teaching Tool for Patients Receiving Oral Agents for Cancer.

    Science.gov (United States)

    Kav, Sultan; Schulmeister, Lisa; Nirenberg, Anita; Barber, Linda; Johnson, Judi; Rittenberg, Cynthia

    2010-05-01

    Oral agents for cancer treatment commonly are prescribed throughout the world. Since oral agents usually are self-administered or administered by lay caregivers, patient education is vital to help ensure that the oral agents are being stored, handled, and taken correctly. When oral agents are taken as prescribed and patients are well informed about signs and symptoms to report, patient outcomes are optimized. Patient education varies globally; consequently, there is a need for a consistent and comprehensive approach to educate patients about oral cancer treatment. To create a teaching tool to be used with patients receiving oral cancer agents for worldwide use. Six oncology nurse experts conducted a literature review and convened as an expert panel to draft a teaching tool for patients receiving oral cancer agents. The tool includes key assessment questions, generic education discussion points, drug-specific education, and evaluation questions to help ensure that patients/caregivers understand the information provided. Eighteen healthcare providers from 15 countries reviewed the tool for clarity and usefulness in practice by scoring each item in the teaching tool on a 0-10 scale ("0 = not at all to "10" = most clear/useful"). Items that scored 5 or below required comments. At the Multinational Association for Supportive Care in Cancer (MASCC) Symposium in 2008, the healthcare providers who reviewed the teaching tool met with the oncology nurse experts who had developed the tool to review the item scores and revise the tool as necessary. All items on the teaching tool received high scores, with the exception of items on refilling prescriptions and insurance issues, which vary from country to country. There was consensus that the MASCC Teaching Tool for Patients Receiving Oral Agents for Cancer was ready to be used and further evaluated in clinical practice. The MASCC Teaching Tool for Patients Receiving Oral Agents for Cancer is an available resource to assist

  13. Tumor-selective coronaviruses as potential anti-cancer agents

    NARCIS (Netherlands)

    Würdinger, Thomas

    2006-01-01

    Despite much progress in the treatment of certain types of cancer, generally the successes of cancer therapy are still largely insufficient and new treatment options are therefore urgently needed. Oncolytic virotherapy may offer an unconventional approach to selectively eradicate cancer cells, while

  14. New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Oltenfreiter, Ruth E-mail: ruth.oltenfreiter@rug.ac.be; Staelens, Ludovicus; Lejeune, Annabelle; Dumont, Filip; Frankenne, Francis; Foidart, Jean-Michel; Slegers, Guido

    2004-05-01

    Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs). MMP-2 and MMP-9 have become attractive targets for cancer research because of their increased expression in human malignant tumor tissues of various organs, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[{sup 123}I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (9) and 2-(4'-[{sup 123}I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionamide (11) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives and resulted in radiochemical yields of 60% {+-} 5% (n = 3) and 70% {+-} 5% (n = 6), respectively. In vitro zymography and enzyme assays showed high inhibition capacities of the inhibitors on gelatinases. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumor. These results warrant further studies of radioiodinated carboxylic and hydroxamic MMP inhibitor tracers as potential SPECT tumor imaging agents.

  15. New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents

    International Nuclear Information System (INIS)

    Oltenfreiter, Ruth; Staelens, Ludovicus; Lejeune, Annabelle; Dumont, Filip; Frankenne, Francis; Foidart, Jean-Michel; Slegers, Guido

    2004-01-01

    Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs). MMP-2 and MMP-9 have become attractive targets for cancer research because of their increased expression in human malignant tumor tissues of various organs, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[ 123 I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (9) and 2-(4'-[ 123 I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionamide (11) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives and resulted in radiochemical yields of 60% ± 5% (n = 3) and 70% ± 5% (n = 6), respectively. In vitro zymography and enzyme assays showed high inhibition capacities of the inhibitors on gelatinases. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumor. These results warrant further studies of radioiodinated carboxylic and hydroxamic MMP inhibitor tracers as potential SPECT tumor imaging agents

  16. Ultrasonic Imaging Techniques for Breast Cancer Detection

    Science.gov (United States)

    Goulding, N. R.; Marquez, J. D.; Prewett, E. M.; Claytor, T. N.; Nadler, B. R.

    2008-02-01

    Improving the resolution and specificity of current ultrasonic imaging technology is needed to enhance its relevance to breast cancer detection. A novel ultrasonic imaging reconstruction method is described that exploits classical straight-ray migration. This novel method improves signal processing for better image resolution and uses novel staging hardware options using a pulse-echo approach. A breast phantom with various inclusions is imaged using the classical migration method and is compared to standard computed tomography (CT) scans. These innovative ultrasonic methods incorporate ultrasound data acquisition, beam profile characterization, and image reconstruction. For an ultrasonic frequency of 2.25 MHz, imaged inclusions of approximately 1 cm are resolved and identified. Better resolution is expected with minor modifications. Improved image quality and resolution enables earlier detection and more accurate diagnoses of tumors thus reducing the number of biopsies performed, increasing treatment options, and lowering remission percentages. Using these new techniques the inclusions in the phantom are resolved and compared to the results of standard methods. Refinement of this application using other imaging techniques such as time-reversal mirrors (TRM), synthetic aperture focusing technique (SAFT), decomposition of the time reversal operator (DORT), and factorization methods is also discussed.

  17. Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration.

    Science.gov (United States)

    Liu, Yiqiao; Zhou, Bo; Qutaish, Mohammed; Wilson, David L

    2016-01-01

    We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register MRI volumes to the cryo bright field reference, we used our standard mutual information, non-rigid registration which proceeded: preprocess → affine → B-spline non-rigid 3D registration. In this report, we created two modified approaches: mask where we registered locally over a smaller rectangular solid, and sliding organ . Briefly, in sliding organ , we segmented the organ, registered the organ and body volumes separately and combined results. Though s liding organ required manual annotation, it provided the best result as a standard to measure other registration methods. Regularization parameters for standard and mask methods were optimized in a grid search. Evaluations consisted of DICE, and visual scoring of a checkerboard display. Standard had accuracy of 2 voxels in all regions except near the kidney, where there were 5 voxels sliding. After mask and sliding organ correction, kidneys sliding were within 2 voxels, and Dice overlap increased 4%-10% in mask compared to standard . Mask generated comparable results with sliding organ and allowed a semi-automatic process.

  18. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    Directory of Open Access Journals (Sweden)

    Palaniselvam Kuppusamy

    2014-06-01

    Full Text Available Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  19. Nutraceuticals as potential therapeutic agents for colon cancer: a review.

    Science.gov (United States)

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-06-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  20. Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution

    Directory of Open Access Journals (Sweden)

    Lee H

    2015-08-01

    Full Text Available Haisung Lee,1 Dongkyung Sung,2 Jinhoon Kim,3 Byung-Tae Kim,3 Tuntun Wang,4 Seong Soo A An,5 Soo-Won Seo,6 Dong Kee Yi4 1Molecular Diagnostics, In Vitro Diagnostics Unit, New Business Division, SK Telecom, 2Department of Life Sciences, Graduate School of Korea University, 3Interdisciplinary Graduate Program of Biomedical Engineering, School of Medicine, Sungkyunkwan University, Samsung Medical Center, 4Department of Chemistry, Myongji University, Seoul, 5Department of Bionanotechnology, Gachon Medical Research Institute, Gachon University, Seongnam, 6Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea Abstract: In this study, fluorescent dye-conjugated magnetic resonance (MR imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium-conjugated nanoparticles in both lung cancer cells and organs in mice. Keywords: dual bioimaging, MR imaging, silica colloid, T1 contrast imaging, nanohybrid

  1. Ultrasound imaging and contrast agents: a safe alternative to MRI?

    NARCIS (Netherlands)

    Wink, Margot H.; Wijkstra, Hessel; de La Rosette, Jean J. M. C. H.; Grimbergen, Cornelis A.

    2006-01-01

    Microbubble contrast media are used to enhance ultrasound images. Because ultrasound is a real-time investigation, contrast-enhanced ultrasound offers possibilities for perfusion imaging. This review is conducted to evaluate the safety of contrast-enhanced ultrasound and its possible role in medical

  2. OPTIMIZATION OF DIAGNOSTIC IMAGING IN BREAST CANCER

    Directory of Open Access Journals (Sweden)

    S. A. Velichko

    2015-01-01

    Full Text Available The paper presents the results of breast imaging for 47200 women. Breast cancer was detected in 862 (1.9% patients, fibroadenoma in 1267 (2.7% patients and isolated breast cysts in 1162 (2.4% patients. Different types of fibrocystic breast disease (adenosis, diffuse fibrocystic changes, local fibrosis and others were observed in 60.1% of women. Problems of breast cancer visualization during mammography, characterized by the appearance of fibrocystic mastopathy (sclerosing adenosis, fibrous bands along the ducts have been analyzed. Data on the development of diagnostic algorithms including the modern techniques for ultrasound and interventional radiology aimed at detecting early breast cancer have been presented.  

  3. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  4. In vitro and In vivo Studies on Stilbene Analogs as Potential Treatment Agents for Colon Cancer

    Science.gov (United States)

    Based upon the potential of resveratrol as a cancer chemopreventive agent, 27 stilbenes analogs were synthesized and tested against colon cancer cell line HT-29. Among these compounds, amino derivative (Z)-4-(3,5-dimethoxystyryl) aniline (4), (Z)-methyl 4-(3,5-dimethoxystyryl) benzoate (6) and (Z)-1...

  5. Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

    Energy Technology Data Exchange (ETDEWEB)

    Gakh, Andrei A; Vovk, Mykhaylo V; Mel& #x27; nychenko, Nina V; Sukach, Volodymyr A

    2012-10-23

    The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

  6. Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

    Energy Technology Data Exchange (ETDEWEB)

    Gakh, Andrei A.; Vovk, Mykhaylo V.; Mel' nychenko, Nina V.; Sukach, Volodymyr A.

    2012-08-14

    The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

  7. Searching for an alternative oral contrast agent for GI tract MR imaging; in vitro phase, initial report

    International Nuclear Information System (INIS)

    Okla, W.; Szeszkowski, W.; Cieszanowski, A.; Golebiowski, M.

    2002-01-01

    MR has been recently considered to be suitable method for detection GI tract pathologies. A few substances (some of a natural origin) seem to act as an efficient oral MR contrast agents. The aim of this study is to find an alternative substance, which can be administrated orally to patients in order to enhance signal intensity (SI). The ideal agent should have a biphase pattern (high SI in T1 and low in T2), and should be nontoxic and cost effective. Phantom experiments were conducted with 1.5 T MR scanner. T1W and T2W sequences were used for initial estimation. Number of different agents such as: water, Gd-DTPA, barium sulfate, green tea, blueberry juice, cranberry juice, blackcurrant juice, and some more were evaluated. Signal intensity was measured by using elliptical region of interest (ROI). MR imaging in one patient with stomach cancer was also performed. In T1W-FFE sequence cranberry juice reached satisfactorily high signal (SI=1760.14). In T2W-TSE sequence this substance reduced signal intensity (SI=23.10) almost to background level. Blueberry juice appear to be the next substance capable to generate high signal (SI=1558.31) in T1W sequence (T1-TSE). MR examination of a patient with stomach adenocarcinoma (using blueberry juice as an oral contrast agent) satisfactorily depicted and delineated tumor mass on both: T1W and T2W images. Cranberry juice and blueberry juice seemed to act effectively as oral contrast agents for gastrointestinal MR imaging. Thus they need further exploration and trials. (author)

  8. Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

    Science.gov (United States)

    Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

    2017-09-01

    Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

  9. Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer

    Science.gov (United States)

    Welge, Weston A.; Barton, Jennifer K.

    2016-03-01

    Aberrant crypt foci (ACF) are abnormal epithelial lesions that precede development of colonic polyps. As the earliest morphological change in the development of colorectal cancer, ACF is a highly studied phenomenon. The most common method of imaging ACF is chromoendoscopy using methylene blue as a contrast agent. Narrow- band imaging is a contrast-agent-free modality for imaging the colonic crypts. Optical coherence tomography (OCT) is an attractive alternative to chromoendoscopy and narrow-band imaging because it can resolve the crypt structure at sufficiently high sampling while simultaneously providing depth-resolved data. We imaged in vivo the distal 15 mm of colon in the azoxymethane (AOM) mouse model of colorectal cancer using a commercial swept-source OCT system and a miniature endoscope designed and built in-house. We present en face images of the colonic crypts and demonstrate that different patterns in healthy and adenoma tissue can be seen. These patterns correspond to those reported in the literature. We have previously demonstrated early detection of colon adenoma using OCT by detecting minute thickening of the mucosa. By combining mucosal thickness measurement with imaging of the crypt structure, OCT can be used to correlate ACF and adenoma development in space and time. These results suggest that OCT may be a superior imaging modality for studying the connection between ACF and colorectal cancer.

  10. X ray imaging microscope for cancer research

    Science.gov (United States)

    Hoover, Richard B.; Shealy, David L.; Brinkley, B. R.; Baker, Phillip C.; Barbee, Troy W., Jr.; Walker, Arthur B. C., Jr.

    1991-01-01

    The NASA technology employed during the Stanford MSFC LLNL Rocket X Ray Spectroheliograph flight established that doubly reflecting, normal incidence multilayer optics can be designed, fabricated, and used for high resolution x ray imaging of the Sun. Technology developed as part of the MSFC X Ray Microscope program, showed that high quality, high resolution multilayer x ray imaging microscopes are feasible. Using technology developed at Stanford University and at the DOE Lawrence Livermore National Laboratory (LLNL), Troy W. Barbee, Jr. has fabricated multilayer coatings with near theoretical reflectivities and perfect bandpass matching for a new rocket borne solar observatory, the Multi-Spectral Solar Telescope Array (MSSTA). Advanced Flow Polishing has provided multilayer mirror substrates with sub-angstrom (rms) smoothnesss for the astronomical x ray telescopes and x ray microscopes. The combination of these important technological advancements has paved the way for the development of a Water Window Imaging X Ray Microscope for cancer research.

  11. Magnetic resonance contrast media sensing in vivo molecular imaging agents: an overview.

    Science.gov (United States)

    Amanlou, Massoud; Siadat, Seyed Davar; Norouzian, Dariush; Ebrahimi, Seyed Esmaeil Sadat; Aghasadeghi, Mohammad Reza; Ghorbani, Masoud; Alavidjeh, Mohammad Shafiee; Inanlou, Davoud Nouri; Arabzadeh, Ali Jabbari; Ardestani, Mehdi Shafiee

    2011-01-01

    Metabolic imaging is commonly performed by nuclear medicine facilities such as PET or SPECT, etc. The production and biomedical applications of bio-molecular sensing in vivo MRI metabolic contrast agents has recently become of great universal research interest, which follows its great success as a potential cost effective, less radioactive, nuclear medicine alternative. Temperature, redox potential, enzyme activity, free radial/metal ion responsive and/or pH sensitive molecular metabolic MR contrast agents are among the famous instances exemplified, which basically promote MR image contrast enhancement ability to distinguish molecular metabolic/gene expression features. Overall, these MRI contrast agents provide a framework to achieve a greater degree of accuracy from MRI as a low cost, more available facility, non radioactive radiation producing and highly sensitive biomedical tool to propound as a new suggesting opponent for PET nuclear medicine imaging. In the present review, the design, development, examination and future of the above agents will be discussed in detail.

  12. Combination of chemotherapy and cancer stem cell targeting agents: Preclinical and clinical studies.

    Science.gov (United States)

    Li, Yanyan; Atkinson, Katharine; Zhang, Tao

    2017-06-28

    The cancer stem cell model claims that the initiation, maintenance, and growth of a tumor are driven by a small population of cancer cells termed cancer stem cells. Cancer stem cells possess a variety of phenotypes associated with therapeutic resistance and often cause recurrence of the diseases. Several strategies have been investigated to target cancer stem cells in a variety of cancers, such as blocking one or more self-renewal signaling pathways, reducing the expression of drug efflux and ATP-binding cassette efflux transporters, modulating epigenetic aberrations, and promoting cancer stem cell differentiation. A number of cell and animal studies strongly support the potential benefits of combining chemotherapeutic drugs with cancer stem cell targeting agents. Clinical trials are still underway to address the pharmacokinetics, safety, and efficacy of combination treatment. This mini-review provides an updated discussion of these preclinical and clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Optical tomographic imaging for breast cancer detection

    Science.gov (United States)

    Cong, Wenxiang; Intes, Xavier; Wang, Ge

    2017-09-01

    Diffuse optical breast imaging utilizes near-infrared (NIR) light propagation through tissues to assess the optical properties of tissues for the identification of abnormal tissue. This optical imaging approach is sensitive, cost-effective, and does not involve any ionizing radiation. However, the image reconstruction of diffuse optical tomography (DOT) is a nonlinear inverse problem and suffers from severe illposedness due to data noise, NIR light scattering, and measurement incompleteness. An image reconstruction method is proposed for the detection of breast cancer. This method splits the image reconstruction problem into the localization of abnormal tissues and quantification of absorption variations. The localization of abnormal tissues is performed based on a well-posed optimization model, which can be solved via a differential evolution optimization method to achieve a stable reconstruction. The quantification of abnormal absorption is then determined in localized regions of relatively small extents, in which a potential tumor might be. Consequently, the number of unknown absorption variables can be greatly reduced to overcome the underdetermined nature of DOT. Numerical simulation experiments are performed to verify merits of the proposed method, and the results show that the image reconstruction method is stable and accurate for the identification of abnormal tissues, and robust against the measurement noise of data.

  14. Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast agents for magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jahanbin, Tania [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Sauriat-Dorizon, Hélène [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France); Spearman, Peter [Faculty of Science, Engineering and Computing, University of Kingston, Penrhyn Road Kingston upon Thames Surrey KT1 2EE, London (United Kingdom); Benderbous, Soraya, E-mail: soraya.benderbous@univ-tlse3.fr [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Korri-Youssoufi, Hafsa, E-mail: hafsa.korri-youssoufi@u-psud.fr [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France)

    2015-07-01

    A novel magnetic resonance imaging (MRI) contrast agent based on gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] conjugated with chitosan nanoparticles has been developed. The chitosan nanoparticles were synthesized following an ionic gelation method and the conditions optimized to generate small nanoparticles (CNs) with a narrow size distribution of 35–65 nm. The gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] was loaded into chitosan nanoparticles by passive adsorption. The interaction of chitosan with Gd(TPyP) has been examined by UV–visible, Fourier transform infrared spectroscopies (FT-IR) and inductively coupled plasma mass spectrometry (ICP-MS), which indicate the successful association of Gd(TPyP) without any structural distortion throughout the chitosan nanoparticles. The potential of Gd(TPyP)-CNs as MRI contrast agent has been investigated by magnetic resonance imaging (MRI) in-vitro. Relaxivities of Gd(TPyP)-CNs obtained from T{sub 1}-weighted images, increased with Gd concentration and attained an optimum r{sub 1} of 38.35 mM{sup −1} s{sup −1}, which is 12-fold higher compared to commercial Gd-DOTA (~ 4 mM{sup −1} s{sup −1} at 3T). The combination of such strong MRI contrast with the known properties of porphyrins in photodynamic therapy and biocompatibility of chitosan, presents a new perspective in using these compounds in cancer theranostics. - Highlights: • Synthesis of chitosan nanoparticles with small size • Study of loading properties with gadolinium porphyrins • In vitro properties of the conjugated complex as contrast agent for MRI imaging • Comparison of MRI properties with commercial contrast agent Gd-DOTA.

  15. Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hamon, Casey L.; Dorsey, Christopher L. [Texas State University, Department of Chemistry and Biochemistry (United States); Özel, Tuğba [Texas State University, Materials Science, Engineering, and Commercialization Program (United States); Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania, E-mail: tb26@txstate.edu [Texas State University, Department of Chemistry and Biochemistry (United States)

    2016-07-15

    Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30–70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.Graphical abstract.

  16. Metal complex-based templates and nanostructures for magnetic resonance/optical multimodal imaging agents

    NARCIS (Netherlands)

    Galindo Millan, Jealemy

    2012-01-01

    In this thesis, new approaches directed towards simple and functional imaging agents (IAs) for magnetic resonance (MR) and fluorescence multimodal imaging are proposed. In Chapter 3, hybrid silver nanostructures (hAgNSs), grown using a polyamino carboxylic acid scaffold, namely

  17. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

    Science.gov (United States)

    Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

    2013-09-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

  18. Flavonoids as Chemopreventive and Therapeutic Agents Against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Albert Cabrera

    2014-05-01

    Full Text Available The objective of the present review is to study the relationship between flavonoids and lung cancer, proposing that their regular consumption in Western diets could be beneficial for protecting patients against lung cancer. An extensive search of the scientific literature was performed in the following electronic specialized databases (PubMed central (PMC-NBCI, Elsevier Journal, SciELO Spain, Scirus, Science Direct, including studies in animals, cells, and humans, in order to establish the effect of flavonoids in the prevention and development of lung cancer. Although in vitro and animal studies show the potential ability of flavonoids to act against different types of cancers, especially against lung cancers, the diverse results reported within epidemiological studies, together with the lack of experiments in humans, are the major factors in limiting making dietary recommendations based on scientific evidence for the management of patients with lung cancer. Therefore, the authors of the present study recommend following the dietary health practice guidelines which promotes the consumption of food enriched in flavonoids and reflects the current state of knowledge of an effective and appropriate diet in lung cancer patients.Erratum in: Rev Esp Nutr Hum Diet. 2013;17(2:91-92Link: http://www.renhyd.org/index.php/renhyd/article/view/6/17

  19. Biochemical Stability Analysis of Nano Scaled Contrast Agents Used in Biomolecular Imaging Detection of Tumor Cells

    Science.gov (United States)

    Kim, Jennifer; Kyung, Richard

    Imaging contrast agents are materials used to improve the visibility of internal body structures in the imaging process. Many agents that are used for contrast enhancement are now studied empirically and computationally by researchers. Among various imaging techniques, magnetic resonance imaging (MRI) has become a major diagnostic tool in many clinical specialties due to its non-invasive characteristic and its safeness in regards to ionizing radiation exposure. Recently, researchers have prepared aqueous fullerene nanoparticles using electrochemical methods. In this paper, computational simulations of thermodynamic stabilities of nano scaled contrast agents that can be used in biomolecular imaging detection of tumor cells are presented using nanomaterials such as fluorescent functionalized fullerenes. In addition, the stability and safety of different types of contrast agents composed of metal oxide a, b, and c are tested in the imaging process. Through analysis of the computational simulations, the stabilities of the contrast agents, determined by optimized energies of the conformations, are presented. The resulting numerical data are compared. In addition, Density Functional Theory (DFT) is used in order to model the electron properties of the compound.

  20. Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer

    Science.gov (United States)

    de Boer, Esther; van der Vegt, Bert; van der Sluis, Tineke; Kooijman, Paulien; Low, Philip S.; van der Zee, Ate G. J.; Arts, Henriette J. G.; van Dam, Gooitzen M.; Bart, Joost

    2015-01-01

    Aims Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-α) has already been identified as a suitable target for cancer therapy and imaging. FR-α is present on ~40% of human cancers. FR-β is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-β expression in solid tumors. Additional or simultaneous expression of FR-β could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-β is evaluated in ovarian, breast and colorectal cancer. Methods FR-β expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis. Results FR-β expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-β expression in macrophages. FR-β status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-β expression (p=0.022). Conclusions FR-β expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-β expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-β is not regarded as a suitable target in colorectal cancer. PMID:26248049

  1. Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Esther de Boer

    Full Text Available Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-α has already been identified as a suitable target for cancer therapy and imaging. FR-α is present on ~40% of human cancers. FR-β is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-β expression in solid tumors. Additional or simultaneous expression of FR-β could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-β is evaluated in ovarian, breast and colorectal cancer.FR-β expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis.FR-β expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-β expression in macrophages. FR-β status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-β expression (p=0.022.FR-β expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-β expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-β is not regarded as a suitable target in colorectal cancer.

  2. Theranostic MUC-1 aptamer targeted gold coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging and photothermal therapy of colon cancer

    DEFF Research Database (Denmark)

    Azhdarzadeh, Morteza; Atyabi, Fatemeh; Saei, Amir Ata

    2016-01-01

    Favorable physiochemical properties and the capability to accommodate targeting moieties make superparamegnetic iron oxide nanoparticles (SPIONs) popular theranostic agents. In this study, we engineered SPIONs for magnetic resonance imaging (MRI) and photothermal therapy of colon cancer cells...

  3. Imaging prostate cancer: an update on positron emission tomography and magnetic resonance imaging

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter

    2010-01-01

    , and molecular imaging information. Developments in imaging technologies, specifically magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), have improved the detection rate of prostate cancer. MRI has improved lesion detection and local staging. Furthermore, MRI...

  4. Motion corrected photoacoustic difference imaging of fluorescent contrast agents

    Science.gov (United States)

    Märk, Julia; Wagener, Asja; Pönick, Sarah; Grötzinger, Carsten; Zhang, Edward; Laufer, Jan

    2016-03-01

    In fluorophores, such as exogenous dyes and genetically expressed proteins, the excited state lifetime can be modulated using pump-probe excitation at wavelengths corresponding to the absorption and fluorescence spectra. Simultaneous pump-probe pulses induce stimulated emission (SE) which, in turn, modulates the thermalized energy, and hence the photoacoustic (PA) signal amplitude. For time-delayed pulses, by contrast, SE is suppressed. Since this is not observed in endogenous chromophores, the location of the fluorophore can be determined by subtracting images acquired using simultaneous and time-delayed pump-probe excitation. This simple experimental approach exploits a fluorophorespecific contrast mechanism, and has the potential to enable deep-tissue molecular imaging at fluences below the MPE. In this study, some of the challenges to its in vivo implementation are addressed. First, the PA signal amplitude generated in fluorophores in vivo is often much smaller than that in blood. Second, tissue motion can give rise to artifacts that correspond to endogenous chromophores in the difference image. This would not allow the unambiguous detection of fluorophores. A method to suppress motion artifacts based on fast switching between simultaneous and time-delayed pump-probe excitation was developed. This enables the acquisition of PA signals using the two excitation modes with minimal time delay (20 ms), thus minimizing the effects of tissue motion. The feasibility of this method is demonstrated by visualizing a fluorophore (Atto680) in tissue phantoms, which were moved during the image acquisition to mimic tissue motion.

  5. Prodigiosins as anti cancer agents: living upto their name.

    Science.gov (United States)

    Pandey, R; Chander, R; Sainis, K B

    2009-01-01

    Prodigiosins are a family of bright red colored bacterial pigment and derive their name from the miraculous (prodigious) events associated with their occurrence. They indeed seem to be living upto their name as a host of activities such as anti-microbial, anti-malarial, anti-cancer and immunosuppressive have been associated with them. Out of these, immunosuppressive and anti-cancer activity has received more importance as it has a clinical promise. Prodigiosins, isolated mostly from Gram negative bacteria are characterized by a common pyrryldipyrrylmethene structure with varying side chains. The review discusses the mechanisms involved in the anti-cancer activity of this class of compounds. In vitro, prodigiosins have been shown to primarily target the cancer cells independently of the p53 status while little or no effect has been observed on normal cells. In addition, prodigiosins are effective in cancer cells with multidrug resistance phenotype and defects in the apoptotic pathways. These make prodigiosins attractive candidates for further development. Though the molecular targets of prodigiosins have not been clearly defined, they have been found to target different signaling pathways possibly through induction of DNA double strand breaks and/ or neutralization of pH gradients leading to changes in cell cycle proteins and apoptosis. The review will discuss the recent findings related to the mechanism involved in the anti-cancer activity of this class of molecules.

  6. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images

    Directory of Open Access Journals (Sweden)

    Suneet Gupta

    2016-01-01

    Full Text Available Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  7. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J

    2011-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...... of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, (18)F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer....... However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline labeled with (18)F or (11)C, (11)C-acetate, and (18)F-fluoride has demonstrated promising results, and other new radiopharmaceuticals are under development and evaluation...

  8. Synthesis of 18F labeled clotrimazole derivatives as a potential PET imaging agent

    International Nuclear Information System (INIS)

    Jung, Soon Jae; Kim, In Jong; Park, Jeong Hoon; Lee, Heung Nae; Kim, Sang Wook; Hur, Min Goo; Choi, Sang Moo; Yang, Seung Dae; Yu, Kook Hyun

    2010-01-01

    Clotrimazole [1- -1H-imidazole, CLT] has been reported to inhibit the proliferation of vascular endothelial and act as an in vitro anti-VEGF drug. It is also shown to inhibit angiogenesis in an animal model. The radioisotope labeled clotrimazole derivative can be utilized to monitor the physiologic processes of cancer. In this study, we synthesized [ 18 F]fluoride labeled clotrimazole derivatives as a new tumor imaging agent for PET. The references were prepared by a refluxing with clotrimazole and an excess of fluoroalkyltosylate in acetonitrile for 36 h and clotrimazole reacted with ditosylalkane to give precursors. [ 18 ]Fluoride labeled reaction was performed with precursor in Kryptofix[2.2.2]/K 2 CO 3 for 10 min at 80 .deg. C. The radiolabeling mixture was passed through a silica Sep-Pak cartridge to remove 18 F - . The [ 18 ]F-clotrimazole derivatives were synthesized with a 20 ∼ 25% yield. In the radiofluoriantion step, we used acetonitrile and DMSO as a solvent and observed a higher at the acetonitrile (25%) reaction compared with the DMSO reaction (5%)

  9. Imaging Primary Mouse Sarcomas After Radiation Therapy Using Cathepsin-Activatable Fluorescent Imaging Agents

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C. [Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Mito, Jeffrey K.; Javid, Melodi P. [Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Ferrer, Jorge M. [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Kim, Yongbaek [Department of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul (Korea, Republic of); Lee, W. David [The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Bawendi, Moungi G. [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Brigman, Brian E. [Department of Orthopedic Surgery, Duke University School of Medicine, Durham, North Carolina (United States); Kirsch, David G., E-mail: david.kirsch@duke.edu [Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States)

    2013-05-01

    Purpose: Cathepsin-activated fluorescent probes can detect tumors in mice and in canine patients. We previously showed that these probes can detect microscopic residual sarcoma in the tumor bed of mice during gross total resection. Many patients with soft tissue sarcoma (STS) and other tumors undergo radiation therapy (RT) before surgery. This study assesses the effect of RT on the ability of cathepsin-activated probes to differentiate between normal and cancerous tissue. Methods and Materials: A genetically engineered mouse model of STS was used to generate primary hind limb sarcomas that were treated with hypofractionated RT. Mice were injected intravenously with cathepsin-activated fluorescent probes, and various tissues, including the tumor, were imaged using a hand-held imaging device. Resected tumor and normal muscle samples were harvested to assess cathepsin expression by Western blot. Uptake of activated probe was analyzed by flow cytometry and confocal microscopy. Parallel in vitro studies using mouse sarcoma cells were performed. Results: RT of primary STS in mice and mouse sarcoma cell lines caused no change in probe activation or cathepsin protease expression. Increasing radiation dose resulted in an upward trend in probe activation. Flow cytometry and immunofluorescence showed that a substantial proportion of probe-labeled cells were CD11b-positive tumor-associated immune cells. Conclusions: In this primary murine model of STS, RT did not affect the ability of cathepsin-activated probes to differentiate between tumor and normal muscle. Cathepsin-activated probes labeled tumor cells and tumor-associated macrophages. Our results suggest that it would be feasible to include patients who have received preoperative RT in clinical studies evaluating cathepsin-activated imaging probes.

  10. Combined blood pool and extracellular contrast agents for pediatric and young adult cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Joyce T. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Robinson, Joshua D. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Deng, Jie [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Rigsby, Cynthia K. [Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2016-12-15

    A comprehensive cardiac magnetic resonance (cardiac MR) study including both late gadolinium enhancement (LGE) and MR angiography may be indicated for patients with a history of acquired or congenital heart disease. To study the novel use of an extracellular agent for assessment of LGE combined with a blood pool contrast agent for detailed MR angiography evaluation to yield a comprehensive cardiac MR study in these patients. We reviewed clinical cardiac MR studies utilizing extracellular and blood pool contrast agents and noted demographics, clinical data and adverse events. We rated LGE image quality and MR angiography image quality for each vascular segment and calculated inter-rater variability. We also quantified contrast-to-noise ratio (CNR). Thirty-three patients (mean age 13.9 ± 3 years) received an extracellular contrast agent (10 gadobenate dimeglumine, 23 gadopentetate dimeglumine) and blood pool contrast agent (33 gadofosveset trisodium). No adverse events were reported. MRI indications included Kawasaki disease (8), cardiomyopathy and coronary anatomy (15), repaired congenital heart disease (8), and other (2). Mean LGE quality was 2.6 ± 0.6 with 97% diagnostic imaging. LGE quality did not vary by type of contrast agent given (P = 0.07). Mean MR angiography quality score was 4.7 ± 0.6, with high inter-rater agreement (k = 0.6-0.8, P < 0.002). MR angiography quality did not vary by type of contrast agent used (P = 0.6). Cardiac MR studies utilizing both extracellular and blood pool contrast agents are feasible and safe and provide excellent-quality LGE and MR angiography images. The use of two contrast agents allows for a comprehensive assessment of both myocardial viability and vascular anatomy during the same exam. (orig.)

  11. Amphetamines and pH-shift agents for brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book gives a review of the results of experimental and clinical research on both I-amphetamine derivatives and pH-shift agents. Virtually all relevant working groups from the USA and Europe have contributed to this volume. The pharmacology of amphetamine and the corresponding receptor theories are described in detail, whereas other chapters deal with the labeling as well as the metabolic process of this drug. In addition to this, new amphetamine derivatives are presented together with other essential products which play a significant role in scintigraphy of the brain function. Finally, there are two chapters on instrumentation problems followed by eight contributions on the clinical results of amphetamine scintigraphy in cerebral vascular diseases, epilepsy, migraine and brain tumors.

  12. Whole-body multicolor spectrally resolved fluorescence imaging for development of target-specific optical contrast agents using genetically engineered probes

    Science.gov (United States)

    Kobayashi, Hisataka; Hama, Yukihiro; Koyama, Yoshinori; Barrett, Tristan; Urano, Yasuteru; Choyke, Peter L.

    2007-02-01

    Target-specific contrast agents are being developed for the molecular imaging of cancer. Optically detectable target-specific agents are promising for clinical applications because of their high sensitivity and specificity. Pre clinical testing is needed, however, to validate the actual sensitivity and specificity of these agents in animal models, and involves both conventional histology and immunohistochemistry, which requires large numbers of animals and samples with costly handling. However, a superior validation tool takes advantage of genetic engineering technology whereby cell lines are transfected with genes that induce the target cell to produce fluorescent proteins with characteristic emission spectra thus, identifying them as cancer cells. Multicolor fluorescence imaging of these genetically engineered probes can provide rapid validation of newly developed exogenous probes that fluoresce at different wavelengths. For example, the plasmid containing the gene encoding red fluorescent protein (RFP) was transfected into cell lines previously developed to either express or not-express specific cell surface receptors. Various antibody-based or receptor ligand-based optical contrast agents with either green or near infrared fluorophores were developed to concurrently target and validate cancer cells and their positive and negative controls, such as β-D-galactose receptor, HER1 and HER2 in a single animal/organ. Spectrally resolved fluorescence multicolor imaging was used to detect separate fluorescent emission spectra from the exogenous agents and RFP. Therefore, using this in vivo imaging technique, we were able to demonstrate the sensitivity and specificity of the target-specific optical contrast agents, thus reducing the number of animals needed to conduct these experiments.

  13. Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

    Directory of Open Access Journals (Sweden)

    Richard C Wang

    Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

  14. Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives?

    Directory of Open Access Journals (Sweden)

    Santa Cirmi

    2016-11-01

    Full Text Available Fruits and vegetables have long been recognized as potentially important in the prevention of cancer risk. Thus, scientific interest in nutrition and cancer has grown over time, as shown by increasing number of experimental studies about the relationship between diet and cancer development. This review attempts to provide an insight into the anti-cancer effects of Citrus fruits, with a focus on their bioactive compounds, elucidating the main cellular and molecular mechanisms through which they may protect against cancer. Scientific literature was selected for this review with the aim of collecting the relevant experimental evidence for the anti-cancer effects of Citrus fruits and their flavonoids. The findings discussed in this review strongly support their potential as anti-cancer agents, and may represent a scientific basis to develop nutraceuticals, food supplements, or complementary and alternative drugs in a context of a multi-target pharmacological strategy in the oncology.

  15. Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives?

    Science.gov (United States)

    Cirmi, Santa; Ferlazzo, Nadia; Lombardo, Giovanni E; Maugeri, Alessandro; Calapai, Gioacchino; Gangemi, Sebastiano; Navarra, Michele

    2016-11-04

    Fruits and vegetables have long been recognized as potentially important in the prevention of cancer risk. Thus, scientific interest in nutrition and cancer has grown over time, as shown by increasing number of experimental studies about the relationship between diet and cancer development. This review attempts to provide an insight into the anti-cancer effects of Citrus fruits, with a focus on their bioactive compounds, elucidating the main cellular and molecular mechanisms through which they may protect against cancer. Scientific literature was selected for this review with the aim of collecting the relevant experimental evidence for the anti-cancer effects of Citrus fruits and their flavonoids. The findings discussed in this review strongly support their potential as anti-cancer agents, and may represent a scientific basis to develop nutraceuticals, food supplements, or complementary and alternative drugs in a context of a multi-target pharmacological strategy in the oncology.

  16. Development of polymer-coated nanoparticle imaging agents for diagnostic applications

    Science.gov (United States)

    Kairdolf, Brad A.

    Cancer is the second most common cause of death in the United States, with over 500,000 deaths expected this year. While significant progress has been made in the treatment and management of cancer, challenges remain because of the complexity and the heterogeneous nature of the disease. The improvement that has been seen in survival rates reflects advancements not only in treatment, but also in early stage detection and diagnostics for certain cancers. In particular, early stage detection and treatment of cancer before it has metastasized to other organs has resulted in a dramatic improvement in patient survival rates. One area of research that has shown considerable promise in further advancing diagnostics and early cancer detection is nanotechnology. Specifically, semiconductor and metal nanoparticles have great potential to provide advanced technology platforms for ultrasensitive and multiplexed detection of disease markers and probe disease on the molecular level. Because they are in the same size regime as biological molecules, these nanoparticles exhibit unique interactions with proteins, nucleic acids and other biomarkers of interest for detecting and diagnosing disease. However, high-quality nanoparticles are often unsuited for use in complex biological environments because of their coatings and surface chemistry. In this dissertation, we describe the design and development of polymer-coated nanoparticle imaging agents for use in blood, cell and tissue diagnostic applications. First, low-molecular weight, amphiphilic polymers, with hydrocarbon chains capable of noncovalent interactions with nanoparticle surface ligands and a hydrophilic backbone to render the nanoparticle water soluble, were synthesized and characterized for use in nanoparticle coating applications. We demonstrate that the hydrophobic and hydrophilic interactions between the nanoparticle surface, the amphiphilic polymer and the aqueous solvent were able to drive the coating and water

  17. Novel imaging strategies for upper gastrointestinal tract cancers

    DEFF Research Database (Denmark)

    Mortensen, Michael Bau

    2015-01-01

    Accurate pretherapeutic imaging is the cornerstone of all cancer treatment. Unfortunately, modern imaging modalities have several unsolved problems and limitations. The differentiation between inflammation and cancer infiltration, false positive and false negative findings as well as lack...... of confirming biopsies in suspected metastases may have serious negative consequences in cancer patients. This review describes some of these problems and challenges the use of conventional imaging by suggesting new combined strategies that include selective use of confirming biopsies and complementary methods...

  18. Diffusion tensor imaging of the prostate cancer

    International Nuclear Information System (INIS)

    Xia Guojin; Gong Honghan; Zeng Xianjun; Jiang Jian; Zhou Fuqing; Hu Zhenzhen

    2012-01-01

    Objective: To explore the diagnostic value of DTI for prostate cancer. Methods: From October 2009 to December 2010,44 patients suspected of prostate cancer received MRI and DTI. The data of MRI and DTI were analyzed retrospectively. By histopathology, prostate cancer was proved in 16 patients,and benign prostatic hyperplasia (BPH) was proved in 28 patients. Differences in ADC and FA values between prostate cancer and BPH were compared by independent samples t test. Diagnostic accuracy of FA value and ADC value for prostate cancer was analyzed by using ROC curve, and the diagnostic threshold of FA value and ADC value for prostate cancer was determined. Results: The mean FA value of the tumor regions and BPH were 0.308±0.084 and 0.203 ±0.029, respectively. The mean ADC value of the tumor regions and BPH were (0.883±0.192) × 10 -3 mm 2 /s and ( 1.408 ±0.130) × 10 -3 mm 2 /s, respectively. There were statistically significant differences in ADC and FA values between tumor regions and BPH (t values were 4.833 and 10.779 respectively, P<0.01). The ADC value area under curve of ROC was 0.996 (95% CI was 0.984 to 1.007); the FA value area under curve of ROC was 0.904 (95% CI was 0.812 to 0.996); Combined the FA and ADC value area under curve of ROC is 0.996 (95% CI was 0.984 to 1.007); Using the ADC value of 0.725 × 10 -3 mm 2 /s as the ROC cut off point, the diagnostic sensitivity and specificity were 100.0% and 96.0%, respectively; Using the FA value of 0.311 as the ROC cut off point,the diagnostic sensitivity and specificity was 100.0% and 68.7%, respectively. Conclusion: DTI imaging can provide valuable information for prostate cancer diagnosis and differential diagnosis, and improve the diagnosis ability of prostate cancer. (authors)

  19. DETECTION OF CANCEROUS LESION BY UTERINE CERVIX IMAGE SEGMENTATION

    Directory of Open Access Journals (Sweden)

    P. Priya

    2014-02-01

    Full Text Available This paper works at segmentation of lesion observed in cervical cancer, which is the second most common cancer among women worldwide. The purpose of segmentation is to determine the location for a biopsy to be taken for diagnosis. Cervix cancer is a disease in which cancer cells are found in the tissues of the cervix. The acetowhite region is a major indicator of abnormality in the cervix image. This project addresses the problem of segmenting uterine cervix image into different regions. We analyze two algorithms namely Watershed, K-means clustering algorithm, Expectation Maximization (EM Image Segmentation algorithm. These segmentations methods are carried over for the colposcopic uterine cervix image.

  20. Folic acid as a cancer-preventing agent.

    Science.gov (United States)

    Jennings, E

    1995-09-01

    Higher intakes of folic acid-rich foods such as vegetables, legumes, and whole grains are associated with lower incidence of carcinomas in international comparisons and case-control studies. Deficiency of folic acid in experimental studies causes DNA damage that resembles the DNA damage seen in cancer cells. The requirement for folic acid in DNA synthesis and DNA methylation provides a plausible mechanism for a mutagenic effect of a low-folate diet. It is suggested that cancer can be initiated by DNA damage that results from folic acid deficiency. The relatively low level of folic acid in North American diets might be the underlying reason for high rates of many cancers in North America.

  1. Cancers related to viral agents that have a direct role in carcinogenesis: pathological and diagnostic techniques.

    Science.gov (United States)

    Carbone, Antonino; De Paoli, Paolo

    2012-08-01

    The International Agency for Research on Cancer has recently reassessed the carcinogenicity of the biological agents classified as 'carcinogenic to humans'. Among the biological agents having a direct role in carcinogenesis, Epstein-Barr virus, Kaposi's sarcoma-associated herpes virus and human papillomavirus contribute to a variety of malignancies worldwide in humans including nasopharyngeal carcinoma, several types of lymphomas, genital tract carcinomas and Kaposi's sarcoma. The authors review the current knowledge on cancers that have been attributed to Epstein-Barr virus, Kaposi's sarcoma-associated herpes virus and human papillomavirus looking at the pathological classification of these cancers and description of the implicated viruses, highlighting a wide range of pathological and virological diagnostic techniques. This review also focuses on the new oncological scenario ahead, once strategies against carcinogenic infectious agents are found to be effective.

  2. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property

    Science.gov (United States)

    Azmi, Asfar S

    2013-01-01

    “ Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating) behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents. PMID:24358870

  3. New cancer cells apoptosis agents: Fluorinated aza-heterocycles

    Science.gov (United States)

    Prima, D. O.; Baev, D. S.; Vorontsova, E. V.; Frolova, T. S.; Bagryanskaya, I. Yu.; Slizhov, Yu. G.; Tolstikova, T. G.; Makarov, A. Yu.; Zibarev, A. V.

    2017-09-01

    Fluorinated benzo-fused 1,3-diazoles, 1,2,3-triazoles, 1,2,5-thia/selenadiazoles and 1,4-diazines were synthesized and tried for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma) cells. The diazoles, triazoles and selenadiazoles were cytotoxic with IC50 = 2.2-26.4 µM and induced the cells apoptosis at concentrations C = 1-25 µM. At the same time, they were nontoxic towards normal cells. Due to this, these scaffolds were used in the computer-aided molecular design of new antitumor agents. Particularly, novel 1,2,3-triazole and 1,3-diazole derivatives for the binding site of the PAS domain of the transcription factor HIF were designed and some of them synthesized for further study. Overall, new anticancer agents featuring apoptotic activity are suggested.

  4. Benzofuran as a promising scaffold for the synthesis of antimicrobial and antibreast cancer agents: A review

    Directory of Open Access Journals (Sweden)

    Ghadamali Khodarahmi

    2015-01-01

    Full Text Available Benzofuran as an important heterocyclic compound is extensively found in natural products as well as synthetic materials. Since benzofuran drivatives display a diverse array of pharmacological activities, an interest in developing new biologically active agents from benzofuran is still under consideration. This review highlights recent findings on biological activities of benzofuran derivatives as antimicrobial and antibreast cancer agents and lays emphasis on the importance of benzofurans as a major source for drug design and development.

  5. Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer

    Science.gov (United States)

    2015-10-01

    AD_________________ (Leave blank) Award Number: W81XWH-13-1-0211 TITLE: Development of Antidepressants as Novel Agents to Treat Small Cell Lung...DATES COVERED 1 Aug 2013 - 31 Jul 2015 4. TITLE AND SUBTITLE Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer 5a... antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells. The candidate drugs activate stress pathways

  6. Gd-based macromolecules and nanoparticles as magnetic resonance contrast agents for molecular imaging.

    Science.gov (United States)

    Huang, Ching-Hui; Tsourkas, Andrew

    2013-01-01

    As we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice. Magnetic resonance (MR) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes. One promising new direction in the development of MR contrast agents involves the labeling and/or loading of nanoparticles with gadolinium (Gd). These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies. In this review, we discuss some of the progress that has recently been made in the development of Gd-based macromolecules and nanoparticles and outline some of the physical and chemical properties that will be important to incorporate into the next generation of contrast agents, including high Gd chelate stability, high "relaxivity per particle" and "relaxivity density", and biodegradability.

  7. Autofluorescent gelatin nanoparticles as imaging probes to monitor matrix metalloproteinase metabolism of cancer cells.

    Science.gov (United States)

    Cai, Bo; Rao, Lang; Ji, Xinghu; Bu, Lin-Lin; He, Zhaobo; Wan, Da; Yang, Yi; Liu, Wei; Guo, Shishang; Zhao, Xing-Zhong

    2016-11-01

    In this paper, autofluorescent gelatin nanoparticles were synthesized as matrix metalloproteinase (MMP) responsive probes for cancer cell imaging. A modified two-step desolvation method was employed to generate these nanoparticles whose size was controllable and had stable autofluorescence. As glutaraldehyde was introduced as the crosslinking agent, the generation of Schiff base (CN) and double carbon bond (CC) between glutaraldehyde and gelatin endowed these gelatin nanoparticles distinct autofluorescence. Considering MMPs were usually overexpressed on the surface of cancer cells and they had degradation ability toward gelatin, we utilized these nanoparticles as imaging probes to responsively monitor the MMP metabolism of cancer cells according to the luminance change. As fluorescent probes, these nanoparticles had facile synthesis procedure and good biocompatibility, and provided a smart strategy to monitor cancer cell behaviors. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2854-2860, 2016. © 2016 Wiley Periodicals, Inc.

  8. Intravenous ultrasound contrast agents versus other imaging methods in pediatric patients with neoplastic diseases - a comparison.

    Science.gov (United States)

    Piskunowicz, Maciej; Kosiak, Wojciech; Batko, Tomasz; Adamkiewicz-Drożyńska, Elżbieta; Szarmach, Arkadiusz

    2013-12-01

    The lack of registration of ultrasound contrast agents for use in patients below the age of 18 is a significant limitation of their usage. Despite this, examinations with the use of contrast agents are conducted in numerous centers, mainly as part of the diagnostic process of vesicoureteral reflux. Examinations after an intravenous administration of contrast agents are conducted rarely. The reason for this is not only the lack of registration, but also the lack of studies on their safety profile in paediatric patients or no guidelines concerning the dosage. It seems that imaging with the use of such agents could help solve certain clinical problems when other diagnostic methods fail. The paper presents selected cases of pediatric patients treated in oncological departments, in whom the examination with the use of ultrasound contrast agents had a considerable influence on the diagnostic and therapeutic process.

  9. EPR and DNP Properties of Certain Novel Single Electron Contrast Agents Intended for Oximetric Imaging

    DEFF Research Database (Denmark)

    Ardenkjær-Larsen, J. H.; Laursen, I; Leunbach, I.

    1998-01-01

    Parameters of relevance to oximetry with Overhauser magnetic resonance imaging (OMRI) have been measured for three single electron contrast agents of the triphenylmethyl type. The single electron contrast agents are stable and water soluble. Magnetic resonance properties of the agents have been...... examined with electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and dynamic nuclear polarization (DNP) at 9.5 mT in water, isotonic saline, plasma, and blood at 23 and 37°C. The relaxivities of the agents are about 0.2–0.4 mM−1s−1and the DNP enhancements extrapolate close...... than 1 μT in water at room temperature. The longitudinal electron spin relaxation rate is calculated from the DNP enhancement curves. The oxygen broadening in water is about 50 μT/mM O2at 37°C. These agents have good properties for oximetry with OMRI....

  10. Antibody-Based Cancer Therapy : Successful Agents and Novel Approaches

    NARCIS (Netherlands)

    Hendriks, D; Choi, G; de Bruyn, M; Wiersma, V R; Bremer, E; Galluzi, Lorenzo; Vitale, Ilio

    2017-01-01

    Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first

  11. Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging

    Science.gov (United States)

    Lu, Guolan; Halig, Luma; Wang, Dongsheng; Qin, Xulei; Chen, Zhuo Georgia; Fei, Baowei

    2014-01-01

    Abstract. Early detection of malignant lesions could improve both survival and quality of life of cancer patients. Hyperspectral imaging (HSI) has emerged as a powerful tool for noninvasive cancer detection and diagnosis, with the advantage of avoiding tissue biopsy and providing diagnostic signatures without the need of a contrast agent in real time. We developed a spectral-spatial classification method to distinguish cancer from normal tissue on hyperspectral images. We acquire hyperspectral reflectance images from 450 to 900 nm with a 2-nm increment from tumor-bearing mice. In our animal experiments, the HSI and classification method achieved a sensitivity of 93.7% and a specificity of 91.3%. The preliminary study demonstrated that HSI has the potential to be applied in vivo for noninvasive detection of tumors. PMID:25277147

  12. Collagen mimetic peptide engineered M13 bacteriophage for collagen targeting and imaging in cancer.

    Science.gov (United States)

    Jin, Hyo-Eon; Farr, Rebecca; Lee, Seung-Wuk

    2014-11-01

    Collagens are over-expressed in various human cancers and subsequently degraded and denatured by proteolytic enzymes, thus making them a target for diagnostics and therapeutics. Genetically engineered bacteriophage (phage) is a promising candidate for the development of imaging or therapeutic materials for cancer collagen targeting due to its promising structural features. We genetically engineered M13 phages with two functional peptides, collagen mimetic peptide and streptavidin binding peptide, on their minor and major coat proteins, respectively. The resulting engineered phage functions as a therapeutic or imaging material to target degraded and denatured collagens in cancerous tissues. We demonstrated that the engineered phages are able to target and label abnormal collagens expressed on A549 human lung adenocarcinoma cells after the conjugation with streptavidin-linked fluorescent agents. Our engineered collagen binding phage could be a useful platform for abnormal collagen imaging and drug delivery in various collagen-related diseases. Published by Elsevier Ltd.

  13. Gadolinium-porphyrins: new potential magnetic resonance imaging contrast agents for melanoma detection

    OpenAIRE

    Daryoush Shahbazi-Gahrouei

    2006-01-01

    BACKGROUND: Two new porphyrin-based magnetic resonance imaging (MRI) contrast agents, Gd-hematoporphyrin (Gd-H) and Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP) were synthesized and tested in nude mice with human melanoma (MM-138) xenografts as new melanoma contrast agents. METHODS: Subcutaneous xenografts of human melanoma cells (MM-138) were studied in 30 (five groups of six) nude mice. The effect of different contrast agents (Gd-TCP, Gd-H, GdCl3 and Gd-DTPA) on proton relaxatio...

  14. The use contrast agent for imaging biological samples

    Czech Academy of Sciences Publication Activity Database

    Dammer, J.; Weyda, František; Sopko, V.; Jakůbek, J.

    2011-01-01

    Roč. 6, C01096 (2011), s. 1-7 ISSN 1748-0221. [International Workshop on Radiation Imaging Detectors /12./. Cambridge, 11.07.2010-15.7.2010] R&D Projects: GA MŠk 2B06005 Grant - others:Research Program(CZ) 6840770029; Research Program(CZ) 6840770040; GA AV ČR(CZ) IAA600550614; GA MŠk(CZ) 2B06007; GA MŠk(CZ) 1PO4LA211; GA MŠk(CZ) LC06041 Program:IA; 2B; LC Institutional research plan: CEZ:AV0Z50070508 Keywords : x-ray radiography and digital radiography (DR) * x-ray detectors * inspections with x-rays Subject RIV: EA - Cell Biology Impact factor: 1.869, year: 2011

  15. Weakly supervised histopathology cancer image segmentation and classification.

    Science.gov (United States)

    Xu, Yan; Zhu, Jun-Yan; Chang, Eric I-Chao; Lai, Maode; Tu, Zhuowen

    2014-04-01

    Labeling a histopathology image as having cancerous regions or not is a critical task in cancer diagnosis; it is also clinically important to segment the cancer tissues and cluster them into various classes. Existing supervised approaches for image classification and segmentation require detailed manual annotations for the cancer pixels, which are time-consuming to obtain. In this paper, we propose a new learning method, multiple clustered instance learning (MCIL) (along the line of weakly supervised learning) for histopathology image segmentation. The proposed MCIL method simultaneously performs image-level classification (cancer vs. non-cancer image), medical image segmentation (cancer vs. non-cancer tissue), and patch-level clustering (different classes). We embed the clustering concept into the multiple instance learning (MIL) setting and derive a principled solution to performing the above three tasks in an integrated framework. In addition, we introduce contextual constraints as a prior for MCIL, which further reduces the ambiguity in MIL. Experimental results on histopathology colon cancer images and cytology images demonstrate the great advantage of MCIL over the competing methods. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

    International Nuclear Information System (INIS)

    Lauffer, R.B.; Greif, W.L.; Stark, D.D.; Vincent, A.C.; Saini, S.; Wedeen, V.J.; Brady, T.J.

    1988-01-01

    A paramagnetic relaxation agent targeted to functioning hepatocytes of the liver and excreted into the bile would be useful in the enhancement of normal liver and biliary anatomy in MR imaging. We sought to demonstrate the feasibility of this approach using the prototype hepatobiliary MR contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine) (Fe(EHPG) - ). The biodistribution, relaxation enhancement, and imaging characteristics of Fe(EHPG) - were compared to those of the non-specific iron chelate iron(III) diethylenetriaminepentaacetic acid (Fe(DTPA) 2- ), which has a comparable effect on water proton relaxation times. (author)

  17. Activation of TRPA1 Channel by Antibacterial Agent Triclosan Induces VEGF Secretion in Human Prostate Cancer Stromal Cells.

    Science.gov (United States)

    Derouiche, Sandra; Mariot, Pascal; Warnier, Marine; Vancauwenberghe, Eric; Bidaux, Gabriel; Gosset, Pierre; Mauroy, Brigitte; Bonnal, Jean-Louis; Slomianny, Christian; Delcourt, Philippe; Dewailly, Etienne; Prevarskaya, Natalia; Roudbaraki, Morad

    2017-03-01

    Accruing evidence indicates that exposure to environmental compounds may adversely affect human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here, we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of vascular endothelial growth factor (VEGF), a factor known to promote tumor growth. This mechanism involves an increase in intracellular calcium levels due to the direct activation of a membrane ion channel. Using calcium imaging and electrophysiology techniques, we show for the first time that environmentally relevant concentrations of TCS activate a cation channel of the TRP family, TRPA1 (Transient Receptor Potential Ankirin 1), in primary cultured human prostate cancer stromal cells. The TCS-induced TRPA1 activation increased basal calcium in stromal cells and stimulated the secretion of VEGF and epithelial cells proliferation. Interestingly, immunofluorescence labeling performed on formalin-fixed paraffin-embedded prostate tissues showed an exclusive expression of the TRPA1 channel in prostate cancer stromal cells. Our data demonstrate an impact of the environmental factor TCS on the tumor microenvironment interactions, by activating a tumor stroma-specific TRPA1 ion channel. Cancer Prev Res; 10(3); 177-87. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Tanshinones as Effective Therapeutic Agents for Prostate Cancer

    Science.gov (United States)

    2011-06-01

    on Multiple Targets. Bio-Pearl River Forum and the 14th Annual Conference of Chinese Biopharmaceutical Association, Guangzhou, China, 2009 (3) Gong...prostate cancer research. The use of plants for medicinal purposes is as old as human history. All traditional and indigenous healing sys- tems used...all, traditional medical systems rely primarily on botanicals as a mainstay of therapy or prevention. Plants and other botanicals have also been the

  19. Optical and Functional Imaging in Lung Cancer

    NARCIS (Netherlands)

    K.H. van der Leest (Cor)

    2010-01-01

    textabstractLung cancer is the second most common cancer in men and women, and is the leading cause of cancer related death. In industrialized countries the mortality rate of lung cancer is higher than the mortality rate of breast, colorectal and prostate cancer combined 1. When lung cancer is

  20. Advances in Optimal Detection of Cancer by Image Processing; Experience with Lung and Breast Cancers.

    Science.gov (United States)

    Mohammadzadeh, Zeinab; Safdari, Reza; Ghazisaeidi, Marjan; Davoodi, Somayeh; Azadmanjir, Zahra

    2015-01-01

    Clinicians should looking for techniques that helps to early diagnosis of cancer, because early cancer detection is critical to increase survival and cost effectiveness of treatment, and as a result decrease mortality rate. Medical images are the most important tools to provide assistance. However, medical images have some limitations for optimal detection of some neoplasias, originating either from the imaging techniques themselves, or from human visual or intellectual capacity. Image processing techniques are allowing earlier detection of abnormalities and treatment monitoring. Because the time is a very important factor in cancer treatment, especially in cancers such as the lung and breast, imaging techniques are used to accelerate diagnosis more than with other cancers. In this paper, we outline experience in use of image processing techniques for lung and breast cancer diagnosis. Looking at the experience gained will help specialists to choose the appropriate technique for optimization of diagnosis through medical imaging.

  1. Glucose-lowering agents and the patterns of risk for cancer

    DEFF Research Database (Denmark)

    van Staa, T P; Patel, D; Gallagher, A M

    2012-01-01

    INTRODUCTION: Recent studies suggesting an increased cancer risk with glucose-lowering agents have received widespread publicity. The objectives of this study were to evaluate the comparability in underlying cancer risk and patterns of cancer risk over time with different glucose-lowering agents....... RESULTS: A total of 206,940 patients was identified. There was no difference in cancer risk and quartile for HbA(1c) value. There were differences in cancer incidence in the first 6 months after starting treatment (adjusted relative rate of 0.83 [95% CI 0.70, 0.99] with thiazolidinediones, 1.34 [95% CI 1.......77 [95% CI 0.56, 1.07] and 0.60 [95% CI 0.36, 1.02], respectively, for 6-24, 25-60 and >60 months). CONCLUSIONS: These findings do not provide evidence of either beneficial or adverse effects of glucose-lowering agents on cancer risk and are consistent with changes in diabetes treatment in the few months...

  2. Gadolinium-porphyrins: new potential magnetic resonance imaging contrast agents for melanoma detection

    Directory of Open Access Journals (Sweden)

    Daryoush Shahbazi-Gahrouei

    2006-11-01

    Full Text Available BACKGROUND: Two new porphyrin-based magnetic resonance imaging (MRI contrast agents, Gd-hematoporphyrin (Gd-H and Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP were synthesized and tested in nude mice with human melanoma (MM-138 xenografts as new melanoma contrast agents. METHODS: Subcutaneous xenografts of human melanoma cells (MM-138 were studied in 30 (five groups of six nude mice. The effect of different contrast agents (Gd-TCP, Gd-H, GdCl3 and Gd-DTPA on proton relaxation times was measured in tumors and other organs. T1 values, signal enhancement and the Gd concentration for different contrast agent solutions were also investigated. RESULTS: The porphyrin agents showed higher relaxivity compared to the clincal agent, Gd-DTPA. A significant 16% and 21% modification in T1 relaxation time of the water in human melanoma tumors grafted in the nude mice was revealed 24 hours after injection of Gd-TCP and Gd-H, respectively. The percentage of injected Gd localized to the tumor measured by inductively coupled plasma atomic emission spectrometry (ICP-AES was approximately 21% for Gd-TCP and 28% for Gd-H which were higher than that of Gd-DTPA (10%. CONCLUSIONS: The high concentration of Gd in the tumor is indicative of a selective retention of the compounds and indicates that Gd-TCP and Gd-H are promising MR imaging contrast agents for melanoma detection. Gd-porphyrins have considerable promise for further diagnostic applications in magnetic resonance imaging. KEY WORDS: MRI, porphyrin-based contrast agent, hematoporphyrin, melanoma.

  3. Identification of early cancerous lesion of esophagus with endoscopic images by hyperspectral image technique (Conference Presentation)

    Science.gov (United States)

    Huang, Shih-Wei; Chen, Shih-Hua; Chen, Weichung; Wu, I.-Chen; Wu, Ming Tsang; Kuo, Chie-Tong; Wang, Hsiang-Chen

    2016-03-01

    This study presents a method to identify early esophageal cancer within endoscope using hyperspectral imaging technology. The research samples are three kinds of endoscopic images including white light endoscopic, chromoendoscopic, and narrow-band endoscopic images with different stages of pathological changes (normal, dysplasia, dysplasia - esophageal cancer, and esophageal cancer). Research is divided into two parts: first, we analysis the reflectance spectra of endoscopic images with different stages to know the spectral responses by pathological changes. Second, we identified early cancerous lesion of esophagus by principal component analysis (PCA) of the reflectance spectra of endoscopic images. The results of this study show that the identification of early cancerous lesion is possible achieve from three kinds of images. In which the spectral characteristics of NBI endoscopy images of a gray area than those without the existence of the problem the first two, and the trend is very clear. Therefore, if simply to reflect differences in the degree of spectral identification, chromoendoscopic images are suitable samples. The best identification of early esophageal cancer is using the NBI endoscopic images. Based on the results, the use of hyperspectral imaging technology in the early endoscopic esophageal cancer lesion image recognition helps clinicians quickly diagnose. We hope for the future to have a relatively large amount of endoscopic image by establishing a hyperspectral imaging database system developed in this study, so the clinician can take this repository more efficiently preliminary diagnosis.

  4. Imaging and Therapy of Pancreatic Cancer with Phosphatidylserine-Targeted Nanovesicles

    Directory of Open Access Journals (Sweden)

    Victor M. Blanco

    2015-06-01

    Full Text Available Pancreatic cancer remains one of the most intractable cancers, with a dismal prognosis reflected by a 5-year survival of ~6%. Since early disease symptoms are undefined and specific biomarkers are lacking, about 80% of patients present with advanced, inoperable tumors that represent a daunting challenge. Despite many clinical trials, no single chemotherapy agent has been reliably associated with objective response rates above 10% or median survival longer than 5 to 7 months. Although combination chemotherapy regimens have in recent years provided some improvement, overall survival (8-11 months remains very poor. There is therefore a critical need for novel therapies that can improve outcomes for pancreatic cancer patients. Here, we present a summary of the current therapies used in the management of advanced pancreatic cancer and review novel therapeutic strategies that target tumor biomarkers. We also describe our recent research using phosphatidylserine-targeted saposin C–coupled dioleoylphosphatidylserine nanovesicles for imaging and therapy of pancreatic cancer.

  5. Application of high-resolution CT imaging data to lung cancer drug development: measuring progress: workshop IX.

    Science.gov (United States)

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estepar, Raul San Jose; Fenton, Laurie; Aldige, Carolyn R

    2013-11-01

    Lung cancer is the leading cause of cancer death and a major public health challenge across the entire world. Computed tomography (CT) imaging of the lung is a rapidly improving medical imaging technique. Spiral CT has been reported to not only improve the early detection of lung cancer in screening high-risk tobacco-exposed populations but also to assist in the clinical assessment of new agents for therapy in lung cancer. The Prevent Cancer Foundation has sponsored a series of workshops to accelerate progress in using quantitative imaging to advance lung cancer research progress, of which this report summarizes the Ninth Workshop. The defining strategy of this forum to support innovation in quantitative research for early lung cancer management was to enable software validations by assembling collections of high-quality images for which long-term clinical follow-up is known. An additional approach was to define a process for high-quality and economical national implementation of lung cancer screening. Representatives from the Quantitative Imaging Biomarker Alliance, the International Association for the Study of Lung Cancer, the Lung Cancer Alliance, and other organizations outlined their efforts in this regard. A major opportunity exists to advance the dialogue on the use of quantitative imaging tools to cross-fertilize and accelerate image-processing research across lung cancer and chronic obstructive pulmonary disease (COPD). The use of high-resolution CT imaging provides a window into a much earlier stage of COPD as well as coronary artery disease, both being tobacco-induced diseases. Progress in this area was reviewed and opportunities for enhanced collaborative progress defined. Key sessions reviewed emerging developments with imaging technology and the infrastructure to support the storage and distribution of these high-content modalities. Cooperation among diverse collaborators is essential to enable the rapid organic evolution of this field, so that

  6. Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent

    Science.gov (United States)

    2011-04-01

    common step in integrin activation (Calderwood, 2004). The effect on integrins mediated by VCN leads to dramatic depression of invasive abil- ity of...experiments: ROM SDS. Performed the experiments: ROM CMH SJZ FKC SDS. Analyzed the data: ROM CMH SDS FSM. Wrote the paper: ROM. Designed and produced

  7. Microenvironment-Sensitive Multimodal Contrast Agent for Prostate Cancer Diagnosis

    Science.gov (United States)

    2015-10-01

    sufficiently dialyzed against DI-H2O and the final product was concentrated using a Sphero™ Fleximag Separator (Spherotech, Lake Forest , IL, USA). The...Tsourkas, A. Superparamagnetic iron oxide nanoparticle probes for molecular imaging. Ann. Biomed . Eng. 2006, 34, 23–38. Int. J. Mol. Sci. 2015, 16 20018

  8. Magnetic resonance imaging of invasive breast cancer | Corr | SA ...

    African Journals Online (AJOL)

    Breast MR is a sensitive but nonspecific imaging investigation to detect breast cancer. MR imaging strengths lie in the accurate staging of the primary tumour, detecting recurrent cancer following lumpectomy and radiation therapy, problem solving in cases where there are equivocal mammographic findings, and screening ...

  9. Encapsulating Ionic Liquid and Fe₃O₄ Nanoparticles in Gelatin Microcapsules as Microwave Susceptible Agent for MR Imaging-guided Tumor Thermotherapy.

    Science.gov (United States)

    Du, Qijun; Ma, Tengchuang; Fu, Changhui; Liu, Tianlong; Huang, Zhongbing; Ren, Jun; Shao, Haibo; Xu, Ke; Tang, Fangqiong; Meng, Xianwei

    2015-06-24

    The combination of therapies and monitoring the treatment process has become a new concept in cancer therapy. Herein, gelatin-based microcapsules have been first reported to be used as microwave (MW) susceptible agent and magnetic resonance (MR) imaging contrast agent for cancer MW thermotherapy. Using the simple coacervation methods, ionic liquid (IL) and Fe3O4 nanoparticles (NPs) were wrapped in microcapsules, and these microcapsules showed good heating efficacy in vitro under MW irradiation. The results of cell tests indicated that gelatin/IL@Fe3O4 microcapsules possessed excellent compatibility in physiological environments, and they could effectively kill cancer cells with exposure to MW. The ICR mice bearing H22 tumors treated with gelatin/IL@Fe3O4 microcapsules were obtained an outstanding MW thermotherapy efficacy with 100% tumor elimination under ultralow density irradiation (1.8 W/cm(2), 450 MHz). In addition, the applicability of the microcapsules as an efficient contrast agent for MR imaging in vivo was evident. Therefore, these multifunctional microcapsules have a great potential for MR imaging-guided MW thermotherapy.

  10. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Hebert Alberto; Sala, Evis; Hricak, Hedvig [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Grimm, Jan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York (United States); Donati, Olivio F. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. (orig.)

  11. Fuzzy-probabilistic multi agent system for breast cancer risk assessment and insurance premium assignment.

    Science.gov (United States)

    Tatari, Farzaneh; Akbarzadeh-T, Mohammad-R; Sabahi, Ahmad

    2012-12-01

    In this paper, we present an agent-based system for distributed risk assessment of breast cancer development employing fuzzy and probabilistic computing. The proposed fuzzy multi agent system consists of multiple fuzzy agents that benefit from fuzzy set theory to demonstrate their soft information (linguistic information). Fuzzy risk assessment is quantified by two linguistic variables of high and low. Through fuzzy computations, the multi agent system computes the fuzzy probabilities of breast cancer development based on various risk factors. By such ranking of high risk and low risk fuzzy probabilities, the multi agent system (MAS) decides whether the risk of breast cancer development is high or low. This information is then fed into an insurance premium adjuster in order to provide preventive decision making as well as to make appropriate adjustment of insurance premium and risk. This final step of insurance analysis also provides a numeric measure to demonstrate the utility of the approach. Furthermore, actual data are gathered from two hospitals in Mashhad during 1 year. The results are then compared with a fuzzy distributed approach. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. ent-Rosane and abietane diterpenoids as cancer chemopreventive agents.

    Science.gov (United States)

    Núñez, Marvin J; Reyes, Carolina P; Jiménez, Ignacio A; Hayashi, Hirotaka; Tokuda, Harukuni; Bazzocchi, Isabel L

    2011-04-01

    Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Nicolatou-Galitis, Ourania; Sarri, Triantafyllia; Bowen, Joanne; Di Palma, Mario; Kouloulias, Vassilios E.; Niscola, Pasquale; Riesenbeck, Dorothea; Stokman, Monique; Tissing, Wim; Yeoh, Eric; Elad, Sharon; Lalla, Rajesh V.

    2013-01-01

    Purpose The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients. Materials and methods A systematic review was conducted by the Mucositis Study

  14. Optical Imaging in Breast Cancer Diagnosis: The Next Evolution

    OpenAIRE

    Herranz, Michel; Ruibal, Alvaro

    2012-01-01

    Breast cancer is one of the most common cancers among the population of the Western world. Diagnostic methods include mammography, ultrasound, and magnetic resonance; meanwhile, nuclear medicine techniques have a secondary role, being useful in regional assessment and therapy followup. Optical imaging is a very promising imaging technique that uses near-infrared light to assess optical properties of tissues and is expected to play an important role in breast cancer detection. Optical breast i...

  15. NaGdF4:Nd3+/Yb3+ Nanoparticles as Multimodal Imaging Agents

    Science.gov (United States)

    Pedraza, Francisco; Rightsell, Chris; Kumar, Ga; Giuliani, Jason; Monton, Car; Sardar, Dhiraj

    Medical imaging is a fundamental tool used for the diagnosis of numerous ailments. Each imaging modality has unique advantages; however, they possess intrinsic limitations. Some of which include low spatial resolution, sensitivity, penetration depth, and radiation damage. To circumvent this problem, the combination of imaging modalities, or multimodal imaging, has been proposed, such as Near Infrared Fluorescence imaging (NIRF) and Magnetic Resonance Imaging (MRI). Combining individual advantages, specificity and selectivity of NIRF with the deep penetration and high spatial resolution of MRI, it is possible to circumvent their shortcomings for a more robust imaging technique. In addition, both imaging modalities are very safe and minimally invasive. Fluorescent nanoparticles, such as NaGdF4:Nd3 +/Yb3 +, are excellent candidates for NIRF/MRI multimodal imaging. The dopants, Nd and Yb, absorb and emit within the biological window; where near infrared light is less attenuated by soft tissue. This results in less tissue damage and deeper tissue penetration making it a viable candidate in biological imaging. In addition, the inclusion of Gd results in paramagnetic properties, allowing their use as contrast agents in multimodal imaging. The work presented will include crystallographic results, as well as full optical and magnetic characterization to determine the nanoparticle's viability in multimodal imaging.

  16. Sea Cucumbers Metabolites as Potent Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Naveena B. Janakiram

    2015-05-01

    Full Text Available Sea cucumbers and their extracts have gained immense popularity and interest among researchers and nutritionists due to their nutritive value, potential health benefits, and use in the treatment of chronic inflammatory diseases. Many areas of the world use sea cucumbers in traditional foods and folk medicine. Though the actual components and their specific functions still remain to be investigated, most sea cucumber extracts are being studied for their anti-inflammatory functions, immunostimulatory properties, and for cancer prevention and treatment. There is large scope for the discovery of additional bioactive, valuable compounds from this natural source. Sea cucumber extracts contain unique components, such as modified triterpene glycosides, sulfated polysaccharides, glycosphingolipids, and esterified phospholipids. Frondanol A5, an isopropyl alcohol/water extract of the enzymatically hydrolyzed epithelia of the edible North Atlantic sea cucumber, Cucumaria frondosa, contains monosulfated triterpenoid glycoside Frondoside A, the disulfated glycoside Frondoside B, the trisulfated glycoside Frondoside C, 12-methyltetradecanoic acid, eicosapentaenoic acid, and fucosylated chondroitin sulfate. We have extensively studied the efficacy of this extract in preventing colon cancer in rodent models. In this review, we discuss the anti-inflammatory, immunostimulatory, and anti-tumor properties of sea cucumber extracts.

  17. Neoflavonoids and tetrahydroquinolones as possible cancer chemopreventive agents

    Science.gov (United States)

    Luqman, Suaib; Meena, Abha; Singh, Pragya; Kondratyuk, Tamara P.; Marler, Laura E.; Pezzuto, John M.; Negi, Arvind Singh

    2012-01-01

    Several lactone and lactam based neoflavonoids and tetrahydroquinolones were synthesized and evaluated for cancer chemopreventive studies using cell and molecular target based in vitro bioassays, namely NFκB, aromatase, and quinone reductase 1 (QR1). These analogues blocked TNF-α-induced NFκB activation in a dose-dependent manner with IC50 values in the range of 0.11–3.2 μM. In addition, compound 8 inhibited aromatase activity with an IC50 value of 12.12 μM and compound 10 affected QR1 induction (IR: 3.6, CD: 19.57 μM). Neoflavonoids 8 and 10 exhibiting good results, can further be optimized for improved therapeutic profiles. However, investigations into the actions of neoflavonoids and tetrahydroquinolones, especially those related to the NFκB signaling pathway, aromatase inhibition, induction of QR1 expression and in vivo studies could provide new insights into the cancer chemopreventive ability of these molecules. PMID:22726671

  18. Calix[4]arenes as Molecular Platforms for Magnetic Resonance Imaging (MRI) Contrast Agents

    NARCIS (Netherlands)

    Schehle, Daniel T.; Schatz, Juergen; Laurent, Sophie; Elst, Luce Vander; Muller, Robert N.; Stuart, Marc C. A.; Peters, Joop A.

    2009-01-01

    An amphiphilic conjugate 1 of a calix[4]arene with four Gd-DOTA chelates (DOTA=1,4,7,10-tetra(carboxymethyl)-1,4,7,10-tetraazacyclododecane) was prepared and the properties relevant to its application as a magnetic resonance imaging (MRI) contrast agent were investigated by NMR, dynamic light

  19. Amphetamines and pH-shift agents for brain imaging: Basic research and clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book contains 18 selections. Some of the titles are: Labelling of amphetamines with /sup 123/I: Receptors for amphetamines; New amphetamine derivatives; Potential new approaches for the development of brain imaging agents for single-photon applications; and IM SPECT with the pinhole collimator.

  20. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

  1. High-relaxivity gadolinium-modified high-density lipoproteins as magnetic resonance imaging contrast agents

    NARCIS (Netherlands)

    Briley-Saebo, Karen C.; Geninatti-Crich, Simonetta; Cormode, David P.; Barazza, Alessandra; Mulder, Willem J. M.; Chen, Wei; Giovenzana, Giovanni B.; Fisher, Edward A.; Aime, Silvio; Fayad, Zahi A.

    2009-01-01

    There is an ongoing desire to produce high-relaxivity, Gd-based magnetic resonance imaging (MRI) contrast agents. These may allow for lower doses to be used, which is especially important in view of the current safety concerns surrounding Gd in patients. Here we report the synthesis of a

  2. Fluorine-19 Mri Contrast Agents for Cell Tracking and Lung Imaging

    Directory of Open Access Journals (Sweden)

    Matthew S. Fox

    2015-01-01

    Full Text Available Fluorine-19 ( 19 F-based contrast agents for magnetic resonance imaging stand to revolutionize imaging-based research and clinical trials in several fields of medical intervention. First, their use in characterizing in vivo cell behavior may help bring cellular therapy closer to clinical acceptance. Second, their use in lung imaging provides novel noninvasive interrogation of the ventilated airspaces without the need for complicated, hard-to-distribute hardware. This article reviews the current state of 19 F-based cell tracking and lung imaging using magnetic resonance imaging and describes the link between the methods across these fields and how they may mutually benefit from solutions to mutual problems encountered when imaging 19 F-containing compounds, as well as hardware and software advancements.

  3. Element-specific spectral imaging of multiple contrast agents: a phantom study

    Science.gov (United States)

    Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

    2018-02-01

    This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

  4. Evolving perspectives of the role of novel agents in androgen-independent prostate cancer

    Directory of Open Access Journals (Sweden)

    Sujith Kalmadi

    2008-01-01

    Full Text Available Metastatic androgen-independent prostate cancer presents an intriguing clinical challenge, with a subtle interaction between hormone-responsive and refractory tumor cell elements. The treatment of advanced prostate carcinoma, which had remained stagnant for several decades following the understanding of the link between androgenic stimulation and carcinogenesis, has now started to make steady headway with chemotherapy and targeted approaches. Metastatic prostate cancer is almost always treated with initial androgen deprivation, in various forms. However, despite such treatment androgen-independent prostate cancer cells eventually emerge and progress to threaten life. The therapeutic objectives for treatment of metastatic prostate cancer are to maintain the quality of life and prolong survival. The out-dated nihilistic dogma of deferring chemotherapy until the most advanced stages in advanced prostate cancer is now falling by the wayside with the development of newer effective, tolerable agents.

  5. Ganoderma lucidum Polysaccharides as An Anti-cancer Agent.

    Science.gov (United States)

    Sohretoglu, Didem; Huang, Shile

    2017-11-13

    The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Proteomics of cancer cell lines resistant to microtubule-stabilizing agents

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Angeletti, Ruth H; Horwitz, Susan Band

    2014-01-01

    was compared with two drug-resistant daughter cell lines, an EpoB-resistant cell line (EpoB8) and an ixabepilone-resistant cell line (Ixab80). All 2D DIGE results were validated by Western blot analyses. A variety of cytoskeletal and cytoskeleton-associated proteins were differentially expressed in drug......Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellular...... resistance to the class of MIAs known as microtubule-stabilizing agents (MSA). The human lung cancer cell line A549 was compared with two drug-resistant daughter cell lines, a taxol-resistant cell line (AT12) and an epothilone B (EpoB)-resistant cell line (EpoB40). The ovarian cancer cell line Hey...

  7. Responsive magnetic resonance imaging contrast agents as chemical sensors for metals in biology and medicine.

    Science.gov (United States)

    Que, Emily L; Chang, Christopher J

    2010-01-01

    This tutorial review highlights progress in the development of responsive magnetic resonance imaging (MRI) contrast agents for detecting and sensing biologically relevant metal ions. Molecular imaging with bioactivatable MRI indicators offers a potentially powerful methodology for studying the physiology and pathology of metals by capturing dynamic three-dimensional images of living systems for research and clinical applications. This emerging area at the interface of inorganic chemistry and the life sciences offers a broad palette of opportunities for researchers with interests ranging from coordination chemistry and spectroscopy to supramolecular chemistry and molecular recognition to metals in biology and medicine.

  8. Availability of perfluoroctylbromide (PFOB) emulsion used as agent in the liver tumor imaging of computed tomography (CT)

    International Nuclear Information System (INIS)

    Ozawa, Takachika

    1986-01-01

    We carried out a fundamental study on the availability of perfluoroctylbromide (PFOB) emulsion used as an agent in the liver tumor imaging of computed tomography (CT). For this study, we used emulsified yolk phospolipid as a surfactant for PFOB emulsion because it is generally considered to have higher safety relative to the administration to the humans. In the rabbits' liver tumor model in which VX 2 tumor cell was implanted into their livers, we observed increases in the CT values of the livers when 5 to 10 ml/kg of PFOB emulsion (20 % w/v) was administered into the vein, and also ringlike enhancement and increases in the CT values on the tumor rim when 20 ml/kg of PFOB emulsion was administered. In addition, in the chemical analysis of a gas chromatography, we also observed significant increases in the PFOB concentration on the tumor rim, compared with those of normal liver parenchyma, when 20 ml/kg of PFOB emulsion was given. In the finding of CT values in the human liver tumor by means of organ perfusion system, we recognized increases in the CT values (induced by the accumulation of PFOB emulsion) on the rim of the metastatic tumor of colon cancer. These results suggest that PFOB emulsion has certain availability as an agent for the liver tumor imaging of computed tomography (CT). (author)

  9. Image-guided radiotherapy and motion management in lung cancer

    DEFF Research Database (Denmark)

    Korreman, Stine

    2015-01-01

    In this review, image guidance and motion management in radiotherapy for lung cancer is discussed. Motion characteristics of lung tumours and image guidance techniques to obtain motion information are elaborated. Possibilities for management of image guidance and motion in the various steps...... of the treatment chain are explained, including imaging techniques and beam delivery techniques. Clinical studies using different motion management techniques are reviewed, and finally future directions for image guidance and motion management are outlined....

  10. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    Science.gov (United States)

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment.

  11. Small animal optoacoustic tomography system for molecular imaging of contrast agents

    Science.gov (United States)

    Su, Richard; Liopo, Anton; Ermilov, Sergey A.; Oraevsky, Alexander A.

    2016-03-01

    We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (exogenous or endogenous optoacoustic contrast agents. As examples, we present in vivo experiments using phantoms and mice with and without tumor injected with contrast agents with indocyanine green (ICG). LOIS-3D was capable of detecting ~1-2 pmole of the ICG, in tissues with relatively low blood content. With its high sensitivity and excellent spatial resolution LOIS-3D is an advanced alternative to fluorescence and bioluminescence based modalities for molecular imaging in live mice.

  12. Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation.

    Science.gov (United States)

    Martinez de Pinillos Bayona, Alejandra; Moore, Caroline M; Loizidou, Marilena; MacRobert, Alexander J; Woodhams, Josephine H

    2016-03-01

    Photochemical internalisation (PCI) is a technique for improving cellular delivery of certain bioactive agents which are prone to sequestration within endolysosomes. There is a wide range of agents suitable for PCI-based delivery including toxins, oligonucleotides, genes and immunoconjugates which demonstrates the versatility of this technique. The basic mechanism of PCI involves triggering release of the agent from endolysosomes within the target cells using a photosensitiser which is selectively retained with the endolysosomal membranes. Excitation of the photosensitiser by visible light leads to disruption of the membranes via photooxidative damage thereby releasing the agent into the cytosol. This treatment enables the drugs to reach their intended subcellular target more efficiently and improves their efficacy. In this review we summarise the applications of this technique with the main emphasis placed on cancer chemotherapy. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  13. Clinical trials of antioxidants as cancer prevention agents: past, present, and future.

    Science.gov (United States)

    Goodman, Michael; Bostick, Roberd M; Kucuk, Omer; Jones, Dean P

    2011-09-01

    The purpose of this review is to summarize the most important human clinical trials of antioxidants as cancer prevention agents conducted to date, provide an overview of currently ongoing studies, and discuss future steps needed to advance research in this field. To date there have been several large (at least 7000 participants) trials testing the efficacy of antioxidant supplements in preventing cancer. The specific agents (diet-derived direct antioxidants and essential components of antioxidant enzymes) tested in those trials included β-carotene, vitamin E, vitamin C, selenium, retinol, zinc, riboflavin, and molybdenum. None of the completed trials produced convincing evidence to justify the use of traditional antioxidant-related vitamins or minerals for cancer prevention. Our search of ongoing trials identified six projects at various stages of completion. Five of those six trials use selenium as the intervention of interest delivered either alone or in combination with other agents. The lack of success to date can be explained by a variety of factors that need to be considered in the next generation research. These factors include lack of good biological rationale for selecting specific agents of interest; limited number of agents tested to date; use of pharmacological, rather than dietary, doses; and insufficient duration of intervention and follow-up. The latter consideration underscores the need for alternative endpoints that are associated with increased risk of neoplasia (i.e., biomarkers of risk), but are detectable prior to tumor occurrence. Although dietary antioxidants are a large and diverse group of compounds, only a small proportion of candidate agents have been tested. In summary, the strategy of focusing on large high-budget studies using cancer incidence as the endpoint and testing a relatively limited number of antioxidant agents has been largely unsuccessful. This lack of success in previous trials should not preclude us from seeking novel

  14. Molecular Imaging Agents Specific for the Annulus Fibrosus of the Intervertebral Disk

    Directory of Open Access Journals (Sweden)

    Summer L. Gibbs-Strauss

    2010-05-01

    Full Text Available Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.

  15. STUDY ON STUDENTS’ AWARENESS CONCERNING ENVIRONMENTAL AND OCCUPATIONAL HAZARDOUS AGENTS OF CANCER RISK AND PREVENTION METHODS

    Directory of Open Access Journals (Sweden)

    Antonina Cebulska-Wasilewska

    2010-09-01

    Full Text Available Background. The aim of our study was to assess the level of awareness and knowledge on environmental and occupational risk of cancer and its prevention among Polish students. We were interested also in their sources of knowledge. Methods. Survey, using the questionnaire, was conducted among 1080 respondents, who are or probably will be in their future work, exposed to harmful agents, due to study profile. Results. Students rated their knowledge on environmental and occupational cancer agents and cancer prevention mostly as limited (over 77%. Participation in “Safety Work and Environment” courses did not differentiate their level of cancer risk awareness. 901 students (84% responded to question about specific substances, which may cause cancer. Almost 2% of students indicated none from 10 given agents as carcinogenic. About 34% of respondents pointed all given agents, 39% pointed on 8–9 of them, 5–7 agents 13.2% of surveyed and 9% of them indicated on 1–4 agents. Students were aware of carcinogenic features of radiation, asbestos, cigarettes smoking (93.2–93.8%, benzene, benzo[?]pirene and pesticides (79,2 –83,6%. Less of them declared carcinogenic features of PAHs (75.4%, heavy metals (73.9%, electromagnetic field (64.8% and infections (60.8%. Only 48% of respondents specified possible lowering of the cancer by risk intervention practices. Medical and engineering profile, as well as attendance in courses covering the issues of health safety at work or environment (SWE significantly decreased percentage of respondents who didn’t specified any procedure (but it was still high: 48–62%. Conclusion. Our results demonstrate that most students, only to some extent, are aware of the most well known cancer-causing substances occurrence. Their knowledge is mostly limited and they do not know prevention procedures and ways to lower or eliminate the risk. Therefore the modernization of educational programs and development of more efficient

  16. Near-infrared Mueller matrix imaging for colonic cancer detection

    Science.gov (United States)

    Wang, Jianfeng; Zheng, Wei; Lin, Kan; Huang, Zhiwei

    2016-03-01

    Mueller matrix imaging along with polar decomposition method was employed for the colonic cancer detection by polarized light in the near-infrared spectral range (700-1100 nm). A high-speed (colonic tissues (i.e., normal and caner) were acquired. Polar decomposition was further implemented on the 16 images to derive the diattentuation, depolarization, and the retardance images. The decomposed images showed clear margin between the normal and cancerous colon tissue samples. The work shows the potential of near-infrared Mueller matrix imaging for the early diagnosis and detection of malignant lesions in the colon.

  17. Ultrasound contrast agent and ultrasound vascular image enhancement system; Choonpa zoeizai oyobi zoei gazo system

    Energy Technology Data Exchange (ETDEWEB)

    Soetanto, K

    1998-09-15

    Ultrasonic diagnosing equipment is effective on the diagnosis of soft tissue inside the body, however, it has a week point in which the ultrasound wave was sheltered by air in hard tissues such as bone and lungs or air in the stomach and intestines. An ultrasound contrast agent was developed to remedy such a basic weak point of ultra wave and to enhance image contrast. As for this contrast agent, several types made of materials such as physiological saline, medicament, gas carbide, and a material containing bubbles have been studied. The most effective one to enhance image contrast among those materials was the ultrasound contrast agent using bubbles. In this paper, the outline of the micro-bubble ultrasound contrast agent was introduced. The week point of the bubble type contrast agent was a short lifetime of bubbles inside blood vessels and the limitation of size and scale. How to overcome the technical problems has become an urgent subject for the development of ultrasound diagnosis. 25 refs., 5 figs.

  18. Highly adaptable triple-negative breast cancer cells as a functional model for testing anticancer agents.

    Directory of Open Access Journals (Sweden)

    Balraj Singh

    Full Text Available A major obstacle in developing effective therapies against solid tumors stems from an inability to adequately model the rare subpopulation of panresistant cancer cells that may often drive the disease. We describe a strategy for optimally modeling highly abnormal and highly adaptable human triple-negative breast cancer cells, and evaluating therapies for their ability to eradicate such cells. To overcome the shortcomings often associated with cell culture models, we incorporated several features in our model including a selection of highly adaptable cancer cells based on their ability to survive a metabolic challenge. We have previously shown that metabolically adaptable cancer cells efficiently metastasize to multiple organs in nude mice. Here we show that the cancer cells modeled in our system feature an embryo-like gene expression and amplification of the fat mass and obesity associated gene FTO. We also provide evidence of upregulation of ZEB1 and downregulation of GRHL2 indicating increased epithelial to mesenchymal transition in metabolically adaptable cancer cells. Our results obtained with a variety of anticancer agents support the validity of the model of realistic panresistance and suggest that it could be used for developing anticancer agents that would overcome panresistance.

  19. Thiol-reducing agents prevent sulforaphane-induced growth inhibition in ovarian cancer cells.

    Science.gov (United States)

    Kim, Seung Cheol; Choi, Boyun; Kwon, Youngjoo

    2017-01-01

    The inhibitory potential of sulforaphane against cancer has been suggested for different types of cancer, including ovarian cancer. We examined whether this effect is mediated by mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS), important signaling molecules related to cell survival and proliferation, in ovarian cancer cells. Sulforaphane at a concentration of 10 μM effectively inhibited the growth of cancer cells. Use of specific inhibitors revealed that activation of MAPK pathways by sulforaphane is unlikely to mediate sulforaphane-induced growth inhibition. Sulforaphane did not generate significant levels of intracellular ROS. Pretreatment with thiol reducers, but not ROS scavengers, prevented sulforaphane-induced growth inhibition. Furthermore, diamide, a thiol-oxidizing agent, enhanced both growth inhibition and cell death induced by sulforaphane, suggesting that the effect of sulforaphane on cell growth may be related to oxidation of protein thiols or change in cellular redox status. Our data indicate that supplementation with thiol-reducing agents should be avoided when sulforaphane is used to treat cancer.

  20. Dawn of Advanced Molecular Medicine: Nanotechnological Advancements in Cancer Imaging and Therapy

    Science.gov (United States)

    Kaittanis, Charalambos; Shaffer, Travis M.; Thorek, Daniel L. J.; Grimm, Jan

    2014-01-01

    Nanotechnology plays an increasingly important role not only in our everyday life (with all its benefits and dangers) but also in medicine. Nanoparticles are to date the most intriguing option to deliver high concentrations of agents specifically and directly to cancer cells; therefore, a wide variety of these nanomaterials has been developed and explored. These span the range from simple nanoagents to sophisticated smart devices for drug delivery or imaging. Nanomaterials usually provide a large surface area, allowing for decoration with a large amount of moieties on the surface for either additional functionalities or targeting. Besides using particles solely for imaging purposes, they can also carry as a payload a therapeutic agent. If both are combined within the same particle, a theranostic agent is created. The sophistication of highly developed nanotechnology targeting approaches provides a promising means for many clinical implementations and can provide improved applications for otherwise suboptimal formulations. In this review we will explore nanotechnology both for imaging and therapy to provide a general overview of the field and its impact on cancer imaging and therapy. PMID:25271430

  1. Biodegradable nanoparticles for targeted ultrasound imaging of breast cancer cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu Jun [Department of Biomedical Engineering, Ohio State University, 270 Bevis Hall, 1080 Carmack Rd, Columbus, OH 43210 (United States); Li Jie [Department of Biomedical Engineering, Ohio State University, 270 Bevis Hall, 1080 Carmack Rd, Columbus, OH 43210 (United States); Rosol, Thomas J [Department of Veterinary Biosciences, Ohio State University, 1925 Coffey Rd, Columbus, OH 43210 (United States); Pan Xueliang [Department of Statistics, Ohio State University, 1958 Neil Avenue, Columbus, OH 43210 (United States); Voorhees, Jeffrey L [Ohio State Biochemistry Program, Ohio State University, 108 Aronoff Building, 318 West 12 Avenue, Columbus, OH 43210 (United States)

    2007-08-21

    Disease-specific enhanced imaging through a targeted agent promises to improve the specificity of medical ultrasound. Nanoparticles may provide unique advantages for targeted ultrasound imaging due to their novel physical and surface properties. In this study, we examined a nanoparticle agent developed from a biodegradable polymer, polylactic acid (PLA). The nanoparticles (mean diameter = 250 nm) were surface conjugated to an anti-Her2 antibody (i.e., Herceptin) for specific binding to breast cancer cells that overexpress Her2 receptors. We examined the targeting specificity and the resultant ultrasound enhancement in Her2-positive and negative cells. Flow cytometry and confocal imaging were used to assess the nanoparticle-cell binding. Her2-positive cells demonstrated substantial staining after incubation with nanoparticle/antibody conjugates, while minimal staining was found in Her2-negative cells, indicating receptor-specific binding of the conjugated PLA nanoparticles. In high-resolution ultrasound B-mode images, the average gray scale of the Her2-positive cells was consistently and significantly higher after nanoparticle treatment (133 {+-} 4 in treated cells versus 109 {+-} 4 in control, p < 0.001, n = 5), while no difference was detected in the cells that did not overexpress the receptors (117 {+-} 3 in treated cells versus 118 {+-} 5 in control). In conclusion, the feasibility of using targeted nanoparticles to enhance ultrasonic images was demonstrated in vitro. This may be a promising approach to target cancer biomarkers for site-specific ultrasound imaging.

  2. New developments in medical imaging to detect breast cancer

    African Journals Online (AJOL)

    medical imaging modalities are used to detect breast cancer, the most common being X-rays (mammography), ultrasound, magnetic resonance imaging (MRI) and various radionuclide techniques.2. The purpose of this article is to review these and other novel medical imaging modalities. The American College of Radiology ...

  3. Study of anti-cancer effects of chemotherapeutic agents and radiotherapy in breast cancer patients using fluorescence spectroscopy

    Science.gov (United States)

    Chithra, K.; Vijayaraghavan, S.; Prakasarao, Aruna; Singaravelu, Ganesan

    2017-02-01

    The analysis of the variations in the spectroscopic patterns of the key bio molecules using Native fluorescence spectroscopy, without exogenous labels, has emerged as a new trend in the characterization of the Physiological State and the Discrimination of Pathological from normal conditions of cells and tissues as the relative concentration of these bio-molecules serve as markers in evaluating the presence of cancer in the body. The aim of this unique study is to use these features of Optical spectroscopy in monitoring the behavior of cells to treatment and thus to evaluate the response to Chemotherapeutic agents and Radiation in Breast Cancer Patients. The results of the study conducted using NFS of Human blood plasma of biopsy proved Breast Cancer patients undergoing treatment are promising, enhancing the scope of Native fluorescence Spectroscopy emerging as a promising technology in the evaluation of Therapeutic Response in Breast Cancer Patients.

  4. Targeting inflammatory pathways by dietary agents for prevention and treatment of cancer

    International Nuclear Information System (INIS)

    Aggarwal, Bharat B.

    2016-01-01

    Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants and high-calorie diet have been recognized as major risk factors for the most common types of cancer. All these risk factors are linked to cancer through inflammation. While acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long-term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors NF-kB and STAT3, two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NFkB and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-kB; fifth, chemotherapeutic agents and γ-irradiation activate NF-kB and lead to chemoresistance and radioresistance; sixth, most gene products linked to inflammation, survival, proliferation, invasion, angiogenesis and metastasis are regulated by NF-kB and STAT3; seventh, suppression of NF-kB and STAT3 inhibits the proliferation and invasion of tumors; and eighth, most chemopreventive agents mediate their effects through inhibition of NF-kB and STAT3 activation pathways. Thus, the suppression of these proinflammatory pathways may provide opportunities for both prevention and treatment of cancer. We will discuss the potential of nutraceuticals derived from spices and from traditional Indian medicine in suppression of inflammatory pathways and their role inprevention and therapy of cancer. (author)

  5. Combination of nanotechnology with vascular targeting agents for effective cancer therapy.

    Science.gov (United States)

    Jahanban-Esfahlan, Rana; Seidi, Khaled; Banimohamad-Shotorbani, Behnaz; Jahanban-Esfahlan, Ali; Yousefi, Bahman

    2018-04-01

    As a young science, nanotechnology promptly integrated into the current oncology practice. Accordingly, various nanostructure particles were developed to reduce drug toxicity and allow the targeted delivery of various diagnostic and therapeutic compounds to the cancer cells. New sophisticated nanosystems constantly emerge to improve the performance of current anticancer modalities. Targeting tumor vasculature is an attractive strategy to fight cancer. Though the idea was swiftly furthered from basic science to the clinic, targeting tumor vasculature had a limited potential in patients, where tumors relapse due to the development of multiple drug resistance and metastasis. The aim of this review is to discuss the advantages of nanosystem incorporation with various vascular targeting agents, including (i) endogen anti-angiogenic agents; (ii) inhibitors of angiogenesis-related growth factors; (iii) inhibitors of tyrosine kinase receptors; (iv) inhibitors of angiogenesis-related signaling pathways; (v) inhibitors of tumor endothelial cell-associated markers; and (vi) tumor vascular disrupting agents. We also review the efficacy of nanostructures as natural vascular targeting agents. The efficacy of each approach in cancer therapy is further discussed. © 2017 Wiley Periodicals, Inc.

  6. A Preclinical Evaluation of Antimycin A as a Potential Antilung Cancer Stem Cell Agent

    Directory of Open Access Journals (Sweden)

    Chi-Tai Yeh

    2013-01-01

    Full Text Available Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs, was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA, was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, β-catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress β-catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate β-catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.

  7. Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model.

    Science.gov (United States)

    Keating, Jane J; Runge, Jeffrey J; Singhal, Sunil; Nims, Sarah; Venegas, Ollin; Durham, Amy C; Swain, Gary; Nie, Shuming; Low, Philip S; Holt, David E

    2017-05-15

    Complete tumor resection is the most important predictor of patient survival with non-small cell lung cancer. Methods for intraoperative margin assessment after lung cancer excision are lacking. This study evaluated near-infrared (NIR) intraoperative imaging with a folate-targeted molecular contrast agent (OTL0038) for the localization of primary lung adenocarcinomas, lymph node sampling, and margin assessment. Ten dogs with lung cancer underwent either video-assisted thoracoscopic surgery or open thoracotomy and tumor excision after an intravenous injection of OTL0038. Lungs were imaged with an NIR imaging device both in vivo and ex vivo. The wound bed was re-imaged for retained fluorescence suspicious for positive tumor margins. The tumor signal-to-background ratio (SBR) was measured in all cases. Next, 3 human patients were enrolled in a proof-of-principle study. Tumor fluorescence was measured both in situ and ex vivo. All canine tumors fluoresced in situ (mean Fluoptics SBR, 5.2 [range, 2.7-8.1]; mean Karl Storz SBR 1.9 [range, 1.4-2.6]). In addition, the fluorescence was consistent with tumor margins on pathology. Three positive lymph nodes were discovered with NIR imaging. Also, a positive retained tumor margin was discovered upon NIR imaging of the wound bed. Human pulmonary adenocarcinomas were also fluorescent both in situ and ex vivo (mean SBR, > 2.0). NIR imaging can identify lung cancer in a large-animal model. In addition, NIR imaging can discriminate lymph nodes harboring cancer cells and also bring attention to a positive tumor margin. In humans, pulmonary adenocarcinomas fluoresce after the injection of the targeted contrast agent. Cancer 2017;123:1051-60. © 2016 American Cancer Society. © 2016 American Cancer Society.

  8. Sup(123)I-methylene blue: an unsatisfactory parathyroid imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J.; Kettle, A.G.; O' Doherty, M.J.; Collins, R.E.C.; Coakley, A.J. (Kent and Canterbury Hospital (United Kingdom))

    1992-07-01

    This study was designed to examine the possible use of {sup 123}I-labelled methylene blue as a parathyroid imaging agent. Five patients were studied, all of whom had parathyroid adenomas which were successfully localized preoperatively with {sup 201}Tl and {sup 99}Tc{sup m}-sestamibi, and which were subsequently proven at surgery. The {sup 123}I-labelled methylene blue localized only one of these adenomas, was negative in two and had equivocal uptake in the remaining two patients. It is therefore concluded that compared to other radionuclide methods for localizing parathyroid adenomas this agent is unsatisfactory. (author).

  9. Sub-second proton imaging of 13C hyperpolarized contrast agents in water.

    Science.gov (United States)

    Truong, Milton L; Coffey, Aaron M; Shchepin, Roman V; Waddell, Kevin W; Chekmenev, Eduard Y

    2014-01-01

    Indirect proton detection of (13)C hyperpolarized contrast agents potentially enables greater sensitivity. Presented here is a study of sub-second projection imaging of hyperpolarized (13)C contrast agent addressing the obstacle posed by water suppression for indirect detection in vivo. Sodium acetate phantoms were used to develop and test water suppression and sub-second imaging with frequency-selective RF pulses using spectroscopic and imaging indirect proton detection. A 9.8 mm aqueous solution of (13)C PHIP hyperpolarized 2-hydroxyethyl-(13)C-propionate-d2,3,3 (HEP),  ~25% was used for demonstration of indirect proton sub-second imaging detection. Balanced 2D FSSFP (fast steady-state free precession) allowed the recording of proton images with a field of view of 64 × 64 mm(2) and spatial resolution 2 × 2 mm(2) with total acquisition time of less than 0.2 s. In thermally polarized sodium 1-(13)C-acetate, (13) C to (1)H polarization transfer efficiency of 45.1% of the theoretically predicted values was observed in imaging detection corresponding to an 11-fold overall sensitivity improvement compared with direct (13)C FSSFP imaging. (13)C to (1)H polarization transfer efficiency of 27% was observed in imaging detection, corresponding to a 3.25-fold sensitivity improvement compared with direct (13)C FSSFP imaging with hyperpolarized HEP. The range of potential applications and limitations of this sub-second and ultra-sensitive imaging approach are discussed. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser.

    Science.gov (United States)

    Liu, Yang; Xu, Ming; Chen, Qing; Guan, Guannan; Hu, Wen; Zhao, Xiuli; Qiao, Mingxi; Hu, Haiyang; Liang, Ying; Zhu, Heyun; Chen, Dawei

    2015-01-01

    Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer.

  11. In vivo imaging of paraCEST agents using frequency labeled exchange transfer MRI.

    Science.gov (United States)

    Lin, Chien-Yuan; Yadav, Nirbhay N; Ratnakar, James; Sherry, A Dean; van Zijl, Peter C M

    2014-01-01

    A main obstacle to in vivo applications of paramagnetic chemical exchange saturation transfer (paraCEST) is interference from endogenous tissue magnetization transfer contrast (MTC). The suitability of excitation-based frequency labeled exchange transfer (FLEX) to separate out such MTC effects in vivo was tested. The FLEX sequence measures modulation of the water signal based on the chemical shift evolution of solute proton magnetization as a function of evolution time. Time-domain analysis of this water signal allows identification of different solute components and provides a mechanism to separate out the rapidly decaying MTC components with short effective transverse relaxation time ( T2*) values. FLEX imaging of paraCEST agents was possible in vitro in phantoms and in vivo in mouse kidneys and bladder. The results demonstrated that FLEX is capable of separating out the MTC signal from tissues in vivo while providing a quantitative exchange rate for the rapidly exchanging paraCEST water protons by fitting the FLEX time-domain signal to FLEX theory. The first in vivo FLEX images of a paraCEST agent were acquired, which allowed separation of the tissue MTC components. These results show that FLEX imaging has potential for imaging the distribution of functional paraCEST agents in biological tissues. Copyright © 2013 Wiley Periodicals, Inc.

  12. Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats

    International Nuclear Information System (INIS)

    Bergsland, J.; Carr, E.A. Jr.; Carroll, M.; Feldman, M.J.; Kung, H.; Wright, J.R.

    1989-01-01

    There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection

  13. Magnetic resonance imaging for clinical management of rectal cancer

    DEFF Research Database (Denmark)

    Beets-Tan, Regina G H; Lambregts, Doenja M J; Maas, Monique

    2018-01-01

    OBJECTIVES: To update the 2012 ESGAR consensus guidelines on the acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for clinical staging and restaging of rectal cancer. METHODS: Fourteen abdominal imaging experts from the European Society of Gastrointestinal and Abdominal...... be used as clinical guidelines for primary staging and restaging of rectal cancer using MRI. KEY POINTS: • These guidelines present recommendations for staging and reporting of rectal cancer. • The guidelines were constructed through consensus amongst 14 pelvic imaging experts. • Consensus was reached...

  14. X-ray Scatter Imaging of Hepatocellular Carcinoma in a Mouse Model Using Nanoparticle Contrast Agents

    Science.gov (United States)

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging. PMID:26511147

  15. Experimental design and instability analysis of coaxial electrospray process for microencapsulation of drugs and imaging agents.

    Science.gov (United States)

    Si, Ting; Zhang, Leilei; Li, Guangbin; Roberts, Cynthia J; Yin, Xiezhen; Xu, Ronald

    2013-07-01

    Recent developments in multimodal imaging and image-guided therapy requires multilayered microparticles that encapsulate several imaging and therapeutic agents in the same carrier. However, commonly used microencapsulation processes have multiple limitations such as low encapsulation efficiency and loss of bioactivity for the encapsulated biological cargos. To overcome these limitations, we have carried out both experimental and theoretical studies on coaxial electrospray of multilayered microparticles. On the experimental side, an improved coaxial electrospray setup has been developed. A customized coaxial needle assembly combined with two ring electrodes has been used to enhance the stability of the cone and widen the process parameter range of the stable cone-jet mode. With this assembly, we have obtained poly(lactide-co-glycolide) microparticles with fine morphology and uniform size distribution. On the theoretical side, an instability analysis of the coaxial electrified jet has been performed based on the experimental parameters. The effects of process parameters on the formation of different unstable modes have been studied. The reported experimental and theoretical research represents a significant step toward quantitative control and optimization of the coaxial electrospray process for microencapsulation of multiple drugs and imaging agents in multimodal imaging and image-guided therapy.

  16. Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shailendra Giri

    Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

  17. Hyperspectral imaging and quantitative analysis for prostate cancer detection

    Science.gov (United States)

    Akbari, Hamed; Halig, Luma V.; Schuster, David M.; Osunkoya, Adeboye; Master, Viraj; Nieh, Peter T.; Chen, Georgia Z.

    2012-01-01

    Abstract. Hyperspectral imaging (HSI) is an emerging modality for various medical applications. Its spectroscopic data might be able to be used to noninvasively detect cancer. Quantitative analysis is often necessary in order to differentiate healthy from diseased tissue. We propose the use of an advanced image processing and classification method in order to analyze hyperspectral image data for prostate cancer detection. The spectral signatures were extracted and evaluated in both cancerous and normal tissue. Least squares support vector machines were developed and evaluated for classifying hyperspectral data in order to enhance the detection of cancer tissue. This method was used to detect prostate cancer in tumor-bearing mice and on pathology slides. Spatially resolved images were created to highlight the differences of the reflectance properties of cancer versus those of normal tissue. Preliminary results with 11 mice showed that the sensitivity and specificity of the hyperspectral image classification method are 92.8% to 2.0% and 96.9% to 1.3%, respectively. Therefore, this imaging method may be able to help physicians to dissect malignant regions with a safe margin and to evaluate the tumor bed after resection. This pilot study may lead to advances in the optical diagnosis of prostate cancer using HSI technology. PMID:22894488

  18. Body Image in Younger Breast Cancer Survivors: A Systematic Review

    Science.gov (United States)

    Paterson, Carly; Lengacher, Cecile A.; Donovan, Kristine A.; Kip, Kevin E.; Tofthagen, Cindy S.

    2015-01-01

    Background Body image is a complex issue with the potential to impact many aspects of cancer survivorship, particularly for the younger breast cancer survivor. Objective The purpose of this review is to synthesize the current state of the science for body image in younger women with breast cancer. Intervention/Methods Combinations of the terms “body image,” “sexuality intervention,” “women,” “younger women,” and “breast cancer” were searched in the PubMed, PsycInfo, CINAHL, Web of Knowledge and Science Direct databases through January 2014. Inclusion criteria for this review were: 1) original research; 2) published in English from the year 2000 forward; 3) measuring body image as an outcome variable; and 4) results included reporting of age-related outcomes. Results Thirty-six articles met the inclusion criteria. The majority of studies were cross-sectional, with extensive variation in body image assessment tools. Age and treatment type had a significant impact on body image, and poorer body image was related to physical and psychological distress, sex and intimacy, and the partnered relationship among younger women. Only one intervention study found a significant improvement in body image post-intervention. Conclusions Findings suggest body image is a complex post-treatment concern for breast cancer survivors, particularly younger women. The findings of this review are limited by the high level of variation in the methods for assessing body image. Implications for Practice Further research of interventions to address body image concerns following treatment for breast cancer is warranted. Improvement of body image may improve the quality of life of younger breast cancer survivors. PMID:25881807

  19. Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

    Directory of Open Access Journals (Sweden)

    Estelrich J

    2015-03-01

    Full Text Available Joan Estelrich,1,2 María Jesús Sánchez-Martín,1 Maria Antònia Busquets1,2 1Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Catalonia, Spain; 2Institut de Nanociència I Nanotecnologia (IN2UB, Barcelona, Catalonia, SpainAbstract: Magnetic resonance imaging (MRI has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions, providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of

  20. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

    Directory of Open Access Journals (Sweden)

    Reuveni T

    2011-11-01

    Full Text Available Tobi Reuveni1, Menachem Motiei1, Zimam Romman2, Aron Popovtzer3, Rachela Popovtzer11Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-ilan University, Ramat Gan, 2GE HealthCare, Tirat Hacarmel, 3Department of Otorhinolaryngology, Head and Neck Surgery and Onology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, IsraelAbstract: In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes.Keywords: functional computed tomography, molecular imaging, gold nanoparticles, biologically targeted in vivo imaging, contrast agents

  1. Automatic spectral imaging protocol selection and iterative reconstruction in abdominal CT with reduced contrast agent dose: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peijie; Liu, Jie; Chai, Yaru; Yan, Xiaopeng; Gao, Jianbo; Dong, Junqiang [The First Affiliated Hospital of Zhengzhou University, Department of Radiology, Zhengzhou, Henan Province (China)

    2017-01-15

    To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) with reduced contrast agent dose in abdominal multiphase CT. One hundred and sixty patients were randomly divided into two scan protocols (n = 80) each; protocol A, 120 kVp/450 mgI/kg, filtered back projection algorithm (FBP); protocol B, spectral CT imaging with ASIS and 40 to 70 keV monochromatic images generated per 300 mgI/kg, ASIR algorithm. Quantitative parameters (image noise and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (image noise, small structures, organ enhancement, and overall image quality) were compared. Monochromatic images at 50 keV and 60 keV provided similar or lower image noise, but higher contrast and overall image quality as compared with 120-kVp images. Despite the higher image noise, 40-keV images showed similar overall image quality compared to 120-kVp images. Radiation dose did not differ between the two protocols, while contrast agent dose in protocol B was reduced by 33 %. Application of ASIR and ASIS to monochromatic imaging from 40 to 60 keV allowed contrast agent dose reduction with adequate image quality and without increasing radiation dose compared to 120 kVp with FBP. (orig.)

  2. Identification of a Common Binding Mode for Imaging Agents to Amyloid Fibrils from Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Skeby, Katrine Kirkeby; Sørensen, Jesper; Schiøtt, Birgit

    2013-01-01

    Amyloid diseases are characterized by the misfolding and deposition of proteins in the body in the form of insoluble amyloid fibrils. Alzheimer’s disease and type 2 diabetes mellitus are two examples of amyloid diseases which are closely related both with respect to the atomic structures of the a...... binding modes for imaging agents is proposed to originate from subtle differences in amino acid composition of the surface grooves on an amyloid fibril, resulting in fine tuning of the binding affinities for a specific amyloid fibril....... experimentally due to the insoluble nature of amyloid fibrils. This study uses molecular dynamics simulations to investigate the interactions between 13 aromatic amyloid imaging agents, entailing 4 different organic scaffolds, and a model of an amyloid fibril. Clustering analysis combined with free energy...

  3. Magnetic resonance molecular imaging in cancer research

    International Nuclear Information System (INIS)

    Wu Peihong; Wang Guohui

    2005-01-01

    The magnetic resonance (MR) molecular imaging can be defined as the in vivo characterization and measurement of biologic processes at the molecular and gene level by the means of MR imaging science. The purpose of molecular imaging is to diagnose tumor more early and specifically and monitor the anti-tumor therapy response. The present researches of molecular imaging focus on the specific MR molecular probes, molecular imaging of tumor angiogenesis, genetic imaging, and magnetic resonance spectroscopic imaging, and so on. Because of it has high spatial resolution and functional imaging, the MR molecular imaging will play an important role in the tumor diagnosis and treatment in 21 century. (authors)

  4. Novelty detection for breast cancer image classification

    Science.gov (United States)

    Cichosz, Pawel; Jagodziński, Dariusz; Matysiewicz, Mateusz; Neumann, Łukasz; Nowak, Robert M.; Okuniewski, Rafał; Oleszkiewicz, Witold

    2016-09-01

    Using classification learning algorithms for medical applications may require not only refined model creation techniques and careful unbiased model evaluation, but also detecting the risk of misclassification at the time of model application. This is addressed by novelty detection, which identifies instances for which the training set is not sufficiently representative and for which it may be safer to restrain from classification and request a human expert diagnosis. The paper investigates two techniques for isolated instance identification, based on clustering and one-class support vector machines, which represent two different approaches to multidimensional outlier detection. The prediction quality for isolated instances in breast cancer image data is evaluated using the random forest algorithm and found to be substantially inferior to the prediction quality for non-isolated instances. Each of the two techniques is then used to create a novelty detection model which can be combined with a classification model and used at the time of prediction to detect instances for which the latter cannot be reliably applied. Novelty detection is demonstrated to improve random forest prediction quality and argued to deserve further investigation in medical applications.

  5. Radiolabeled antibodies for cancer imaging and therapy.

    Science.gov (United States)

    Barbet, Jacques; Bardiès, Manuel; Bourgeois, Mickael; Chatal, Jean-François; Chérel, Michel; Davodeau, François; Faivre-Chauvet, Alain; Gestin, Jean-François; Kraeber-Bodéré, Françoise

    2012-01-01

    Radiolabeled antibodies were studied first for tumor detection by single-photon imaging, but FDG PET stopped these developments. In the meantime, radiolabeled antibodies were shown to be effective in the treatment of lymphoma. Radiolabeling techniques are well established and radiolabeled antibodies are a clinical and commercial reality that deserves further studies to advance their application in earlier phase of the diseases and to test combination and adjuvant therapies including radiolabeled antibodies in hematological diseases. In solid tumors, more resistant to radiations and less accessible to large molecules such as antibodies, clinical efficacy remains limited. However, radiolabeled antibodies used in minimal or small-size metastatic disease have shown promising clinical efficacy. In the adjuvant setting, ongoing clinical trials show impressive increase in survival in otherwise unmanageable tumors. New technologies are being developed over the years: recombinant antibodies and pretargeting approaches have shown potential in increasing the therapeutic index of radiolabeled antibodies. In several cases, clinical trials have confirmed preclinical studies. Finally, new radionuclides, such as lutetium-177, with better physical properties will further improve the safety of radioimmunotherapy. Alpha particle and Auger electron emitters offer the theoretical possibility to kill isolated tumor cells and microscopic clusters of tumor cells, opening the perspective of killing the last tumor cell, which is the ultimate challenge in cancer therapy. Preliminary preclinical and preliminary clinical results confirm the feasibility of this approach.

  6. Polypyrrole coated phase-change contrast agents for sono-photoacoustic imaging (Conference Presentation)

    Science.gov (United States)

    Li, David S.; Yoon, Soon Joon; Matula, Thomas J.; O'Donnell, Matthew; Pozzo, Lilo D.

    2017-03-01

    A new light and sound sensitive nanoemulsion contrast agent is presented. The agents feature a low boiling point liquid perfluorocarbon core and a broad light spectrum absorbing polypyrrole (PPy) polymer shell. The PPy coated nanoemulsions can reversibly convert from liquid to gas phase upon cavitation of the liquid perfluorocarbon core. Cavitation can be initiated using a sufficiently high intensity acoustic pulse or from heat generation due to light absorption from a laser pulse. The emulsions can be made between 150 and 350 nm in diameter and PPy has a broad optical absorption covering both the visible spectrum and extending into the near-infrared spectrum (peak absorption 1053 nm). The size, structure, and optical absorption properties of the PPy coated nanoemulsions were characterized and compared to PPy nanoparticles (no liquid core) using dynamic light scattering, ultraviolet-visible spectrophotometry, transmission electron microscopy, and small angle X-ray scattering. The cavitation threshold and signal intensity were measured as a function of both acoustic pressure and laser fluence. Overlapping simultaneous transmission of an acoustic and laser pulse can significantly reduce the activation energy of the contrast agents to levels lower than optical or acoustic activation alone. We also demonstrate that simultaneous light and sound cavitation of the agents can be used in a new sono-photoacoustic imaging method, which enables greater sensitivity than traditional photoacoustic imaging.

  7. Ultrasound-guided photoacoustic imaging of lymph nodes with biocompatible gold nanoparticles as a novel contrast agent (Conference Presentation)

    Science.gov (United States)

    Sun, In-Cheol; Dumani, Diego; Emelianov, Stanislav Y.

    2017-02-01

    A key step in staging cancer is the diagnosis of metastasis that spreads through lymphatic system. For this reason, researchers develop various methods of sentinel lymph node mapping that often use a radioactive tracer. This study introduces a safe, cost-effective, high-resolution, high-sensitivity, and real-time method of visualizing the sentinel lymph node: ultrasound-guided photoacoustic (US/PA) imaging augmented by a contrast agent. In this work, we use clearable gold nanoparticles covered by a biocompatible polymer (glycol chitosan) to enhance cellular uptake by macrophages abundant in lymph nodes. We incubate macrophages with glycol-chitosan-coated gold nanoparticles (0.05 mg Au/ml), and then fix them with paraformaldehyde solution for an analysis of in vitro dark-field microscopy and cell phantom. The analysis shows enhanced cellular uptake of nanoparticles by macrophages and strong photoacoustic signal from labeled cells in tissue-mimicking cell phantoms consisting gelatin solution (6 %) with silica gel (25 μm, 0.3%) and fixed macrophages (13 X 105 cells). The in-vivo US/PA imaging of cervical lymph nodes in healthy mice (nu/nu, female, 5 weeks) indicates a strong photoacoustic signal from a lymph node 10 minutes post-injection (2.5 mg Au/ml, 80 μl). The signal intensity and the nanoparticle-labeled volume of tissue within the lymph node continues to increase until 4 h post-injection. Histological analysis further confirms the accumulation of gold nanoparticles within the lymph nodes. This work suggests the feasibility of molecular/cellular US/PA imaging with biocompatible gold nanoparticles as a photoacoustic contrast agent in the diagnosis of lymph-node-related diseases.

  8. Modern dose-finding designs for cancer phase I trials drug combinations and molecularly targeted agents

    CERN Document Server

    Hirakawa, Akihiro; Daimon, Takashi; Matsui, Shigeyuki

    2018-01-01

    This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent developments of adaptive dose-finding methods as well as providing practitioners in biostatistics and clinical investigators with advanced materials for designing, conducting, monitoring, and analyzing adaptive dose-finding trials. The topics in the book are mainly related to cancer clinical trials, but many of those topics are potentially applicable or can be extended to trials for other diseases. The focus is mainly on model-based dose-finding methods for two kinds of phase I trials. One is clinical trials with combinations of tw...

  9. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

    2017-04-15

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  10. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    International Nuclear Information System (INIS)

    Ayyala, Rama S.; Teot, Lisa A.; Perez Rossello, Jeanette M.

    2017-01-01

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  11. [99mTcN(PNP5)(NOEt)]+. A novel potential myocardial perfusion imaging agent

    International Nuclear Information System (INIS)

    Jinfeng Chu; Bin Li; Dejing Kong; Xuebin Wang; Junbo Zhang

    2006-01-01

    The asymmetrical [ 99m TcN(PNP5)(NOEt)] + heterocomplex containing a terminal technetium-nitrogen multiple bond coordinated to the diphosphine ligand (PNP5) and the dithiocarbamate ligand (NOEt), was prepared through ligand exchange reaction. Its radiochemical purity was over 90% as measured by TLC and HPLC. Biodistribution in mice and SPECT imaging in dog were studied. The results showed that [ 99m TcN(PNP5)(NOEt)] + possessed high myocardial uptake and good retention, and high target to non-target ratios, suggesting that it may be a potential myocardial perfusion imaging agent. (author)

  12. Synthesis and labelled with 99Tcm of serotonin (5-HT1A) receptor imaging agent

    International Nuclear Information System (INIS)

    Jiang Quanfu; Wu Chunying; Lu Chunxiong; Chen Zhengping; Wang Songpei; Zhang Tongxing; Li Xiaomin

    2006-01-01

    The synthesis and labelled with 99 Tc m of serotonin (5-HT 1A ) receptor imaging agent derived from way-100635 are reported. The precursor is synthesized by chlorization of N 2 S 2 and condensation with 2-(1-piperazino) phenol, then reduction and deprotection are carried. The labelling ratio is over 90% and the radiochemical purity is over 95% determined by thin layer chromatography (TLC). (authors)

  13. Molecular imaging in the framework of personalized cancer medicine.

    Science.gov (United States)

    Belkić, Dzevad; Belkić, Karen

    2013-11-01

    With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers.

  14. Evaluation of chirp reversal power modulation sequence for contrast agent imaging

    Science.gov (United States)

    Novell, A.; Sennoga, CA; Escoffre, JM; Chaline, J.; Bouakaz, A.

    2014-09-01

    Over the last decade, significant research effort has been focused on the use of chirp for contrast agent imaging because chirps are known to significantly increase imaging contrast-to-noise ratio (CNR). New imaging schemes, such as chirp reversal (CR), have been developed to improve contrast detection by increasing non-linear microbubble responses. In this study we evaluated the contrast enhancement efficiency of various chirped imaging sequences in combination with well-established imaging schemes such as power modulation (PM) and pulse inversion (PI). The imaging schemes tested were implemented on a fully programmable open scanner and evaluated by ultrasonically scanning (excitation frequency of 2.5 MHz amplitude of 350 kPa) a tissue-mimicking flow phantom comprising a 4 mm diameter tube through which aqueous dispersions (dilution fraction of 1/2000) of the commercial ultrasound contrast agent, SonoVue® were continuously circulated. The recovery of non-linear microbubble responses after chirp compression requires the development and the optimization of a specific filter. A compression filter was therefore designed and used to compress and extract several non-linear components from the received microbubble responses. The results showed that using chirps increased the image CNR by approximately 10 dB, as compared to conventional Gaussian apodized sine burst excitation but degraded the axial resolution by a factor of 1.4, at -3 dB. We demonstrated that the highest CNR and contrast-to-noise ratio (CTR) were achievable when CR was combined with PM as compared to other imaging schemes such as PI.

  15. Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent.

    Science.gov (United States)

    Bayat, S; Le Duc, G; Porra, L; Berruyer, G; Nemoz, C; Monfraix, S; Fiedler, S; Thomlinson, W; Suortti, P; Standertskjöld-Nordenstam, C G; Sovijärvi, A R

    2001-12-01

    Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.

  16. Natural Forms of Vitamin E as Effective Agents for Cancer Prevention and Therapy.

    Science.gov (United States)

    Jiang, Qing

    2017-11-01

    Initial research on vitamin E and cancer has focused on α-tocopherol (αT), but recent clinical studies on cancer-preventive effects of αT supplementation have shown disappointing results, which has led to doubts about the role of vitamin E, including different vitamin E forms, in cancer prevention. However, accumulating mechanistic and preclinical animal studies show that other forms of vitamin E, such as γ-tocopherol (γT), δ-tocopherol (δT), γ-tocotrienol (γTE), and δ-tocotrienol (δTE), have far superior cancer-preventive activities than does αT. These vitamin E forms are much stronger than αT in inhibiting multiple cancer-promoting pathways, including cyclo-oxygenase (COX)- and 5-lipoxygenase (5-LOX)-catalyzed eicosanoids, and transcription factors such as nuclear transcription factor κB (NF-κB) and signal transducer and activator of transcription factor 3 (STAT3). These vitamin E forms, but not αT, cause pro-death or antiproliferation effects in cancer cells via modulating various signaling pathways, including sphingolipid metabolism. Unlike αT, these vitamin E forms are quickly metabolized to various carboxychromanols including 13'-carboxychromanols, which have even stronger anti-inflammatory and anticancer effects than some vitamin precursors. Consistent with mechanistic findings, γT, δT, γTE, and δTE, but not αT, have been shown to be effective for preventing the progression of various types of cancer in preclinical animal models. This review focuses on cancer-preventive effects and mechanisms of γT, δT, γTE, and δTE in cells and preclinical models and discusses current progress in clinical trials. The existing evidence strongly indicates that these lesser-known vitamin E forms are effective agents for cancer prevention or as adjuvants for improving prevention, therapy, and control of cancer. © 2017 American Society for Nutrition.

  17. Mitochondrial complex II, a novel target for anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Klučková, Katarína; Bezawork-Geleta, A.; Rohlena, Jakub; Dong, L.; Neužil, Jiří

    2013-01-01

    Roč. 1827, č. 5 (2013), s. 552-564 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP301/12/1851 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrion * Complex II * Anti- cancer agent Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.829, year: 2013

  18. The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Xing Zhanwen; Ke Hengte; Yue Xiuli; Dai Zhifei [Nanobiotechnology Division, State Key Laboratory of Urban Water Resources and Environment, School of Sciences, Harbin Institute of Technology, Harbin 150080 (China); Wang Jinrui; Zhao Bo [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Liu Jibin, E-mail: zhifei.dai@hit.edu.cn, E-mail: ji-bin.liu@jefferson.edu [Ultrasound Research and Education Institute, Thomas Jefferson University, Philadelphia, PA 19107 (United States)

    2010-04-09

    Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

  19. Preparation and Biodistribution of 99mTc-Pamidronate as Bone Imaging Agent

    Directory of Open Access Journals (Sweden)

    LUO Hong-yi

    2016-02-01

    Full Text Available Labeling of Pamidronate (PAM with 99mTc was studied by a direct labeling method in the presence of SnCl2•2H2O as reducing agent. The influences of the concentration of SnCl2•2H2O, PAM concentration and pH value, reaction time on labeling yield were investigated. The optimum labeling was determined. The results showed that the radiochemistry purity of 99mTc-PAM was more than 95%. Biodistribution studies in normal mice and rats showed very high uptake of 99mTc-PAM and long retain in bone. 99mTc-PAM was washed out from the blood very quickly. In addition, considerable uptake in the kidneys indicated this complex was excreted mainly by renal pathway. On the other hand, the radioactivity in liver, lung and heart was negligible. It could be known from SPECT images that 99mTc-PAM would be an excellent bone-imaging agent. Bone uptake of 99mTc-PAM was higher than that of 99mTc-MDP in mice. This study suggested that 99mTc-PAM was a promising bone imaging agent and further study was worthwhile.

  20. MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

    Science.gov (United States)

    Rasaneh, Samira; Rajabi, Hossein; Babaei, Mohammad Hossein; Akhlaghpoor, Shahram

    2011-06-01

    In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 ± 2.5 and 41 ± 15 nm (size range: 15-87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1-3.5. TMNs were non-toxic to the cells below the 30 μg (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.

  1. MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira; Rajabi, Hossein, E-mail: hrajabi@modares.ac.ir [Tarbiat Modares University, Department of Medical Physics (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Science and Technology Research Institute, Department of Radioisotope (Iran, Islamic Republic of); Akhlaghpoor, Shahram [Sina Hospital, Tehran Medical University, Noor Medical Imaging Center (Iran, Islamic Republic of)

    2011-06-15

    In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 {+-} 2.5 and 41 {+-} 15 nm (size range: 15-87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1-3.5. TMNs were non-toxic to the cells below the 30 {mu}g (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.

  2. Cancer imaging phenomics toolkit: quantitative imaging analytics for precision diagnostics and predictive modeling of clinical outcome.

    Science.gov (United States)

    Davatzikos, Christos; Rathore, Saima; Bakas, Spyridon; Pati, Sarthak; Bergman, Mark; Kalarot, Ratheesh; Sridharan, Patmaa; Gastounioti, Aimilia; Jahani, Nariman; Cohen, Eric; Akbari, Hamed; Tunc, Birkan; Doshi, Jimit; Parker, Drew; Hsieh, Michael; Sotiras, Aristeidis; Li, Hongming; Ou, Yangming; Doot, Robert K; Bilello, Michel; Fan, Yong; Shinohara, Russell T; Yushkevich, Paul; Verma, Ragini; Kontos, Despina

    2018-01-01

    The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

  3. Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

    Directory of Open Access Journals (Sweden)

    Vera ePaefgen

    2015-09-01

    Full Text Available Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given.

  4. PET Imaging to Monitor Cancer Therapy

    NARCIS (Netherlands)

    Malviya, Gaurav; Nayak, Tapan K.

    2013-01-01

    Improved knowledge and understanding of key aspects of cancer has led to the development of novel cancer therapeutics acting through complex pathways and mode of actions. The success of these novel cancer therapeutics is often difficult to predict using standard response criteria based on anatomic

  5. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    Science.gov (United States)

    2016-12-01

    Award Number: W81XWH-12-1-0168 TITLE: Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer PRINCIPAL INVESTIGATOR: Jackilen...Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0168 5c. PROGRAM ELEMENT NUMBER...overexpression, lipid accumulation, lipid oxidation, and tumor aggressiveness will be explored using metabolomics. Plan: Employing a cross-sectional

  6. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2013-09-01

    also rare cases of stromal tumors in the breast that includes benign fibroadenomas , sarcomas, and phyllodes tumors. Fibroadenomas is the most common...Enabled Optical Molecular Imaging of Breast Cancer PRINCIPAL INVESTIGATOR: Rebekah Drezek, Ph.D...Imaging of Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Rebekah Drezek, Ph.D. 5e. TASK NUMBER

  7. 1,3-Bis(2-chloroethyl-1-nitrosourea-loaded bovine serum albumin nanoparticles with dual magnetic resonance–fluorescence imaging for tracking of chemotherapeutic agents

    Directory of Open Access Journals (Sweden)

    Wei KC

    2016-08-01

    Full Text Available Kuo-Chen Wei,1 Feng-Wei Lin,2 Chiung-Yin Huang,1 Chen-Chi M Ma,3 Ju-Yu Chen,1 Li-Ying Feng,1 Hung-Wei Yang2 1Department of Neurosurgery, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, 2Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 3Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China Abstract: To date, knowing how to identify the location of chemotherapeutic agents in the human body after injection is still a challenge. Therefore, it is urgent to develop a drug delivery system with molecular imaging tracking ability to accurately understand the distribution, location, and concentration of a drug in living organisms. In this study, we developed bovine serum albumin (BSA-based nanoparticles (NPs with dual magnetic resonance (MR and fluorescence imaging modalities (fluorescein isothiocyanate [FITC]-BSA-Gd/1,3-bis(2-chloroethyl-1-nitrosourea [BCNU] NPs to deliver BCNU for inhibition of brain tumor cells (MBR 261-2. These BSA-based NPs are water dispersible, stable, and biocompatible as confirmed by XTT cell viability assay. In vitro phantoms and in vivo MR and fluorescence imaging experiments show that the developed FITC-BSA-Gd/BCNU NPs enable dual MR and fluorescence imaging for monitoring cellular uptake and distribution in tumors. The T1 relaxivity (R1 of FITC-BSA-Gd/BCNU NPs was 3.25 mM-1 s-1, which was similar to that of the commercial T1 contrast agent (R1 =3.36 mM-1 s-1. The results indicate that this multifunctional drug delivery system has potential bioimaging tracking of chemotherapeutic agents ability in vitro and in vivo for cancer therapy. Keywords: drug tracking, fluorescence imaging, MR imaging, BSA nanoparticles, cancer therapy

  8. Magnetic Resonance Imaging for Therapy Selection in Breast Cancer

    NARCIS (Netherlands)

    Schmitz, A.M.Th.

    2016-01-01

    More accurate characterization of breast cancer is desirable prior to therapy. MR imaging may ultimately help to resolve the discordant preoperative information from conventional diagnostic workup of breast cancer. Breast MRI has shown potential to provide information on tumor biology, which is

  9. Imaging tumor vascularization for detection and diagnosis of breast cancer

    NARCIS (Netherlands)

    Heijblom, M.; Klaase, J. M.; van den Engh, F. M.; van Leeuwen, T. G.; Steenbergen, W.; Manohar, S.

    2011-01-01

    Breast cancer is one of the major causes of morbidity and mortality in western women. Current screening and diagnostic imaging modalities, like x-ray mammography and ultrasonography, focus on morphological changes of breast tissue. However, these techniques still miss some cancers and often falsely

  10. DWI as an Imaging Biomarker for Bladder Cancer

    NARCIS (Netherlands)

    Yoshida, Soichiro; Takahara, Taro; Kwee, Thomas C.; Waseda, Yuma; Kobayashi, Shuichiro; Fujii, Yasuhisa

    OBJECTIVE. DWI has been increasingly applied in the management of bladder cancer. In this article, we discuss the role of DWI as an imaging biomarker for bladder cancer. CONCLUSION. The DWI signal is derived from the motion of water molecules, which represents the physiologic characteristics of the

  11. Bone-Targeted Imaging and Radionuclide Therapy in Prostate Cancer.

    Science.gov (United States)

    Iagaru, Andrei H; Mittra, Erik; Colletti, Patrick M; Jadvar, Hossein

    2016-10-01

    Although selective metabolic and receptor-based molecular agents will surely be included in the future of prostate cancer diagnosis and therapy, currently available inorganic compounds-such as 18 F-NaF for the diagnosis of bony disease and 223 RaCl 2 for the therapy of bone metastases-were recently shown to be superior to standard 99m Tc-phosphonates for diagnosis and 153 Sm-ethylenediaminetetramethylene phosphonate or 89 SrCl 2 for therapy. The advantages of 18 F-NaF include improved lesion detection and, when used in combination with CT, improved diagnostic confidence and specificity. In addition to being the first approved α-emitter, 223 RaCl 2 is the first radiopharmaceutical to show an increase in overall survival, a decrease in skeletal events, palliation of bone pain, and a low profile of adverse reactions (which are mild and manageable). The management of metastatic bone disease with 223 RaCl 2 is uniquely satisfying, as patients can be monitored directly during their monthly treatment visits. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  12. Microwave Imaging for Breast Cancer Detection

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Fhager, Andreas; Jensen, Peter Damsgaard

    2011-01-01

    Still more research groups are promoting microwave imaging as a viable supplement or substitution to more conventional imaging modalities. A widespread approach for microwave imaging of the breast is tomographic imaging in which one seeks to reconstruct the distributions of permittivity and condu......Still more research groups are promoting microwave imaging as a viable supplement or substitution to more conventional imaging modalities. A widespread approach for microwave imaging of the breast is tomographic imaging in which one seeks to reconstruct the distributions of permittivity...

  13. Targeting tumors with nanobodies for cancer imaging and therapy.

    Science.gov (United States)

    Oliveira, Sabrina; Heukers, Raimond; Sornkom, Jirawas; Kok, Robbert J; van Bergen En Henegouwen, Paul M P

    2013-12-28

    The use of monoclonal antibodies has revolutionized both cancer therapy and cancer imaging. Antibodies have been used to directly inhibit tumor cell proliferation or to target drugs to tumors. Also in molecular imaging, monoclonal antibodies have found their way to the clinic. Nevertheless, distribution within tumors is hampered by their size, leading to insufficient efficacy of cancer treatment and irregular imaging. An attractive alternative for monoclonal antibodies are nanobodies or VHHs. These are the variable domain of heavy-chain antibodies from animals from the Camelidae family that were first discovered in 1993. Stimulated by the ease of nanobody selection, production, and low immunogenicity potential, a number of nanobodies specific to different disease-related targets have been developed. For cancer therapy, nanobodies have been employed as antagonistic drugs, and more recently, as targeting moieties of effector-domaINS and of drug delivery systems. In parallel, nanobodies have also been employed for molecular imaging with modalities such as nuclear and optical imaging. In this review, we discuss recent developments in the application of nanobodies as targeting moieties in cancer therapy and cancer imaging. With such a wide range of successful applications, nanobodies have become much more than simple antagonists. © 2013.

  14. Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.

    Science.gov (United States)

    Manning, H Charles; Buck, Jason R; Cook, Rebecca S

    2016-02-01

    Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  15. Development of multimodal imaging strategies for the pharmacology of anticancer agents

    International Nuclear Information System (INIS)

    Brulle, Laura

    2012-01-01

    Preclinical imaging in oncology is booming. It allows, using representative animal models of human cancers, to understand the mechanisms of development of pathologies and to assess the therapeutic efficiency of a new treatment. The main objective of this work was to develop two ortho-topic models of cancer (pancreas and colon) and to assess on them the reference treatments as well as a new therapeutic strategy by non-thermal plasma so called Plasma Gun. The two cancer models developed showed good representation in relation to human cancers, with the appearance of distant metastases and hypoxia. 5-fluorouracil for the HCT116-luc ortho-topic model of colorectal carcinoma and gemcitabine for the MIA PaCa2-luc pancreatic adenocarcinoma model, have induced discrete effects at low dose which can be detected thanks imaging modalities. After validation of our experimental steps, a new therapeutic strategy, Plasma Gun was evaluated and showed significant effects on tumor growth inhibition. The second objective was to carry out tools for the induction and the characterization of bone metastases and for high resolution imaging of the vasculature. On the one hand, bone metastases obtained by injection of PC3M-luc cells intracardially, was evaluated and quantified with different imaging modalities (bioluminescence, scintigraphy and Computed Tomography). And the other hand, the achievement of a high resolution imaging of vascularization, was possible by the casting method that restores the 3D structure of the vascular architecture following injection of a resin in the circulation. Developments makes during this thesis are new tools for preclinical evaluation of novel anticancer therapies. (author) [fr

  16. Detection of Melanoma Skin Cancer in Dermoscopy Images

    Science.gov (United States)

    Eltayef, Khalid; Li, Yongmin; Liu, Xiaohui

    2017-02-01

    Malignant melanoma is the most hazardous type of human skin cancer and its incidence has been rapidly increasing. Early detection of malignant melanoma in dermoscopy images is very important and critical, since its detection in the early stage can be helpful to cure it. Computer Aided Diagnosis systems can be very helpful to facilitate the early detection of cancers for dermatologists. In this paper, we present a novel method for the detection of melanoma skin cancer. To detect the hair and several noises from images, pre-processing step is carried out by applying a bank of directional filters. And therefore, Image inpainting method is implemented to fill in the unknown regions. Fuzzy C-Means and Markov Random Field methods are used to delineate the border of the lesion area in the images. The method was evaluated on a dataset of 200 dermoscopic images, and superior results were produced compared to alternative methods.

  17. Magnetic Resonance Imaging of Cells Overexpressing MagA, an Endogenous Contrast Agent for Live Cell Imaging

    Directory of Open Access Journals (Sweden)

    Donna E. Goldhawk

    2009-05-01

    Full Text Available Molecular imaging with magnetic resonance imaging (MRI may benefit from the ferrimagnetic properties of magnetosomes, membrane-enclosed iron biominerals whose formation in magnetotactic bacteria is encoded by multiple genes. One such gene is MagA, a putative iron transporter. We have examined expression of MagA in mouse neuroblastoma N2A cells and characterized their response to iron loading and cellular imaging by MRI. MagA expression augmented both Prussian blue staining and the elemental iron content of N2A cells, without altering cell proliferation, in cultures grown in the presence of iron supplements. Despite evidence for iron incorporation in both MagA and a variant, MagAE137V, only MagA expression produced intracellular contrast detectable by MRI at 11 Tesla. We used this stable expression system to model a new sequence for cellular imaging with MRI, using the difference between gradient and spin echo images to distinguish cells from artifacts in the field of view. Our results show that MagA activity in mammalian cells responds to iron supplementation and functions as a contrast agent that can be deactivated by a single point mutation. We conclude that MagA is a candidate MRI reporter gene that can exploit more fully the superior resolution of MRI in noninvasive medical imaging.

  18. Development of 99mTc agents for imaging central neural system receptors

    International Nuclear Information System (INIS)

    2004-01-01

    Radiopharmaceuticals that bind to central neural system (CNS) receptors in vivo are potentially useful for understanding the pathophysiology of anumber of neurological and psychiatric disorders, their diagnosis and treatment. Carbon-11 labelled compounds and positron emission tomography(PET) imaging have played a vital role in establishing the usefulness of imaging the dopaminergic, cholinergic, serotonergic and benzodiazapine receptors, and relating the receptor density to disease status. Since the use of 11C agents is constrained due to their 20 min half-life, various radiohalogenated analogues based on the structure of 11C compounds have been successfully developed, providing comparable information. Iodine- 123 is the most widely employed of these radioisotopes; it has a longer, 13 h, half-life. Through the use of 123I, there has been a steady growth in CNS receptor imaging studies employing single photon emission computerized tomography (SPECT). SPECT, as compared with PET, has slightly inferior image resolution but has the advantage of being readily available worldwide. However, the 123I radiopharmaceutical is expensive and the distribution system outside of the major markets is not well developed for its supply on a routine basis. The ideal radioisotope for SPECT imaging is 99mTc, due to its low cost per dose, availability through commercially available generator systems and physical decay characteristics. Over 80% of all diagnostic nuclear medicine imaging studies worldwide are conducted using this radioisotope. Development of 99mTc radiopharmaceuticals for imaging CNS receptors is therefore of considerable importance. On the basis of the recommendations of a consultants meeting, the International Atomic Energy Agency (IAEA) initiated in 1996 a Co-ordinated Research Project (CRP) on Development of Agents for Imaging CNS Receptors based on 99mTc. At that time there were no 99mTc CNS receptor imaging radiopharmaceuticals available even though work on

  19. In vivo 3D PIXE-micron-CT imaging of Drosophila melanogaster using a contrast agent

    Science.gov (United States)

    Matsuyama, Shigeo; Hamada, Naoki; Ishii, Keizo; Nozawa, Yuichiro; Ohkura, Satoru; Terakawa, Atsuki; Hatori, Yoshinobu; Fujiki, Kota; Fujiwara, Mitsuhiro; Toyama, Sho

    2015-04-01

    In this study, we developed a three-dimensional (3D) computed tomography (CT) in vivo imaging system for imaging small insects with micrometer resolution. The 3D CT imaging system, referred to as 3D PIXE-micron-CT (PIXEμCT), uses characteristic X-rays produced by ion microbeam bombardment of a metal target. PIXEμCT was used to observe the body organs and internal structure of a living Drosophila melanogaster. Although the organs of the thorax were clearly imaged, the digestive organs in the abdominal cavity could not be clearly discerned initially, with the exception of the rectum and the Malpighian tubule. To enhance the abdominal images, a barium sulfate powder radiocontrast agent was added. For the first time, 3D images of the ventriculus of a living D. melanogaster were obtained. Our results showed that PIXEμCT can provide in vivo 3D-CT images that reflect correctly the structure of individual living organs, which is expected to be very useful in biological research.

  20. DNA Repair and Cancer Therapy: Targeting APE1/Ref-1 Using Dietary Agents

    Directory of Open Access Journals (Sweden)

    Julian J. Raffoul

    2012-01-01

    Full Text Available Epidemiological studies have demonstrated the cancer protective effects of dietary agents and other natural compounds isolated from fruits, soybeans, and vegetables on neoplasia. Studies have also revealed the potential for these natural products to be combined with chemotherapy or radiotherapy for the more effective treatment of cancer. In this paper we discuss the potential for targeting the DNA base excision repair enzyme APE1/Ref-1 using dietary agents such as soy isoflavones, resveratrol, curcumin, and the vitamins ascorbate and α-tocopherol. We also discuss the potential role of soy isoflavones in sensitizing cancer cells to the effects of radiotherapy. A comprehensive review of the dual nature of APE1/Ref-1 in DNA repair and redox activation of cellular transcription factors, NF-κB and HIF-1α, is also discussed. Further research efforts dedicated to delineating the role of APE1/Ref-1 DNA repair versus redox activity in sensitizing cancer cells to conventional treatment are warranted.

  1. Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yan Hu

    Full Text Available Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by the adverse effects of cytotoxic agents. Targeted drug delivery may reduce the non-specific toxicity of chemotherapy by selectively directing anticancer drugs to tumor cells. MUC1 protein is an attractive target for tumor-specific drug delivery owning to its overexpression in most adenocarcinomas. In this study, a novel MUC1 aptamer is exploited as the targeting ligand for carrying doxorubicin (Dox to cancer cells. We developed an 86-base DNA aptamer (MA3 that bound to a peptide epitope of MUC1 with a K(d of 38.3 nM and minimal cross reactivity to albumin. Using A549 lung cancer and MCF-7 breast cancer cells as MUC1-expressing models, MA3 was found to preferentially bind to MUC1-positive but not MUC1-negative cells. An aptamer-doxorubicin complex (Apt-Dox was formulated by intercalating doxorubicin into the DNA structure of MA3. Apt-Dox was found capable of carrying doxorubicin into MUC1-positive tumor cells, while significantly reducing the drug intake by MUC1-negative cells. Moreover, Apt-Dox retained the efficacy of doxorubicin against MUC1-positive tumor cells, but lowered the toxicity to MUC1-negative cells (P<0.01. The results suggest that the MUC1 aptamer may have potential utility as a targeting ligand for selective delivery of cytotoxic agent to MUC1-expressing tumors.

  2. Tea: age-old beverage as an effective cancer chemopreventive agent

    Directory of Open Access Journals (Sweden)

    Jasmine George

    2011-12-01

    Full Text Available Cancer is the major public health problem, causing approximately 7 million deaths every year worldwide. The existing treatment approaches and surgical techniques have not been able to cope effectively with this dreaded disease. Because of this, the concept of chemoprevention is now considered a valid approach to reduce the incidence of cancer. There is convincing epidemiological and experimental evidence to show that dietary polyphenolic plant-derived compounds have cancer preventive properties. Based on evidence from in vitro, in vivo data and epidemiological studies, tea has received considerable attention over recent years for reducing the risk of several cancers. Much of the cancer preventive effects of tea, and in particular green tea, appear to be mediated by the polyphenols they contain. In addition to inhibiting mutagenesis and proliferation, tea is relatively non-toxic, is low cost, and can be taken orally or as a part of the daily diet. Therefore it is logical that future clinical studies should focus on examining the efficacy of tea and its active constituents, such as epigallocatechin- 3-gallate (EGCG and theaflavins (TFs, in chemoprevention as an alternative to pharmacological agents. In this review, we address the use of tea and its constituents for the prevention and treatment of cancer. Further mechanistic and dose-response studies will help us to understand the effects of tea consumption on human carcinogenesis.

  3. Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

    Science.gov (United States)

    Rabinowicz, Noa; Mangala, Lingegowda S.; Brown, Kevin R.; Checa-Rodriguez, Cintia; Castiel, Asher; Moskovich, Oren; Zarfati, Giulia; Trakhtenbrot, Luba; Levy-Barda, Adva; Jiang, Dahai; Rodriguez-Aguayo, Cristian; Pradeep, Sunila; van Praag, Yael; Lopez-Berestein, Gabriel; David, Ahuvit; Novikov, Ilya; Huertas, Pablo; Rottapel, Robert; Sood, Anil K.; Izraeli, Shai

    2017-01-01

    Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer. PMID:28423708

  4. Non-degradable contrast agent with selective phagocytosis for cellular and hepatic magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fei-Yan [Nanchang University, College of Chemistry (China); Gu, Zhe-Jia [Nanchang University, Institute for Advanced Study (China); Zhao, Dawen [UT Southwestern Medical Center, Department of Radiology (United States); Tang, Qun, E-mail: tangqun@ncu.edu.cn [Nanchang University, Institute for Advanced Study (China)

    2015-09-15

    Degradation is the long-existing toxic issue of metal-containing inorganic medicine. In this paper, we fully investigated the degradation of dextran-coated KMnF{sub 3} nanocube in the in vitro and in vivo surroundings. Different from the general decomposing and ion releasing events, this special agent is resistant to acidic environment, as well as ion exchange. Non-degradability was proved by simulated and real cellular experiments. Moreover, it can be engulfed in the macrophage cells and kept stable in the lysosome. Due to its stability and highly selective phagocytosis, implanted liver cancer can be clearly visualized after administration.

  5. MO-DE-206-00: Joint AAPM-WMIS Symposium: Metabolic Imaging of Cancer

    International Nuclear Information System (INIS)

    2016-01-01

    In this symposium jointly sponsored by the World Molecular Imaging Society (WMIS) and the AAPM, luminary speakers on imaging metabolism will discuss three impactful topics. The first presentation on Cellular Metabolism of FDG will be given by Guillem Pratx (Stanford). This presentation will detail new work on looking at how the most common molecular imaging agent, fluoro-deoxy-glucose is metabolized at a cellular level. This will be followed by a talk on an improved approach to whole-body PET imaging by Simon Cherry (UC Davis). Simon’s work on a new whole-body PET imaging system promises to have dramatic improvement in our ability to detect and characterize cancer using PET. Finally, Jim Bankson (MD Anderson) will discuss extremely sophisticated approaches to quantifying hyperpolarized-13-C pyruvate metabolism using MR imaging. This technology promises to compliment the exquisite sensitivity of PET with an ability to measure not just uptake, but tumor metabolism. Learning Objectives: Understand the metabolism of FDG at a cellular level. Appreciate the engineering related to a novel new high-sensitivity whole-body PET imaging system. Understand the process of hyperpolarization, how pyruvate relates to metabolism and how advanced modeling can be used to better quantify this data. G. Pratx, Funding: 5R01CA186275, 1R21CA193001, and Damon Runyon Cancer Foundation. S. Cherry, National Institutes of Health; University of California, Davis; Siemens Medical SolutionsJ. Bankson, GE Healthcare; NCI P30-CA016672; CPRIT PR140021-P5

  6. PET Imaging of Estrogen Metabolism in Breast Cancer

    Science.gov (United States)

    2001-06-01

    metastases from colorectal cancer .. ASCO Proceedings 15:448, 1996. 36. Kemeny MM: Tratamiento De La Recidiva En Ca’ncer De Colon. Utilidad Del Diagnostic© Y...AD Award Number: DAMD17-99-1-9089 TITLE: PET Imaging of Estrogen Metabolism in Breast Cancer PRINCIPAL INVESTIGATOR: Yu-Shin Ding, Ph.D...REPORT TYPE AND DATES COVERED Annual (1 June 00-31 May 01) 4. TITLE AND SUBTITLE PET Imaging of Estrogen Metabolism in Breast Cancer 6. AUTHOR(S

  7. Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[18f]fluorobenzoate

    International Nuclear Information System (INIS)

    Jonson, Stephanie D.; Welch, Michael J.

    1999-01-01

    Cholesteryl-p-[ 18 F]fluorobenzoate ([ 18 F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [ 18 F]CFB. The synthesis of [ 18 F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [ 18 F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [ 18 F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [ 18 F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [ 18 F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [ 18 F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [ 18 F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders

  8. Imaging of ex vivo nonmelanoma skin cancers in the optical and terahertz spectral regions optical and terahertz skin cancers imaging.

    Science.gov (United States)

    Joseph, Cecil S; Patel, Rakesh; Neel, Victor A; Giles, Robert H; Yaroslavsky, Anna N

    2014-05-01

    We tested the hypothesis that polarization sensitive optical and terahertz imaging may be combined for accurate nonmelanoma skin cancer (NMSC) delineation. Nine NMSC specimens were imaged. 513 μm and 440 nm wavelengths were used for terahertz and optical imaging, respectively. Histopathology was processed for evaluation. Terahertz reflectance of NMSC was quantified. Our results demonstrate that cross-polarized terahertz images correctly identified location of the tumours, whereas cross-polarized and polarization difference optical images accurately presented morphological features. Cross-polarized terahertz images exhibited lower reflectivity values in cancer as compared to normal tissue. Combination of optical and terahertz imaging shows promise for intraoperative delineation of NMSC. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. REVIEW ON LUNG CANCER DETECTION USING IMAGE PROCESSING TECHNIQUE

    OpenAIRE

    Anam Quadri; Rashida Shujaee; Nishat Khan

    2016-01-01

    This paper presents a review on the lung cancer detection method using image processing. In recent years the image processing mechanisms are used widely in several medical areas for improving earlier detection and treatment stages.Also the different procedures and design methodologies for the same have also been discussed

  10. Prototype of Microwave Imaging System for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Zhurbenko, Vitaliy

    2009-01-01

    Microwave imaging for breast-cancer detection has received the attention of a large number of research groups in the last decade. In this paper, the imaging system currently being developed at the Technical university of Denmark is presented. This includes a description of the antenna system, the...

  11. Barium sulfate suspension as a negative oral contrast agent for MR imaging

    International Nuclear Information System (INIS)

    Li, K.C.P.; Tart, R.P.; Fitzsimmons, J.R.; Storm, B.; Mao, J.

    1989-01-01

    Proton spectroscopy with linewidth measurements and MR imaging were performed on various commercially available barium sulfate suspensions as well as inorganic sulfates and barium salts. Approximately 500 mL of 20%, 40%, 60%, and 70% wt/wt single-contrast oral barium sulfate suspensions were administered to four normal volunteers, and MR imaging was performed with both a 1.5-T and a 0.15-T MR imager. As much as 80% of the small bowel and the entire colon were well visualized with the 60% or 70% wt/wt single-contrast barium sulfate suspensions. The authors conclude that barium sulfate suspensions are useful as oral MR contrast agents

  12. Gold nanoparticle incorporation in the cancer cells : imaging and treatment

    Science.gov (United States)

    Ahn, Sungsook; Jung, Sung Yong; Seo, Eun Seok; Ryu, Jeongeun; Lee, Sang Joon

    2011-11-01

    Surface modified gold nanoparticles (~ 20 nm) are selectively incorporated in the various cancer cells. Depending on the attached molecules on the gold nanoparticle surface, incorporation efficiency of the gold nanoparticles in the cancer cells are differentiated. Two-photon fluorescence microscopy, energy dispersive X-ray spectroscopy (EDS) and second ion mass spectroscopy (SIMS) are utilized to quantify the gold nanoparticles incorporated in the cancer cells. Static images of the cancer cell are obtained by scanning electron microscopy (SEM) and zone-plate X-ray nanoscopy. On the other hand, dynamic flow images are captured by dynamic X-ray imaging. To enhance the selective incorporation into the cancer cells, specially designed aptamer is introduced on the gold nanoparticles, which changes the mechanisms of gold nanoparticle incorporation through the cancer cell membrane. Anti-cancer drugs are also incorporated, by which sustained drug delivery mechanisms are investigated. This study would contribute to the basic understanding on the nanoparticle- mediated disease treatment and advanced imaging technology.

  13. Early Access to Investigational Agents through the National Cancer Institute's Treatment Referral Center.

    Science.gov (United States)

    Johnson, Tali M; Boron, Matthew J

    2012-12-01

    The National Cancer Institute's (NCI) Division of Cancer Treatment and Diagnosis (DCTD), as an investigational new drug sponsor, may provide early access to investigational agents for treatment use. Until recently, the NCI had 3 protocol mechanisms for distributing investigational agents through the Treatment Referral Center (TRC), a service provided by the Pharmaceutical Management Branch (PMB) within the Cancer Therapy Evaluation Program of the NCI's DCTD. The first mechanism is the Group C protocol, the second mechanism is the TRC protocol, and the third, and most common, mechanism is the Special Exception protocol. The purpose of this article is to describe and report on the activities of the TRC at the PMB since 2000 through the end of 2011. Capital Technology Information Services performed PMB data mining for all treatment protocols from January 1, 2000, to December 31, 2011. Requests to PMB were sorted in spreadsheet format by disposition, either as referred, approved, or denied, and were counted by type, either as Group C, TRC, or Special Exception. More than 60% of requests were either referred or approved between 2000 and 2011. The peak number of requests was 1664 between 2000 and 2011 and occurred in 2003. The peak was mostly a result of Special Exception requests; however, more than 400 TRC requests and 20 Group C requests were approved that year. The total number of requests dropped precipitously after 2003, and since 2008 have totaled fewer than 50 annually. All Group C and TRC protocols were completed by March 2006. The lowest number of treatment use requests occurred in 2011. Providing agents through the Special Exception mechanism is one way that promising investigational new drug agents can get to patients with life-threatening illnesses. In general, the PMB's TRC is a useful drug information resource for sites conducting clinical research in oncology, and it provides a valuable service to the oncology community.

  14. Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging.

    Science.gov (United States)

    Ferroni, Letizia; Gardin, Chiara; Della Puppa, Alessandro; Sivolella, Stefano; Brunello, Giulia; Scienza, Renato; Bressan, Eriberto; D'Avella, Domenico; Zavan, Barbara

    2015-11-01

    Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of brain cancer, specifically malignant gliomas, does not yet exist. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood-brain barrier. Nanotechnology today offers a unique opportunity to develop more effective brain cancer imaging and therapeutics. In particular, the development of nanocarriers that can be conjugated with several functional molecules including tumor-specific ligands, anticancer drugs, and imaging probes, can provide new devices which are able to overcome the difficulties of the classical strategies. Nanotechnology-based approaches hold great promise for revolutionizing brain cancer medical treatments, imaging, and diagnosis.

  15. Ferric ammonium citrate as a positive bowel contrast agent for MR imaging of the upper abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Kivelitz, D.; Taupitz, M.; Hamm, B. [Universitaetsklinikum Charite, Berlin (Germany). Inst. fuer Radiologie; Gehl, H.B. [Medizinische Univ. Luebeck (Germany). Inst. fuer Radiologie; Heuck, A. [Muenchen Univ. (Germany). Radiologische Klinik; Krahe, T. [Koeln Univ. (Germany). Inst. fuer Radiologische Diagnostik; Lodemann, K.P. [Bracco-Byk Gulden GmbH, Konstanz (Germany)

    1999-07-01

    Purpose: To evaluate the safety and diagnostic efficacy of two different doses of ferric ammonium citrate as a paramagnetic oral contrast agent for MR imaging of the upper abdomen. Material and methods: Ninety-nine adult patients referred for MR imaging for a known or suspected upper abdominal pathology were included in this randomized multicenter double-blind clinical trial. Imaging was performed with spin-echo (T1- and T2-weighted) and gradient-echo (T1-weighted) techniques before and after administration of either 1200 mg or 2400 mg of ferric ammonium citrate dissolved in 600 ml of water. Safety analysis included monitoring of vital signs, assessment of adverse events, and laboratory testing. Efficacy with regard to organ distension, contrast distribution, bowel enhancement and delineation of adjacent structures was graded qualitatively. Results: No serious adverse events were reported for either of the two concentrations. A total of 31 minor side effects were noted, of which significantly more occurred in the higher dose group (p<0.01). The diagnostic confidence in defining or excluding disease was graded as better after contrast administration for 48% of all images. Marked or moderate enhancement of the upper gastrointestinal tract was achieved at both doses in 69.5% of cases with no evident difference between the two doses. The higher dose tended to show better results in terms of the contrast assessment parameters. Conclusion: Ferric ammonium citrate is a safe and effective oral contrast agent for MR imaging of the upper abdomen at two different dose levels. The higher dose showed a tendency toward better imaging results while the lower dose caused significantly fewer side effects. Therefore, the 1200 mg dose can be recommended in view of the risk-to-benefit ratio. (orig.)

  16. Thermal dependence of ultrasound contrast agents scattering efficiency for echographic imaging techniques

    Science.gov (United States)

    Biagioni, Angelo; Bettucci, Andrea; Passeri, Daniele; Alippi, Adriano

    2015-06-01

    Ultrasound contrast agents are used in echographic imaging techniques to enhance image contrast. In addition, they may represent an interesting solution to the problem of non-invasive temperature monitoring inside the human body, based on some thermal variations of their physical properties. Contrast agents, indeed, are inserted into blood circulation and they reach the most important organs inside the human body; consequently, any thermometric property that they may possess, could be exploited for realizing a non-invasive thermometer. They essentially are a suspension of microbubbles containing a gas enclosed in a phospholipid membrane; temperature variations induce structural modifications of the microbubble phospholipid shell, thus causing thermal dependence of contrast agent's elastic characteristics. In this paper, the acoustic scattering efficiency of a bulk suspension of of SonoVue® (Bracco SpA Milan, Italy) has been studied using a pulse-echo technique in the frequency range 1-17 MHz, as it depends upon temperatures between 25 and 65°C. Experimental data confirm that the ultrasonic attenuation coefficient of SonoVue® depends on temperature between 25 and 60°C. Chemical composition of the bubble shell seem to support the hypothesis that a phase transition in the microstructure of lipid-coated microbubbles could play a key role in explaining such effect.

  17. ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Neri, E.; Boraschi, P.; Bartolozzi, C. [University of Pisa, Department of Diagnostic and Interventional Radiology, Pisa (Italy); Bali, M.A.; Matos, C. [Hopital Erasme, MRI Clinics, Department of Radiology, Bruxelles (Belgium); Ba-Ssalamah, A. [The General Hospital of the Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Brancatelli, G. [University of Palermo, Department of Radiology, Palermo (Italy); Alves, F.C. [University Hospital of Coimbra, Medical Imaging Department and Faculty of Medicine, Coimbra (Portugal); Grazioli, L. [Spedali Civili di Brescia, Department of Radiology, Brescia (Italy); Helmberger, T. [Academic Teaching Hospital of the Technical University, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich (Germany); Lee, J.M. [Seoul National University College of Medicine, Division of Abdominal Imaging, Department of Radiology, Seoul (Korea, Republic of); Manfredi, R. [University of Verona, Department of Radiology, Verona (Italy); Marti-Bonmati, L. [Hospital Universitario y Politecnico La Fe, Area Clinica de Imagen Medica, Valencia (Spain); Merkle, E.M. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland); Op De Beeck, B. [Antwerp University Hospital, Department of Radiology, Edegem (Belgium); Schima, W. [KH Goettlicher Heiland, Krankenhaus der Barmherzigen Schwestern and Sankt Josef-Krankenhaus, Department of Diagnostic and Interventional Radiology, Vienna (Austria); Skehan, S. [St Vincent' s University Hospital, Department of Radiology, Dublin (Ireland); Vilgrain, V. [Assistance Publique-Hopitaux de Paris, APHP, Hopital Beaujon, Radiology Department, Clichy, Paris (France); Zech, C. [Universitaetsspital Basel, Abteilungsleiter Interventionelle Radiologie, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland)

    2016-04-15

    To develop a consensus and provide updated recommendations on liver MR imaging and the clinical use of liver-specific contrast agents. The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a multinational European panel of experts, selected on the basis of a literature review and their leadership in the field of liver MR imaging. A modified Delphi process was adopted to draft a list of statements. Descriptive and Cronbach's statistics were used to rate levels of agreement and internal reliability of the consensus. Three Delphi rounds were conducted and 76 statements composed on MR technique (n = 17), clinical application of liver-specific contrast agents in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84 (SD ±0.17). Full consensus was reached in 22 % of all statements in all working groups, with no full consensus reached on diffuse and vascular diseases. The consensus provided updated recommendations on the methodology, and clinical indications, of MRI with liver specific contrast agents in the study of liver diseases. (orig.)

  18. Image processing based detection of lung cancer on CT scan images

    Science.gov (United States)

    Abdillah, Bariqi; Bustamam, Alhadi; Sarwinda, Devvi

    2017-10-01

    In this paper, we implement and analyze the image processing method for detection of lung cancer. Image processing techniques are widely used in several medical problems for picture enhancement in the detection phase to support the early medical treatment. In this research we proposed a detection method of lung cancer based on image segmentation. Image segmentation is one of intermediate level in image processing. Marker control watershed and region growing approach are used to segment of CT scan image. Detection phases are followed by image enhancement using Gabor filter, image segmentation, and features extraction. From the experimental results, we found the effectiveness of our approach. The results show that the best approach for main features detection is watershed with masking method which has high accuracy and robust.

  19. Comparing stochastic differential equations and agent-based modelling and simulation for early-stage cancer.

    Science.gov (United States)

    Figueredo, Grazziela P; Siebers, Peer-Olaf; Owen, Markus R; Reps, Jenna; Aickelin, Uwe

    2014-01-01

    There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm.

  20. An agent harms a victim: A functional magnetic resonance imaging study on specific moral emotions

    International Nuclear Information System (INIS)

    Kedia, G.; Kedia, G.; Martinot, J.L.; Kedia, G.; Martinot, J.L.; Kedia, G.; Hilton, D.; Berthoz, S.; Wessa, M.

    2008-01-01

    The statement 'An agent harms a victim' depicts a situation that triggers moral emotions. Depending on whether the agent and the victim are the self or someone else, it can lead to four different moral emotions: self-anger ('I harm myself'), guilt ('I harm someone'), other-anger ('someone harms me'), and compassion ('someone harms someone'). In order to investigate the neural correlates of these emotions, we examined brain activation patterns elicited by variations in the agent (self vs. other) and the victim (self vs. other) of a harmful action. Twenty-nine healthy participants underwent functional magnetic resonance imaging while imagining being in situations in which they or someone else harmed themselves or someone else. Results indicated that the three emotional conditions associated with the involvement of other, either as agent or victim (guilt, other-anger, and compassion conditions), all activated structures that have been previously associated with the Theory of Mind (ToM, the attribution of mental states to others), namely, the dorsal medial prefrontal cortex, the precuneus, and the bilateral temporo-parietal junction. Moreover, the two conditions in which both the self and other were concerned by the harmful action (guilt and other-anger conditions) recruited emotional structures (i. e., the bilateral amygdala, anterior cingulate, and basal ganglia). These results suggest that specific moral emotions induce different neural activity depending on the extent to which they involve the self and other. (authors)

  1. Syntheses and biological evaluation of F-18 and I-123 labeled porphyrins as potential tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H.; Ji, D. Y. [Inha University, Incheon (Korea, Republic of); Moon, B. S.; Lee, T. S.; Lee, D. H.; Lee, K. C.; Ahn, G. I.; Yang, S. D.; Choi, C. W.; Jun, K. S. [KIRAMS, Seoul (Korea, Republic of)

    2005-07-01

    Photofrin has currently been approved for general use by licensing authorities to treatment for solid tumor and cancer using photodynamic therapy (PDT) that treat to photochemical effect induced by light. Recently, meso-tetra(3-hydroxyphenyl)porphyrin has been developed as one of best tumor localizer and also shown a favorable tissue distribution. We have studied to develop I-123 labeled meso-tetra(3-methoxyphenyl)porphyrins for tumor imaging. We have studied to develop iodine-123 labeled meso-tetra(3-carboxymethoxy phenyl)porphyrin for tumor imaging agent. The radioiodinated porphyrin compound was obtained by the iodination reaction of tin precursor (50 ig) of porphyrin with Na-123I (200 {mu}L, 100-200 mCi), in the presence of peracetic acid (40 {mu}L) in ethanol. Iodine-123 labeled porphyrin derivative was obtained in 20-30% radiochemical yield and purified by HPLC at 2 mL/min using EtOH/water gradient condition and the fraction at 24-26 min was collected and characterized to desired compound by co injection with cold porphyrin analogue. Total time was around 120 min. The in vitro and in vivo of I-123 labeled porphyrin derivative is under studying.

  2. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  3. Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging.

    Science.gov (United States)

    Mooberry, Linda K; Sabnis, Nirupama A; Panchoo, Marlyn; Nagarajan, Bhavani; Lacko, Andras G

    2016-01-01

    Malignant tumors display remarkable heterogeneity to the extent that even at the same tissue site different types of cells with varying genetic background may be found. In contrast, a relatively consistent marker the scavenger receptor type B1 (SR-B1) has been found to be consistently overexpressed by most tumor cells. Scavenger Receptor Class B Type I (SR-BI) is a high density lipoprotein (HDL) receptor that facilitates the uptake of cholesterol esters from circulating lipoproteins. Additional findings suggest a critical role for SR-BI in cholesterol metabolism, signaling, motility, and proliferation of cancer cells and thus a potential major impact in carcinogenesis and metastasis. Recent findings indicate that the level of SR-BI expression correlate with aggressiveness and poor survival in breast and prostate cancer. Moreover, genomic data show that depending on the type of cancer, high or low SR-BI expression may promote poor survival. This review discusses the importance of SR-BI as a diagnostic as well as prognostic indicator of cancer to help elucidate the contributions of this protein to cancer development, progression, and survival. In addition, the SR-B1 receptor has been shown to serve as a potential gateway for the delivery of therapeutic agents when reconstituted high density lipoprotein nanoparticles are used for their transport to cancer cells and tumors. Opportunities for the development of new technologies, particularly in the areas of cancer therapy and tumor imaging are discussed.

  4. Imaging Prostate Cancer (PCa) Phenotype and Evolution

    Science.gov (United States)

    2016-10-01

    to variable cell uptake (4-6), limited lifetime of cellular label (ə week) (7-8), and because exogenous iron contrast agents influence TAM Figure...Current methods to non-invasively assess and monitor tumor associated macrophages (TAM) infiltration by MRI is limited by the contrast agent itself due...values necessary for survival or proliferation. MRI screening of mice/patients (liver, spleen, tumor) to determine the relative amounts of endogenous

  5. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer.

    Science.gov (United States)

    Chamie, Karim; DeVere White, Ralph W; Lee, Dennis; Ok, Joon-Ha; Ellison, Lars M

    2008-11-01

    It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006. All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n=6214) or unexposed (n=6930) to Agent Orange. Strata-specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate-specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi-square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression. Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75-2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31-3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange-exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9-60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8-63.6 years), had a 2-fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%-27%) compared with unexposed men (10.5%; 95% CI, 5

  6. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Anup Sharma

    Full Text Available Colorectal cancer (CRC is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment. For irinotecan (IRI, growth diminished by 16-62 fold as assessed, by both proliferation (IC50 and anchorage independent cell growth soft agar assays. Treatment of resistant HCT116 cell line along with in-vivo, for CRC line xenografts, AZA plus IRI again exhibits this synergistic response with significant improvement in survival and tumor regression in the mice. Genome-wide expression correlates changes in pathways for cell adhesion and DNA repair with the above responses. A Phase 1/2 clinical trial testing this concept is already underway testing the clinical efficacy of this concept in IRI resistant, metastatic CRC (NCT01896856.

  7. Cell-permeable Ln(III) chelate-functionalized InP quantum dots as multimodal imaging agents

    NARCIS (Netherlands)

    Stasiuk, Graeme J.; Tamang, Sudarsan; Imbert, Daniel; Poillot, Cathy; Giardiello, Marco; Tisseyre, Céline; Barbier, Emmanuel L.; Fries, Pascal Henry; de Waard, Michel; Reiss, Peter; Mazzanti, Marinella

    2011-01-01

    Quantum dots (QDs) are ideal scaffolds for the development of multimodal imaging agents, but their application in clinical diagnostics is limited by the toxicity of classical CdSe QDs. A new bimodal MRI/optical nanosized contrast agent with high gadolinium payload has been prepared through direct

  8. The potential for substance P antagonists as anti-cancer agents in brain tumours.

    Science.gov (United States)

    Harford-Wright, Elizabeth; Lewis, Kate M; Vink, Robert

    2013-04-01

    Despite recent advances in cancer treatment and diagnosis, the prognosis for patients with CNS tumours remains extremely poor. This is, in part, due to the difficulty in completely removing tumours surgically, and also because of the presence of the blood brain barrier, which can prevent the entry of chemotherapeutic agents typically used in cancer treatment. Despite the presence of the blood brain barrier, tumour cells are capable of entering and colonising the brain to form secondary brain tumours. Additionally, tumour related disruption of the blood brain barrier is associated with the clinical presentation of many patients, with accompanying increases in intracranial pressure due, in part, to the development of vasogenic oedema. Vasogenic oedema results because the newly formed angiogenic vessels within brain tumours do not retain the highly selective properties of the blood brain barrier, and thus allow for the extravasation of plasma proteins and water into the brain parenchyma. Tachykinins, and in particular substance P, have been implicated in blood brain barrier disruption and the genesis of cerebral oedema in other CNS insults via a process known as neurogenic inflammation. Recent evidence suggests that substance P may play a similar role in CNS tumours. It has been well established that an upregulation of substance P and its receptors occurs in a number of different cancer types, including CNS neoplasms. In addition to disrupting blood brain barrier permeability, substance P and the NK1 receptors facilitate promotion of tumour growth and the development of cerebral oedema. Accordingly, recent patents describe the potential of NK1 receptor antagonists as anti-cancer agents suggesting that substance P may provide a novel cancer treatment target. This review will examine the role of substance P in the development of CNS tumours.

  9. Performance characteristics of magnetic resonance imaging without contrast agents or sedation in pediatric appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Didier, Ryne A.; Hopkins, Katharine L.; Coakley, Fergus V.; Foster, Bryan R. [Oregon Health and Science University, Department of Diagnostic Radiology, Portland, OR (United States); Krishnaswami, Sanjay [Oregon Health and Science University, Department of Surgery, Portland, OR (United States); Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States); Spiro, David M. [Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States)

    2017-09-15

    Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated. To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis. We included patients ages 4-18 years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy. Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7 mm and ≥2 mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (P<0.01), with sensitivities of 91% and 97% and specificities of 60% and 50%. For examinations in which the appendix was not identified by one or both reviewers (23/98), the clinical outcome was negative. Rapid MRI without contrast agents or sedation is accurate for diagnosis of pediatric appendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7 mm for diameter and ≥2 mm for wall

  10. Chitosan-coated nickel-ferrite nanoparticles as contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Ahmad, Tanveer; Bae, Hongsub; Iqbal, Yousaf; Rhee, Ilsu; Hong, Sungwook; Chang, Yongmin; Lee, Jaejun; Sohn, Derac

    2015-01-01

    We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe 2 O 4 ) nanoparticles as both T 1 and T 2 contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T 1 and T 2 relaxivities were 0.858±0.04 and 1.71±0.03 mM −1 s −1 , respectively. In animal experimentation, both a 25% signal enhancement in the T 1 -weighted mage and a 71% signal loss in the T 2 -weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T 1 and T 2 contrast agents in MRI. We note that the applicability of our nanoparticles as both T 1 and T 2 contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe 2 O 4 ) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T 1 and T 2 contrast agents for MRI by measuring T 1 and T 2 relaxation times as a function of iron concentration. • Both T 1 and T 2 effects were also observed in animal experimentation

  11. Performance characteristics of magnetic resonance imaging without contrast agents or sedation in pediatric appendicitis

    International Nuclear Information System (INIS)

    Didier, Ryne A.; Hopkins, Katharine L.; Coakley, Fergus V.; Foster, Bryan R.; Krishnaswami, Sanjay; Spiro, David M.

    2017-01-01

    Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated. To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis. We included patients ages 4-18 years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy. Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7 mm and ≥2 mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (P<0.01), with sensitivities of 91% and 97% and specificities of 60% and 50%. For examinations in which the appendix was not identified by one or both reviewers (23/98), the clinical outcome was negative. Rapid MRI without contrast agents or sedation is accurate for diagnosis of pediatric appendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7 mm for diameter and ≥2 mm for wall

  12. CT imaging of coexisting pulmonary tuberculosis and lung cancer

    International Nuclear Information System (INIS)

    Lv Yan; Xie Ruming; Zhou Xinhua; Zhou Zhen; Xu Jinping; He Wei; Guo Lifang; Ning Fenggang

    2013-01-01

    Objective: To study the CT characteristics of coexisting pulmonary tuberculosis and lung cancer. Methods: One hundred and four patients of coexisting pulmonary tuberculosis and lung cancer proved by histology, cytology or clinical underwent CT examination. All patients were divided into two groups, group Ⅰ were the patients with the lung cancer after tuberculosis or both found simultaneously (group Ⅰ a with peripheral lung cancer and group Ⅰ b with central lung cancer), group Ⅱ with tuberculosis during lung cancer chemotherapy (group Ⅱ a with peripheral lung cancer and group Ⅱ b with central lung cancer). Imaging characteristics of tuberculosis and lung cancer were compared. χ 2 test and t test were used for the statistical analysis. Results: Of 104 patients, there were 92 patients (88.5%) in group Ⅰ and 12 patients (11.5%) in group Ⅱ. Seventy patients (76.1%) of lung cancer and tuberculosis were located in the same lobe and 22 patients (23.9%) in the different lobes in group Ⅰ. There was no significant difference in distribution of tuberculosis between group Ⅰ and group Ⅱ (χ 2 = 4.302, P = 0.507). The fibrous stripes, nodules of calcification and pleural adhesion of tuberculosis were statistically significant between the two groups (χ 2 = 22.737, 15.193, 27.792, P < 0.05). There were 33 central lung cancers and 71 peripheral lung cancers. In group Ⅰ a (64 patients of peripheral lung cancers), 39 patients (60.9%) had typical manifestations and most of the lesions were ≥ 3 cm (n = 49, 76.6%), solid lesions showed variable enhancement. Conclusions: Secondary tuberculosis during lung cancer chemotherapy has the same CT characteristics with the common active tuberculosis. The morphology, enhancement pattern of lesion and follow-up are helpful for the diagnosis of lung cancer after tuberculosis. (authors)

  13. One-Step 18F-Labeling of Estradiol Derivative for PET Imaging of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hongbo Huang

    2018-01-01

    Full Text Available Positron emission tomography (PET imaging is a useful method to evaluate in situ estrogen receptor (ER status for the early diagnosis of breast cancer and optimization of the appropriate treatment strategy. The 18F-labeled estradiol derivative has been successfully used to clinically assess the ER level of breast cancer. In order to simplify the radiosynthesis process, one-step 18F-19F isotope exchange reaction was employed for the 18F-fluorination of the tracer of [18F]AmBF3-TEG-ES. The radiotracer was obtained with the radiochemical yield (RCY of ~61% and the radiochemical purity (RCP of >98% within 40 min. Cell uptake and blocking assays indicated that the tracer could selectively accumulate in the ER-positive human breast cancer cell lines MCF-7 and T47D. In vivo PET imaging on the MCF-7 tumor-bearing mice showed relatively high tumor uptake (1.4~2.3 %D/g and tumor/muscle uptake ratio (4~6. These results indicated that the tracer is a promising PET imaging agent for ER-positive breast cancers.

  14. Characterization of renal cell carcinoma using agent detection imaging: comparison with gray-scale US

    International Nuclear Information System (INIS)

    Park, Byung Kwan; Kim, Seung Hyup; Choi, Hyuok Jae

    2005-01-01

    We wanted to compare the imaging features of renal cell carcinoma (RCC) and their diagnostic accuracy on agent detection imaging (ADI) and gray-scale ultrasonography (US). Thirty non-consecutive patients (age range; 32-80 years, mean age; 53.7 years) with 30 RCCs were examined with gray-scale US and with ADI in conjunction with using SH U 508A. We described the imaging features of the renal tumors obtained from ADI according to their enhancement pattern, the intratumoral anechoic areas and the presence of any pseudocapsule. The imaging features and diagnostic accuracy of ADI and gray-scale US were then compared. On the ADI exam, the RCCs were shown as being heterogeneous in 87% of the cases (26/30), homogeneous in 7% of the cases (2/30), and there was peripheral irregular enhancement in 7% of the cases (2/30). Intratumoral anechoic areas and pseudocapsule were seen in 87% and 77% of the RCCs on the ADI exam, whereas these features were seen in 53% and 17% of the cases on the gray-scale US, respectively. The diagnostic sensitivity, specificity, and accuracy for RCC with ADI were 97%, 93%, and 95%, respectively. However, those for RCC with using gray-scale US were 70%, 86%, and 78%, respectively. There was a significant difference for the diagnostic accuracy of RCC between ADI and gray-scale US (ρ < 0.05). Agent detection imaging can help visualize the enhancement pattern of RCC and improve the diagnostic accuracy of this tumor by better displaying the intratumoral anechoic areas and the pseudocapsule than does the gray-scale US

  15. Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery

    Directory of Open Access Journals (Sweden)

    Summer L. Gibbs-Strauss

    2011-03-01

    Full Text Available Nerve damage is the major morbidity of many surgeries, resulting in chronic pain, loss of function, or both. The sparing of nerves during surgical procedures is a vexing problem because surrounding tissue often obscures them. To date, systemically administered nerve-highlighting contrast agents that can be used for nerve-sparing image-guided surgery have not been reported. In the current study, physicochemical and optical properties of 4,4‘-[(2-methoxy-1,4-phenylenedi-(1E-2,1-ethenediyl]bis-benzenamine (BMB and a newly synthesized, red-shifted derivative 4-[(1E-2-[4-[(1E-2-[4-aminophenyl]ethenyl]-3-methoxyphenyl]ethenyl]-benzonitrile (GE3082 were characterized in vitro and in vivo. Both agents crossed the blood-nerve barrier and blood-brain barrier and rendered myelinated nerves fluorescent after a single systemic injection. Although both BMB and GE3082 also exhibited significant uptake in white adipose tissue, GE3082 underwent a hypsochromic shift in adipose tissue that provided a means to eliminate the unwanted signal using hyperspectral deconvolution. Dose and kinetic studies were performed in mice to determine the optimal dose and drug-imaging interval. The results were confirmed in rat and pig, with the latter used to demonstrate, for the first time, simultaneous fluorescence imaging of blood vessels and nerves during surgery using the FLARE™ (Fluorescence-Assisted Resection and Exploration imaging system. These results lay the foundation for the development of ideal nerve-highlighting fluorophores for image-guided surgery.

  16. Anti-VEGF agents in metastatic colorectal cancer (mCRC: are they all alike?

    Directory of Open Access Journals (Sweden)

    Saif MW

    2013-06-01

    Full Text Available Muhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States, VEGF receptors (eg, ramucirumab, and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors. The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012, using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC, tyrosine kinase inhibitor (TKI, vascular endothelial growth factor (VEGF

  17. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  18. SU-E-J-10: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, L [Yale University, New Haven, CT (United States); Bai, S [Sichuan University, Chengdu, Sichuan (China); Zhang, Y [Key laboratory of Carcinogenesis and Translational Research, Ministry of Ed, Beijing, Beijing (China); Deng, J [Yale University, New Haven, CT (United States)

    2015-06-15

    Purpose: To systematically evaluate imaging doses and cancer risks to organs-at-risk as a Result of cumulative doses from various radiological imaging procedures in image-guided radiotherapy (IGRT) in a large cohort of cancer patients. Methods: With IRB approval, imaging procedures (computed tomography, kilo-voltage portal imaging, megavoltage portal imaging and kilo-voltage cone-beam computed tomography) of 4832 cancer patients treated during 4.5 years were collected with their gender, age and circumference. Correlations between patient’s circumference and Monte Carlo simulated-organ dose were applied to estimate organ doses while the cancer risks were reported as 1+ERR using BEIR VII models. Results: 80 cGy or more doses were deposited to brain, lungs and RBM in 273 patients (maximum 136, 278 and 267 cGy, respectively), due largely to repetitive imaging procedures and non-personalized imaging settings. Regardless of gender, relative cancer risk estimates for brain, lungs, and RBM were 3.4 (n = 55), 2.6 (n = 49), 1.8 (n = 25) for age group of 0–19; 1.2 (n = 87), 1.4 (n = 98), 1.3 (n = 51) for age group of 20–39; 1.0 (n = 457), 1.1 (n = 880), 1.8 (n=360) for age group of 40–59; 1.0 (n = 646), 1.1 (n = 1400), 2.3 (n = 716) for age group of 60–79 and 1.0 (n = 108),1.1 (n = 305),1.6 (n = 147) for age group of 80–99. Conclusion: The cumulative imaging doses and associated cancer risks from multi-imaging procedures were patient-specific and site-dependent, with up to 2.7 Gy imaging dose deposited to critical structures in some pediatric patients. The associated cancer risks in brain and lungs for children of age 0 to 19 were 2–3 times larger than those for adults. This study indicated a pressing need for personalized imaging protocol to maximize its clinical benefits while reducing associated cancer risks. Sichuan University Scholarship.

  19. Feasibility of using lower doses of chemopreventive agents in a combination regimen for cancer protection.

    Science.gov (United States)

    Ip, C

    1988-04-01

    In experimental cancer chemoprevention studies, the doses of the agent used to produce an inhibitory response are generally very high, sometimes bordering on levels that will result in toxicity to the test animals. The present study was designed to test the hypothesis that low doses of two or more agents may be just as effective as high doses of a single agent. An earlier report from our laboratory showed that vitamin E, although ineffective by itself, potentiates the anti-carcinogenic potency of selenite. Our objective was to complete a comprehensive set of dose titration experiments in the quantitative analysis of the synergism between selenium (Se) and vitamin E. Results indicated that the minimal amount of vitamin E required was around 500 ppm, which when combined with as little as 1 ppm Se, produced a significant protective effect in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumor model. This level of Se is 5 times below the marginal toxicity level of 5 ppm observed in our previous experience. With a 3-agent combination protocol involving Se (1 ppm), vitamin E (500 ppm) and vitamin A (66 ppm), it was found that vitamin A at this particular dose did not contribute any further chemoprevention than that provided by the Se/vitamin E duo. Both Se and vitamin E were present at a concentration 10 times, while vitamin A was present at 30 times their respective nutritional requirement. Our findings thus suggest that the minimum effective dose has to be systematically established for each micronutrient, and that it is feasible to use lower doses of a combination of agents if the threshold level of each agent can be determined under a prescribed set of conditions.

  20. Image processings of radiographs in the gastric cancer cases

    International Nuclear Information System (INIS)

    Inamoto, Kazuo; Yamashita, Kazuya; Morikawa, Kaoru; Takigawa, Atsushi

    1987-01-01

    For improving detectability of the gastric lesions in the X-ray examinations, the computer image processing methods were studied in radiographs of a stomach phantom and gastric cancer lesions by the A/D conversion. After several kinds of the basic processing methods were examined in the artificially made lesions in the stomach phantom and true gastric cancer lesions in 26 X-ray pictures of the 8 gastric cancer cases, we concluded that pathological changes on the edge or mucosal folds in the stomach were stressed by the image processing method using negative to positive conversion, density gradient control, edge enhancement (Sobel operation) and subtraction of the Sobel image from the original image. These methods contributed to interpretation of the gastric cancer by enhancement of the contour and mucosal pattern inside the lesion. The results were applied for follow up studies of the gastric cancer. Tumor expansions could be clarified, but it was yet difficult to catch a precancer lesion by retrospective studies. However, these methods would be expected in future application in the mass survey examination of the gastric cancer detection. (author)

  1. Chemistry of paramagnetic and diamagnetic contrast agents for Magnetic Resonance Imaging and Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Mayoral, Elena [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Departamento de Quimica Inorganica y Quimica Tecnica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Negri, Viviana; Soler-Padros, Jordi [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Cerdan, Sebastian [Laboratorio de Imagen Espectroscopica por Resonancia Magnetica (LIERM), Instituto de Investigaciones Biomedicas ' Alberto Sols' , CSIC/UAM, c/Arturo Duperier 4, E-28029 Madrid (Spain); Ballesteros, Paloma [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain)], E-mail: pballesteros@ccia.uned.es

    2008-09-15

    We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T{sub 1} and T{sub 2} of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH{sub e}) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH{sub e}, independent of water relaxivity, diffusion or exchange.

  2. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy

    Directory of Open Access Journals (Sweden)

    Gann Ting

    2010-01-01

    Full Text Available Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, α-, β-, and γ-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients.

  3. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy

    Science.gov (United States)

    Ting, Gann; Chang, Chih-Hsien; Wang, Hsin-Ell; Lee, Te-Wei

    2010-01-01

    Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, α-, β-, and γ-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients. PMID:20811605

  4. Cancer nanotheranostics

    CERN Document Server

    Gopinath, P; Matai, Ishita; Bhushan, Bharat; Malwal, Deepika; Sachdev, Abhay; Dubey, Poornima

    2015-01-01

    This Brief provides a clear insight of the recent advances in the field of cancer theranostics with special emphasis upon nano scale carrier molecules (polymeric, protein and lipid based) and imaging agents (organic and inorganic).

  5. Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, J.M.; Santoni-Rugiu, E.; Chabanova, E.; Logager, V.; Hansen, A.B.; Thomsen, H.S. [Depts. of Radiology and Pathology, Copenhagen Univ. Hospital, Herlev (Denmark)

    2007-02-15

    Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

  6. Radiolabeled phosphonium salts as mitocondrial voltage sensors for positron emission tomography myocardial imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Yon; Min, Jung Joon [Dept. of Nuclear Medicine,Chonnam National University Medical School and Hwasun Hospital, Gwangju (Korea, Republic of)

    2016-09-15

    Despite substantial advances in the diagnosis of cardiovascular disease, {sup 18}F-labeled positron emission tomography (PET) radiopharmaceuticals remain necessary to diagnose heart disease because clinical use of current PET tracers is limited by their short half-life. Lipophilic cations such as phosphonium salts penetrate the mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to negative inner-transmembrane potentials. Radiolabeled tetraphenyl phosphonium cation derivatives have been developed as myocardial imaging agents for PET. In this review, a general overview of these radiotracers, including their radiosynthesis, in vivo characterization, and evaluation is provided and clinical perspectives are discussed.

  7. Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model

    International Nuclear Information System (INIS)

    Boucher, Marianne

    2016-01-01

    This work takes place in the context of molecular imaging, which aims at tailoring medical treatments and therapies to the individual context by revealing molecular or cellular phenomenon of medical interest in the less invasive manner. In particular, it can be achieved with MRI molecular imaging using engineered iron-oxide contrast agent.This PhD thesis focuses on the study of a new class of iron-oxide contrast agent for high field MRI. Indeed, magnetosomes are natural iron-oxide vesicles produced by magneto-tactic bacteria. These bacteria synthesized such magnetic vesicles and ordered them like a nano-compass in order to facilitate their navigation in sediments. This explains why magnetosomes are awarded with tremendous magnetic properties: around 50 nm, mono-crystalline, single magnetic domain and high saturation magnetization. Furthermore, a wide variety of bacterial strains exist in nature and size and shape of magnetosomes are highly stable within strain and can be very different between strains. Finally, magnetosomes are naturally coated with a bi-lipidic membrane whose content is genetically determined. Lately, researchers have unravelled magnetosomes membrane protein contents, opening the way to create functionalized magnetosomes thanks to fusion of the gene coding for a protein of interest with the gene coding for an abundant protein at magnetosomes membrane.A new alternative path using living organisms to tackle the production of engineered high efficiency molecular imaging probes have been investigated with magneto-tactic bacteria in this PhD. The production and engineering of magnetosomes have been carried out by our partner, the Laboratoire de Bio-energetique Cellulaire (LBC, CEA Cadarache), and will be presented and discussed. We then characterized magnetosomes as contrast agent for high field MRI. We showed they present very promising contrasting properties in vitro, and assessed this observation in vivo by establishing they can be used as efficient

  8. Image-Based Brachytherapy for the Treatment of Cervical Cancer

    International Nuclear Information System (INIS)

    Harkenrider, Matthew M.; Alite, Fiori; Silva, Scott R.; Small, William

    2015-01-01

    Cervical cancer is a disease that requires considerable multidisciplinary coordination of care and labor in order to maximize tumor control and survival while minimizing treatment-related toxicity. As with external beam radiation therapy, the use of advanced imaging and 3-dimensional treatment planning has generated a paradigm shift in the delivery of brachytherapy for the treatment of cervical cancer. The use of image-based brachytherapy, most commonly with magnetic resonance imaging (MRI), requires additional attention and effort by the treating physician to prescribe dose to the proper volume and account for adjacent organs at risk. This represents a dramatic change from the classic Manchester approach of orthogonal radiographic images and prescribing dose to point A. We reviewed the history and currently evolving data and recommendations for the clinical use of image-based brachytherapy with an emphasis on MRI-based brachytherapy

  9. CT/FMT dual-model imaging of breast cancer based on peptide-lipid nanoparticles

    Science.gov (United States)

    Xu, Guoqiang; Lin, Qiaoya; Lian, Lichao; Qian, Yuan; Lu, Lisen; Zhang, Zhihong

    2016-03-01

    Breast cancer is one of the most harmful cancers in human. Its early diagnosis is expected to improve the patients' survival rate. X-ray computed tomography (CT) has been widely used in tumor detection for obtaining three-dimentional information. Fluorescence Molecular Tomography (FMT) imaging combined with near-infrared fluorescent dyes provides a powerful tool for the acquisition of molecular biodistribution information in deep tissues. Thus, the combination of CT and FMT imaging modalities allows us to better differentiate diseased tissues from normal tissues. Here we developed a tumor-targeting nanoparticle for dual-modality imaging based on a biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier. By incorporation of CT contrast agents (iodinated oil) and far-infrared fluorescent dyes (DiR-BOA) into the hydrophobic core of HPPS, we obtained the FMT and CT signals simultaneously. Increased accumulation of the nanoparticles in the tumor lesions was achieved through the effect of the tumor-targeting peptide on the surface of nanoparticle. It resulted in excellent contrast between lesions and normal tissues. Together, the abilities to sensitively separate the lesions from adjacent normal tissues with the aid of a FMT/CT dual-model imaging approach make the targeting nanoparticles a useful tool for the diagnostics of breast cancer.

  10. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps

    Science.gov (United States)

    Sharma, Padmanee; Wagner, Klaus; Wolchok, Jedd D.; Allison, James P.

    2012-01-01

    The US Food and Drug Administration (FDA) recently approved two novel immunotherapy agents, sipuleucel-T and ipilimumab, which showed a survival benefit for patients with metastatic prostate cancer and melanoma, respectively. The mechanisms by which these agents provide clinical benefit are not completely understood. However, knowledge of these mechanisms will be crucial for probing human immune responses and tumour biology in order to understand what distinguishes responders from non-responders. The following next steps are necessary: first, the development of immune-monitoring strategies for the identification of relevant biomarkers; second, the establishment of guidelines for the assessment of clinical end points; and third, the evaluation of combination therapy strategies to improve clinical benefit. PMID:22020206

  11. Dynamic MR imaging of pancreatic cancer

    International Nuclear Information System (INIS)

    Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo

    1994-01-01

    Dynamic MRI was performed on 21 patients with pancreatic duct cell carcinoma. Turbo-FLASH or FLASH3D was performed immediately following rapid bolus injection of gadopentetate dimeglumine, and these FLASH images and conventional spin echo images were evaluated about detectability of the lesion. All images were classified into three groups of detectability of the lesion ; good, fair, and poor. On T 1 weighted image, 23% of cases were 'good' and 48% were evaluated as 'fair'. On the other hand, on dynamic MRI, 62% of cases were 'good' and 33% of cases were evaluated as 'fair'. Both T 2 weighted image and enhanced T 1 weighted image were not useful for depiction of the lesion. Direct comparison between T 1 weighted image and dynamic MRI was also done. In 55% of cases, dynamic MRI was superior to T 1 weighted image and in 40% of cases, dynamic MRI was equal to T 1 weighted image. Thus, dynamic MRI was superior to conventional spin echo images for detection of duct cell carcinoma. In 17 patients of duct cell carcinoma who underwent FLASH3D, contrast/noise ratio (CNR) was calculated before and after injection of gadopentetate dimeglumine. The absolute value of CNR became significantly larger by injection of contrast material. In nine resectable pancreatic carcinomas, two cases of INF α and two cases of medullary type were well depicted. It was concluded that dynamic MRI was useful for evaluation of pancreatic carcinoma. (author)

  12. A nanocomposite of Au-AgI core/shell dimer as a dual-modality contrast agent for x-ray computed tomography and photoacoustic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orza, Anamaria; Wu, Hui; Li, Yuancheng; Mao, Hui, E-mail: hmao@emory.edu, E-mail: Xiangyang.Tang@emory.edu [Department of Radiology and Imaging Sciences and Center for Systems Imaging, Emory University School of Medicine, Atlanta, Georgia 30322 (United States); Yang, Yi; Tang, Xiangyang, E-mail: hmao@emory.edu, E-mail: Xiangyang.Tang@emory.edu [Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia 30322 (United States); Feng, Ting; Wang, Xueding [Department of Biomedical Engineering, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 (United States); Yang, Lily [Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322 (United States)

    2016-01-15

    Purpose: To develop a core/shell nanodimer of gold (core) and silver iodine (shell) as a dual-modal contrast-enhancing agent for biomarker targeted x-ray computed tomography (CT) and photoacoustic imaging (PAI) applications. Methods: The gold and silver iodine core/shell nanodimer (Au/AgICSD) was prepared by fusing together components of gold, silver, and iodine. The physicochemical properties of Au/AgICSD were then characterized using different optical and imaging techniques (e.g., HR- transmission electron microscope, scanning transmission electron microscope, x-ray photoelectron spectroscopy, energy-dispersive x-ray spectroscopy, Z-potential, and UV-vis). The CT and PAI contrast-enhancing effects were tested and then compared with a clinically used CT contrast agent and Au nanoparticles. To confer biocompatibility and the capability for efficient biomarker targeting, the surface of the Au/AgICSD nanodimer was modified with the amphiphilic diblock polymer and then functionalized with transferrin for targeting transferrin receptor that is overexpressed in various cancer cells. Cytotoxicity of the prepared Au/AgICSD nanodimer was also tested with both normal and cancer cell lines. Results: The characterizations of prepared Au/AgI core/shell nanostructure confirmed the formation of Au/AgICSD nanodimers. Au/AgICSD nanodimer is stable in physiological conditions for in vivo applications. Au/AgICSD nanodimer exhibited higher contrast enhancement in both CT and PAI for dual-modality imaging. Moreover, transferrin functionalized Au/AgICSD nanodimer showed specific binding to the tumor cells that have a high level of expression of the transferrin receptor. Conclusions: The developed Au/AgICSD nanodimer can be used as a potential biomarker targeted dual-modal contrast agent for both or combined CT and PAI molecular imaging.

  13. The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

    Science.gov (United States)

    Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

    2000-05-25

    DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

  14. Terahertz imaging applied to cancer diagnosis

    Science.gov (United States)

    Brun, M.-A.; Formanek, F.; Yasuda, A.; Sekine, M.; Ando, N.; Eishii, Y.

    2010-08-01

    We report on terahertz (THz) time-domain spectroscopy imaging of 10 µm thick histological sections. The sections are prepared according to standard pathological procedures and deposited on a quartz window for measurements in reflection geometry. Simultaneous acquisition of visible images enables registration of THz images and thus the use of digital pathology tools to investigate the links between the underlying cellular structure and specific THz information. An analytic model taking into account the polarization of the THz beam, its incidence angle, the beam shift between the reference and sample pulses as well as multiple reflections within the sample is employed to determine the frequency-dependent complex refractive index. Spectral images are produced through segmentation of the extracted refractive index data using clustering methods. Comparisons of visible and THz images demonstrate spectral differences not only between tumor and healthy tissues but also within tumors. Further visualization using principal component analysis suggests different mechanisms as to the origin of image contrast.

  15. High-affinity Near-infrared Fluorescent Small-molecule Contrast Agents for In Vivo Imaging of Prostate-specific Membrane Antigen

    Directory of Open Access Journals (Sweden)

    Valerie Humblet

    2005-10-01

    Full Text Available Surgical resection remains a definitive treatment for prostate cancer. Yet, prostate cancer surgery is performed without image guidance for tumor margin, extension beyond the capsule and lymph node positivity, and without verification of other occult metastases in the surgical field. Recently, several imaging systems have been described that exploit near-infrared (NIR fluorescent light for sensitive, real-time detection of disease pathology intraoperatively. In this study, we describe a high-affinity (9 nM, single nucleophile-containing, small molecule specific for the active site of the enzyme PSMA. We demonstrate production of a tetra-sulfonated heptamethine indocyanine NIR fluorescent derivative of this molecule using a high-yield LC/MS purification strategy. Interestingly, NIR fluorophore conjugation improves affinity over 20-fold, and we provide mechanistic insight into this observation. We describe the preparative production of enzymatically active PSMA using a baculovirus expression system and an adenovirus that co-expresses PSMA and GFP. We demonstrate sensitive and specific in vitro imaging of endogenous and ectopically expressed PSMA in human cells and in vivo imaging of xenograft tumors. We also discuss chemical strategies for improving performance even further. Taken together, this study describes nearly complete preclinical development of an optically based small-molecule contrast agent for image-guided surgery.

  16. Molecular predictors of therapeutic response to specific anti-cancer agents

    Energy Technology Data Exchange (ETDEWEB)

    Spellman, Paul T.; Gray, Joe W.; Sadanandam, Anguraj; Heiser, Laura M.; Gibb, William J.; Kuo, Wen-lin; Wang, Nicholas J.

    2016-11-29

    Herein is described the use of a collection of 50 breast cancer cell lines to match responses to 77 conventional and experimental therapeutic agents with transcriptional, proteomic and genomic subtypes found in primary tumors. Almost all compounds produced strong differential responses across the cell lines produced responses that were associated with transcriptional and proteomic subtypes and produced responses that were associated with recurrent genome copy number abnormalities. These associations can now be incorporated into clinical trials that test subtype markers and clinical responses simultaneously.

  17. Systematic review of natural agents for the management of oral mucositis in cancer patients

    DEFF Research Database (Denmark)

    Yarom, Noam; Ariyawardana, Anura; Hovan, Allan

    2013-01-01

    , suggestion, and no guideline possible. RESULTS: A total of 49 papers across 15 interventions were examined. A new suggestion was developed in favor of systemic zinc supplements administered orally in the prevention of oral mucositis in oral cancer patients receiving radiation therapy or chemoradiation (Level...... III evidence). A recommendation was made against the use of intravenous glutamine for the prevention of oral mucositis in patients receiving high-dose chemotherapy prior to hematopoietic stem cell transplant (Level II evidence). No guideline was possible for any other agent, due to inadequate and...

  18. Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients

    DEFF Research Database (Denmark)

    Jensen, Siri Beier; Jarvis, Virginia; Zadik, Yehuda

    2013-01-01

    : A total of 32 papers across 10 interventions were examined. New suggestions were developed against the use of systemic pilocarpine administered orally for prevention of OM during RT in head and neck cancer patients and in patients receiving high-dose chemotherapy, with or without total body irradiation......, prior to hematopoietic stem cell transplantation. A suggestion was also made against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed due to inadequate and...

  19. Evaluation of microbubbles as contrast agents for ultrasonography and magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Ling Li

    Full Text Available BACKGROUND: Microbubbles (MBs can serve as an ultrasound contrast agent, and has the potential for magnetic resonance imaging (MRI. Due to the relatively low effect of MBs on MRI, it is necessary to develop new MBs that are more suitable for MRI. In this study, we evaluate the properties of SonoVue® and custom-made Fe(3O(4-nanoparticle-embedded microbubbles (Fe(3O(4-MBs in terms of contrast agents for ultrsonography (US and MRI. METHODOLOGY/PRINCIPAL FINDINGS: A total of 20 HepG2 subcutaneous-tumor-bearing nude mice were randomly assigned to 2 groups (i.e., n = 10 mice each group, one for US test and the other for MRI test. Within each group, two tests were performed for each mouse. The contrast agent for the first test is SonoVue®, and the second is Fe(3O(4-MBs. US was performed using a Technos(MPX US system (Esaote, Italy with a contrast-tuned imaging (CnTI™ mode. MRI was performed using a 7.0T Micro-MRI (PharmaScan, Bruker Biospin GmbH, Germany with an EPI-T(2* sequence. The data of signal-to-noise ratio (SNR from the region-of-interest of each US and MR image was calculated by ImageJ (National Institute of Health, USA. In group 1, enhancement of SonoVue® was significantly higher than Fe(3O(4-MBs on US (P0.05. The SNR analysis of the enhancement process reveals a strong negative correlation in both cases (i.e., SonoVue® r = -0.733, Fe(3O(4-MBs r = -0.903, with P<0.05. CONCLUSIONS: It might be important to change the Fe(3O(4-MBs' shell structure and/or the imagining strategy of US to improve the imaging quality of Fe(3O(4-MBs on US. As an intriguing prospect that can be detected by US and MRI, MBs are worthy of further study.

  20. Consistent metagenes from cancer expression profiles yield agent specific predictors of chemotherapy response

    DEFF Research Database (Denmark)

    Li, Qiyuan; Eklund, Aron Charles; Birkbak, Nicolai Juul

    2011-01-01

    : We describe an unsupervised method to extract robust, consistent metagenes from multiple analogous data sets. We applied this method to expression profiles from five "double negative breast cancer" (DNBC) (not expressing ESR1 or HER2) cohorts and derived four metagenes. We assessed these metagenes...... in four similar but independent cohorts and found strong associations between three of the metagenes and agent-specific response to neoadjuvant therapy. Furthermore, we applied the method to ovarian and early stage lung cancer, two tumor types that lack reliable predictors of outcome, and found...... that the metagenes yield predictors of survival for both. CONCLUSIONS: These results suggest that the use of multiple data sets to derive potential biomarkers can filter out data set-specific noise and can increase the efficiency in identifying clinically accurate biomarkers....

  1. Finding more active antioxidants and cancer chemoprevention agents by elongating the conjugated links of resveratrol.

    Science.gov (United States)

    Tang, Jiang-Jiang; Fan, Gui-Juan; Dai, Fang; Ding, De-Jun; Wang, Qi; Lu, Dong-Liang; Li, Ran-Ran; Li, Xiu-Zhuang; Hu, Li-Mei; Jin, Xiao-Ling; Zhou, Bo

    2011-05-15

    Resveratrol is the subject of intense research as a natural antioxidant and cancer chemopreventive agent. There has been a great deal of interest and excitement in understanding its action mechanism and developing analogs with antioxidant and cancer chemoprevention activities superior to that of the parent compound in the past decade. This work delineates that elongation of the conjugated links is an important strategy to improve the antioxidant activity of resveratrol analogs, including hydrogen atom- or electron-donating ability in homogeneous solutions and antihemolysis activity in heterogeneous media. More importantly, C3, a triene bearing 4,4'-dihydroxy groups, surfaced as an important lead compound displaying remarkably increased antioxidant, cytotoxic, and apoptosis-inducing activities compared with resveratrol. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Polyetherimide-grafted Fe₃O₄@SiO2₂ nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging.

    Science.gov (United States)

    Li, Tingting; Shen, Xue; Chen, Yin; Zhang, Chengchen; Yan, Jie; Yang, Hong; Wu, Chunhui; Zeng, Hongjun; Liu, Yiyao

    2015-01-01

    Engineering a safe and high-efficiency delivery system for efficient RNA interference is critical for successful gene therapy. In this study, we designed a novel nanocarrier system of polyethyleneimine (PEI)-modified Fe3O4@SiO2, which allows high efficient loading of VEGF small hairpin (sh)RNA to form Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for VEGF gene silencing as well as magnetic resonance (MR) imaging. The size, morphology, particle stability, magnetic properties, and gene-binding capacity and protection were determined. Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed. The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification. The qualitative and quantitative analysis of cellular internalization into MCF-7 human breast cancer cells by Prussian blue staining and inductively coupled plasma atomic emission spectroscopy analysis, respectively, demonstrated that the Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could be easily internalized by MCF-7 cells, and they exhibited significant inhibition of VEGF gene expression. Furthermore, the MR cellular images showed that the superparamagnetic iron oxide core of our Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could also act as a T2-weighted contrast agent for cancer MR imaging. Our data highlight multifunctional Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.

  3. Classification of normal and abnormal images of lung cancer

    Science.gov (United States)

    Bhatnagar, Divyesh; Tiwari, Amit Kumar; Vijayarajan, V.; Krishnamoorthy, A.

    2017-11-01

    To find the exact symptoms of lung cancer is difficult, because of the formation of the most cancers tissues, wherein large structure of tissues is intersect in a different way. This problem can be evaluated with the help of digital images. In this strategy images will be examined with basic operation of PCA Algorithm. In this paper, GLCM method is used for pre-processing of the snap shots and function extraction system and to test the level of diseases of a patient in its premature stage get to know it is regular or unusual. With the help of result stage of cancer will be evaluated. With the help of dataset and result survival rate of cancer patient can be estimated. Result is based totally on the precise and wrong arrangement of the patterns of tissues.

  4. Development of NMR imaging using CEST agents: application to brain tumor in a rodent model

    International Nuclear Information System (INIS)

    Flament, J.

    2012-01-01

    The study aimed at developing saturation transfer imaging of lipoCEST contrast agents for the detection of angiogenesis in a U87 mouse brain tumor model. A lipoCEST with a sensitivity threshold of 100 pM in vitro was optimized in order to make it compatible with CEST imaging in vivo. Thanks to the development of an experimental setup dedicated to CEST imaging, we evaluated lipoCEST to detect specifically tumor angiogenesis. We demonstrated for the first time that lipoCEST visualization was feasible in vivo in a mouse brain after intravenous injection. Moreover, the integrin α v β 3 over expressed during tumor angiogenesis can be specifically targeted using a functionalized lipoCEST with RGD peptide. The specific association between the RGD-lipoCEST and its target α v β 3 was confirmed by immunohistochemical data and fluorescence microscopy. Finally, in order to tend to a molecular imaging protocol by CEST-MRI, we developed a quantification tool of lipoCEST contrast agents. This tool is based on modeling of proton exchange processes in vivo. By taking into account both B0 and B1 fields inhomogeneities which can dramatically alter CEST contrast, we showed that the accuracy of our quantification tool was 300 pM in vitro. The tool was applied on in vivo data acquired on the U87 mouse model and the maximum concentration of RGD-lipoCEST linked to their molecular targets was evaluated to 1.8 nM. (author) [fr

  5. Nanoparticle delivered vascular disrupting agents (VDAs): use of TNF-alpha conjugated gold nanoparticles for multimodal cancer therapy.

    Science.gov (United States)

    Shenoi, Mithun M; Iltis, Isabelle; Choi, Jeunghwan; Koonce, Nathan A; Metzger, Gregory J; Griffin, Robert J; Bischof, John C

    2013-05-06

    Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors. Unfortunately, there is still an unmet need for VDAs with more favorable safety profiles and fewer side effects. Recent work has demonstrated that conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor necrosis factor alpha, TNF-α). In this report, we show the potential of a gold conjugated TNF-α nanoparticle (NP-TNF) to improve multimodal cancer therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of prostate cancer, we found that NP-TNF disrupts endothelial barrier function and induces a significant increase in vascular permeability within the first 1-2 h followed by a dramatic 80% drop in perfusion 2-6 h after systemic administration. We also demonstrate that the tumor response to the nanoparticle can be verified using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in clinical use. Additionally, multimodal treatment with thermal therapies at the perfusion nadir in the sub- and supraphysiological temperature regimes increases tumor volumetric destruction by over 60% and leads to significant tumor growth delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance thermal therapy in the absence of neutrophil recruitment, suggesting that immune/inflammatory regulation is not central to its power as part of a multimodal approach. Our data demonstrate the potential of nanoparticle-conjugated VDAs to significantly improve cancer therapy by preconditioning tumor vasculature to a secondary insult in a targeted

  6. A Review of Imaging Methods for Prostate Cancer Detection

    Directory of Open Access Journals (Sweden)

    Saradwata Sarkar

    2016-01-01

    Full Text Available Imaging is playing an increasingly important role in the detection of prostate cancer (PCa. This review summarizes the key imaging modalities–multiparametric ultrasound (US, multiparametric magnetic resonance imaging (MRI, MRI-US fusion imaging, and positron emission tomography (PET imaging–-used in the diagnosis and localization of PCa. Emphasis is laid on the biological and functional characteristics of tumors that rationalize the use of a specific imaging technique. Changes to anatomical architecture of tissue can be detected by anatomical grayscale US and T2-weighted MRI. Tumors are known to progress through angiogenesis–-a fact exploited by Doppler and contrast-enhanced US and dynamic contrast-enhanced MRI. The increased cellular density of tumors is targeted by elastography and diffusion-weighted MRI. PET imaging employs several different radionuclides to target the metabolic and cellular activities during tumor growth. Results from studies using these various imaging techniques are discussed and compared.

  7. Medical image diagnosis of liver cancer using artificial intelligence

    International Nuclear Information System (INIS)

    Kondo, Tadashi; Ueno, Junji; Takao, Shoichiro

    2010-01-01

    A revised Group Method of Data Handling (GMDH)-type neural network algorithm using artificial intelligence technology for medical image diagnosis is proposed and is applied to medical image diagnosis of liver cancer. In this algorithm, the knowledge base for medical image diagnosis are used for organizing the neural network architecture for medical image diagnosis. Furthermore, the revised GMDH-type neural network algorithm has a feedback loop and can identify the characteristics of the medical images accurately using feedback loop calculations. The optimum neural network architecture fitting the complexity of the medical images is automatically organized so as to minimize the prediction error criterion defined as Prediction Sum of Squares (PSS). It is shown that the revised GMDH-type neural network can be easily applied to the medical image diagnosis. (author)

  8. Detection and impact on cancer causation of persons exhibiting abnormal susceptibility to carcinogenic agents

    International Nuclear Information System (INIS)

    Gentner, N.E.; Morrison, D.P.

    1988-01-01

    The so-called 'late biological effects', like cancer and genetic consequences and cytotoxic effects (cell killing, at higher doses), were once thought to be an inevitable consequence of a given level of exposure, whether to background radiation, to chemicals in our biosphere, or form spontaneous damage, the 'wear and tear' of living. The measurement of exposure, which results in living organisms in the formation of a related amount of DNA damage, became a surrogate for the end-effects that constitute risk. This may not be entirely appropriate. The concept of 'equal exposure -- equal risk' assumes a homogeneous response of individuals. However, there are subgroups within the human population of persons whose cultured cells exhibit abnormal sensitivity to specific carcinogenic agents and who may be at increased risk of cancer induced by these of similar agents. Modern molecular biology has shown that the majority of the damage in DNA is repaired by enzymatic DNA repair processes that restitute or ameliorate the lesions and restore normal DNA structure and function. In this view, it is not the initial damage that is of consequence but rather the residual damage left after the repair processes have acted. Since the vast majority of the initial DNA damage undergoes repair normally, variation in the efficiency of these processes in different persons may affect the actual risk of exposure. The human side of the cancer causation formula, that is, considerable importance. To understand how human DNA repair processes function, our laboratories at Chalk River have studied 'mutant' human cell strains in tissue culture. Generally, these DNA repair-defective cell strains are derived from individual donors with heritable disorders that are associated with carcinogen-hypersensitivity and cancer-proneness. Such studies, together with related epidemiological research, have highlighted the importance of this new 'human' factor in carcinogenesis

  9. Complications from the use of intravenous gadolinium-based contrast agents for magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Elias Junior, Jorge; Santos, Antonio Carlos dos; Nogueira-Barbosa, Marcello Henrique; Muglia, Valdair Francisco; Koenigkam-Santos, Marcel [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Hospital das Clinicas. Centro de Ciencias das Imagens e Fisica Medica]. E-mail: jejunior@fmrp.usp.br

    2008-07-15

    Gadolinium-based contrast agents are much safer than the iodinated ones; however complications may occur and should be recognized for appropriate orientation and management. The total incidence of adverse reactions to contrast agents in magnetic resonance imaging ranges between 2% and 4%. Cases of severe acute reactions to gadolinium, such as laryngospasm and anaphylactic shock, are rare. Chronic complications secondary to the use of gadolinium also can occur and, recently an association between its use and a rare dermatologic disease occurring in patients with renal failure has been reported. Nephrogenic systemic fibrosis was the subject of an official health notification issued by the American Food and Drug Administration. This progressive disease is characterized by hardened skin with fibrotic nodules and plaques which may involve other parts of the body. Patients who have been affected by this disorder presented chronic renal failure, with metabolic acidosis and had been submitted to magnetic resonance angiography, probably involving exposure to large amounts of intravenous paramagnetic contrast. This review is aimed at presenting a succinct description of the gadolinium-based contrast agent types, possible secondary complications, their preventive measures and management. (author)

  10. Preparation, purification and primary bioevaluation of radioiodinated ofloxacin. An imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Kandil, Shaban; Seddik, Usama; Hussien, Hiba; Shaltot, Mohamed [Atomic Energy Authority, Cairo (Egypt). Cyclotron Project; El-Tabl, Abdou [Monofia Univ. (Egypt). Faculty of Science

    2015-07-01

    The broad-spectrum antibiotic agents have been demonstrated as promising diagnostic tools for early detection of infectious lesions. We set out ofloxacin (Oflo), a second-generation fluoroquinolone, for the radioiodination process. In particular, this was carried out with {sup 125}I via an electrophilic substitution reaction. The radiochemical yield was influenced by different factors; drug concentration, different oxidizing agents, e.g. chloramine-T, iodogen and n-bromosuccinimide, pH of medium, reaction time, temperature and different organic media. These parameters were studied to optimize the best conditions for labeling with ofloxacin. We found that radiolabeling in ethanol medium showed a 70% radiochemical yield of {sup 125}I-ofloxacin. The radioiodination was determined by means of TLC and HPLC. The cold labeled Oflo ({sup 127}I-Oflo) was prepared and controlled by HPLC. The cold labeled Oflo was also confirmed by NMR and MS techniques. Furthermore, biodistribution studies for labeled {sup 125}I-Oflo were examined in two independent groups (3 mice in each one); control and E. Coli-injected (inflamed). The radiotracer showed a good localization in muscle of thigh for inflamed group as compared to control. In conclusion, ofloxacine might be a promising target as an anti-inflammatory imaging agent.

  11. Hyperspectral Imaging for Cancer Surgical Margin Delineation: Registration of Hyperspectral and Histological Images.

    Science.gov (United States)

    Lu, Guolan; Halig, Luma; Wang, Dongsheng; Chen, Zhuo Georgia; Fei, Baowei

    2014-03-12

    The determination of tumor margins during surgical resection remains a challenging task. A complete removal of malignant tissue and conservation of healthy tissue is important for the preservation of organ function, patient satisfaction, and quality of life. Visual inspection and palpation is not sufficient for discriminating between malignant and normal tissue types. Hyperspectral imaging (HSI) technology has the potential to noninvasively delineate surgical tumor margin and can be used as an intra-operative visual aid tool. Since histological images provide the ground truth of cancer margins, it is necessary to warp the cancer regions in ex vivo histological images back to in vivo hyperspectral images in order to validate the tumor margins detected by HSI and to optimize the imaging parameters. In this paper, principal component analysis (PCA) is utilized to extract the principle component bands of the HSI images, which is then used to register HSI images with the corresponding histological image. Affine registration is chosen to model the global transformation. A B-spline free form deformation (FFD) method is used to model the local non-rigid deformation. Registration experiment was performed on animal hyperspectral and histological images. Experimental results from animals demonstrated the feasibility of the hyperspectral imaging method for cancer margin detection.

  12. Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells.

    Science.gov (United States)

    Agarwal, B; Bhendwal, S; Halmos, B; Moss, S F; Ramey, W G; Holt, P R

    1999-08-01

    Beta-hydroxy-beta-methylglutaryl coA reductase inhibitors (HRIs) inhibit isoprenylation of several members of the Ras superfamily of proteins and therefore have important cellular effects, including the reduction of proliferation and increasing apoptosis. Significant toxicity at high doses has precluded the use of HRIs as a monotherapy for cancers. We therefore studied whether combinations of the HRI lovastatin with standard chemotherapeutic agents would augment apoptosis in colon cancer cells. In the colon cancer cell lines SW480, HCT116, LoVo, and HT29, lovastatin induced apoptosis with differing sensitivity. Pretreatment with lovastatin significantly increased apoptosis induced by 5-fluorouracil (5-FU) or cisplatin in all four cell lines. Lovastatin treatment resulted in decreased expression of the antiapoptotic protein bcl-2 and increased the expression of the proapoptotic protein bax. The addition of geranylgeranylpyrophospate (10 microM) prevented lovastatin-induced augmentation of 5-FU and cisplatin-induced apoptosis; mevalonate (100 microM) was partially effective, whereas cotreatment with farnesyl pyrophosphate (100 microM) had no effect. These data imply that lovastatin acts by inhibiting geranylgeranylation and not farnesylation of target protein(s). Our data suggest that lovastatin may potentially be combined with 5-FU or cisplatin as chemotherapy for colon cancers.

  13. Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

    Science.gov (United States)

    Power, D G; Ilson, D H

    2009-11-01

    Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

  14. Developing a cassette microdosing approach to enhance the throughput of PET imaging agent screening.

    Science.gov (United States)

    Xiao, Hao; Sun, Mi