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Sample records for cancer imaging agents

  1. New Agents and Techniques for Imaging Prostate Cancer

    PubMed Central

    Zaheer, Atif; Cho, Steve Y.; Pomper, Martin G.

    2012-01-01

    The successful management of prostate cancer requires early detection, appropriate risk assessment, and optimum treatment. An unmet goal of prostate cancer imaging is to differentiate indolent from aggressive tumors, as treatment may vary for different grades of the disease. Different modalities have been tested to diagnose, stage, and monitor prostate cancer during therapy. This review briefly describes the key clinical issues in prostate cancer imaging and therapy and summarizes the various new imaging modalities and agents in use and on the horizon. PMID:19690043

  2. Combined ultrasound and photoacoustic imaging of pancreatic cancer using nanocage contrast agents

    NASA Astrophysics Data System (ADS)

    Homan, Kimberly; Shah, Jignesh; Gomez, Sobeyda; Gensler, Heidi; Karpiouk, Andrei; Brannon-Peppas, L.; Emelianov, Stanislav

    2009-02-01

    A new metallodielectric nanoparticle consisting of a silica core and silver outer cage was developed for the purpose of enhancing photoacoustic imaging contrast in pancreatic tissue. These nanocages were injected into an ex vivo porcine pancreas and imaged using a combined photoacoustic and ultrasound (PAUS) assembly. This custom-designed PAUS assembly delivered 800 nm light through a fiber optical light delivery system integrated with 128 element linear array transducer operating at 7.5 MHz center frequency. Imaging results prove that the nanocage contrast agents have the ability to enhance photoacoustic imaging contrast. Furthermore, the value of the combined PAUS imaging modality was demonstrated as the location of nanocages against background native tissue was evident. Future applications of these nanocage contrast agents could include targeting them to pancreatic cancer for enhancement of photoacoustic imaging for diagnosis and therapy.

  3. PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy.

    PubMed

    Cheng, Liang; Gong, Hua; Zhu, Wenwen; Liu, Jingjing; Wang, Xiaoyong; Liu, Gang; Liu, Zhuang

    2014-12-01

    Theranostic agents with both imaging and therapeutic functions have attracted enormous interests in cancer diagnosis and treatment in recent years. In this work, we develop a novel theranostic agent based on Prussian blue nanocubes (PB NCs), a clinically approved agent with strong near-infrared (NIR) absorbance and intrinsic paramagnetic property, for in vivo bimodal imaging-guided photothermal therapy. After being coated with polyethylene glycol (PEG), the obtained PB-PEG NCs are highly stable in various physiological solutions. In vivo T1-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) bimodal imaging uncover that PB-PEG NCs after intravenous (i.v.) injection show high uptake in the tumor. Utilizing the strong and super stable NIR absorbance of PB, in vivo cancer treatment is then conducted upon i.v. injection of PB-PEG NCs followed by NIR laser irradiation of the tumors, achieving excellent therapeutic efficacy in a mouse tumor model. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of PB-PEG NCs to mice at our tested dose, which is two-fold of the imaging/therapy dose, within two months. Our work highlights the great promise of Prussian blue with well engineered surface coating as a multifunctional nanoprobe for imaging-guided cancer therapy. PMID:25239041

  4. Advances in molecular imaging: targeted optical contrast agents for cancer diagnostics

    PubMed Central

    Hellebust, Anne; Richards-Kortum, Rebecca

    2012-01-01

    Over the last three decades, our understanding of the molecular changes associated with cancer development and progression has advanced greatly. This has led to new cancer therapeutics targeted against specific molecular pathways; such therapies show great promise to reduce mortality, in part by enabling physicians to tailor therapy for patients based on a molecular profile of their tumor. Unfortunately, the tools for definitive cancer diagnosis – light microscopic examination of biopsied tissue stained with nonspecific dyes – remain focused on the analysis of tissue ex vivo. There is an important need for new clinical tools to support the molecular diagnosis of cancer. Optical molecular imaging is emerging as a technique to help meet this need. Targeted, optically active contrast agents can specifically label extra-and intracellular biomarkers of cancer. Optical images can be acquired in real time with high spatial resolution to image-specific molecular targets, while still providing morphologic context. This article reviews recent advances in optical molecular imaging, highlighting the advances in technology required to improve early cancer detection, guide selection of targeted therapy and rapidly evaluate therapeutic efficacy. PMID:22385200

  5. Current status of nanoparticle-based imaging agents for early diagnosis of cancer and atherosclerosis.

    PubMed

    Saravanakumar, Gurusamy; Kim, Kwangmeyung; Park, Jae Hyung; Rhee, Kyehan; Kwon, Ick Chan

    2009-02-01

    Endothelium plays a vital role in various vascular functions, and its dysfunction is a key underlying process closely related to diverse array of diseases such as atherosclerosis and tumor. Therefore, early detection of endothelial dysfunction at the functional or molecular level is of high importance for effective therapy. Recent advances in nanotechnology and our understanding in cellular and molecular biology have provided various biomedical imaging modalities and nanosized multimodal imaging agents. Multimodal nanoparticles that encompass the targeting ligands and magnetic/optical imaging labels enable us to visualize the pathophysiological process of various diseases using multiple imaging techniques. To visualize the specific pathogenic process at the molecular level, the imaging probe needs to be surface-functionalized with specific affinity ligands such as monoclonal antibodies (mAb). Combining the functional imaging agents along with therapeutic drugs has great potential for effective early detection, accurate diagnosis, and treatment of disease. The current review will highlight the application of various nanoparticle-based imaging agents and their recent developments in diagnosing endothelium dysfunction with a special emphasis on atherosclerosis and cancer.

  6. Mesoporous silica nanoparticles as a breast cancer targeting contrast agent for ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Milgroom, Andrew Carson

    Current clinical use of ultrasound for breast cancer diagnostics is strictly limited to a role as a supplementary detection method to other modalities, such as mammography or MRI. A major reason for ultrasound’s role as a secondary method is its inability to discern between cancerous and non-cancerous bodies of similar density, like dense calcifications or benign fibroadenomas. Its detection capabilities are further diminished by the variable density of the surrounding breast tissue with the progression of age. Preliminary studies suggest that mesoporous silica nanoparticles (MSNs) are a good candidate as an in situ contrast agent for ultrasound. By tagging the silica particle surface with the cancer-targeting antibody trastuzumab (Herceptin), suspect regions of interest can be better identified in real time with standard ultrasound equipment. Once the silica-antibody conjugate is injected into the bloodstream and enters the cancerous growth’s vasculature, the antibody arm will bind to HER2, a cell surface receptor known to be dysfunctional or overexpressed in certain types of breast cancer. As more particles aggregate at the cell surface, backscatter of the ultrasonic waves increases as a result of the higher porous silica concentration. This translates to an increased contrast around the lesion boundary. Tumor detection through ultrasound contrast enhancement provides a tremendous advantage over current cancer diagnostics because is it significantly cheaper and can be monitored in real time. Characterization of MCM-41 type MSNs suggests that these particles have sufficient stability and particle size distribution to penetrate through fenestrated tumor vasculature and accumulate in HER2+ breast cancer cells through the enhanced permeation and retention (EPR) effect. A study of acoustic properties showed that particle concentration is linearly correlated to image contrast in clinical frequency-range ultrasound, although less pronounced than typical microbubble

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

    NASA Astrophysics Data System (ADS)

    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 (< 1 g) and early stage (≤ stage II) masses to prevent rapid progression to late stages and ultimately death. The second challenge is differentiating malignant from benign tissue to avoid costly and invasive surgeries (19.5 surgeries are required to find 1 cancer even with multiple screenings). First-line diagnostic tests such as ultrasound and serum marker tests (e.g. CA-125) aid in diagnosis but they lack the sensitivity and specificity required to overcome both challenges. Magnetic resonance imaging (MRI), a second-line diagnostic aided by gadolinium based contrast agents (CAs), offers higher resolution pictures for classifying indeterminate ovarian masses. But as currently practiced, MRI still lacks the sensitivity and specificity required to alter patient outcomes. In this work we develop a new paradigm for EOC diagnosis that targets the 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.

  8. Computed Tomography Imaging of Primary Lung Cancer in Mice Using a Liposomal-Iodinated Contrast Agent

    PubMed Central

    Badea, Cristian T.; Athreya, Khannan K.; Espinosa, Gabriela; Clark, Darin; Ghafoori, A. Paiman; Li, Yifan; Kirsch, David G.; Johnson, G. Allan; Annapragada, Ananth; Ghaghada, Ketan B.

    2012-01-01

    Purpose To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer. Methods Primary lung cancers with mutations in K-ras alone (KrasLA1) or in combination with p53 (LSL-KrasG12D;p53FL/FL) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules. Results A good correlation was seen between volume and diameter-based assessment of nodules (R2>0.8) for both lung cancer models. The LSL-KrasG12D;p53FL/FL model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in KrasLA1 mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-KrasG12D;p53FL/FL mice compared to nodules in KrasLA1 mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules. Conclusions The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring. PMID:22485175

  9. Optical contrast agents and imaging systems for detection and diagnosis of cancer

    PubMed Central

    Pierce, Mark C.; Javier, David J.; Richards-Kortum, Rebecca

    2010-01-01

    Molecular imaging has rapidly emerged as a discipline with the potential to impact fundamental biomedical research and clinical practice. Within this field, optical imaging offers several unique capabilities, based on the ability of cells and tissues to effect quantifiable changes in the properties of visible and near-infrared light. Beyond endogenous optical properties, the development of molecularly targeted contrast agents enables disease-specific morphologic and biochemical processes to be labeled with unique optical signatures. Optical imaging systems can then provide real-time visualization of pathophysiology at spatial scales from the sub-cellular to whole organ levels. In this article, we review fundamental techniques and recent developments in optical molecular imaging, emphasizing laboratory and clinical systems that aim to visualize the microscopic and macroscopic hallmarks of cancer. PMID:18712733

  10. Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging.

    PubMed

    Xue, Shenghui; Yang, Hua; Qiao, Jingjuan; Pu, Fan; Jiang, Jie; Hubbard, Kendra; Hekmatyar, Khan; Langley, Jason; Salarian, Mani; Long, Robert C; Bryant, Robert G; Hu, Xiaoping Philip; Grossniklaus, Hans E; Liu, Zhi-Ren; Yang, Jenny J

    2015-05-26

    With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd(3+) toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd(3+) and a 10(11)-fold greater selectivity for Gd(3+) over Zn(2+) compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol(-1)⋅s(-1)/89.2 mmol(-1)⋅s(-1) per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

  11. Development of novel epidermal growth receptor-basedradiopharmaceuticals: Imaging agents for breast cancer

    SciTech Connect

    Van Brocklin, Henry F.

    2001-09-25

    The goal of this research was to develop epidermal growthfactor receptor (EGFR) nuclear medicine breast cancer imaging agents. Ourapproach was to synthesize small molecule inhibitors of the EGFR tyrosinekinase (tk) suitable for labeling with single photon or positron-emittingradioisotopes and evaluate the imaging potential of these new molecules.We have synthesized and fully characterized 22 quinazoline compounds. Allcompounds inhibit EGFR tk phosphorylation activity in the nanomolarrange. All compounds tested exhibited specificity for the EGFR tk versusthe ErbB2 and ErbB4 tyrosine kinases. A radiometric binding assay usingan iodine-125 labeled quinazoline was developed to determine the affinityof the quinazolines for the EGFR tk ATP binding site. The affinitiesranged from 0.4-51 nM. The octanol/water partition coefficients (Log P;lipophilicity) of the new compounds ranged from 2.2-5.5. Six compoundshave been labeled with fluorine-18. Biodistribution in EGFRoverexpressing tumor bearing mice demonstrated tumor uptake buthighlighted delivery and metabolism issues. The 2-fluoro quinazoline wasnot metabolized in an in vitro hepatocyte study. From this work a breadthof agent characteristics was created establishing the foundation forfuture research toward the optimal EGFR imaging agent.

  12. Estrogen Receptor-Targeted Contrast Agents for Molecular Magnetic Resonance Imaging of Breast Cancer Hormonal Status.

    PubMed

    Pais, Adi; Degani, Hadassa

    2016-01-01

    The estrogen receptor (ER) α is overexpressed 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 and in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging (MRI) 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 upregulating cMyc oncogene and downregulating 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 revealed that this

  13. Estrogen Receptor-Targeted Contrast Agents for Molecular Magnetic Resonance Imaging of Breast Cancer Hormonal Status

    PubMed Central

    Pais, Adi; Degani, Hadassa

    2016-01-01

    The estrogen receptor (ER) α is overexpressed 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 and in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging (MRI) 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 upregulating cMyc oncogene and downregulating 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 revealed that this

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    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.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. Electronic supplementary information (ESI) available: Competition studies with free apoferritin, Fig. S1; APO-FITC intracellular distribution by

  16. Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent

    PubMed Central

    Kossatz, Susanne; Brand, Christian; Gutiontov, Stanley; Liu, Jonathan T. C.; Lee, Nancy Y.; Gönen, Mithat; Weber, Wolfgang A.; Reiner, Thomas

    2016-01-01

    Earlier and more accurate detection of oral squamous cell carcinoma (OSCC) is essential to improve the prognosis of patients and to reduce the morbidity of surgical therapy. Here, we demonstrate that the nuclear enzyme Poly(ADP-ribose)Polymerase 1 (PARP1) is a promising target for optical imaging of OSCC with the fluorescent dye PARPi-FL. In patient-derived OSCC specimens, PARP1 expression was increased 7.8 ± 2.6-fold when compared to normal tissue. Intravenous injection of PARPi-FL allowed for high contrast in vivo imaging of human OSCC models in mice with a surgical fluorescence stereoscope and high-resolution imaging systems. The emitted signal was specific for PARP1 expression and, most importantly, PARPi-FL can be used as a topical imaging agent, spatially resolving the orthotopic tongue tumors in vivo. Collectively, our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve as a screening tool and help to guide surgical resections. PMID:26900125

  17. An imaging agent to detect androgen receptor and its active splice variants in prostate cancer

    PubMed Central

    Imamura, Yusuke; Tien, Amy H.; Pan, Jinhe; Leung, Jacky K.; Banuelos, Carmen A.; Jian, Kunzhong; Wang, Jun; Mawji, Nasrin R.; Fernandez, Javier Garcia; Lin, Kuo-Shyan; Andersen, Raymond J.; Sadar, Marianne D.

    2016-01-01

    Constitutively active splice variants of androgen receptor (AR-Vs) lacking ligand-binding domain (LBD) are a mechanism of resistance to androgen receptor LBD–targeted (AR LBD–targeted) therapies for metastatic castration-resistant prostate cancer (CRPC). There is a strong unmet clinical need to identify prostate cancer patients with AR-V–positive lesions to determine whether they will benefit from further AR LBD–targeting therapies or should receive taxanes or investigational drugs like EPI-506 or galeterone. Both EPI-506 (NCT02606123) and galeterone (NCT02438007) are in clinical trials and are proposed to have efficacy against lesions that are positive for AR-Vs. AR activation function-1 (AF-1) is common to the N-terminal domains of full-length AR and AR-Vs. Here, we provide proof of concept for developing imaging compounds that directly bind AR AF-1 to detect both AR-Vs and full-length AR. 123I-EPI-002 had specific binding to AR AF-1, which enabled direct visualization of CRPC xenografts that express full-length AR and AR-Vs. Our findings highlight the potential of 123I-EPI-002 as an imaging agent for the detection of full-length AR and AR-Vs in CRPC. PMID:27525313

  18. Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging.

    PubMed

    Mouffouk, Fouzi; Simão, Teresa; Dornelles, Daniel F; Lopes, André D; Sau, Pablo; Martins, Jorge; Abu-Salah, Khalid M; Alrokayan, Salman A; Rosa da Costa, Ana M; dos Santos, Nuno R

    2015-01-01

    Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI.

  19. Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents

    PubMed Central

    John, Renu; Nguyen, Freddy T.; Kolbeck, Kenneth J.; Chaney, Eric J.; Marjanovic, Marina; Suslick, Kenneth S.; Boppart, Stephen A.

    2012-01-01

    Purpose In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications. Procedures A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to αvβ3 integrin receptors that are over-expressed in tumors and atherosclerotic lesions. Results These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres. Conclusions Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance. PMID:21298354

  20. A Compressive Sensing Approach for 3D Breast Cancer Microwave Imaging With Magnetic Nanoparticles as Contrast Agent.

    PubMed

    Bevacqua, Martina T; Scapaticci, Rosa

    2016-02-01

    In microwave breast cancer imaging magnetic nanoparticles have been recently proposed as contrast agent. Due to the non-magnetic nature of human tissues, magnetic nanoparticles make possible the overcoming of some limitations of conventional microwave imaging techniques, thus providing reliable and specific diagnosis of breast cancer. In this paper, a Compressive Sensing inspired inversion technique is introduced for the reconstruction of the magnetic contrast induced within the tumor. The applicability of Compressive Sensing theory is guaranteed by the fact that the underlying inverse scattering problem is linear and the searched magnetic perturbation is sparse. From the numerical analysis, performed in realistic conditions in 3D geometry, it has been pointed out that the adoption of this new tool allows improving resolution and accuracy of the reconstructions, as well as reducing the number of required measurements.

  1. GRPR-targeted Protein Contrast Agents for Molecular Imaging of Receptor Expression in Cancers by MRI

    PubMed Central

    Pu, Fan; Qiao, Jingjuan; Xue, Shenghui; Yang, Hua; Patel, Anvi; Wei, Lixia; Hekmatyar, Khan; Salarian, Mani; Grossniklaus, Hans E.; Liu, Zhi-Ren; Yang, Jenny J.

    2015-01-01

    Gastrin-releasing peptide receptor (GRPR) is differentially expressed on the surfaces of various diseased cells, including prostate and lung cancer. However, monitoring temporal and spatial expression of GRPR in vivo by clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capability and tumor penetration. Here, we report the development of a GRPR-targeted MRI contrast agent by grafting the GRPR targeting moiety into a scaffold protein with a designed Gd3+ binding site (ProCA1.GRPR). In addition to its strong binding affinity for GRPR (Kd = 2.7 nM), ProCA1.GRPR has high relaxivity (r1 = 42.0 mM−1s−1 at 1.5 T and 25 °C) and strong Gd3+ selectivity over physiological metal ions. ProCA1.GRPR enables in vivo detection of GRPR expression and spatial distribution in both PC3 and H441 tumors in mice using MRI. ProCA1.GRPR is expected to have important preclinical and clinical implications for the early detection of cancer and for monitoring treatment effects. PMID:26577829

  2. Harnessing the power of cell-penetrating peptides: activatable carriers for targeting systemic delivery of cancer therapeutics and imaging agents.

    PubMed

    MacEwan, Sarah R; Chilkoti, Ashutosh

    2013-01-01

    Targeted delivery of cancer therapeutics and imaging agents aims to enhance the accumulation of these molecules in a solid tumor while avoiding uptake in healthy tissues. Tumor-specific accumulation has been pursued with passive targeting by the enhanced permeability and retention effect, as well as with active targeting strategies. Active targeting is achieved by functionalization of carriers to allow specific interactions between the carrier and the tumor environment. Functionalization of carriers with ligands that specifically interact with overexpressed receptors on cancer cells represents a classic approach to active tumor targeting. Cell-penetrating peptides (CPPs) provide a non-specific and receptor-independent mechanism to enhance cellular uptake that offers an exciting alternative to traditional active targeting approaches. While the non-specificity of CPP-mediated internalization has the intriguing potential to make this approach applicable to a wide range of tumor types, their promiscuity is, however, a significant barrier to their clinical utility for systemically administered applications. Many approaches have been investigated to selectively turn on the function of systemically delivered CPP-functionalized carriers specifically in tumors to achieve targeted delivery of cancer therapeutics and imaging agents.

  3. J-aggregate Nanoparticles as Photoacoustic Contrast Agents for Prostate Cancer Imaging

    NASA Astrophysics Data System (ADS)

    Shakiba, Mojdeh

    Management of early stage prostate cancer (PCa) is plagued with the dilemma between active surveillance that risks progression, and aggressive treatments of potentially indolent disease that significantly reduces quality of life. This results from the inability of current diagnostic techniques to accurately distinguish between indolent and aggressive disease, which has resulted in overtreatment of PCa. Photoacoutic imaging allows for imaging of specific molecular constituents in tissue. To enable for its use in PCa imaging, we designed a novel organic nanoparticle that combines the unique spectral properties and efficient photon capture of nature's photosynthetic apparatus with the stable and specific delivery offered by nanoparticles. These Jaggregate nanoparticles are shown to produce an intense, narrow photo acoustic signal and to have nanoparticle-dependent photonic properties that enable for assessment of the state of the particle. Preliminary assessment of their use in an orthotopic PCa model showed accumulation in and delineation of the tumor boundary.

  4. Molecular imaging of EGFR/HER2 cancer biomarkers by protein MRI contrast agents

    PubMed Central

    Qiao, Jingjuan; Xue, Shenghui; Pu, Fan; White, Natalie; Jiang, Jie; Liu, Zhi-Ren

    2014-01-01

    Epidermal growth factor receptor (EGFR) and HER2 are major prognosis biomarkers and drug targets overexpressed in various types of cancer cells. There is a pressing need to develop MRI contrast agents capable of enhancing the contrast between normal tissues and tumors with high relaxivity, capable of targeting tumors, and with high intratumoral distribution and minimal toxicity. In this review, we first discuss EGFR signaling and its role in tumor progression as a major drug target. We then report our progress in the development of protein contrast agents with significant improvement of both r1 and r2 relaxivities, pharmacokinetics, in vivo retention time, and in vivo dose efficiency. Finally, we report our effort in the development of EGFR-targeted protein contrast agents with the capability to cross the endothelial boundary and with good tissue distribution across the entire tumor mass. The noninvasive capability of MRI to visualize spatially and temporally the intratumoral distribution as well as quantify the levels of EGFR and HER2 would greatly improve our ability to track changes of the biomarkers during tumor progression, monitor treatment efficacy, aid in patient selection, and further develop novel targeted therapies for clinical application. PMID:24366655

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

    PubMed Central

    Day, Emily S; Bickford, Lissett R; Slater, John H; Riggall, Nicholas S; Drezek, Rebekah A; West, Jennifer L

    2010-01-01

    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 over-express 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. PMID:20957166

  6. Cancer nanotechnology: a new commercialization pipeline for diagnostics, imaging agents, and therapies

    NASA Astrophysics Data System (ADS)

    Ptak, Krzysztof; Farrell, Dorothy; Hinkal, George; Panaro, Nicholas J.; Hook, Sara; Grodzinski, Piotr

    2011-06-01

    Nanotechnology - the science and engineering of manipulating matter at the molecular scale to create devices with novel chemical, physical and biological properties - has the potential to radically change oncology. Research sponsored by the NCI Alliance for Nanotechnology in Cancer has led to the development of nanomaterials as platforms of increasing complexity and devices of superior sensitivity, speed and multiplexing capability. Input from clinicians has guided researchers in the design of technologies to address specific needs in the areas of cancer therapy and therapeutic monitoring, in vivo imaging, and in vitro diagnostics. The promising output from the Alliance has led to many new companies being founded to commercialize their nanomedical product line. Furthermore, several of these technologies, which are discussed in this paper, have advanced to clinically testing.

  7. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer

    PubMed Central

    Ghaghada, Ketan B.; Sato, Amy F.; Starosolski, Zbigniew A.; Berg, John; Vail, David M.

    2016-01-01

    Objectives Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. Materials and Methods The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Results Liposomal-I resulted in significant (p < 0.05) enhancement and uniform opacification of the vascular compartment. Non-renal, reticulo-endothelial systemic clearance of the contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. Conclusions The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small

  8. Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer

    PubMed Central

    Hu, Jia; Feng, Yi; Hasegawa, Kosei; Peng, Xiaohui; Duan, Xingmei; Zhao, Aizhi; Mikitsh, John L.; Muzykantov, Vladimir R.; Chacko, Ann-Marie; Pryma, Daniel A.; Dunn, Steven M.; Coukos, George

    2014-01-01

    Tumor Endothelial Marker-1 (TEM1/CD248) is a tumor vascular marker with high therapeutic and diagnostic potentials. Immuno-imaging with TEM1-specific antibodies can help to detect cancerous lesions, monitor tumor responses, and select patients that are most likely to benefit from TEM1-targeted therapies. In particular, near infrared(NIR) optical imaging with biomarker-specific antibodies can provide real-time, tomographic information without exposing the subjects to radioactivity. To maximize the theranostic potential of TEM1, we developed a panel of all human, multivalent Fc-fusion proteins based on a previously identified single chain antibody (scFv78) that recognizes both human and mouse TEM1. By characterizing avidity, stability, and pharmacokinectics, we identified one fusion protein, 78Fc, with desirable characteristics for immuno-imaging applications. The biodistribution of radiolabeled 78Fc showed that this antibody had minimal binding to normal organs, which have low expression of TEM1. Next, we developed a 78Fc-based tracer and tested its performance in different TEM1-expressing mouse models. The NIR imaging and tomography results suggest that the 78Fc-NIR tracer performs well in distinguishing mouse- or human-TEM1 expressing tumor grafts from normal organs and control grafts in vivo. From these results we conclude that further development and optimization of 78Fc as a TEM1-targeted imaging agent for use in clinical settings is warranted. PMID:25051365

  9. Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

    NASA Astrophysics Data System (ADS)

    Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing; Yang, Jenny J.

    2016-06-01

    Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 +/- 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 +/- 0.1 × 10-22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM-1 s-1 and r2 of 37.9 mM-1 s-1 per Gd (55.2 and 75.8 mM-1 s-1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM-1 s-1 per Gd (188.0 mM-1 s-1 per molecule) and r1 of 18.6 mM-1 s-1 per Gd (37.2 mM-1 s-1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI.Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high

  10. Non-carrier-added 186, 188Re labeled 17a-ethynylestradiol : a potential breast cancer imaging and therapy agent

    SciTech Connect

    Fassbender, M. E.; Phillips, Dennis R.; Peterson, E. J.; Ott, K. C.; Arterburn, J. B.

    2001-01-01

    Receptor-targeted radiopharmaceuticals constitute potential agents for the diagnosis and therapy of cancer. Breast cancer is the most prevalent form of diagnosed cancer in women in the United States, and it accounts for the second highest number of cases of cancer fatalities (1). In Approximately two-thirds of the breast tumors, estrogen and progesterone steroid hormone receptors can be found. Such tumors can often be treated successfully with anti-estrogen hormone therapy (2). Hence, the ability to determine the estrogen receptor (ER) contend of the breast tumor is essential for making the most appropriate choice of treatment for the patient. Along with this diagnostic aspect, steroid-based radiopharmaceuticals with high specific activity offer an encouraging prospect for therapeutic applications: {sup 186,188}Re labeled steroids binding to receptors expressed by cancer cells appear to be potential agents for the irradiation of small to medium-sized tumors. {sup 186}Re has been regarded as an ideal radionuclide for radiotherapy due to its appropriate half-live of 90 h and {beta}-energy of 1.07 MeV. Moreover, the {gamma}-emission of 137 keV that allows in vivo imaging while in therapy is an additional bonus. {sup 188}Re is obtained from a {sup 188}W/{sup 188}Re radionuclide generator system, representing an advantage for availability at radiopharmacy laboratory by daily elution. In addition, {sup 188}Re emits high energy beta particles with an average energy of 769 keV, and the emission of the 155 keV allows simultaneous imaging for biodistribution evaluation in vivo. In order to avoid competitive saturation of the binding sites of the ligand receptor, Re labeled steroids with high specific activity are required, and the removal of all excess unlabeled ligands is mandatory. {sup 188}Re is eluted from a {sup 188}W/{sup 188}Re generator produced and provided by Oak Ridge National Laboratory (3). This paper outlines the solid phase-supported preparation of an n

  11. Quantum dots decorated gold nanorod as fluorescent-plasmonic dual-modal contrasts agent for cancer imaging.

    PubMed

    Wu, Qiong; Chen, Lu; Huang, Liang; Wang, Jing; Liu, Jiawei; Hu, Chao; Han, Heyou

    2015-12-15

    Constructing integrative optical bioprobe with both fluorophores and plasmonic functional groups is of particular interest in precise co-localized bio-imaging probe development. Herein, we fabricated a novel hierarchical complex nanoparticle with fluorescent and plasmonic components spatially separated, which is composed of highly brilliant CdSe/CdS/ZnS QDs decorated gold nanorod (AuNR) with silicon coating. This complex structure served as an efficient dual-modality imaging contrast agent, where the potential fluorescence resonance energy transfer (FRET) between QDs and AuNR was avoided by the intermediate silica layer as well as minimized spectral overlap between QDs and AuNRs. The high-density loading of QDs was achieved by thiol-metal affinity driven assembly of hydrophobic QDs with thiolated AuNR@SiO2 substrate, which is able to show a strong fluorescence emission. After amphiphilic organosilica-mediated phase transferring and functionalization with transferrin (Tf), these nanoparticles entered A549 cells and exhibited high contrasting fluorescent and dark-field signals for co-localized cancer cells imaging. The results demonstrate that these nanoparticles are potential candidates as dual modal probes for fluorescence and dark-field image.

  12. N-Terminal Labeling Of Filamentous Phage To Create Cancer Marker Imaging Agents

    PubMed Central

    Carrico, Zachary M.; Farkas, Michelle E.; Zhou, Yu; Hsiao, Sonny C.; Marks, James D.; Chokhawala, Harshal; Clark, Douglas S.; Francis, Matthew B.

    2012-01-01

    We report a convenient new technique for the labeling of filamentous phage capsid proteins. Previous reports have shown that phage coat protein residues can be modified, but the lack of chemically distinct amino acids in the coat protein sequences makes it difficult to attach high levels of synthetic molecules without altering the binding capabilities of the phage. To modify the phage with polymer chains, imaging groups, and other molecules, we have developed chemistry to convert the N-terminal amines of the ~4,200 coat proteins into ketone groups. These sites can then serve as chemospecific handles for the attachment of alkoxyamine groups through oxime formation. Specifically, we demonstrate the attachment of fluorophores and up to 3,000 molecules of 2 kD poly(ethylene glycol) (PEG2k) to each of the phage capsids without significantly affecting the binding of phage-displayed antibody fragments to EGFR and HER2 (two important epidermal growth factor receptors). We also demonstrate the utility of the modified phage for the characterization of breast cancer cells using multicolor fluorescence microscopy. Due to the widespread use of filamentous phage as display platforms for peptide and protein evolution, we envision that the ability to attach large numbers of synthetic functional groups to their coat proteins will be of significant value to the biological and materials communities. PMID:22830952

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

    NASA Astrophysics Data System (ADS)

    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.

  14. GCPII Imaging and Cancer

    PubMed Central

    Foss, C.A.; Mease, R.C.; Cho, S.Y.; Kim, H.J.; Pomper, M.G.

    2014-01-01

    Glutamate carboxypeptidase II (GCPII) in the central nervous system is referred to as the prostate-specific membrane antigen (PSMA) in the periphery. PSMA serves as a target for imaging and treatment of prostate cancer and because of its expression in solid tumor neovasculature has the potential to be used in this regard for other malignancies as well. An overview of GCPII/PSMA in cancer, as well as a discussion of imaging and therapy of prostate cancer using a wide variety of PSMA-targeting agents is provided. PMID:22304713

  15. Exploring a new SPION-based MRI contrast agent with excellent water-dispersibility, high specificity to cancer cells and strong MR imaging efficacy.

    PubMed

    Ma, Xuehua; Gong, An; Chen, Bin; Zheng, Jianjun; Chen, Tianxiang; Shen, Zheyu; Wu, Aiguo

    2015-02-01

    Advances in contrast agents have greatly enhanced the sensitivity of magnetic resonance imaging (MRI) technique for early diagnosis of cancer. However, the commercial superparamagnetic iron oxide nanoparticles (SPION)-based contrast agents synthesized by co-precipitation method are not monodisperse with irregular morphologies and ununiform sizes. Other reported SPION-based contrast agents synthesized by solvothermal method or thermal decomposition method are limited by the bad water-dispersibility and low specificity to cancer cells. Herein, we propose a new strategy for exploring SPION-based MRI contrast agents with excellent water-dispersibility and high specificity to cancer cells. The SPION was synthesized by a polyol method and then entrapped into albumin nanospheres (AN). After that, a ligand folic acid (FA) was conjugated onto the surface of the AN to construct a SPION-AN-FA composite. The transmission electron microscope (TEM) and dynamic light scattering (DLS) results indicate that the SPION-AN-FA has a spherical shape, a uniform size and an excellent water-dispersibility (polydispersity index (PDI) <0.05). The results of laser scanning confocal microscope (LSCM) and flow cytometry demonstrate that the SPION-AN-FA nanoparticles are highly specific to MCF-7 and SPC-A-1 cells due to the recognition of ligand FA and folate receptor α (FRα). The r2/r1 value of SPION-AN-FA is around 40, which is much higher than that of Resovist(®) indicating that our SPION-AN-FA has a stronger T2 shortening effect. The T2-weighted images of MCF-7 cells incubated with SPION-AN-FA are significantly darker than those of MCF-7 cells incubated with AN, indicating that our SPION-AN-FA has a strong MR imaging efficacy. In view of the excellent water-dispersibility, the high specificity to cancer cells and the strong MR imaging efficacy, our SPION-AN-FA can be used as a negative MR contrast agent.

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

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

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

    2015-02-20

    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. PMID:25642737

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Imaging and cancer: a review.

    PubMed

    Fass, Leonard

    2008-08-01

    Multiple biomedical imaging techniques are used in all phases of cancer management. Imaging forms an essential part of cancer clinical protocols and is able to furnish morphological, structural, metabolic and functional information. Integration with other diagnostic tools such as in vitro tissue and fluids analysis assists in clinical decision-making. Hybrid imaging techniques are able to supply complementary information for improved staging and therapy planning. Image guided and targeted minimally invasive therapy has the promise to improve outcome and reduce collateral effects. Early detection of cancer through screening based on imaging is probably the major contributor to a reduction in mortality for certain cancers. Targeted imaging of receptors, gene therapy expression and cancer stem cells are research activities that will translate into clinical use in the next decade. Technological developments will increase imaging speed to match that of physiological processes. Targeted imaging and therapeutic agents will be developed in tandem through close collaboration between academia and biotechnology, information technology and pharmaceutical industries.

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

    PubMed Central

    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 10th 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 (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast 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. PMID:27570547

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

    PubMed

    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 (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast 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. PMID:27570547

  2. Hypoxia imaging agents labeled with positron emitters.

    PubMed

    Hoigebazar, Lathika; Jeong, Jae Min

    2013-01-01

    Imaging hypoxia using positron emission tomography (PET) is of great importance for therapy of cancer. [(18)F]Fluoromisonidazole (FMISO) was the first PET agent for hypoxia imaging, and various radiolabeled nitroimidazole derivatives such as [(18)F]fluoroerythronitroimidazole (FETNIM), [(18)F]1-α-D: -(2-deoxy-2-fluoroarabinofuranosyl)-2-nitroimidazole (FAZA), [(18)F]2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF-5), and [(18)F]fluoroetanidazole (FETA) have been developed successively. To overcome the high cost of cyclotron installation, (68)Ga-labeled nitroimidazole derivatives also have been developed. Another important hypoxia imaging agent is (64)Cu-diacetyl-bis(N (4)-methylthiosemicarbazone) ((64)Cu-ATSM), which can distribute in cancer tissue rapidly due to high lipophilicity. However, its application is limited due to high cost of radionuclide production. Although various hypoxia imaging agents have been reported and tested, hypoxia PET images still have to be improved, because of the low blood flow in hypoxic tissues and resulting low uptake of the agents.

  3. Synthesis and characterization of a porphyrazine–Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model

    PubMed Central

    Trivedi, Evan R.; Ma, Zhidong; Waters, Emily A.; Macrenaris, Keith W.; Subramanian, Rohit; Barrettf, Anthony G. M.; Meade, Thomas J.; Hoffman, Brian M.

    2015-01-01

    Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu–Pz–Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or ‘click’ chemistry between an azide functionalized Pz and alkyne functionalized DOTA–Gd(III) analog for use as an MRI contrast agent. This agent, Cu–Pz–Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1 = 11.5 mm−1 s−1) that is approximately four times higher than that of a clinically used monomeric Gd (III) contrast agent, DOTA–Gd(III). Breast tumor cells (MDA-MB-231) associate with Cu–Pz–Gd(III) in vitro, where significant contrast enhancement (9.336 ± 0.335 contrast-to-noise ratio) is observed in phantom cell pellet MR images. This novel contrast agent was administered in vivo to an orthotopic breast tumor model in athymic nude mice and MR images were collected. The average T1 of tumor regions in mice treated with 50 mg kg−1 Cu–Pz–Gd (III) decreased relative to saline-treated controls. Furthermore, the decrease in T1 was persistent relative to mice treated with the monomeric Gd(III) contrast agent. An ex vivo biodistribution study confirmed that Cu–Pz–Gd(III) accumulates in the tumors and is rapidly cleared, primarily through the kidneys. Differential accumulation and T1 enhancement by Cu–Pz–Gd(III) in the tumor's core relative to the periphery offer preliminary evidence that this agent would find application in the imaging of necrotic tissue. PMID:24706615

  4. Molecular Imaging of Pancreatic Cancer with Antibodies

    PubMed Central

    2015-01-01

    Development of novel imaging probes for cancer diagnostics remains critical for early detection of disease, yet most imaging agents are hindered by suboptimal tumor accumulation. To overcome these limitations, researchers have adapted antibodies for imaging purposes. As cancerous malignancies express atypical patterns of cell surface proteins in comparison to noncancerous tissues, novel antibody-based imaging agents can be constructed to target individual cancer cells or surrounding vasculature. Using molecular imaging techniques, these agents may be utilized for detection of malignancies and monitoring of therapeutic response. Currently, there are several imaging modalities commonly employed for molecular imaging. These imaging modalities include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, optical imaging (fluorescence and bioluminescence), and photoacoustic (PA) imaging. While antibody-based imaging agents may be employed for a broad range of diseases, this review focuses on the molecular imaging of pancreatic cancer, as there are limited resources for imaging and treatment of pancreatic malignancies. Additionally, pancreatic cancer remains the most lethal cancer with an overall 5-year survival rate of approximately 7%, despite significant advances in the imaging and treatment of many other cancers. In this review, we discuss recent advances in molecular imaging of pancreatic cancer using antibody-based imaging agents. This task is accomplished by summarizing the current progress in each type of molecular imaging modality described above. Also, several considerations for designing and synthesizing novel antibody-based imaging agents are discussed. Lastly, the future directions of antibody-based imaging agents are discussed, emphasizing the potential applications for personalized medicine. PMID:26620581

  5. Targeting of Cancer Cells Using Quantum Dot-Polypeptide Hybrid Assemblies that Function as Molecular Imaging Agents and Carrier Systems

    PubMed Central

    Atmaja, Bayu; Lui, Bertrand H.; Hu, Yuhua; Beck, Stayce E.; Frank, Curtis W.; Cochran, Jennifer R.

    2015-01-01

    We report a highly tunable quantum dot (QD)-polypeptide hybrid assembly system with potential uses for both molecular imaging and delivery of biomolecular cargo to cancer cells. In this work, we demonstrate the tunability of the assembly system, its application for imaging cancer cells, and its ability to carry a biomolecule. The assemblies are formed through the self-assembly of carboxyl-functionalized QDs and poly(diethylene glycol-L-lysine)-poly(L-lysine) (PEGLL-PLL) diblock copolypeptide molecules, and they are modified with peptide ligands containing a cyclic arginine-glycine-aspartate [c(RGD)] motif that has affinity for αvβ3 and αvβ5 integrins overexpressed on the tumor vasculature. To illustrate the tunability of the QD-polypeptide assembly system, we show that binding to U87MG glioblastoma cells can be modulated and optimized by changing either the conditions under which the assemblies are formed or the relative lengths of the PEGLL and PLL blocks in the PEGLL-PLL molecules. The optimized c(RGD)-modified assemblies bind integrin receptors on U87MG cells and are endocytosed, as demonstrated by flow cytometry and live-cell imaging. Binding specificity is confirmed by competition with an excess of free c(RGD) peptide. Finally, we show that the QD-polypeptide assemblies can be loaded with fluorescently labeled ovalbumin, as a proof-of-concept for their potential use in biomolecule delivery. PMID:25750609

  6. Characterization and performance of a near-infrared 2-deoxyglucose optical imaging agent for mouse cancer models.

    PubMed

    Kovar, Joy L; Volcheck, William; Sevick-Muraca, Eva; Simpson, Melanie A; Olive, D Michael

    2009-01-15

    Malignant neoplasms exhibit an elevated rate of glycolysis over normal cells. This characteristic can be exploited for optical imaging of tumors in mice. A near-infrared fluorophore, IRDye 800CW, emission maximum 794 nm, was conjugated to 2-deoxyglucose (2-DG). An immunofluorescent cell-based assay was used to evaluate specificity and sensitivity of the conjugate in cultured cell monolayers. Dose-dependent uptake was established with increasing concentrations of IRDye 800CW 2-DG for epithelial and prostate carcinomas. IRDye 800CW 2-DG was specifically blocked by an antibody against GLUT1 glucose transporter, and by excess unlabeled 2-DG or d-glucose. Signal was increased by a phorbol ester activator of glucose transport. Fluorescence microscopy data confirmed localization of the conjugate in the cytoplasm. Subsequent in vivo studies optimized dose, clearance, and timing for signal capture in nude mouse xenografts. In all cases, tumors were clearly imaged with good signal-to-noise characteristics. These data indicate that IRDye 800CW 2-DG is a broadly applicable optical imaging agent for in vivo imaging of neoplasms in mice. PMID:18938129

  7. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  8. Synthesis and positron emission tomography evaluation of 18F-Glu-Urea-Lys, a prostate-specific membrane antigen-based imaging agent for prostate cancer

    PubMed Central

    FAN, WEIWEI; ZHANG, ZHIWEI; ZHU, ZHENG; YANG, DEYONG; CHEN, XIAOCHI; WANG, JIANBO; CHEN, FENG; SONG, XISHUANG

    2015-01-01

    In recent years, single-photon emission computed tomography and positron emission tomography (PET) have also been used, in addition to computed tomography and magnetic resonance imaging, in targeting the diagnosis of prostate cancer. The aim of this study was to synthesize the prostate-specific membrane antigen (PSMA)-based imaging agent 2-{3-[1-Carboxy-5-(4-[18F] fluoro-benzoylamino)-pentyl]-ureido}-pentanedioic acid (18F-Glu-Urea-Lys, [18F]3) and to detect its PET imaging efficiency for high PSMA expression in prostate cancer. In this study, 18F-Glu-Urea-Lys was synthesized in two steps from the p-methoxybenzyl-protected Glu-Urea-Lys precursor using N-Hydroxysuccinimidyl-4-[18F] fluorobenzoate ([18F]SFB). PET imaging evaluation was conducted in nude mice using LNCaP (PSMA+), and PC-3, 231 and A549 (all PSMA−) xenograft models. The results indicated that 18F-Glu-Urea-Lys was produced in radiochemical yields of 28.7%. The radiochemical purity was 99.1% and the mean total synthesis time was 168 min. In nude mice models 18F-Glu-Urea-Lys clearly delineated PSMA+ LNCaP prostate tumor xenografts on PET imaging. At 4 h post-injection, the contrast agents were only observed in renal, liver, bladder and PSMA+ LNCaP tumors. The PSMA− tumor (PC-3, 231 and A549) was clear. In conclusion, 18F-Glu-Urea-Lys was found to be easily synthesized. This radiotracer demonstrated high tumor and low-to-normal tissue uptake, fast clearance from non-target tissues and retention in PSMA+ prostate tumor xenografts. PMID:26622838

  9. Targeted Nanotechnology for Cancer Imaging

    PubMed Central

    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

  10. Cancer imaging archive available

    Cancer.gov

    NCI’s Cancer Imaging Program has inaugurated The Cancer Imaging Archive (TCIA), a web-accessible and unique clinical imaging archive linked to The Cancer Genome Atlas (TCGA) tissue repository. It contains a large proportion of original, pre-surgical MRIs from cases that have been genomically characterized in TCGA.

  11. Self-assembled IR780-loaded transferrin nanoparticles as an imaging, targeting and PDT/PTT agent for cancer therapy

    PubMed Central

    Wang, Kaikai; Zhang, Yifan; Wang, Juan; Yuan, Ahu; Sun, Minjie; Wu, Jinhui; Hu, Yiqiao

    2016-01-01

    Combination of photothermal and photodynamic therapy (PTT/PDT) offer unique advantages over PDT alone. However, to achieve synergetic PDT/PTT effect, one generally needs two lasers with different wavelengths. Near-infrared dye IR-780 could be used as photosensitizer both for PTT and PDT, but its lipophilicity limits its practical use and in vivo efficiency. Herein, a simple multifunctional IR780-loaded nanoplatform based on transferrin was developed for targeted imaging and phototherapy of cancer compatible with a single-NIR-laser irradiation. The self-assembled transferrin-IR780 nanoparticles (Tf-IR780 NPs) exhibited narrow size distribution, good photo-stability, and encouraging photothermal performance with enhanced generation of ROS under laser irradiation. Following intravenous injection, Tf-IR780 NPs had a high tumor-to-background ratio in CT26 tumor-bearing mice. Treatment with Tf-IR780 NPs resulted in significant tumor suppression. Overall, the Tf-IR780 NPs show notable targeting and theranostic potential in cancer therapy. PMID:27263444

  12. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    PubMed Central

    Fu, Lei; Ke, Heng-Te

    2016-01-01

    Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs) an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles (SPIOs), CuS nanoparticles, DNA, siRNA, gold nanoparticles (GNPs), gold nanorods (GNRs), gold nanoshell (GNS), graphene oxides (GOs), polypyrrole (PPy) nanocapsules, Prussian blue (PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics. PMID:27807499

  13. In Vivo Imaging in Cancer

    PubMed Central

    Condeelis, John; Weissleder, Ralph

    2010-01-01

    Imaging has become an indispensable tool in the study of cancer biology and in clinical prognosis and treatment. The rapid advances in high resolution fluorescent imaging at single cell level and MR/PET/CT image registration, combined with new molecular probes of cell types and metabolic states, will allow the physical scales imaged by each to be bridged. This holds the promise of translation of basic science insights at the single cell level to clinical application. In this article, we describe the recent advances in imaging at the macro- and micro-scale and how these advances are synergistic with new imaging agents, reporters, and labeling schemes. Examples of new insights derived from the different scales of imaging and relevant probes are discussed in the context of cancer progression and metastasis. PMID:20861158

  14. 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.

    PubMed

    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.

  15. Molecular imaging in cervical cancer.

    PubMed

    Khan, Sairah R; Rockall, Andrea G; Barwick, Tara D

    2016-06-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed. PMID:26859085

  16. Cancer Stratification by Molecular Imaging

    PubMed Central

    Weber, Justus; Haberkorn, Uwe; Mier, Walter

    2015-01-01

    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. PMID:25749472

  17. Photoacoustic Imaging for Cancer Detection and Staging

    PubMed Central

    Mehrmohammadi, Mohammad; Yoon, Soon Joon; Yeager, Douglas; Emelianov, Stanislav Y.

    2013-01-01

    Cancer is one of the leading causes of death in the world. Diagnosing a cancer at its early stages of development can decrease the mortality rate significantly and reduce healthcare costs. Over the past two decades, photoacoustic imaging has seen steady growth and has demonstrated notable capabilities to detect cancerous cells and stage cancer. Furthermore, photoacoustic imaging combined with ultrasound imaging and augmented with molecular targeted contrast agents is capable of imaging cancer at the cellular and molecular level, thus opening diverse opportunities to improve diagnosis of tumors, detect circulating tumor cells and identify metastatic lymph nodes. In this paper we introduce the principles of photoacoustic imaging, and review recent developments in photoacoustic imagingas an emerging imaging modality for cancer diagnosis and staging. PMID:24032095

  18. Precursors to radiopharmaceutical agents for tissue imaging

    DOEpatents

    Srivastava, Prem C.; Knapp, Jr., Furn F.

    1988-01-01

    A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

  19. Imaging of esophageal cancer

    PubMed Central

    Iyer, R; DuBrow, R

    2004-01-01

    Esophageal cancer is a relatively uncommon gastrointestinal malignancy but carries a poor prognosis unless it is of early stage and can be surgically resected for cure. Resectability is determined by the stage of disease at diagnosis and therefore accurate staging is of importance in patients diagnosed with esophageal cancer. Imaging studies that play a role in the evaluation of esophageal cancer include barium studies, computed tomography, endoscopic ultrasound and positron emission tomography. Imaging provides important information regarding the local extent and any distant spread of disease, which in turn helps in determining optimal management for these patients. This review discusses the imaging findings that may be encountered with various imaging modalities in the diagnosis, staging and follow-up of esophageal cancer. PMID:18250021

  20. Infectious Agents and Cancer Epidemiology Research Webinar Series

    Cancer.gov

    Infectious Agents and Cancer Epidemiology Research Webinar Series highlights emerging and cutting-edge research related to infection-associated cancers, shares scientific knowledge about technologies and methods, and fosters cross-disciplinary discussions on infectious agents and cancer epidemiology.

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

    PubMed Central

    Chan, Minnie

    2016-01-01

    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. PMID:27398218

  2. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  3. Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2014-01-01

    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. PMID:24938638

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

    PubMed

    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.

  6. Anti-cancer agents counteracting tumor glycolysis

    PubMed Central

    Granchi, Carlotta

    2012-01-01

    Can we consider cancer as a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have to deal with increased needs for both energy and biosynthetic intermediates, in order to support their growth and invasiveness. However, their high proliferation rate often generates regions that are not sufficiently oxygenated. Therefore, their carbohydrate metabolism has to rely mostly on a glycolytic process that is uncoupled from oxidative phosphorylation. This metabolic switch, also known as the “Warburg Effect”, constitutes a fundamental adaptation of the tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumor glycolysis may constitute an attractive target for cancer therapy. This approach has often raised concerns that anti-glycolytic agents may cause serious side effects on normal cells. Actually, the key for a selective action against cancer cells can be found in their hyperbolic addiction to glycolysis, which may be exploited to generate new anti-cancer drugs showing minimal toxicity. In fact, there is growing evidence that supports many glycolytic enzymes and transporters as suitable candidate targets for cancer therapy. Herein we review some of the most relevant anti-glycolytic agents that have been investigated so far for the treatment of cancer. PMID:22684868

  7. Bone-targeting agents in prostate cancer.

    PubMed

    Suzman, Daniel L; Boikos, Sosipatros A; Carducci, Michael A

    2014-09-01

    Bone metastases are present in the vast majority of men with advanced prostate cancer, representing the main cause for morbidity and mortality. Recurrent or metastatic disease is managed initially with androgen deprivation but the majority of the patients eventually will progress to castration-resistant prostate cancer, with patients developing bone metastases in most of the cases. Survival and growth of the metastatic prostate cancer cells is dependent on a complex microenvironment (onco-niche) that includes the osteoblasts, the osteoclasts, the endothelium, and the stroma. This review summarizes agents that target the pathways involved in this complex interaction between prostate cancer and bone microenvironment and aim to transform lethal metastatic prostate cancer into a chronic disease.

  8. Bone-targeting agents in prostate cancer

    PubMed Central

    Suzman, Daniel L.; Boikos, Sosipatros A.; Carducci, Michael A.

    2014-01-01

    Bone metastases are present in the vast majority of men with advanced prostate cancer, representing the main cause for morbidity and mortality. Recurrent or metastatic disease is managed initially with androgen deprivation but the majority of the patients eventually will progress to castration-resistant prostate cancer, with patients developing bone metastases in most of the cases. Survival and growth of the metastatic prostate cancer cells is dependent on a complex microenvironment (onco-niche) that includes the osteoblasts, the osteoclasts, the endothelium, and the stroma. This review summarizes agents that target the pathways involved in this complex interaction between prostate cancer and bone micro-environment and aim to transform lethal metastatic prostate cancer into a chronic disease. PMID:24398856

  9. Targeted contrast agents--an adjunct to whole-body imaging: current concepts.

    PubMed

    Foran, Paul; Bolster, Ferdia; Crosbie, Ian; MacMahon, Peter; O'Kennedy, Richard; Eustace, Stephen J

    2010-03-01

    This article reviews the potential use of a combination of whole-body imaging and targeted contrast agents in improving diagnostics, with a particular focus on oncology imaging. It looks at the rationale for nanoparticles and their development as targeted contrast agents. It subsequently describes many of the advances made thus far in developing tissue-specific contrast agents capable of targeting tumors that combined with whole-body imaging may enable superior cancer detection and characterization.

  10. Molecular imaging agents: impact on diagnosis and therapeutics in oncology

    PubMed Central

    Seaman, Marc E.; Contino, Gianmarco; Bardeesy, Nabeel; Kelly, Kimberly A.

    2011-01-01

    Imaging has become a crucial tool in oncology throughout the course of disease detection and management and is an integral part of clinical trials. Anatomic and functional imaging led the way, providing valuable information used in the diagnosis of disease, including data regarding the size and location of the tumor and on physiologic processes such as blood flow and perfusion. As understanding of cancer pathogenesis has advanced through the identification of genetic, biochemical, and cellular alterations in evolving tumors, emphasis has been made on developing methods to detect and serially monitor such alterations. This class of approaches is referred to as molecular imaging. Molecular imaging offers the potential for increasingly sensitive and specific visualization and quantification of biological processes at the cellular and molecular level. These approaches have become established as essential tools for cancer research, early cancer detection and staging and monitoring and predicting response to targeted therapies. Here, we will discuss recent advances in the development of molecular imaging agents and their implementation in basic cancer research as well as in more rationalized approaches to cancer care. PMID:20633310

  11. ICMICs - Cancer Imaging Program

    Cancer.gov

    ICMIC grants facilitate interaction among scientists from a variety of fields to conduct multidisciplinary research on cellular and molecular imaging related to cancer. Pre-ICMIC planning grants have provided time and funds for investigators and institutions to prepare themselves, organizationally and scientifically, to establish ICMICs.

  12. Translational Molecular Imaging of Prostate Cancer

    PubMed Central

    Kiess, Ana P.; Cho, Steve Y.; Pomper, Martin G.

    2013-01-01

    Prostate cancer is a heterogeneous disease, and its management is now evolving to become more personalized and to incorporate new targeted therapies. With these new changes comes a demand for molecular imaging techniques that can not only detect disease but also assess biology and treatment response. This review article summarizes current molecular imaging approaches in prostate cancer (e.g. 99mTc bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography) and highlights emerging clinical and preclinical imaging agents, with an emphasis on mechanism and clinical application. Emerging agents at various stages of clinical translation include radiolabeled analogs of lipid, amino acid, and nucleoside metabolism, as well as agents more specifically targeting prostate cancer biomarkers including androgen receptor, prostate-specific membrane antigen and others. We also highlight new techniques and targeted contrast agents for magnetic resonance imaging and spectroscopy. For all these imaging techniques, a growing and important unmet need is for well-designed prospective clinical trials to establish clear indications with clinical benefit in prostate cancer. PMID:24159427

  13. A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells.

    PubMed

    He, Huan; Li, Dong-Wei; Yang, Li-Yun; Fu, Li; Zhu, Xun-Jin; Wong, Wai-Kwok; Jiang, Feng-Lei; Liu, Yi

    2015-01-01

    Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment. PMID:26337336

  14. A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells

    PubMed Central

    He, Huan; Li, Dong-Wei; Yang, Li-Yun; Fu, Li; Zhu, Xun-Jin; Wong, Wai-Kwok; Jiang, Feng-Lei; Liu, Yi

    2015-01-01

    Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment. PMID:26337336

  15. Meninges in cancer imaging.

    PubMed

    Mahendru, G; Chong, V

    2009-10-02

    Primary malignant tumours arising from the meninges are distinctly uncommon, and when they occur, they are usually sarcomas. In contrast, metastatic meningeal involvement is increasingly seen as advances in cancer therapy have changed the natural history of malignant disease and prolonged the life span of cancer patients. The meninges can either be infiltrated by contiguous extension of primary tumours of the central nervous system, paranasal sinuses and skull base origin or can be diffusely infiltrated from haematogenous dissemination from distant primary malignancies. Imaging in these patients provides crucial information in planning management. This article reviews the pertinent anatomy that underlies imaging findings, discusses the mechanism of meningeal metastasis and highlights different imaging patterns of meningeal carcinomatosis and the pitfalls.

  16. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy.

  17. Curcumin: a promising agent targeting cancer stem cells.

    PubMed

    Zang, Shufei; Liu, Tao; Shi, Junping; Qiao, Liang

    2014-01-01

    Cancer stem cells are a subset of cells that are responsible for cancer initiation and relapse. They are generally resistant to the current anticancer agents. Successful anticancer therapy must consist of approaches that can target not only the differentiated cancer cells, but also cancer stem cells. Emerging evidence suggested that the dietary agent curcumin exerted its anti-cancer activities via targeting cancer stem cells of various origins such as those of colorectal cancer, pancreatic cancer, breast cancer, brain cancer, and head and neck cancer. In order to enhance the therapeutic potential of curcumin, this agent has been modified or used in combination with other agents in the experimental therapy for many cancers. In this mini-review, we discussed the effect of curcumin and its derivatives in eliminating cancer stem cells and the possible underlying mechanisms.

  18. Imaging agent and method of use

    DOEpatents

    Wieland, Donald M.; Brown, Lawrence E.; Beierwaltes, William H.; Wu, Jiann-long

    1986-04-22

    A new radiopharmaceutical composition for use in nuclear medicine comprises a radioiodinated meta-iodobenzylguanidine. The composition is used as an imaging agent for the heart, adrenal medulla, and tumors of the adrenal medulla and can be used for treatment of tumors of the adrenal medulla.

  19. Imaging agent and method of use

    DOEpatents

    Wieland, D.M.; Brown, L.E.; Beierwaltes, W.H.; Wu, J.L.

    1986-04-22

    A new radiopharmaceutical composition for use in nuclear medicine comprises a radioiodinated meta-iodobenzylguanidine. The composition is used as an imaging agent for the heart, adrenal medulla, and tumors of the adrenal medulla and can be used for treatment of tumors of the adrenal medulla. No Drawings

  20. Inflammation and cancer: advances and new agents.

    PubMed

    Crusz, Shanthini M; Balkwill, Frances R

    2015-10-01

    Tumour-promoting inflammation is considered one of the enabling characteristics of cancer development. Chronic inflammatory disease increases the risk of some cancers, and strong epidemiological evidence exists that NSAIDs, particularly aspirin, are powerful chemopreventive agents. Tumour microenvironments contain many different inflammatory cells and mediators; targeting these factors in genetic, transplantable and inducible murine models of cancer substantially reduces the development, growth and spread of disease. Thus, this complex network of inflammation offers targets for prevention and treatment of malignant disease. Much potential exists in this area for novel cancer prevention and treatment strategies, although clinical research to support targeting of cancer-related inflammation and innate immunity in patients with advanced-stage cancer remains in its infancy. Following the initial successes of immunotherapies that modulate the adaptive immune system, we assert that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data. The adaptive immune response is heavily dependent on innate immunity, therefore, inhibiting some of the tumour-promoting immunosuppressive actions of the innate immune system might enhance the potential of immunotherapies that activate a nascent antitumour response. PMID:26122183

  1. Modular Strategies for PET Imaging Agents

    PubMed Central

    Hooker, Jacob M

    2009-01-01

    Summary of Recent Advances In recent years, modular and simplified chemical and biological strategies have been developed for the synthesis and implementation of positron emission tomography (PET) radiotracers. New developments in bioconjugation and synthetic methodologies, in combination with advances in macromolecular delivery systems and gene-expression imaging, reflect a need to reduce radiosynthesis burden in order to accelerate imaging agent development. These new approaches, which are often mindful of existing infrastructure and available resources, are anticipated to provide a more approachable entry point for researchers interested in using PET to translate in vitro research to in vivo imaging. PMID:19880343

  2. Dietary agents for chemoprevention of prostate cancer

    PubMed Central

    Syed, Deeba N; Suh, Yewseok; Afaq, Farrukh; Mukhtar, Hasan

    2011-01-01

    Prostate cancer (CaP) is the leading cause of cancer-related deaths in American men, responsible for over 29,000 deaths in the year 2007. Chemoprevention is a plausible and cost-effective approach to reduce cancer morbidity and mortality through inhibition of precancerous events before the occurrence of clinical disease. Indeed, CaP is an ideal candidate disease for chemopreventive intervention as it is typically diagnosed in the elderly population with a relatively slower rate of growth and progression. The potential of dietary substances to act as chemopreventive agents against CaP is increasingly appreciated. Furhter, epidemiological studies have identified significant correlations between CaP incidence and dietary habits. It is hoped that, combining the knowledge based on agents with targets, we will be able to build an armamentarium of naturally occurring chemopreventive substances that could prevent or slow down the development and progression of CaP. In this review, we have summarized the findings from clinical and preclinical studies on dietary agents including green tea, pomegranate, lupeol, fisetin and delphinidin that are currently being investigated in our laboratory for their chemopreventive potential against CaP. PMID:18395333

  3. Antibody Based Imaging Strategies of Cancer

    PubMed Central

    Warram, Jason M; de Boer, Esther; Sorace, Anna G; Chung, Thomas K; Kim, Hyunki; Pleijhuis, Rick G; van Dam, Gooitzen M; Rosenthal, Eben L

    2014-01-01

    Although mainly developed for preclinical research and therapeutic use, antibodies have high antigen specificity, which can be used as a courier to selectively deliver a diagnostic probe or therapeutic agent to cancer. It is generally accepted that the optimal antigen for imaging will depend on both the expression in the tumor relative to normal tissue and the homogeneity of expression throughout the tumor mass and between patients. For the purpose of diagnostic imaging, novel antibodies can be developed to target antigens for disease detection, or current FDA-approved antibodies can be repurposed with the covalent addition of an imaging probe. Reuse of therapeutic antibodies for diagnostic purposes reduces translational costs since the safety profile of the antibody is well defined and the agent is already available under conditions suitable for human use. In this review, we will explore a wide range of antibodies and imaging modalities that are being translated to the clinic for cancer identification and surgical treatment. PMID:24913898

  4. Reengineered tricyclic anti-cancer agents.

    PubMed

    Kastrinsky, David B; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S; Narla, Goutham; Ohlmeyer, Michael

    2015-10-01

    The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. PMID:26372073

  5. IND Regulatory & Manufacturing Resources - Cancer Imaging Program

    Cancer.gov

    The Cancer Imaging Program has been creating Investigational New Drug Applications (IND) for imaging agents in order to engage in multi-center clinical trials of these materials. A subset of the documents filed is being made available to the research community to implement routine synthesis of tracers at their own facilities and to assist investigators with the filing of their own INDs. The first of these document sets is for F-18 fluorothymidine (FLT).

  6. Virtual cancer image data warehouse.

    PubMed

    Oyama, H; Wakao, F; Mishina, T; Lu, Y; Honjo, A

    1997-01-01

    We previously developed a system with which we have created more than 100 virtual cancer images from CT or MR data of individual patients with cancer (Cancer Edutainment Virtual Reality Theater: CEVRT). These images can be used to help explain procedures, findings, etc. to the patient, to obtain informed consent, to simulate surgery, and to estimate cancer invasion to surrounding organs. We recently developed a web-based object-oriented database both to access these cancer images and to register medical images at international research sites via the Internet. In this report, we introduce an international medical VR data warehouse created using an object-oriented database.

  7. Information Systems - Cancer Imaging Program

    Cancer.gov

    The Lung Image Database Consortium (LIDC) represents an effort by CIP grantees in a consortium to create a database of spiral CT images of the lung for use in CAD (computer-aided detection) algorithm research. The Imaging Database Resources Initiative (IDRI) is extending the efforts of the LIDC, to create a larger database of spiral CT imaging of the lung for use in CAD algorithm research. Image Archive Resources contains links to Web sites related to the interests of the NCI CIP Image Archive Committee. The Molecular Imaging and Contrast Agent Database (MICAD) is a database of research data on in vivo molecular imaging and contrast agents.

  8. Cancer stem cells targeting agents--a review.

    PubMed

    Shi, A-M; Tao, Z-Q; Li, H; Wang, Y-Q; Zhao, J

    2015-11-01

    Major current cancer strategies like surgery, radiotherapy, and chemotherapy are compromised due to major problem of recurrence, which usually lead to mortality. The widely accepted reason for this is resistance offered by cancer cells towards cancer drugs or inability of a therapeutic procedure to target real culprits viz. cancer-initiating cells (cancer stem cells). So, there is a current need of development of new agents targeting these cancer stem cells in order to overcome resistance to therapeutic procedures. The present review article is focused on new cancer cell targeting agents like salinomycin, apopotin etc and their mechanisms to target cancer stems cells will be discussed.

  9. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    NASA Astrophysics Data System (ADS)

    Sinharay, Sanhita; Pagel, Mark D.

    2016-06-01

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection.

  10. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    PubMed Central

    Sinharay, Sanhita; Pagel, Mark D.

    2016-01-01

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

  11. Intraoperative imaging using intravascular contrast agent

    NASA Astrophysics Data System (ADS)

    Watson, Jeffrey R.; Martirosyan, Nikolay; Garland, Summer; Lemole, G. Michael; Romanowski, Marek

    2016-03-01

    Near-infrared (NIR) contrast agents are becoming more frequently studied in medical imaging due to their advantageous characteristics, most notably the ability to capture near-infrared signal across the tissue and the safety of the technique. This produces a need for imaging technology that can be specific for both the NIR dye and medical application. Indocyanine green (ICG) is currently the primary NIR dye used in neurosurgery. Here we report on using the augmented microscope we described previously for image guidance in a rat glioma resection. Luc-C6 cells were implanted in a rat in the left-frontal lobe and grown for 22 days. Surgical resection was performed by a neurosurgeon using augmented microscopy guidance with ICG contrast. Videos and images were acquired to evaluate image quality and resection margins. ICG accumulated in the tumor tissue due to enhanced permeation and retention from the compromised bloodbrain- barrier. The augmented microscope was capable of guiding the rat glioma resection and intraoperatively highlighted tumor tissue regions via ICG fluorescence under normal illumination of the surgical field.

  12. Application of GFP imaging in cancer.

    PubMed

    Hoffman, Robert M

    2015-04-01

    Multicolored proteins have allowed the color-coding of cancer cells growing in vivo and enabled the distinction of host from tumor with single-cell resolution. Non-invasive imaging with fluorescent proteins enabled the dynamics of metastatic cancer to be followed in real time in individual animals. Non-invasive imaging of cancer cells expressing fluorescent proteins has allowed the real-time determination of efficacy of candidate antitumor and antimetastatic agents in mouse models. The use of fluorescent proteins to differentially label cancer cells in the nucleus and cytoplasm can visualize the nuclear-cytoplasmic dynamics of cancer cells in vivo including: mitosis, apoptosis, cell-cycle position, and differential behavior of nucleus and cytoplasm that occurs during cancer-cell deformation and extravasation. Recent applications of the technology described here include linking fluorescent proteins with cell-cycle-specific proteins such that the cells change color from red to green as they transit from G1 to S phases. With the macro- and micro-imaging technologies described here, essentially any in vivo process can be imaged, giving rise to the new field of in vivo cell biology using fluorescent proteins.

  13. Application of GFP imaging in cancer.

    PubMed

    Hoffman, Robert M

    2015-04-01

    Multicolored proteins have allowed the color-coding of cancer cells growing in vivo and enabled the distinction of host from tumor with single-cell resolution. Non-invasive imaging with fluorescent proteins enabled the dynamics of metastatic cancer to be followed in real time in individual animals. Non-invasive imaging of cancer cells expressing fluorescent proteins has allowed the real-time determination of efficacy of candidate antitumor and antimetastatic agents in mouse models. The use of fluorescent proteins to differentially label cancer cells in the nucleus and cytoplasm can visualize the nuclear-cytoplasmic dynamics of cancer cells in vivo including: mitosis, apoptosis, cell-cycle position, and differential behavior of nucleus and cytoplasm that occurs during cancer-cell deformation and extravasation. Recent applications of the technology described here include linking fluorescent proteins with cell-cycle-specific proteins such that the cells change color from red to green as they transit from G1 to S phases. With the macro- and micro-imaging technologies described here, essentially any in vivo process can be imaged, giving rise to the new field of in vivo cell biology using fluorescent proteins. PMID:25686095

  14. Molecular Imaging of Ovarian Cancer

    PubMed Central

    Sharma, Sai Kiran; Nemieboka, Brandon; Sala, Evis; Lewis, Jason S.; Zeglis, Brian M.

    2016-01-01

    Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer. PMID:27127223

  15. Imaging agents for in vivo molecular profiling of disseminated prostate cancer--targeting EGFR receptors in prostate cancer: comparison of cellular processing of [111In]-labeled affibody molecule Z(EGFR:2377) and cetuximab.

    PubMed

    Malmberg, Jennie; Tolmachev, Vladimir; Orlova, Anna

    2011-04-01

    Expression of receptor tyrosine-kinase (RTK) EGFR is low in normal prostate, but increases in prostate cancer. This receptor is significantly up-regulated as tumors progress into higher grade, androgen-insensitive and metastatic lesions. The up-regulated receptors could serve as targets for novel selective anti-cancer drugs, e.g. antibodies and tyrosine kinase inhibitors. Radionuclide imaging of RTK can facilitate patient stratification and monitoring of anti-RTK therapy of prostate cancer. The goal of the study was to evaluate binding and cellar processing of radiolabeled EGFR-targeting conjugates by prostate cancer cell lines. Receptor expression of EGFR was studied in three prostate cancer cell lines: DU145 (brain metastasis of PC, hormone insensitive), PC3 (bone metastasis of PC) and LNCaP (lymph node metastasis of PC, androgen and estrogen receptor positive). Uptake and internalization of anti-EGFR mAbs (cetuximab) and affibody molecule (Z2377) labeled with indium-111 was investigated. EGFR expression on prostate cancer cell lines was clearly demonstrated. Both labelled conjugates 111In-Z2377 and 111In-cetuximab bound to prostate cancer cells in the receptor mediated model. Expression levels were modest but correlate with degree of hormone independence. Internalization of Affibody molecules was relatively slow in all cell lines. Internalization of mAbs was more rapid. The level of EGFR expression in these cell lines is sufficient for in vivo molecular imaging. Slow internalization indicates possibility of the use of non-residualizing labels for affibody molecules. PMID:21253675

  16. Cancers in Australia in 2010 attributable to infectious agents

    PubMed Central

    Antonsson, Annika; Wilson, Louise F; Kendall, Bradley J; Bain, Christopher J; Whiteman, David C; Neale, Rachel E

    2015-01-01

    Objectives To estimate the proportion and numbers of cancers in Australia in 2010 attributable to infectious agents. Methods The population attributable fraction (PAF) and number of cancers caused by hepatitis B and C viruses (HBV, HCV), Helicobacter pylori and human immunodeficiency virus (HIV) were calculated using standard formulae incorporating prevalence of infection in the Australian population, the relative risks associated with that infection and cancer incidence. For cancers with very strong associations to the infectious agent (Epstein-Barr virus [EBV], human papillomavirus [HPV] and HIV/Kaposi's sarcoma herpes virus [KSHV]), calculations were based on viral prevalence in the tumour. Results An estimated 3,421 cancers (2.9% of all cancers) in Australia in 2010 were attributable to infections. Infectious agents causing the largest numbers of cancers were HPV (n=1,706), H. pylori (n=793) and HBV/HCV (n=518). Cancer sites with the greatest number of cancers caused by infections were cervix (n=818), stomach (n=694) and liver (n=483). Cancers with highest proportions attributable to infectious agents were Kaposi's sarcoma (100%), cervix (100%), nasopharynx (87%), anus (84%) and vagina (70%). Conclusions Infectious agents cause more than 3,000 cancers annually in Australia. Implications Opportunities for cancer prevention through infection control are considerable, even in a ‘first world’ nation like Australia. PMID:26437730

  17. Nuclear medicine for imaging of epithelial ovarian cancer.

    PubMed

    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.

  18. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy. PMID:26874530

  19. Advance of Molecular Imaging Technology and Targeted Imaging Agent in Imaging and Therapy

    PubMed Central

    Chen, Zhi-Yi; Wang, Yi-Xiang; Lin, Yan; Zhang, Jin-Shan; Yang, Feng; Zhou, Qiu-Lan; Liao, Yang-Ying

    2014-01-01

    Molecular imaging is an emerging field that integrates advanced imaging technology with cellular and molecular biology. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. Molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imaging signal with molecular event. Recently, the application of new emerging chemical technology and nanotechnology has stimulated the development of imaging agents. Nanoparticles modified with small molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. Therapeutic drug or gene is incorporated into nanoparticles to construct multifunctional imaging agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imaging, the novel imaging agent including targeted imaging agent and multifunctional imaging agent, as well as cite some examples of their application in molecular imaging and therapy. PMID:24689058

  20. Prostate cancer (image)

    MedlinePlus

    Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

  1. Tobacco and cancer (image)

    MedlinePlus

    Tobacco and its various components increase the risk of several types of cancer especially cancer of the lung, mouth, larynx, esophagus, bladder, kidney, pancreas, and cervix. Smoking also increases ...

  2. Specialized Initiatives - Cancer Imaging Program

    Cancer.gov

    CIP has sponsored a number of programs for specific purposes, using set-aside funds. Among these are Phase 2 N01 ProgramIn-Vivo Cellular & Molecular Imaging Centers (ICMICs) Quantitative Imaging for Evaluation of Responses to Cancer Therapies (QIN) Network for Translational Research (NTR): Optical Imaging in Multimodal Platforms Small Animal Imaging Resource Program (SAIRP) Development of Preclinical Drugs and Enhancers (DCIDE) program.

  3. Functional imaging in lung cancer

    PubMed Central

    Harders, S W; Balyasnikowa, S; Fischer, B M

    2014-01-01

    Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An increasing awareness on smoking cessation as an important mean to reduce lung cancer incidence and mortality, an increasing number of therapy options and a steady focus on early diagnosis and adequate staging have resulted in a modestly improved survival. For early diagnosis and precise staging, imaging, especially positron emission tomography combined with CT (PET/CT), plays an important role. Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT) and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results within this field. The purpose of this review is to provide the reader with a brief and balanced introduction to these three functional imaging modalities and their current or potential application in the care of patients with lung cancer. PMID:24289258

  4. Urologic cancer risks for veterans exposed to Agent Orange.

    PubMed

    Hoenemeyer, Lori A

    2013-01-01

    Agent Orange, an herbicide widely used during the Vietnam War, has been linked to various health risks, including urologic malignancy. Exposed veterans are at risk for prostate cancer and may be entitled to compensation if diagnosed with prostate cancer. Current research studies are aimed at mitigating prostate dysplasia and prostate cancer PMID:23734554

  5. The role of infectious agents in urogenital cancers

    PubMed Central

    2012-01-01

    Since the late 1990s, infectious agents have been thought to play a role in the pathogenesis of approximately 15% of cancers. It is now widely accepted that infection of stomach tissue with the bacteria Helicobacter pylori is an important cause of stomach adenocarcinoma. In addition, oncogenic viruses, such as papilloma viruses, herpes viruses, and hepadnaviruses are strongly associated with increased risk of cervical cancer, lymphomas, liver cancer, amongst others. However, in the scientific community the percentage of cancers caused by pathogens is believed to be far higher than 15%. A significant volume of data collected to date show an association between infectious agents and urogenital cancers. These agents include Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma genitalium and certain viruses that have been implicated in ovarian cancer. Other pathogens include the hepatitis C and Epstein-Barr viruses, which are potentially involved in kidney cancer. In addition, infections with Schistosoma haematobium, the human papillomavirus, and human polyomaviruses are strongly associated with an increased risk of urinary bladder cancer. This article reviews publications available to date on the role of infectious agents in urogenital cancers. A greater understanding of the role of such agents could aid the identification of novel methods of urogenital cancer treatment. PMID:23198689

  6. Molecular Imaging of Prostate Cancer.

    PubMed

    Wibmer, Andreas G; Burger, Irene A; Sala, Evis; Hricak, Hedvig; Weber, Wolfgang A; Vargas, Hebert Alberto

    2016-01-01

    Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. PMID:26587888

  7. Optical contrast agents to visualize molecular expression in breast cancer

    NASA Astrophysics Data System (ADS)

    Langsner, Robert James

    Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care. The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence. This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxyglucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation. To image these contrast agents in cancerous

  8. Molecular photoacoustic imaging using gold nanoparticles as a contrast agent

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher P.; Zhang, Qiang; Cobley, Claire M.; Xia, Younan; Wang, Lihong V.

    2010-02-01

    Gold nanoparticles have received much attention due to their potential diagnostic and therapeutic applications. Gold nanoparticles are attractive in many biomedical applications because of their biocompatibility, easily modifiable surfaces for targeting, lack of heavy metal toxicity, wide range of sizes (35-100 nm), tunable plasmonic resonance peak, encapsulated site-specific drug delivery, and strong optical absorption in the near-infrared regime. Specifically, due to their strong optical absorption, gold nanoparticles have been used as a contrast agent for molecular photoacoustic (PA) imaging of tumor. The plasmonic resonance peak of the gold nanocages (AuNCs) was tuned to the near-infrared region, and the ratio of the absorption cross-section to the extinction cross-section was approximately ~70%, as measured by PA sensing. We used PEGylated gold nanocages (PEG-AuNCs) as a passive targeting contrast agent on melanomas. After 6-h intravenous injection of PEG-AuNCs, PA amplitude was increased by ~14 %. These results strongly suggest PA imaging paired with AuNCs is a promising diagnostic tool for early cancer detection.

  9. Quantitative imaging as cancer biomarker

    NASA Astrophysics Data System (ADS)

    Mankoff, David A.

    2015-03-01

    The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

  10. Chemopreventive Agent Development | Division of Cancer Prevention

    Cancer.gov

    This group promotes and supports research on early chemopreventive agent development, from preclinical studies to pha | Research on early chemopreventive agent development, from preclinical studies to phase I clinical trials.

  11. Tailored Near-Infrared Contrast Agents for Image Guided Surgery

    PubMed Central

    Njiojob, Costyl N.; Owens, Eric A.; Narayana, Lakshminarayana; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

    2015-01-01

    The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge. PMID:25711712

  12. Tailored near-infrared contrast agents for image guided surgery.

    PubMed

    Njiojob, Costyl N; Owens, Eric A; Narayana, Lakshminarayana; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

    2015-03-26

    The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge.

  13. Imaging Virus-Associated Cancer

    PubMed Central

    Fu, De-Xue; Foss, Catherine A.; Nimmagadda, Sridhar; Ambinder, Richard F.; Pomper, Martin G.

    2012-01-01

    Cancer remains an important and growing health problem. Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer formation and progression. Molecular imaging can identify appropriate patients for targeted cancer therapy and may detect early biochemical changes in tumors during therapy, some of which may have important prognostic implications. Progress in this field continues largely due to a union between molecular genetics and advanced imaging technology. This review details uses of molecular-genetic imaging in the context of tumor-associated viruses. Under certain conditions, and particularly during pharmacologic stimulation, gammaherpesviruses will express genes that enable imaging and therapy in vivo. The techniques discussed are readily translatable to the clinic. PMID:18991718

  14. Rectal Cancer Magnetic Resonance Imaging: Imaging Beyond Morphology.

    PubMed

    Prezzi, D; Goh, V

    2016-02-01

    Magnetic resonance imaging (MRI) has in recent years progressively established itself as one of the most valuable modalities for the diagnosis, staging and response assessment of rectal cancer and its use has largely focused on accurate morphological assessment. The potential of MRI, however, extends beyond detailed anatomical depiction: aspects of tissue physiology, such as perfusion, oxygenation and water molecule diffusivity, can be assessed indirectly. Functional MRI is rapidly evolving as a promising non-invasive assessment tool for tumour phenotyping and assessment of response to new therapeutic agents. In spite of promising experimental data, the evidence base for the application of functional MRI techniques in rectal cancer remains modest, reflecting the relatively poor agreement on technical protocols, image processing techniques and quantitative methodology to date, hampering routine integration into clinical management. This overview outlines the established strengths and the critical limitations of anatomical MRI in rectal cancer; it then introduces some of the functional MRI techniques and quantitative analysis methods that are currently available, describing their applicability in rectal cancer and reviewing the relevant literature; finally, it introduces the concept of a multi-parametric quantitative approach to rectal cancer.

  15. Rectal Cancer Magnetic Resonance Imaging: Imaging Beyond Morphology.

    PubMed

    Prezzi, D; Goh, V

    2016-02-01

    Magnetic resonance imaging (MRI) has in recent years progressively established itself as one of the most valuable modalities for the diagnosis, staging and response assessment of rectal cancer and its use has largely focused on accurate morphological assessment. The potential of MRI, however, extends beyond detailed anatomical depiction: aspects of tissue physiology, such as perfusion, oxygenation and water molecule diffusivity, can be assessed indirectly. Functional MRI is rapidly evolving as a promising non-invasive assessment tool for tumour phenotyping and assessment of response to new therapeutic agents. In spite of promising experimental data, the evidence base for the application of functional MRI techniques in rectal cancer remains modest, reflecting the relatively poor agreement on technical protocols, image processing techniques and quantitative methodology to date, hampering routine integration into clinical management. This overview outlines the established strengths and the critical limitations of anatomical MRI in rectal cancer; it then introduces some of the functional MRI techniques and quantitative analysis methods that are currently available, describing their applicability in rectal cancer and reviewing the relevant literature; finally, it introduces the concept of a multi-parametric quantitative approach to rectal cancer. PMID:26586163

  16. Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium

    SciTech Connect

    Konno, T. )

    1990-11-01

    Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors.

  17. Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors.

    PubMed

    Rivlin, Michal; Navon, Gil

    2016-01-01

    The efficacy of glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) as agents for chemical exchange saturation transfer (CEST) magnetic resonance molecular imaging of tumors is demonstrated. Both agents reflect the metabolic activity and malignancy of the tumors. The method was tested in two types of tumors implanted orthotopically in mice: 4T1 (mouse mammary cancer cells) and MCF7 (human mammary cancer cells). 4T1 is a more aggressive type of tumor than MCF7 and exhibited a larger CEST effect. Two methods of administration of the agents, intravenous (IV) and oral (PO), gave similar results. The CEST MRI observation of lung metastasis was confirmed by histology. The potential of the clinical application of CEST MRI with these agents for cancer diagnosis is strengthened by their lack of toxicity as can be indicated from their wide use as food supplements. PMID:27600054

  18. Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors

    PubMed Central

    Rivlin, Michal; Navon, Gil

    2016-01-01

    The efficacy of glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) as agents for chemical exchange saturation transfer (CEST) magnetic resonance molecular imaging of tumors is demonstrated. Both agents reflect the metabolic activity and malignancy of the tumors. The method was tested in two types of tumors implanted orthotopically in mice: 4T1 (mouse mammary cancer cells) and MCF7 (human mammary cancer cells). 4T1 is a more aggressive type of tumor than MCF7 and exhibited a larger CEST effect. Two methods of administration of the agents, intravenous (IV) and oral (PO), gave similar results. The CEST MRI observation of lung metastasis was confirmed by histology. The potential of the clinical application of CEST MRI with these agents for cancer diagnosis is strengthened by their lack of toxicity as can be indicated from their wide use as food supplements. PMID:27600054

  19. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET Imaging Agent for Prostate Cancer

    PubMed Central

    Chen, Ying; Pullambhatla, Mrudula; Foss, Catherine A.; Byun, Youngjoo; Nimmagadda, Sridhar; Srinivasan, Senthamil; Sgouros, George; Mease, Ronnie C.; Pomper, Martin G.

    2011-01-01

    Purpose We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen, PSMA. PSMA is upregulated in prostate cancer epithelia as well as in the neovasculature of most solid tumors. Experimental Design [18F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) for introduction of 18F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PC3 PSMA+ and PSMA− xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0. Results DCFPyL displays a Ki value of 1.1 ± 0.1 nM for PSMA. [18F]DCFPyL was produced in radiochemical yields of 36-53% (decay corrected) and specific radioactivities of 340 – 480 Ci/mmol (12.6 – 17.8 GBq/μmol, n = 3). In an immunocompromised mouse model [18F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 h post-injection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PIP tumor, with a ratio of 358:1 of uptake within PIP to PSMA− PC3 flu tumor placed in the opposite flank. At or after 1 h post-injection, minimal non-target tissue uptake of [18F]DCFPyL was observed. The bladder wall is the dose-limiting organ. Conclusions These data suggest [18F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues. PMID:22042970

  20. DIETARY AGENTS FOR PREVENTION AND TREATMENT OF LUNG CANCER

    PubMed Central

    Khan, Naghma; Mukhtar, Hasan

    2015-01-01

    Lung cancer is a prominent cause of cancer-associated mortality worldwide. The main reason for high mortality due to lung cancer is attributable to the fact that the diagnosis is generally made when it has spread beyond a curable stage and cannot be treated surgically or with radiation therapy. Therefore, new approaches like dietary modifications could be extremely useful in reducing lung cancer incidences. Several fruits and vegetables offer a variety of bioactive compounds to afford protection against several diseases, including lung cancer. A number of research studies involving dietary agents provide strong evidence for their role in the prevention and treatment of lung cancer, and have identified their molecular mechanisms of action and potential targets. In this review article, we summarize data from in-vitro and in-vivo studies and where available, in clinical trials, on the effects of some of the most promising dietary agents against lung cancer. PMID:25644088

  1. Basal cell cancer (image)

    MedlinePlus

    ... is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure rate of more than 95%, but regular examination ...

  2. Intelligent design of nano-scale molecular imaging agents.

    PubMed

    Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

    2012-12-12

    Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on-off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

  3. Intelligent Design of Nano-Scale Molecular Imaging Agents

    PubMed Central

    Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

    2012-01-01

    Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents. PMID:23235326

  4. Gold nanoclusters as contrast agents for fluorescent and X-ray dual-modality imaging.

    PubMed

    Zhang, Aili; Tu, Yu; Qin, Songbing; Li, Yan; Zhou, Juying; Chen, Na; Lu, Qiang; Zhang, Bingbo

    2012-04-15

    Multimodal imaging technique is an alternative approach to improve sensitivity of early cancer diagnosis. In this study, highly fluorescent and strong X-ray absorption coefficient gold nanoclusters (Au NCs) are synthesized as dual-modality imaging contrast agents (CAs) for fluorescent and X-ray dual-modality imaging. The experimental results show that the as-prepared Au NCs are well constructed with ultrasmall sizes, reliable fluorescent emission, high computed tomography (CT) value and fine biocompatibility. In vivo imaging results indicate that the obtained Au NCs are capable of fluorescent and X-ray enhanced imaging.

  5. Gold nanoparticles as novel agents for cancer therapy

    PubMed Central

    Jain, S; Hirst, D G; O'Sullivan, J M

    2012-01-01

    Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed. PMID:22010024

  6. Polypyrrole Hollow Microspheres as Echogenic Photothermal Agent for Ultrasound Imaging Guided Tumor Ablation

    NASA Astrophysics Data System (ADS)

    Zha, Zhengbao; Wang, Jinrui; Qu, Enze; Zhang, Shuhai; Jin, Yushen; Wang, Shumin; Dai, Zhifei

    2013-08-01

    Ultrasound (US) imaging provides a valuable opportunity to administer photothermal therapy (PTT) of cancer with real-time guidance to ensure proper targeting, but only a few theranostic agents were developed by physically grafting near infrared (NIR)-absorbing inorganic nanomaterials to ready-made ultrasound contrast agents (UCAs) for US imaging guided PTT. In this paper, NIR absorbing hollow microspheres were generated from polypyrrole merely using a facile one-step microemulsion method. It was found that the obtained polypyrrole hollow microspheres (PPyHMs) can act as an efficient theranostic agent not only to enhance US imaging greatly, but also exhibit excellent photohyperthermic effects. The contrast consistently sustained the echo signals for no less than 5 min and the NIR laser light ablated the tumor completely within two weeks in the presence of PPyHMs. More importantly, no use of additional NIR absorber substantially minimizes an onetime dose of the theranostic agent.

  7. Polypyrrole Hollow Microspheres as Echogenic Photothermal Agent for Ultrasound Imaging Guided Tumor Ablation

    PubMed Central

    Zha, Zhengbao; Wang, Jinrui; Qu, Enze; Zhang, Shuhai; Jin, Yushen; Wang, Shumin; Dai, Zhifei

    2013-01-01

    Ultrasound (US) imaging provides a valuable opportunity to administer photothermal therapy (PTT) of cancer with real-time guidance to ensure proper targeting, but only a few theranostic agents were developed by physically grafting near infrared (NIR)-absorbing inorganic nanomaterials to ready-made ultrasound contrast agents (UCAs) for US imaging guided PTT. In this paper, NIR absorbing hollow microspheres were generated from polypyrrole merely using a facile one-step microemulsion method. It was found that the obtained polypyrrole hollow microspheres (PPyHMs) can act as an efficient theranostic agent not only to enhance US imaging greatly, but also exhibit excellent photohyperthermic effects. The contrast consistently sustained the echo signals for no less than 5 min and the NIR laser light ablated the tumor completely within two weeks in the presence of PPyHMs. More importantly, no use of additional NIR absorber substantially minimizes an onetime dose of the theranostic agent. PMID:23912977

  8. AEG-1 promoter-mediated imaging of prostate cancer

    PubMed Central

    Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C.; Gabrielson, Matthew; Sysa, Polina; Minn, Il; Green, Gilbert; Simmons, Brian; Gabrielson, Kathleen; Sarkar, Siddik; Fisher, Paul B.; Pomper, Martin G.

    2014-01-01

    We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single photon emission-computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for non-invasive clinical imaging. Further, the approach compares favorably to accepted and emerging clinical standards, including positron emission tomography with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. PMID:25145668

  9. Microtubule-binding agents: a dynamic field of cancer therapeutics

    PubMed Central

    Dumontet, Charles; Jordan, Mary Ann

    2010-01-01

    Preface Microtubules are dynamic filamentous cytoskeletal proteins that are an important therapeutic target in tumor cells. Microtubule binding agents have been part of the pharmacopoeia of cancer for decades, and until the advent of targeted therapy microtubules were the only alternative to DNA as a therapeutic target in cancer. The screening of a variety of botanical species and marine organisms has yielded promising new antitubulin agents with novel properties. Enhanced tumor specificity, reduced neurotoxicity, and insensitivity to chemoresistance mechanisms are the three main objectives in the current search for novel microtubule binding agents. PMID:20885410

  10. Quantitative Imaging in Cancer Clinical Trials.

    PubMed

    Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L

    2016-01-15

    As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.

  11. Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy

    PubMed Central

    Rajora, Maneesha A.; Zheng, Gang

    2016-01-01

    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 tumors 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. PMID:27729859

  12. Spectral imaging detects breast cancer in fresh unstained specimens

    NASA Astrophysics Data System (ADS)

    Chung, Alice; Gaon, Mark; Jeong, Jihoon; Karlan, Scott; Lindsley, Erik; Wachsmann-Hogiu, Sebastian; Xiong, Yizhi; Zhao, Tong; Farkas, Daniel L.

    2006-02-01

    Spectral imaging has recently been introduced in the biomedical field as a noninvasive, quantitative means of studying biological tissues. Many of its potential applications have been demonstrated (in vitro and, to a lesser degree, in vivo) with the use of stains or dyes. Successful translation to the clinical environment has been largely lagging, due to safety considerations and regulatory limitations preventing use of contrast agents in humans. We report experiments showing the feasibility of high-resolution spectral imaging of breast cancer without the use of contrast agents, thus completing the continuum of translational research, to in vivo imaging that will be directly applicable in the clinical environment. Our initial work focused on image acquisition using Fourier transform microinterferometry and subsequent segmentation of both stained and unstained breast cancer slides-derived image sets. We then applied our techniques to imaging fresh unstained ex vivo specimens of rat breast cancer and sentinel lymph nodes. We also investigated multiple methods of classification to optimize our image analyses, and preliminary results for the best algorithm tested yielded an overall sensitivity of 96%, and a specificity of 92% for cancer detection. Using spectral imaging and classification techniques, we were able to demonstrate that reliable detection of breast cancer in fixed and fresh unstained specimens of breast tissue is possible.

  13. Radiology Network (ACRIN) - Cancer Imaging Program

    Cancer.gov

    ACRIN is funded to improve the quality and utility of imaging in cancer research and cancer care through expert, multi-institutional clinical evaluation of discoveries and technological innovations relevant to imaging science as applied in clinical oncology.

  14. Novel targeted agents for the treatment of advanced breast cancer.

    PubMed

    de la Vega, Máximo; Díaz-Cantón, Enrique; Alvarez, Ricardo H

    2012-05-01

    The discovery of the molecular processes involved in cancer development has led to the design of an array of targeted agents. These agents, directed to specific proteins in the machinery of cancer cells, interfere with vital cascades involved in cell invasion, metastasis, apoptosis, cell-cycle control and angiogenesis. In breast cancer, the main pathways studied and targeted by drugs are the HER2 pathway, EGFR, VEGF, PI3K/Akt/mammalian target of rapamycin (PI3K-M-Tor), IGF/IGFR, poly(ADP ribose) polymerase 1, HDAC and many others. In this review, we present the most promising studies of these new targeted therapies and novel combination of targeted therapies with cytotoxic agents for the treatment of breast cancer patients. PMID:22571614

  15. ICMIC Institutions - Cancer Imaging Program

    Cancer.gov

    ICMIC grants facilitate interaction among scientists from a variety of fields to conduct multidisciplinary research on cellular and molecular imaging related to cancer. Pre-ICMIC planning grants have provided time and funds for investigators and institutions to prepare themselves, organizationally and scientifically, to establish ICMICs.

  16. Progress in prostate cancer imaging

    PubMed Central

    Gulley, James L.; Emberton, Mark; Kurhanewicz, John; Choyke, Peter

    2013-01-01

    There are multiple new technologies being developed for imaging of advanced prostate cancer. This Seminar article highlights several of these emerging modalities that were discussed at the Society of Urologic Oncology annual meeting in Bethesda, MD. © 2012 Elsevier Inc. All rights reserved. PMID:23218070

  17. Mixed lanthanide oxide nanoparticles as dual imaging agent in biomedicine

    NASA Astrophysics Data System (ADS)

    Xu, Wenlong; Bony, Badrul Alam; Kim, Cho Rong; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Lee, Gang Ho

    2013-11-01

    There is no doubt that the molecular imaging is an extremely important technique in diagnosing diseases. Dual imaging is emerging as a step forward in molecular imaging technique because it can provide us with more information useful for diagnosing diseases than single imaging. Therefore, diverse dual imaging modalities should be developed. Molecular imaging generally relies on imaging agents. Mixed lanthanide oxide nanoparticles could be valuable materials for dual magnetic resonance imaging (MRI)-fluorescent imaging (FI) because they have both excellent and diverse magnetic and fluorescent properties useful for dual MRI-FI, depending on lanthanide ions used. Since they are mixed nanoparticles, they are compact, robust, and stable, which is extremely useful for biomedical applications. They can be also easily synthesized with facile composition control. In this study, we explored three systems of ultrasmall mixed lanthanide (Dy/Eu, Ho/Eu, and Ho/Tb) oxide nanoparticles to demonstrate their usefulness as dual T2 MRI-FI agents.

  18. A targeted molecular probe for colorectal cancer imaging

    NASA Astrophysics Data System (ADS)

    Attramadal, T.; Bjerke, R.; Indrevoll, B.; Moestue, S.; Rogstad, A.; Bendiksen, R.; Healey, A.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. Morbidity, mortality and healthcare costs can be reduced if the disease can be detected at an early stage. Screening is a viable approach as there is a clear link to risk factors such as age. We have developed a fluorescent contrast agent for use during colonoscopy. The agent is administered intravenously and is targeted to an early stage molecular marker for colorectal cancer. The agent consists of a targeting section comprising a peptide, and a fluorescent reporter molecule. Clinical imaging of the agent is to be performed with a far red fluorescence imaging channel (635 nm excitation/660-700 nm emission) as an adjunct to white light colonoscopy. Preclinical proof of mechanism results are presented. The compound has a K d of ~3nM. Two human xenograft tumour models were used. Tumour cells were implanted and grown subcutaneously in nude mice. Imaging using a fluorescence reflectance imaging system and quantitative biodistribution studies were performed. Substances tested include the targeted agent, and a scrambled sequence of the peptide (no binding) used as a negative control. Competition studies were also performed by co-administration of 180 times excess unlabelled peptide. Positive imaging contrast was shown in the tumours, with a clear relationship to expression levels (confirmed with quantitative biodistribution data). There was a significant difference between the positive and negative control substances, and a significant reduction in contrast in the competition experiment.

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

    PubMed

    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.

  20. Gadolinium oxide nanoparticles as potential multimodal imaging and therapeutic agents.

    PubMed

    Kim, Tae Jeong; Chae, Kwon Seok; Chang, Yongmin; Lee, Gang Ho

    2013-01-01

    Potentials of hydrophilic and biocompatible ligand coated gadolinium oxide nanoparticles as multimodal imaging agents, drug carriers, and therapeutic agents are reviewed. First of all, they can be used as advanced T1 magnetic resonance imaging (MRI) contrast agents because they have r1 larger than those of Gd(III)-chelates due to a high density of Gd(III) per nanoparticle. They can be further functionalized by conjugating other imaging agents such as fluorescent imaging (FI), X-ray computed tomography (CT), positron emission tomography (PET), and single photon emission tomography (SPECT) agents. They can be also useful for drug carriers through morphology modifications. They themselves are also potential CT and ultrasound imaging (USI) contrast and thermal neutron capture therapeutic (NCT) agents, which are superior to commercial iodine compounds, air-filled albumin microspheres, and boron ((10)B) compounds, respectively. They, when conjugated with targeting agents such as antibodies and peptides, will provide enhanced images and be also very useful for diagnosis and therapy of diseases (so called theragnosis).

  1. Lung cancer and angiogenesis imaging using synchrotron radiation

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

    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.

  2. Clinical photoacoustic imaging of cancer.

    PubMed

    Valluru, Keerthi S; Willmann, Juergen K

    2016-10-01

    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. PMID:27669961

  3. Clinical photoacoustic imaging of cancer

    PubMed Central

    2016-01-01

    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. PMID:27669961

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

    PubMed

    D'Hollander, Antoine; Mathieu, Evelien; Jans, Hilde; Vande Velde, Greetje; Stakenborg, Tim; Van Dorpe, Pol; Himmelreich, Uwe; Lagae, Liesbet

    2016-01-01

    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. PMID:27536107

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

    PubMed Central

    D’Hollander, Antoine; Mathieu, Evelien; Jans, Hilde; Vande Velde, Greetje; Stakenborg, Tim; Van Dorpe, Pol; Himmelreich, Uwe; Lagae, Liesbet

    2016-01-01

    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. PMID:27536107

  6. Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

    PubMed Central

    Chopra, Arvind; Shan, Liang; Eckelman, W. C.; Leung, Kam; Latterner, Martin; Bryant, Stephen H.; Menkens, Anne

    2011-01-01

    The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov) to students, researchers and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, x-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration (FDA) as well as a CSV file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, preclinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments or suggestions for further improvement of the database by writing to the editors at: micad@nlm.nih.gov PMID:21989943

  7. Chromatin-modifying agents in anti-cancer therapy.

    PubMed

    Seidel, Carole; Florean, Cristina; Schnekenburger, Michael; Dicato, Mario; Diederich, Marc

    2012-11-01

    Epigenetic alterations are involved in every step of carcinogenesis. The development of chromatin-modifying agents (CMAs) has provided the ability to fight cancer by reversing these alterations. Currently, four CMAs have been approved for cancer treatment; two DNA demethylating agents and two deacetylase inhibitors. A number of promising CMAs are undergoing clinical trials in several cancer types. Moreover, already approved CMAs are still under clinical investigation to improve their efficacy and to extend their use to a broader panel of cancers. Combinatorial treatments with CMAs are already considered a promising strategy to improve clinical benefits and to limit side effects. The real mechanisms by which these CMAs allow the improvement and remission of patients are still obscure. A deeper analysis of the molecular features expressed by responding patients should be performed to reveal this information. In this review, we focus on clinical trials with CMAs, discussing the success and the pitfalls of this new class of anti-cancer drugs.

  8. DCIDE - Cancer Imaging Program

    Cancer.gov

    DCIDE is no longer taking applications, as of August 2009. Imaging drug development resources should be requested through the new NExT/CBC program which has its own application and review process. See NCI Experimental Therapeutics Program (NExT). There are 4 review dates per year, instead of the previous DCIDE submission and review process.

  9. Molecular imaging in ovarian cancer.

    PubMed

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  10. Medical imaging in lung cancer

    SciTech Connect

    Heelan, R.T.; Bains, M.S.; Yeh, S.

    1987-10-01

    The routine imaging work-up of suspected lung cancer should include posteroanterior and lateral chest radiographs and, in most cases, a computed tomographic (CT) scan of the entire thorax and adrenal glands. In asymptomatic patients with adenocarcinoma of the lung, there is justification for doing routine contrast-enhanced CT examination of the brain. Further imaging workup will be suggested by the patient's history, physical findings, and laboratory findings. Magnetic resonance imaging of the chest in patients with lung cancer is being investigated, but current studies comparing it with CT demonstrate no definite advantage at this time, with the possible exception of the lung apex in which T1 weighted thin-section coronal views are useful.

  11. Dendrimer-entrapped metal colloids as imaging agents.

    PubMed

    Li, Du; Wen, Shihui; Shi, Xiangyang

    2015-01-01

    This review reports the recent advances in dendrimer-entrapped metal colloids as contrast agents for biomedical imaging applications. The versatile dendrimer scaffolds with 3-dimensional spherical shape, highly branched internal cavity, tunable surface conjugation chemistry, and excellent biocompatibility and nonimmunogenicity afford their uses as templates to create multifunctional dendrimer-entrapped metal colloids for mono- or multi- mode molecular imaging applications. In particular, multifunctional dendrimer-entrapped gold nanoparticles with different surface modifications have been used for fluorescence imaging, targeted tumor computed tomography (CT) imaging, enhanced blood pool CT imaging, dual mode CT/MR imaging, and tumor theranostics (combined CT imaging and chemotherapy) will be introduced and discussed in detail.

  12. Quantitative imaging of cell-permeable magnetic resonance contrast agents using x-ray fluorescence.

    PubMed

    Endres, Paul J; Macrenaris, Keith W; Vogt, Stefan; Allen, Matthew J; Meade, Thomas J

    2006-01-01

    The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III) chelator with a cellular transduction moiety. Specifically, we coupled Gd(III)-diethylenetriaminepentaacetic acid DTPA and Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8-amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-(N,N-dimethylamino)stilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF). Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 10(3) better than (153)Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T(1) analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination. PMID:17150161

  13. Phase 2 N01 Program - Cancer Imaging Program

    Cancer.gov

    The Phase 2 N01 Program is a CTEP-CIP collaboration includes 7 contractors, most of whom consist of multi-institutional consortia, and includes a total of 22 NCI-designated Cancer Centers. These sites carry out early clinical trials with CTEP and CIP-held IND agents, with an emphasis on phase 2 trials, but including phase 1 trials as well. These trials include the evaluation of novel imaging agents and methods to enhance the evaluation of novel therapeutics.

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Metabolic alterations in bladder cancer: applications for cancer imaging.

    PubMed

    Whyard, Terry; Waltzer, Wayne C; Waltzer, Douglas; Romanov, Victor

    2016-02-01

    uptake of glucose by BC cells gives an opportunity to develop NMR based imaging procedures where glucose or its derivatives can serve as a contrasting agent. In addition, metabolic alterations observed in BC cells could provide the basis for development of new anti-cancer therapeutics. PMID:26808412

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

    PubMed Central

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

    2014-01-01

    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. PMID:25530615

  17. Spectroscopic Imaging of Bladder Cancer

    SciTech Connect

    Demos, S G; Gandour-Edwards, R; Ramsamooj, R; deVere White, R

    2003-01-01

    The feasibility of developing bladder cancer detection methods using intrinsic tissue optical properties is the focus of this investigation. In vitro experiments have been performed using polarized elastic light scattering in combination with tissue autofluorescence in the NIR spectral region under laser excitation in the green and red spectral regions. The experimental results obtained from a set of tissue specimens from 25 patients reveal the presence of optical fingerprint characteristics suitable for cancer detection with high contrast and accuracy. These photonic methods are compatible with existing endoscopic imaging modalities which make them suitable for in-vivo application.

  18. [Molecular targeting agents for advanced or recurrent gastric cancer patients].

    PubMed

    Fuse, Nozomu

    2012-10-01

    The combination of fluoropyrimidine and platinum with or without epirubicin or docetaxel has been regarded as standard chemotherapy for advanced or recurrent gastric cancer patients. Recently, trastuzumab with conventional chemotherapy for human epidermal growth factor receptor(HER)2 positive gastric cancer patients was proved to be effective in terms of survival benefit and has become one of standard treatment options. Other molecular target agents, such as HER1, HER2, vascular endothelial growth factor, hepatocyte growth factor/c-Met, fibroblast growth factor and mammalian target of rapamycin inhibitors were and are being evaluated in clinical trials. However, no agents other than trastuzumab have shown clear survival benefit. The predictive biomarker seems to be necessary for developing new molecular targeting agents for gastric cancer with heterogeneity.

  19. PET/SPECT imaging agents for neurodegenerative diseases

    PubMed Central

    Zhu, Lin; Ploessl, Karl; Kung, Hank F.

    2014-01-01

    Single photon emission computed tomography (SPECT) or positron emission computed tomography (PET) imaging agents for neurodegenerative disease have a significant impact on clinical diagnosis and patient care. The examples of Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) imaging agents described in this paper provide a general view on how imaging agents, ie radioactive drugs, are selected, chemically prepared and applied in humans. Imaging the living human brain can provide unique information on the pathology and progression of neurodegenerative diseases, such as AD and PD. The imaging method will also facilitate preclinical and clinical trials of new drugs offering specific information related to drug binding sites in the brain. In the future, chemists will continue to play important roles in identifying specific targets, synthesizing target-specific probes for screening and ultimately testing them by in vitro and in vivo assays. PMID:24676152

  20. Optimal flushing agents for integrated optical and acoustic imaging systems

    NASA Astrophysics Data System (ADS)

    Li, Jiawen; Minami, Hataka; Steward, Earl; Ma, Teng; Mohar, Dilbahar; Robertson, Claire; Shung, Kirk; Zhou, Qifa; Patel, Pranav; Chen, Zhongping

    2015-05-01

    An increasing number of integrated optical and acoustic intravascular imaging systems have been developed and hold great promise for accurately diagnosing vulnerable plaques and guiding atherosclerosis treatment. However, in any intravascular environment, the vascular lumen is filled with blood, a high-scattering source for optical and high-frequency ultrasound signals. Blood must be flushed away to provide clearer images. To our knowledge, no research has been performed to find the ideal flushing agent for combined optical and acoustic imaging techniques. We selected three solutions as potential flushing agents for their image-enhancing effects: mannitol, dextran, and iohexol. Testing of these flushing agents was performed in a closed-loop circulation model and in vivo on rabbits. We found that a high concentration of dextran was the most useful for simultaneous intravascular ultrasound and optical coherence tomography imaging.

  1. Optimal flushing agents for integrated optical and acoustic imaging systems

    PubMed Central

    Li, Jiawen; Minami, Hataka; Steward, Earl; Ma, Teng; Mohar, Dilbahar; Robertson, Claire; Shung, Kirk; Zhou, Qifa; Patel, Pranav; Chen, Zhongping

    2015-01-01

    Abstract. An increasing number of integrated optical and acoustic intravascular imaging systems have been developed and hold great promise for accurately diagnosing vulnerable plaques and guiding atherosclerosis treatment. However, in any intravascular environment, the vascular lumen is filled with blood, a high-scattering source for optical and high-frequency ultrasound signals. Blood must be flushed away to provide clearer images. To our knowledge, no research has been performed to find the ideal flushing agent for combined optical and acoustic imaging techniques. We selected three solutions as potential flushing agents for their image-enhancing effects: mannitol, dextran, and iohexol. Testing of these flushing agents was performed in a closed-loop circulation model and in vivo on rabbits. We found that a high concentration of dextran was the most useful for simultaneous intravascular ultrasound and optical coherence tomography imaging. PMID:25985096

  2. Intravascular contrast agents suitable for magnetic resonance imaging. [Dogs

    SciTech Connect

    Runge, V.M.; Clanton, J.A.; Herzer, W.A.; Gibbs, S.J.; Price, A.C.; Partain, C.L.; James, A.E. Jr.

    1984-10-01

    Two paramagnetic chelates, chromium EDTA and gadolinium DTPA, were evaluated as potential intravenous contrast agents for magnetic resonance imaging. After evaluating both agents in vitro, in vivo studies were conducted in dogs to document changes in renal appearance produced by contrast injection. Acute splenic and renal infarction were diagnosed with contrast-enhanced MR and confirmed by gamma camera imaging following administration of Tc-99m-labeled DMSA and sulfur colloid. The authors conclude that intravenous paramagnetic contrast agents presently offer the best mechanism for assessment of tissue function and changes in perfusion with MR.

  3. Botanical Agents for the Treatment of Nonmelanoma Skin Cancer

    PubMed Central

    2013-01-01

    Nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are common neoplasms worldwide and are the most common cancers in the United States. Standard therapy for cutaneous neoplasms typically involves surgical removal. However, there is increasing interest in the use of topical alternatives for the prevention and treatment of nonmelanoma skin cancer, particularly superficial variants. Botanicals are compounds derived from herbs, spices, stems, roots, and other substances of plant origin and may be used in the form of dried or fresh plants, extracted plant material, or specific plant-derived chemicals. They possess multiple properties including antioxidant, anti-inflammatory, and immunomodulatory properties and are, therefore, believed to be possible chemopreventive agents or substances that may suppress or reverse the process of carcinogenesis. Here, we provide a review of botanical agents studied for the treatment and prevention of nonmelanoma skin cancers. PMID:23983679

  4. Hereditary cancer syndromes as model systems for chemopreventive agent development.

    PubMed

    Walcott, Farzana L; Patel, Jigar; Lubet, Ronald; Rodriguez, Luz; Calzone, Kathleen A

    2016-02-01

    Research in chemoprevention has undergone a shift in emphasis for pragmatic reasons from large, phase III randomized studies to earlier phase studies focused on safety, mechanisms, and utilization of surrogate endpoints such as biomarkers instead of cancer incidence. This transition permits trials to be conducted in smaller populations and at substantially reduced costs while still yielding valuable information. This article will summarize some of the current chemoprevention challenges and the justification for the use of animal models to facilitate identification and testing of chemopreventive agents as illustrated though four inherited cancer syndromes. Preclinical models of inherited cancer syndromes serve as prototypical systems in which chemopreventive agents can be developed for ultimate application to both the sporadic and inherited cancer settings. PMID:26970132

  5. Molecular targeting agents in cancer therapy: science and society.

    PubMed

    Shaikh, Asim Jamal

    2012-01-01

    The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.

  6. Inorganic nanoparticle-based contrast agents for molecular imaging

    PubMed Central

    Cho, Eun Chul; Glaus, Charles; Chen, Jingyi; Welch, Michael J.; Xia, Younan

    2010-01-01

    Inorganic nanoparticles including semiconductor quantum dots, iron oxide nanoparticles, and gold nanoparticles have been developed as contrast agents for diagnostics by molecular imaging. Compared to traditional contrast agents, nanoparticles offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size, and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multi-modal imaging. Here, we review recent advances in the development of contrast agents based on inorganic nanoparticles for molecular imaging, with a touch on contrast enhancement, surface modification, tissue targeting, clearance, and toxicity. As research efforts intensify, contrast agents based on inorganic nanoparticles that are highly sensitive, target-specific, and safe to use are expected to enter clinical applications in the near future. PMID:21074494

  7. Magnetic resonance imaging of penile cancer.

    PubMed

    Gupta, Sumit; Rajesh, Arumugam

    2014-05-01

    Penile cancer is a rare neoplasm that, although rare in the developed world, has devastating physical and psychological consequences for the patient. Novel MR imaging techniques such as lymphotropic nanoparticle-enhanced MR imaging may help identify metastatic lymph node disease. This article reviews the normal penile anatomy and MR imaging techniques and features of primary and metastatic penile cancer. Recent advances in penile cancer imaging are discussed.

  8. Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities

    PubMed Central

    Zehri, Aqib H.; Ramey, Wyatt; Georges, Joseph F.; Mooney, Michael A.; Martirosyan, Nikolay L.; Preul, Mark C.; Nakaji, Peter

    2014-01-01

    Background: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. Methods: A comprehensive literature search was performed utilizing PubMed and key words: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. Results: Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. Conclusion: In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery. PMID:24872922

  9. Ideal flushing agents for integrated optical acoustic imaging systems

    NASA Astrophysics Data System (ADS)

    Li, Jiawen; Minami, Hataka; Steward, Earl; Ma, Teng; Mohar, Dilbahar; Robertson, Claire; Shung, K. Kirk; Zhou, Qifa; Patel, Pranav M.; Chen, Zhongping

    2015-02-01

    An increased number of integrated optical acoustic intravascular imaging systems have been researched and hold great hope for accurate diagnosing of vulnerable plaques and for guiding atherosclerosis treatment. However, in any intravascular environment, vascular lumen is filled with blood, which is a high-scattering source for optical and high frequency ultrasound signals. Blood must be flushed away to make images clear. To our knowledge, no research has been performed to find the ideal flushing agent that works for both optical and acoustic imaging techniques. We selected three solutions, mannitol, dextran and iohexol, as flushing agents because of their image-enhancing effects and low toxicities. Quantitative testing of these flushing agents was performed in a closed loop circulation model and in vivo on rabbits.

  10. Recent Advances in Molecular Image-Guided Cancer Radionuclide Therapy.

    PubMed

    Gao, Duo; Sun, Xianlei; Gao, Liquan; Liu, Zhaofei

    2015-01-01

    Cancer-targeted radionuclide therapy is a promising approach for the treatment of a wide variety of malignancies, especially those resistant to conventional therapies. However, to improve the use of targeted radionuclide therapy for the management of cancer patients, the in vivo behaviors, dosimetry, and efficacy of radiotherapeutic agents need to be well characterized and monitored. Molecular imaging, which is a powerful tool for the noninvasive characterization and quantification of biological processes in living subjects at the cellular and molecular levels, plays an important role in the guidance of cancer radionuclide therapy. In this review, we introduce the radiotherapeutics for cancer-targeted therapy and summarize the most recent evidence supporting the use of molecular imaging to guide cancer radionuclide therapy.

  11. Enhanced sensitivity carbon nanotubes as targeted photoacoustic molecular imaging agents

    NASA Astrophysics Data System (ADS)

    de la Zerda, Adam; Liu, Zhuang; Zavaleta, Cristina; Bodapati, Sunil; Teed, Robert; Vaithilingam, Srikant; Ma, Te-Jen; Oralkan, Omer; Chen, Xiaoyuan; Khuri-Yakub, Butrus T.; Dai, Hongjie; Gambhir, Sanjiv S.

    2009-02-01

    Photoacoustic imaging of living subjects offers high spatial resolution at increased tissue depths compared to purely optical imaging techniques. We have recently shown that intravenously injected single walled carbon nanotubes (SWNTs) can be used as targeted photoacoustic imaging agents in living mice using RGD peptides to target αvβ3 integrins. We have now developed a new targeted photoacoustic imaging agent based on SWNTs and Indocyanine Green (SWNT-ICG) with absorption peak at 780nm. The photoacoustic signal of the new imaging agent is enhanced by ~20 times as compared to plain SWNTs. The particles are synthesized from SWNT-RGD that noncovalently attach to multiple ICG molecules through pi-pi stacking interactions. Negative control particles had RAD peptide instead of RGD. We measured the serum stability of the particles and verified that the RGD/RAD conjugation did not alter the particle's absorbance spectrum. Finally, through cell uptake studies with U87MG cells we verified that the particles bind selectively to αvβ3 integrin. In conclusion, the extremely high absorption of the SWNT-ICG particles shows great promise for high sensitivity photoacoustic imaging of molecular targets in-vivo. This work lays the foundations for future in-vivo studies that will use the SWNT-ICG particles as imaging agents administered systemically.

  12. Modified natural nanoparticles as contrast agents for medical imaging

    PubMed Central

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

    2009-01-01

    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 advantages as delivery platforms such as biodegradability. In addition, our understanding of natural nanoparticles is quite advanced, allowing their adaptation as contrast agents. They can be labeled with small molecules or ions such as Gd3+ to act as contrast agents for magnetic resonance imaging, 18F to act as positron emission tomography contrast agents or fluorophores to act as contrast agents for fluorescence techniques. Additionally, inorganic nanoparticles such as iron oxide, gold nanoparticles or quantum dots can be incorporated to add further contrast functionality. Furthermore, these natural nanoparticle contrast agents can be rerouted from their natural targets via the attachment of targeting molecules. In this review, we discuss the various modified natural nanoparticles that have been exploited as contrast agents. PMID:19900496

  13. Rational Choice of Antiemetic Agents during Cancer Chemotherapy

    PubMed Central

    Brigden, Malcolm L.; Wilson, Kenneth S.; Barnett, Jeffrey B.

    1983-01-01

    Nausea and vomiting are major limitations in cancer chemotherapy. Individual susceptibility to nausea varies enormously. There is no ideal antiemetic, but some work with some chemotherapeutic agents, and some are more effective in younger patients. This article describes a flexible, stepped approach using the phenothiazines, metoclopramide, cannabinoids, anticholinergics, antihistamines and others. PMID:21283402

  14. Simulating Cancer Growth with Multiscale Agent-Based Modeling

    PubMed Central

    Wang, Zhihui; Butner, Joseph D.; Kerketta, Romica; Cristini, Vittorio; Deisboeck, Thomas S.

    2014-01-01

    There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models. PMID:24793698

  15. Dietary Agents in Cancer Prevention: An Immunological Perspective †

    PubMed Central

    Zheng, Ya Ying; Viswanathan, Bharathi; Kesarwani, Pravin; Mehrotra, Shikhar

    2013-01-01

    Skin cancer is the most common form of cancer diagnosed in the United States. Exposure to solar ultraviolet (UV) radiations is believed to be the primary cause for skin cancer. Excessive UV radiation can lead to genetic mutations and damage in the skin's cellular DNA that in turn can lead to skin cancer. Lately, chemoprevention by administering naturally occurring non-toxic dietary compounds has proven to be a potential strategy to prevent the occurrence of tumors. Attention has been drawn towards several natural dietary agents such as resveratrol, one of the major components found in grapes, red wines, berries and peanuts, proanthocyanidins from grape seeds, (-)-epigallocatechin-3-gallate (EGCG) from green tea etc. However, the effect these dietary agents have on the immune system and the immunological mechanisms involved there in are still being explored. In this review we shall focus on the role of key chemopreventive agents on various immune cells and discuss their potential as anti-tumor agents with an immunological perspective. PMID:22372381

  16. Cobalt Zinc Ferrite Nanoparticles as a Potential Magnetic Resonance Imaging Agent: An In vitro Study

    PubMed Central

    Ghasemian, Zeinab; Shahbazi-Gahrouei, Daryoush; Manouchehri, Sohrab

    2015-01-01

    Background: Magnetic Nanoparticles (MNP) have been used for contrast enhancement in Magnetic Resonance Imaging (MRI). In recent years, research on the use of ferrite nanoparticles in T2 contrast agents has shown a great potential application in MR imaging. In this work, Co0.5Zn0.5Fe2O4 and Co0.5Zn0.5Fe2O4-DMSA magnetic nanoparticles, CZF-MNPs and CZF-MNPs-DMSA, were investigated as MR imaging contrast agents. Methods: Cobalt zinc ferrite nanoparticles and their suitable coating, DMSA, were investigated under in vitro condition. Human prostate cancer cell lines (DU145 and PC3) with bare (uncoated) and coated magnetic nanoparticles were investigated as nano-contrast MR imaging agents. Results: Using T2-weighted MR images identified that signal intensity of bare and coated MNPs was enhanced with increasing concentration of MNPs in water. The values of 1/T2 relaxivity (r2) for bare and coated MNPs were found to be 88.46 and 28.80 (mM−1 s−1), respectively. Conclusion: The results show that bare and coated MNPs are suitable as T2-weighted MR imaging contrast agents. Also, the obtained r2/r1 values (59.3 and 50) for bare and coated MNPs were in agreement with the results of other previous relevant works. PMID:26140183

  17. Pharmacological inhibitors of autophagy as novel cancer therapeutic agents.

    PubMed

    Wang, Cheng; Hu, Qidong; Shen, Han-Ming

    2016-03-01

    Autophagy is an evolutionarily conserved cellular degradative process in which intracellular components (cellular proteins and organelles) are engulfed in autophagosomes which then fuse with lysosomes to form autolysosome for degradation. Autophagy is closely implicated in various physio-pathological processes and human diseases. Among them, the roles of autophagy in cancer have been extensively studied. Increasing evidence has demonstrated that inhibiting autophagy is a novel and promising approach in cancer therapy, based on the notion that autophagy is a pro-survival mechanism in cancer cells under therapeutic stress, and induction of autophagy is associated with chemoresistance of cancer cells to chemotherapeutic agents. Thus, suppression of autophagy would sensitize resistance tumor cells to cancer therapeutic agents, thereby supporting the clinical application of autophagy inhibitors. In recent years, significant progress has been achieved in developing autophagy inhibitors and testing their therapeutical potential, either as standalone or as adjuvant therapeutic agents, in cell and animal models, and more importantly in clinical trials. In this review, we will discuss some of these recent advances in development of novel small molecules autophagy inhibitors and their mechanisms of action, together with their applications in clinical trials. PMID:26826398

  18. Imaging agents for in vivo magnetic resonance and scintigraphic imaging

    DOEpatents

    Engelstad, Barry L.; Raymond, Kenneth N.; Huberty, John P.; White, David L.

    1991-01-01

    Methods are provided for in vivo magnetic resonance imaging and/or scintigraphic imaging of a subject using chelated transition metal and lanthanide metal complexes. Novel ligands for these complexes are provided.

  19. Imaging agents for in vivo magnetic resonance and scintigraphic imaging

    DOEpatents

    Engelstad, B.L.; Raymond, K.N.; Huberty, J.P.; White, D.L.

    1991-04-23

    Methods are provided for in vivo magnetic resonance imaging and/or scintigraphic imaging of a subject using chelated transition metal and lanthanide metal complexes. Novel ligands for these complexes are provided. No Drawings

  20. Molecular imaging using PET for breast cancer.

    PubMed

    Kurihara, Hiroaki; Shimizu, Chikako; Miyakita, Yasuji; Yoshida, Masayuki; Hamada, Akinobu; Kanayama, Yousuke; Yonemori, Kan; Hashimoto, Jun; Tani, Hitomi; Kodaira, Makoto; Yunokawa, Mayu; Yamamoto, Harukaze; Watanabe, Yasuyoshi; Fujiwara, Yasuhiro; Tamura, Kenji

    2016-01-01

    Molecular imaging can visualize the biological processes at the molecular and cellular levels in vivo using certain tracers for specific molecular targets. Molecular imaging of breast cancer can be performed with various imaging modalities, however, positron emission tomography (PET) is a sensitive and non-invasive molecular imaging technology and this review will focus on PET molecular imaging of breast cancer, such as FDG-PET, FLT-PET, hormone receptor PET, and anti-HER2 PET.

  1. "Keyhole" method for accelerating imaging of contrast agent uptake.

    PubMed

    van Vaals, J J; Brummer, M E; Dixon, W T; Tuithof, H H; Engels, H; Nelson, R C; Gerety, B M; Chezmar, J L; den Boer, J A

    1993-01-01

    Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeroes for the missing data is followed, blurring results. Substituting instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be usefully accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradient- and spin-echo images are shown. The method is believed to be compatible with other acceleration methods such as half-Fourier reconstruction and reading of more than one line of k space per excitation.

  2. Recent Advances in Higher-order Multimodal Biomedical Imaging Agents

    PubMed Central

    Rieffel, James; Chitgupi, Upendra

    2015-01-01

    Advances in biomedical imaging have spurred the development of integrated multimodal scanners, usually capable of two simultaneous imaging modes. The long-term vision of higher-order multimodality is to improve diagnostics or guidance through analysis of complementary, data-rich, co-registered images. Synergies achieved through combined modalities could enable researchers to better track diverse physiological and structural events, analyze biodistribution and treatment efficacy, and compare established and emerging modalities. Higher-order multimodal approaches stand to benefit from molecular imaging probes and in recent years, contrast agents that have hypermodal characteristics have increasingly been reported in preclinical studies. Given the chemical requirements for contrast agents representing various modalities to be integrated into a single entity, higher-order multimodal agents reported so far tend to be of nanoparticulate form. To date, the majority of reported nanoparticles have included components that are active for magnetic resonance. Herein, we review recent progress in higher-order multimodal imaging agents, which span a range of material and structural classes, that have demonstrated utility in three (or more) imaging modalities. PMID:26185099

  3. Perfusion Imaging with a Freely Diffusible Hyperpolarized Contrast Agent

    PubMed Central

    Grant, Aaron K.; Vinogradov, Elena; Wang, Xiaoen; Lenkinski, Robert E.; Alsop, David C.

    2011-01-01

    Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized 13C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic 13C images acquired in rat brain with a balanced steady-state free precession (bSSFP) sequence following administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2–4s temporal resolution, 2mm slice thickness, and 700 micron in-plane resolution while retaining adequate signal-to-noise ratio. 13C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4T yield T1=46±4s and T2=0.55±0.03s. In the rat brain at 4.7T, analysis of the temporal dynamics of the bSSFP image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T2 of roughly 2–4s and a T1 of 43±24s. In addition, the images indicate that 2-methylpropan-2-ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2-methylpropan-2-ol is a promising agent for robust and quantitative perfusion imaging in the brain and body. PMID:21432901

  4. Contrast agents in diagnostic imaging: Present and future.

    PubMed

    Caschera, Luca; Lazzara, Angelo; Piergallini, Lorenzo; Ricci, Domenico; Tuscano, Bruno; Vanzulli, Angelo

    2016-08-01

    Specific contrast agents have been developed for x ray examinations (mainly CT), sonography and Magnetic Resonance Imaging. Most of them are extracellular agents which create different enhancement on basis of different vascularization or on basis of different interstitial network in tissues, but some can be targeted to a particular cell line (e.g. hepatocyte). Microbubbles can be used as carrier for therapeutic drugs which can be released in specific targets under sonographic guidance, decreasing systemic toxicity and increasing therapeutic effect. Radiologists have to choose a particular contrast agent knowing its physical and chemical properties and the possibility of adverse reactions and balancing them with the clinical benefits of a more accurate diagnosis. As for any drug, contrast agents can cause adverse events, which are more frequent with Iodine based CA, but also with Gd based CA and even with sonographic contrast agents hypersensitivity reaction can occur. PMID:27168225

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

    NASA Astrophysics Data System (ADS)

    Alcantara, David; Pernia Leal, Manuel; Garcia, Irene; Garcia-Martin, Maria Luisa

    2014-12-01

    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.

  6. Molecular imaging of breast cancer: present and future directions

    PubMed Central

    Alcantara, David; Leal, Manuel Pernia; García-Bocanegra, Irene; García-Martín, Maria L.

    2014-01-01

    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 tumor 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 tumor 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. PMID:25566530

  7. Targeting Microtubules by Natural Agents for Cancer Therapy

    PubMed Central

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Mukhtar, Hasan

    2014-01-01

    Natural compounds that target microtubules and disrupt the normal function of the mitotic spindle have proven to be one of the best classes of cancer chemotherapeutic drugs available in clinics to date. There is increasing evidence showing that even minor alteration of microtubule dynamics can engage the spindle checkpoint, arresting cell cycle progression at mitosis and subsequently leading to cell death. Our improved understanding of tumor biology and our continued appreciation for what the microtubule target agents (MTAs) can do has helped pave the way for a new era in the treatment of cancer. The effectiveness of these agents for cancer therapy has been impaired, however, by various side effects and drug resistance. Several new MTAs have shown potent activity against the proliferation of various cancer cells, including resistance to the existing MTAs. Sustained investigation of the mechanisms of action of MTAs, development and discovery of new drugs, and exploring new treatment strategies that reduce side effects and circumvent drug resistance could provide more effective therapeutic options for cancer patients. This review focuses on the successful cancer chemotherapy from natural compounds in clinical settings and the challenges that may abort their usefulness. PMID:24435445

  8. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  9. 4-haloethenylphenyl tropane:serotonin transporter imaging agents

    DOEpatents

    Goodman, Mark M.; Martarello, Laurent

    2005-01-18

    A series of compounds in the 4-fluoroalkyl-3-halophenyl nortropanes and 4-haloethenylphenyl tropane families are described as diagnostic and therapeutic agents for diseases associated with serotonin transporter dysfunction. These compounds bind to serotonin transporter protein with high affinity and selectivity. The invention provides methods of synthesis which incorporate radioisotopic halogens at a last step which permit high radiochemical yield and maximum usable product life. The radiolabeled compounds of the invention are useful as imaging agents for visualizing the location and density of serotonin transporter by PET and SPECT imaging.

  10. User-agent cooperation in multiagent IVUS image segmentation.

    PubMed

    Bovenkamp, E G P; Dijkstra, J; Bosch, J G; Reiber, J H C

    2009-01-01

    Automated interpretation of complex images requires elaborate knowledge and model-based image analysis, but often needs interaction with an expert as well. This research describes expert interaction with a multiagent image interpretation system using only a restricted vocabulary of high-level user interactions. The aim is to minimize inter- and intra-observer variability by keeping the total number of interactions as low and simple as possible. The multiagent image interpretation system has elaborate high-level knowledge-based control over low-level image segmentation algorithms. Agents use contextual knowledge to keep the number of interactions low but, when in doubt, present the user with the most likely interpretation of the situation. The user, in turn, can correct, supplement, and/or confirm the results of image-processing agents. This is done at a very high level of abstraction such that no knowledge of the underlying segmentation methods, parameters or agent functioning is needed. High-level interaction thereby replaces more traditional contour correction methods like inserting points and/or (re)drawing contours. This makes it easier for the user to obtain good results, while inter- and intra-observer variability are kept minimal, since the image segmentation itself remains under control of image-processing agents. The system has been applied to intravascular ultrasound (IVUS) images. Experiments show that with an average of 2-3 high-level user interactions per correction, segmentation results substantially improve while the variation is greatly reduced. The achieved level of accuracy and repeatability is equivalent to that of manual drawing by an expert. PMID:19116192

  11. Anti-angiogenic agents in metastatic colorectal cancer

    PubMed Central

    Konda, Bhavana; Shum, Helen; Rajdev, Lakshmi

    2015-01-01

    Colorectal cancer (CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various anti-angiogenic agents in patients with metastatic CRC (mCRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in mCRC patients. Despite the discovery of several promising anti-angiogenic agents, mCRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients. PMID:26191351

  12. The benefits of paired-agent imaging in molecular-guided surgery: an update on methods and applications (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tichauer, Kenneth M.

    2016-03-01

    One of the major complications with conventional imaging-agent-based molecular imaging, particularly for cancer imaging, is variability in agent delivery and nonspecific retention in biological tissue. Such factors can account to "swamp" the signal arising from specifically bound imaging agent, which is presumably indicative of the concentration of targeted biomolecule. In the 1950s, Pressman et al. proposed a method of accounting for these delivery and retention effects by normalizing targeted antibody retention to the retention of a co-administered "untargeted"/control imaging agent [1]. Our group resurrected the approach within the last 5 years, finding ways to utilize this so-called "paired-agent" imaging approach to directly quantify biomolecule concentration in tissue (in vitro, ex vivo, and in vivo) [2]. These novel paired-agent imaging approaches capable of quantifying biomolecule concentration provide enormous potential for being adapted to and optimizing molecular-guided surgery, which has a principle goal of identifying distinct biological tissues (tumor, nerves, etc…) based on their distinct molecular environment. This presentation will cover the principles and nuances of paired-agent imaging, as well as the current status of the field and future applications. [1] D. Pressman, E. D. Day, and M. Blau, "The use of paired labeling in the determination of tumor-localizing antibodies," Cancer Res, 17(9), 845-50 (1957). [2] K. M. Tichauer, Y. Wang, B. W. Pogue et al., "Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging," Phys Med Biol, 60(14), R239-69 (2015).

  13. Molecular Targeted Viral Nanoparticles as Tools for Imaging Cancer

    PubMed Central

    Cho, C.F.; Sourabh, S.; Simpson, E.J.; Steinmetz, N.F.; Luyt, L.G.; Lewis, J.D.

    2015-01-01

    Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application. PMID:24243252

  14. Molecular targeted agents for gastric and gastroesophageal junction cancer.

    PubMed

    Oshima, Takashi; Masuda, Munetaka

    2012-04-01

    Despite recent improvements in surgical techniques and chemotherapy, advanced cancers of the stomach and gastroesophageal junction (GEJ) continue to have poor clinical outcomes. However, molecules intimately related to cancer cell proliferation, invasion, and metastasis have been studied as candidates for molecular targeted agents. Target molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways are considered to be promising candidates for molecular targeted therapy for gastric and GEJ cancer. In this review we focus on the recent developments in targeting relevant pathways in these types of cancer.

  15. Production of anti-cancer agent using microbial biotransformation.

    PubMed

    Roh, Changhyun; Kang, ChanKyu

    2014-01-01

    Microbial biotransformation is a great model system to produce drugs and biologically active compounds. In this study, we elucidated the fermentation and production of an anti-cancer agent from a microbial process for regiospecific hydroxylation of resveratrol. Among the strains examined, a potent strain showed high regiospecific hydroxylation activity to produce piceatannol. In a 5 L (w/v 3 L) jar fermentation, this wild type Streptomyces sp. in the batch system produced 205 mg of piceatannol (i.e., 60% yields) from 342 mg of resveratrol in 20 h. Using the product, an in vitro anti-cancer study was performed against a human cancer cell line (HeLa). It showed that the biotransformed piceatannol possessed a significant anticancer activity. This result demonstrates that a biotransformation screening method might be of therapeutic interest with respect to the identification of anti-cancer drugs. PMID:25325153

  16. Metal-Organic Frameworks as Sensory Materials and Imaging Agents

    PubMed Central

    Liu, Demin; Lu, Kuangda; Poon, Christopher

    2014-01-01

    Metal-organic frameworks (MOFs) are a class of hybrid materials self-assembled from organic bridging ligands and metal ion/cluster connecting points. The combination of a variety of organic linkers, metal ions/clusters, and structural motifs can lead to an infinite array of new materials with interesting properties for many applications. In this Forum article, we discuss the design and applications of MOFs in chemical sensing and biological imaging. The first half of this article focuses on the development of MOFs as chemical sensors by highlighting how unique attributes of MOFs can be utilized to enhance sensitivity and selectivity. We also discuss some of the issues that need to be addressed in order to develop practically useful MOF sensors. The second half of this article focuses on the design and applications of nanoscale metal-organic frameworks (NMOFs) as imaging contrast agents. NMOFs possess several interesting attributes, such as high cargo loading capacity, ease of post-modification, tunable size and shape, and intrinsic biodegradability, to make them excellent candidates as imaging contrast agents. We discuss the use of representative NMOFs in magnetic resonance imaging (MRI), X-ray computed tomography (CT), and optical imaging (OI). Although still in their infancy, we believe that the compositional tunability and mild synthetic conditions of NMOF imaging agents should greatly facilitate their further development for clinical translation. PMID:24251853

  17. Metal-organic frameworks as sensory materials and imaging agents.

    PubMed

    Liu, Demin; Lu, Kuangda; Poon, Christopher; Lin, Wenbin

    2014-02-17

    Metal-organic frameworks (MOFs) are a class of hybrid materials self-assembled from organic bridging ligands and metal ion/cluster connecting points. The combination of a variety of organic linkers, metal ions/clusters, and structural motifs can lead to an infinite array of new materials with interesting properties for many applications. In this Forum Article, we discuss the design and applications of MOFs in chemical sensing and biological imaging. The first half of this article focuses on the development of MOFs as chemical sensors by highlighting how unique attributes of MOFs can be utilized to enhance sensitivity and selectivity. We also discuss some of the issues that need to be addressed in order to develop practically useful MOF sensors. The second half of this article focuses on the design and applications of nanoscale MOFs (NMOFs) as imaging contrast agents. NMOFs possess several interesting attributes, such as high cargo loading capacity, ease of postmodification, tunable size and shape, and intrinsic biodegradability, to make them excellent candidates as imaging contrast agents. We discuss the use of representative NMOFs in magnetic resonance imaging (MRI), X-ray computed tomography (CT), and optical imaging. Although still in their infancy, we believe that the compositional tunability and mild synthetic conditions of NMOF imaging agents should greatly facilitate their further development for clinical translation.

  18. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

    PubMed Central

    Thoppil, Roslin J; Bishayee, Anupam

    2011-01-01

    Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called “isoprenoids”) are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed. PMID:21969877

  19. Bone-targeted agents in the treatment of lung cancer

    PubMed Central

    Silva, Shobha C.; Wilson, Caroline

    2015-01-01

    Over a third of patients with lung cancer will develop bone metastases during the course of their disease, resulting in symptoms of pain and immobility, and skeletal-related events (SREs) such as fracture, hypercalcaemia, surgery or radiotherapy to bones, and malignant spinal cord compression. These reduce quality of life and increase mortality. Preclinical research has identified the interactions between tumour cells and bone that are key to tumour cell survival and associated osteolysis. These data have led to the development of drugs to prevent osteoclast-mediated bone breakdown, such as zoledronic acid and denosumab, which are now licensed for use in patients with bone metastases from solid tumours. Both zoledronic acid and denosumab reduce the risk of SREs and increase time to first SRE, with minimal side effects. In addition, denosumab improved survival in patients with lung cancer compared with zoledronic acid. Ongoing trials are testing whether these drugs can prevent the development of bone metastases from lung cancer. New bone-targeted agents showing promise in breast and prostate cancer include radium-223, cabozantinib and Src inhibitors. These agents require further evaluation in patients with lung cancer. PMID:26136853

  20. Recombinant mumps virus as a cancer therapeutic agent

    PubMed Central

    Ammayappan, Arun; Russell, Stephen J; Federspiel, Mark J

    2016-01-01

    Mumps virus belongs to the family of Paramyxoviridae and has the potential to be an oncolytic agent. Mumps virus Urabe strain had been tested in the clinical setting as a treatment for human cancer four decades ago in Japan. These clinical studies demonstrated that mumps virus could be a promising cancer therapeutic agent that showed significant antitumor activity against various types of cancers. Since oncolytic virotherapy was not in the limelight until the beginning of the 21st century, the interest to pursue mumps virus for cancer treatment slowly faded away. Recent success stories of oncolytic clinical trials prompted us to resurrect the mumps virus and to explore its potential for cancer treatment. We have obtained the Urabe strain of mumps virus from Osaka University, Japan, which was used in the earlier human clinical trials. In this report we describe the development of a reverse genetics system from a major isolate of this Urabe strain mumps virus stock, and the construction and characterization of several recombinant mumps viruses with additional transgenes. We present initial data demonstrating these recombinant mumps viruses have oncolytic activity against tumor cell lines in vitro and some efficacy in preliminary pilot animal tumor models. PMID:27556105

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Image-guided cancer surgery using near-infrared fluorescence

    PubMed Central

    Vahrmeijer, Alexander L.; Hutteman, Merlijn; van der Vorst, Joost R.; van de Velde, C.J.H.; Frangioni, John V.

    2013-01-01

    Paradigm shifts in surgery arise when surgeons are empowered to perform surgery faster, better, and/or less expensively. Optical imaging that exploits invisible near-infrared fluorescent light has the potential to improve cancer surgery outcomes while minimizing anesthesia time and lowering healthcare costs. Because of this, the last few years have witnessed an explosion of proof-of-concept clinical trials in the field. In this review, we introduce the concept of near-infrared fluorescence imaging for cancer surgery, review the clinical trial literature to date, outline the key issues pertaining to imaging system and contrast agent optimization, discuss limitations and leverage, and provide a framework for making the technology available for the routine care of cancer patients in the near future. PMID:23881033

  3. Theranostic agents for intracellular gene delivery with spatiotemporal imaging

    PubMed Central

    Knipe, Jennifer M.; Peters, Jonathan T.; Peppas, Nicholas A.

    2013-01-01

    Gene therapy is the modification of gene expression to treat a disease. However, efficient intracellular delivery and monitoring of gene therapeutic agents is an ongoing challenge. Use of theranostic agents with suitable targeted, controlled delivery and imaging modalities has the potential to greatly advance gene therapy. Inorganic nanoparticles including magnetic nanoparticles, gold nanoparticles, and quantum dots have been shown to be effective theranostic agents for the delivery and spatiotemporal tracking of oligonucleotides in vitro and even a few cases in vivo. Major concerns remain to be addressed including cytotoxicity, particularly of quantum dots; effective dosage of nanoparticles for optimal theranostic effect; development of real-time in vivo imaging; and further improvement of gene therapy efficacy. PMID:23606894

  4. A Brief Account of Nanoparticle Contrast Agents for Photoacoustic Imaging

    PubMed Central

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

    2014-01-01

    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. PMID:23983210

  5. Hepatobiliary MR Imaging with Gadolinium Based Contrast Agents

    PubMed Central

    Frydrychowicz, Alex; Lubner, Meghan G.; Brown, Jeffrey J.; Merkle, Elmar M.; Nagle, Scott K.; Rofsky, Neil M.; Reeder, Scott B.

    2011-01-01

    The advent of gadolinium-based “hepatobiliary” contrast agents offers new opportunities for diagnostic MRI and has triggered a great interest for innovative imaging approaches to the liver and bile ducts. In this review article we will discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the USA, gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We will review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared towards optimizing workflow and imaging quality will also be discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents, and will stimulate the reader‘s pursuit of new applications for future benefit. PMID:22334493

  6. Capsaicin: From Plants to a Cancer-Suppressing Agent.

    PubMed

    Chapa-Oliver, Angela M; Mejía-Teniente, Laura

    2016-01-01

    Capsaicinoids are plant secondary metabolites, capsaicin being the principal responsible for the pungency of chili peppers. It is biosynthesized through two pathways involved in phenylpropanoid and fatty acid metabolism. Plant capsaicin concentration is mainly affected by genetic, environmental and crop management factors. However, its synthesis can be enhanced by the use of elicitors. Capsaicin is employed as food additive and in pharmaceutical applications. Additionally, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer. This review is an approach in contextualizing the use of controlled stress on the plant to increase the content of capsaicin, highlighting its synthesis and its potential use as anticancer agent. PMID:27472308

  7. Capsaicin: From Plants to a Cancer-Suppressing Agent.

    PubMed

    Chapa-Oliver, Angela M; Mejía-Teniente, Laura

    2016-07-27

    Capsaicinoids are plant secondary metabolites, capsaicin being the principal responsible for the pungency of chili peppers. It is biosynthesized through two pathways involved in phenylpropanoid and fatty acid metabolism. Plant capsaicin concentration is mainly affected by genetic, environmental and crop management factors. However, its synthesis can be enhanced by the use of elicitors. Capsaicin is employed as food additive and in pharmaceutical applications. Additionally, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer. This review is an approach in contextualizing the use of controlled stress on the plant to increase the content of capsaicin, highlighting its synthesis and its potential use as anticancer agent.

  8. Nano-theranostics and Nitroxyl Radical-labeled Antitumor Agents for Magnetic Resonance Imaging.

    PubMed

    Aoki, Ichio

    2016-01-01

    The advent of functional contrast agents and nanoparticle drug delivery systems (nano-DDS) is opening new pathways to understanding pathophysiology using magnetic resonance imaging (MRI). Nitroxyl radical compounds are promising functional contrast agents for redox evaluation. We have developed a novel nitroxyl radical theranostic compound for noninvasive real-time imaging of blood-brain barrier-permeable antitumor drugs. Divalent manganese ions (Mn(2+)) can also be used as an intracellular functional MRI contrast agent. Manganese-enhanced MRI (MEMRI) provides a unique opportunity to study neuronal activation and architecture. Extracellular Mn(2+) can enter cells through NMDA receptors for glutamate and/or voltage-gated calcium channels. Thus, Mn(2+) can behave as a functional contrast agent depending on the cellular activity/viability. This paper summarizes the recent progress in MEMRI for neuroimaging and cancer research. Nanocarriers for DDS can contain multiple functional elements, such as therapeutic drugs, MRI contrast agents, fluorescent dyes, and radioisotopes, without significant changes in the particle kinetics/dynamics. Various materials have also been reported as nano-DDS carriers, including micelles, liposomes, dendrimers, quantum dots, and carbon materials such as fullerenes, with each material providing a different set of characteristics as a nano-DDS carrier. Our recent research into nano-DDS-based contrast agents and the theranostic applications is also outlined. PMID:27477722

  9. Nano-theranostics and Nitroxyl Radical-labeled Antitumor Agents for Magnetic Resonance Imaging.

    PubMed

    Aoki, Ichio

    2016-01-01

    The advent of functional contrast agents and nanoparticle drug delivery systems (nano-DDS) is opening new pathways to understanding pathophysiology using magnetic resonance imaging (MRI). Nitroxyl radical compounds are promising functional contrast agents for redox evaluation. We have developed a novel nitroxyl radical theranostic compound for noninvasive real-time imaging of blood-brain barrier-permeable antitumor drugs. Divalent manganese ions (Mn(2+)) can also be used as an intracellular functional MRI contrast agent. Manganese-enhanced MRI (MEMRI) provides a unique opportunity to study neuronal activation and architecture. Extracellular Mn(2+) can enter cells through NMDA receptors for glutamate and/or voltage-gated calcium channels. Thus, Mn(2+) can behave as a functional contrast agent depending on the cellular activity/viability. This paper summarizes the recent progress in MEMRI for neuroimaging and cancer research. Nanocarriers for DDS can contain multiple functional elements, such as therapeutic drugs, MRI contrast agents, fluorescent dyes, and radioisotopes, without significant changes in the particle kinetics/dynamics. Various materials have also been reported as nano-DDS carriers, including micelles, liposomes, dendrimers, quantum dots, and carbon materials such as fullerenes, with each material providing a different set of characteristics as a nano-DDS carrier. Our recent research into nano-DDS-based contrast agents and the theranostic applications is also outlined.

  10. Beyond Histologic Staging: Emerging Imaging Strategies in Colorectal Cancer with Special Focus on Magnetic Resonance Imaging.

    PubMed

    Fraum, Tyler J; Owen, Joseph W; Fowler, Kathryn J

    2016-09-01

    Imaging plays an increasingly important role in the staging and management of colorectal cancer. In recent years, magnetic resonance imaging (MRI) has supplanted transrectal ultrasound as the preferred modality for the locoregional staging of rectal cancer. Furthermore, the advent of both diffusion-weighted imaging and hepatobiliary contrast agents has significantly enhanced the ability of MRI to detect colorectal liver metastases. In clinical practice, MRI routinely provides prognostic information, helps to guide surgical strategy, and determines the need for neoadjuvant therapies related to both the primary tumor and metastatic disease. Expanding on these roles for MRI, positron emission tomography (PET)/MRI is the newest clinical hybrid imaging modality and combines the metabolic information of PET with the high soft tissue contrast of MRI. The addition of PET/MRI to the clinical staging armamentarium has the potential to provide comprehensive state-of-the-art colorectal cancer staging in a single examination. PMID:27582645

  11. Nanoparticle-enabled terahertz imaging for cancer diagnosis.

    PubMed

    Oh, Seung Jae; Kang, Jinyoung; Maeng, Inhee; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo; Son, Joo-Hiuk

    2009-03-01

    This paper demonstrates the principle of the nanoparticle-contrast-agent-enabled terahertz imaging (CATHI) technique, which yields a dramatic sensitivity of the differential signal from cancer cells with nanoparticles. The terahertz (THz) reflection signal increased beam by 20% in the cancer cells with nanoparticles of gold nano-rods (GNRs) upon their irradiation with a infrared (IR) laser, due to the temperature rise of water in cancer cells by surface plasma ploritons. In the differential mode, the THz signal from the cancer cells with GNRs was 30 times higher than that from the cancer cells without GNRs. As the high sensitivity is achieved by the surface plasmon resonance through IR laser irradiation, the resolution of the CATHI technique can be as good as a few microns and THz endoscopy becomes more feasible.

  12. De Novo Designed Imaging Agents Based on Lanthanide Peptides Complexes.

    PubMed

    Peacock, A F A

    2016-01-01

    Herein are discussed a selection of lanthanide peptide/protein complexes in view of their potential applications as imaging agents, both in terms of luminescence detection and magnetic resonance imaging. Though this chapter covers a range of different peptides and protein, if focuses specifically on the opportunities afforded by the de novo design of coiled coils, miniature protein scaffolds, and the development on lanthanide-binding sites into these architectures. The requirements for lanthanide coordination and the challenges that need to be addressed when preparing lanthanide peptides with a view to their potential adoption as clinical imaging applications, will be highlighted. PMID:27586349

  13. Leukemia after therapy with alkylating agents for childhood cancer

    SciTech Connect

    Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.; Stovall, M.; Oberlin, O.; Stone, B.J.; Birch, J.; Voute, P.A.; Hoover, R.N.; Fraumeni, J.F. Jr.

    1987-03-01

    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.

  14. Evaluation of the Efficacy of Targeted Imaging Agents.

    PubMed

    Graham, Michael M; Weber, Wolfgang A

    2016-04-01

    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

  15. Killer beacons for combined cancer imaging and therapy.

    PubMed

    Stefflova, Klara; Chen, Juan; Zheng, Gang

    2007-01-01

    Precisely localizing therapeutic agents in neoplastic areas would greatly improve their efficacy for killing tumor cells and reduce their toxicity to normal cells. Photodynamic therapy (PDT) is a promising cancer treatment modality, and near-infrared fluorescence imaging (NIRF-I) is a sensitive and noninvasive approach for in vivo cancer detection. This review focuses on the current efforts to engineer single molecule constructs that allow these two modalities to be combined to achieve a high level of selectivity for cancer treatment. The primary component of these so called killer beacons is a fluorescent photosensitizer responsible for both imaging and therapy. By attaching other components, e.g. various DNA- or peptide-based linkers, quenchers or cancer cell-specific delivery vehicles, their primary diagnostic and therapeutic functions as well as their target specificity and pharmacological properties can be modulated. This modular design makes these agents customizable, offering the ability to assemble a few simple and often interchangeable functional modules into beacons with totally different functions. This review will summarize following three types of killer beacons: photodynamic molecular beacons, traceable beacons and beacons with built-in apoptosis sensor. Despite the rapid progress in killer beacon development, numerous challenges remain before these beacons can be translated into clinics, such as photobleaching, delivery efficiency and cancer-specificity. In this review we outline the basic principles of killer beacons, the current achievements and future directions, including possible cancer targets and different therapeutic applications.

  16. Anatomical and molecular imaging of skin cancer

    PubMed Central

    Hong, Hao; Sun, Jiangtao; Cai, Weibo

    2008-01-01

    Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼ 5%) and nonmelanoma (∼ 95%), which can be further categorized into basal cell carcinoma, squamous cell carcinoma, and some rare skin cancer types. Biopsy is still the gold standard for skin cancer evaluation in the clinic. Various anatomical imaging techniques have been used to evaluate different types of skin cancer lesions, including laser scanning confocal microscopy, optical coherence tomography, high-frequency ultrasound, terahertz pulsed imaging, magnetic resonance imaging, and some other recently developed techniques such as photoacoustic microscopy. However, anatomical imaging alone may not be sufficient in guiding skin cancer diagnosis and therapy. Over the last decade, various molecular imaging techniques (in particular single photon emission computed tomography and positron emission tomography) have been investigated for skin cancer imaging. The pathways or molecular targets that have been studied include glucose metabolism, integrin αvβ3, melanocortin-1 receptor, high molecular weight melanoma-associated antigen, and several other molecular markers. Preclinical molecular imaging is thriving all over the world, while clinical molecular imaging has not lived up to the expectations because of slow bench-to-bedside translation. It is likely that this situation will change in the near future and molecular imaging will truly play an important role in personalized medicine of melanoma patients. PMID:21437135

  17. Nanoengineered multimodal contrast agent for medical image guidance

    NASA Astrophysics Data System (ADS)

    Perkins, Gregory J.; Zheng, Jinzi; Brock, Kristy; Allen, Christine; Jaffray, David A.

    2005-04-01

    Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged in vivo residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 +/- 7.1 mg/mL of iodine for iohexol and 9.8 +/- 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 +/- 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 +/- 1.1% and 11.2 +/- 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following in vivo administration, the contrast agent maintained a relative contrast enhancement of 81.4 +/- 13.05 differential Hounsfield units (ΔHU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 +/- 144.2 differential signal intensity (ΔSI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 +/- 5.1 ΔHU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 +/- 41.4 ΔSI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 +/- 1.7 ΔHU (94% decrease from the peak signal value achieved 3 minutes

  18. Cellular image segmentation using n-agent cooperative game theory

    NASA Astrophysics Data System (ADS)

    Dimock, Ian B.; Wan, Justin W. L.

    2016-03-01

    Image segmentation is an important problem in computer vision and has significant applications in the segmentation of cellular images. Many different imaging techniques exist and produce a variety of image properties which pose difficulties to image segmentation routines. Bright-field images are particularly challenging because of the non-uniform shape of the cells, the low contrast between cells and background, and imaging artifacts such as halos and broken edges. Classical segmentation techniques often produce poor results on these challenging images. Previous attempts at bright-field imaging are often limited in scope to the images that they segment. In this paper, we introduce a new algorithm for automatically segmenting cellular images. The algorithm incorporates two game theoretic models which allow each pixel to act as an independent agent with the goal of selecting their best labelling strategy. In the non-cooperative model, the pixels choose strategies greedily based only on local information. In the cooperative model, the pixels can form coalitions, which select labelling strategies that benefit the entire group. Combining these two models produces a method which allows the pixels to balance both local and global information when selecting their label. With the addition of k-means and active contour techniques for initialization and post-processing purposes, we achieve a robust segmentation routine. The algorithm is applied to several cell image datasets including bright-field images, fluorescent images and simulated images. Experiments show that the algorithm produces good segmentation results across the variety of datasets which differ in cell density, cell shape, contrast, and noise levels.

  19. Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

    PubMed Central

    Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

    2012-01-01

    Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

  20. Neem components as potential agents for cancer prevention and treatment.

    PubMed

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2014-08-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  1. Neem components as potential agents for cancer prevention and treatment.

    PubMed

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2014-08-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment.

  2. Neem components as potential agents for cancer prevention and treatment

    PubMed Central

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2016-01-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  3. Monoclonal antibodies: new agents for cancer detection and targeted therapy

    SciTech Connect

    Baldwin, R.W.; Byers, V.S. )

    1991-01-01

    Antibodies directed against markers on cancer cells are gaining in importance for the purpose of targeting diagnostic and therapeutic agents. In the past, this approach has had very limited success principally because the classical methods for producing antibodies from blood serum of animals immunized with cancer cells or extracts were unsatisfactory. The situation has changed dramatically since 1975 following the design of procedures for 'immortalizing' antibody-producing cells (lymphocytes) by fusing them with cultured myeloma cells to form hybridomas which continuously secrete antibodies. Since these hybridomas produce antibodies coded for by a single antibody-producing cell, the antibodies are called monoclonal. Building on these advances in biomedical research, it is now possible to reproducibly manufacture monoclonal antibodies on a scale suitable for use in cancer detection and therapy.

  4. Functional imaging of the lungs with gas agents.

    PubMed

    Kruger, Stanley J; Nagle, Scott K; Couch, Marcus J; Ohno, Yoshiharu; Albert, Mitchell; Fain, Sean B

    2016-02-01

    This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)-hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas--and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children.

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

    NASA Astrophysics Data System (ADS)

    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

  6. Small conjugate-based theranostic agents: an encouraging approach for cancer therapy.

    PubMed

    Kumar, Rajesh; Shin, Weon Sup; Sunwoo, Kyoung; Kim, Won Young; Koo, Seyoung; Bhuniya, Sankarprasad; Kim, Jong Seung

    2015-10-01

    The advances in genomics, proteomics, and bioinformatics have directed the development of new anticancer agents to reduce drug abuse and increase safe and specific drug treatment. Theranostics, combining therapy and diagnosis, is an appealing approach for chemotherapy in medicine which exhibits improved biodistribution, selective cancer targeting ability, reduced toxicity, masked drug efficacy, and minimum side effects. The role of diagnosis tools in theranostics is to collect the information of the diseased state before and after specific treatment. Magnetic particle-, mesoporous silica-, various carbon allotrope-, and polymer nanoparticle-based theranostic systems are well accepted and clinically significant. Currently, small conjugate-based systems have received much attention for cancer treatment and diagnosis. The structural architecture of these systems is relatively simple, compact, biocompatible, and unidirectional. In this tutorial review, we summarize the latest developments on small conjugate based theranostic agents for tumor treatment and diagnosis using fluorescence and magnetic resonance imaging (MRI).

  7. Screening CEST contrast agents using ultrafast CEST imaging

    NASA Astrophysics Data System (ADS)

    Xu, Xiang; Yadav, Nirbhay N.; Song, Xiaolei; McMahon, Michael T.; Jerschow, Alexej; van Zijl, Peter C. M.; Xu, Jiadi

    2016-04-01

    A chemical exchange saturation transfer (CEST) experiment can be performed in an ultrafast fashion if a gradient field is applied simultaneously with the saturation pulse. This approach has been demonstrated for studying dia- and para-magnetic CEST agents, hyperpolarized Xe gas and in vivo spectroscopy. In this study we present a simple method for the simultaneous screening of multiple samples. Furthermore, by interleaving a number of saturation and readout periods within the TR, a series of images with different saturation times can be acquired, allowing for the quantification of exchange rates using the variable saturation time (QUEST) approach in a much accelerated fashion, thus enabling high throughput screening of CEST contrast agents.

  8. Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl contrast agents.

    PubMed

    Matsumoto, Ken-ichiro; Narazaki, Michiko; Ikehira, Hiroo; Anzai, Kazunori; Ikota, Nobuo

    2007-07-01

    The resolution and signal to noise ratio of EPR imaging and T(1)-weighted MRI were compared using an identical phantom. Several solutions of nitroxyl contrast agents with different EPR spectral shapes were tested. The feasibility of T(1)-weighted MRI to detect nitroxyl contrast agents was described. T(1)-weighted MRI can detect nitroxyl contrast agents with a complicated EPR spectrum easier and quicker; however, T(1)-weighted MRI has less quantitative ability especially for lipophilic nitroxyl contrast agents, because T(1)-relaxivity, i.e. accessibility to water, is affected by the hydrophilic/hydrophobic micro-environment of a nitroxyl contrast agent. The less quantitative ability of T(1)-weighted MRI may not be a disadvantage of redox imaging, which obtains reduction rate of a nitroxyl contrast. Therefore, T(1)-weighted MRI has a great advantage to check the pharmacokinetics of newly modified and/or designed nitroxyl contrast agents. PMID:17433743

  9. Lung Cancer Mutations and Use of Targeted Agents in Hispanics

    PubMed Central

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

    2015-01-01

    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. PMID:25626064

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

    PubMed

    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.

  11. uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection

    PubMed Central

    Yang, Lily; Sajja, Hari Krishna; Cao, Zehong; Qian, Weiping; Bender, Laura; Marcus, Adam I.; Lipowska, Malgorzata; Wood, William C.; Wang, Y. Andrew

    2014-01-01

    Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery. PMID:24396518

  12. Molecular Imaging with MRI: Potential Application in Pancreatic Cancer

    PubMed Central

    Chen, Chen; Wu, Chang Qiang; Chen, Tian Wu; Tang, Meng Yue; Zhang, Xiao Ming

    2015-01-01

    Despite the variety of approaches that have been improved to achieve a good understanding of pancreatic cancer (PC), the prognosis of PC remains poor, and the survival rates are dismal. The lack of early detection and effective interventions is the main reason. Therefore, considerable ongoing efforts aimed at identifying early PC are currently being pursued using a variety of methods. In recent years, the development of molecular imaging has made the specific targeting of PC in the early stage possible. Molecular imaging seeks to directly visualize, characterize, and measure biological processes at the molecular and cellular levels. Among different imaging technologies, the magnetic resonance (MR) molecular imaging has potential in this regard because it facilitates noninvasive, target-specific imaging of PC. This topic is reviewed in terms of the contrast agents for MR molecular imaging, the biomarkers related to PC, targeted molecular probes for MRI, and the application of MRI in the diagnosis of PC. PMID:26579537

  13. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    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

  14. Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer

    PubMed Central

    Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei

    2014-01-01

    Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer. PMID:25988156

  15. Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer.

    PubMed

    Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei

    2014-01-01

    Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer.

  16. Direct evidence of mitochondrial G-quadruplex DNA by using fluorescent anti-cancer agents.

    PubMed

    Huang, Wei-Chun; Tseng, Ting-Yuan; Chen, Ying-Ting; Chang, Cheng-Chung; Wang, Zi-Fu; Wang, Chiung-Lin; Hsu, Tsu-Ning; Li, Pei-Tzu; Chen, Chin-Tin; Lin, Jing-Jer; Lou, Pei-Jen; Chang, Ta-Chau

    2015-12-01

    G-quadruplex (G4) is a promising target for anti-cancer treatment. In this paper, we provide the first evidence supporting the presence of G4 in the mitochondrial DNA (mtDNA) of live cells. The molecular engineering of a fluorescent G4 ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC), can change its major cellular localization from the nucleus to the mitochondria in cancer cells, while remaining primarily in the cytoplasm of normal cells. A number of BMVC derivatives with sufficient mitochondrial uptake can induce cancer cell death without damaging normal cells. Fluorescence studies of these anti-cancer agents in live cells and in isolated mitochondria from HeLa cells have demonstrated that their major target is mtDNA. In this study, we use fluorescence lifetime imaging microscopy to verify the existence of mtDNA G4s in live cells. Bioactivity studies indicate that interactions between these anti-cancer agents and mtDNA G4 can suppress mitochondrial gene expression. This work underlines the importance of fluorescence in the monitoring of drug-target interactions in cells and illustrates the emerging development of drugs in which mtDNA G4 is the primary target. PMID:26487635

  17. Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating agent.

    PubMed

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Vasaitis, Tadas S; Bruno, Robert D; Gediya, Lalji K; Njar, Vincent C O

    2008-04-01

    The search for novel androgen receptor (AR) down-regulating agents by catalyst HipHop pharmacophore modeling led to the discovery of some lead molecules. Unexpectedly, the effect of these leads on human prostate cancer LNCaP cell viability did not correlate with the ability of the compounds to cause down-regulation of AR protein expression. Through rational synthetic optimization of the lead compound (BTB01434), we have discovered a series of novel substituted diaryl molecules as potent anti-prostate cancer agents. Some compounds (1-6) were shown to be extremely potent inhibitors of LNCaP cell viability with GI(50) values in the nanomolar range (1.45-83 nM). The most potent compound (4-methylphenyl)[(4-methylphenyl)sulfonyl]amine (5) with a GI(50) value of 1.45 nM is 27,000 times more potent than our lead compound BTB01434 (GI(50)=39.8 microM). In addition, some of the compounds exhibited modest anti-androgenic activities and one was also a potent inhibitor (GI(50)=850 nM) of PC-3 (AR-null) cell growth. A clear structure-activity relationship (SAR) has been established for activity against LNCaP cells, where potent molecules possess two substituted/unsubstituted aromatic rings connected through a sulfonamide linker. These novel compounds are strong candidates for development for the treatment of hormone-sensitive and importantly hormone-refractory prostate cancers in humans. PMID:18316193

  18. Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating agent.

    PubMed

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Vasaitis, Tadas S; Bruno, Robert D; Gediya, Lalji K; Njar, Vincent C O

    2008-04-01

    The search for novel androgen receptor (AR) down-regulating agents by catalyst HipHop pharmacophore modeling led to the discovery of some lead molecules. Unexpectedly, the effect of these leads on human prostate cancer LNCaP cell viability did not correlate with the ability of the compounds to cause down-regulation of AR protein expression. Through rational synthetic optimization of the lead compound (BTB01434), we have discovered a series of novel substituted diaryl molecules as potent anti-prostate cancer agents. Some compounds (1-6) were shown to be extremely potent inhibitors of LNCaP cell viability with GI(50) values in the nanomolar range (1.45-83 nM). The most potent compound (4-methylphenyl)[(4-methylphenyl)sulfonyl]amine (5) with a GI(50) value of 1.45 nM is 27,000 times more potent than our lead compound BTB01434 (GI(50)=39.8 microM). In addition, some of the compounds exhibited modest anti-androgenic activities and one was also a potent inhibitor (GI(50)=850 nM) of PC-3 (AR-null) cell growth. A clear structure-activity relationship (SAR) has been established for activity against LNCaP cells, where potent molecules possess two substituted/unsubstituted aromatic rings connected through a sulfonamide linker. These novel compounds are strong candidates for development for the treatment of hormone-sensitive and importantly hormone-refractory prostate cancers in humans.

  19. Development of Anti-EGF Receptor Peptidomimetics (AERP) as Tumor Imaging Agent

    PubMed Central

    Ponde, Datta E.; Su, ZiFen; Berezov, Alan; Zhang, Hongtao; Alavi, Abbas; Greene, Mark I.; Murali, Ramachandran

    2011-01-01

    EGFR is over-expressed in several solid tumors including breast, prostate, pancreas and lung cancers and is correlated to the metastasic potential of the tumor. Anti-EGFR receptor-binding peptidomimetics (AERP) were examined to assess the small molecule's potential use as tumor-specific imaging agents. The aim of this work was to design and characterize the binding specificity of the radiolabeled peptidomimetics to EGFR over-expressing cell lysate and to A431 xenograft tumors. Our newly designed peptidomimetic, AERP, was conjugated to DTPA and labeled with 99mTc. The in vivo tumor accumulation of [99mTc] DTPA-AERP-2 was 1.6 ± 0.1 %ID/g and tumor to muscle ratio was 5.5. Our studies suggest that this novel peptidomimetic, AERP-2, warrants further development as an EGFR-specific tumor-imaging agent. PMID:21392985

  20. Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

    PubMed Central

    Liang, Wenjie; Ni, Yicheng; Chen, Feng

    2016-01-01

    The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID:26812886

  1. Development of [F-18]-Labeled Amyloid Imaging Agents for PET

    SciTech Connect

    Mathis, CA

    2007-05-09

    The applicant proposes to design and synthesize a series of fluorine-18-labeled radiopharmaceuticals to be used as amyloid imaging agents for positron emission tomography (PET). The investigators will conduct comprehensive iterative in vitro and in vivo studies based upon well defined acceptance criteria in order to identify lead agents suitable for human studies. The long term goals are to apply the selected radiotracers as potential diagnostic agents of Alzheimer's disease (AD), as surrogate markers of amyloid in the brain to determine the efficacy of anti-amyloid therapeutic drugs, and as tools to help address basic scientific questions regarding the progression of the neuropathology of AD, such as testing the "amyloid cascade hypothesis" which holds that amyloid accumulation is the primary cause of AD.

  2. Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy.

    PubMed

    Li, Wanwan; Rong, Pengfei; Yang, Kai; Huang, Peng; Sun, Kang; Chen, Xiaoyuan

    2015-03-01

    In this study we report semimetal nanomaterials of antimony (Sb) as highly efficient agent for photoacoustic imaging (PAI) and photothermal therapy (PTT). The Sb nanorod bundles have been synthesized through a facile route by mixing 1-octadecane (ODE) and oleyl amine (OAm) as the solvent. The aqueous dispersion of PEGylated Sb NPs, due to its broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, is applicable as a photothermal agent driven by 808 nm laser with photothermal conversion efficiency up to 41%, noticeably higher than most of the PTT agents reported before. Our in vitro experiments also showed that cancer cell ablation effect of PEGylated Sb NPs was dependent on laser power. By intratumoral administration of PEGylated Sb NPs, 100% tumor ablation can be realized by using NIR laser irradiation with a lower power of 1 W/cm(2) for 5 min (or 0.5 W/cm(2) for 10 min) and no obvious toxic side effect is identified after photothermal treatment. Moreover, intense PA signal was also observed after intratumoral injection of PEGylated Sb NPs and NIR laser irradiation due to their strong NIR photoabsorption, suggesting PEGylated Sb NPs as a potential NIR PA agent. Based on the findings of this work, further development of using other semimetal nanocrystals as highly efficient NIR agents can be achieved for vivo tumor imaging and PTT.

  3. Molecular application of spectral photoacoustic imaging in pancreatic cancer pathology

    NASA Astrophysics Data System (ADS)

    Lakshman, Minalini; Hupple, Clinton; Lohse, Ines; Hedley, David; Needles, Andrew; Theodoropoulos, Catherine

    2012-12-01

    Spectral imaging is an advanced photo-acoustic (PA) mode that can discern optical absorption of contrast agent(s) in the tissue micro-environment. This advancement is made possible by precise control of optical wavelength using a tunable pulsed laser, ranging from 680-970 nm. Differential optical absorption of blood oxygenation states makes spectral imaging of hemoglobin ideal to investigate remodeling of the tumor microenvironment- a molecular change that renders resistance to standard cancer treatment. Approach: Photo-acoustic imaging was performed on the Vevo® LAZR system (VisualSonics) at 5-20 Hz. Deep abdominal imaging was accomplished with a LZ250D probe at a center frequency of 21MHz and an axial resolution of 75 μm. The tumor model was generated in an immune compromised mouse by surgical implantation of primary patient derived tumors, in the pancreas. Results: Spectral imaging for oxygen saturation at 750 nm and 850 nm characterized this tumor with a poorly oxygenated core surrounded by a well oxygenated periphery. Multispectral imaging identified a sub region in the core with a four-fold signal exclusively at 750 and 800 nm. A co-registered 2D image of this region was shown to be echogenic and calcification was suspected. Perfusion imaging with contrast enhanced ultrasound using microbubbles (Vevo MicroMarker® contrast agents, VisualSonics) identified functional vessels towards this sub region. Histology confirmed calcification and vascularization in the tumor core. Taken together, non-invasive characterization of the tumor microenvironment using photo-acoustics rendered spectral imaging a sensitive tool to monitor molecular changes representative of progression of pancreatic cancer that kills within 6 months of diagnosis.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Triple-negative breast cancer: role of antiangiogenic agents.

    PubMed

    Greenberg, Sally; Rugo, Hope S

    2010-01-01

    New blood vessel formation plays an important role in breast cancer growth, invasion, and metastasis. Tumor growth is preceded by the development of new blood vessels, which provide a pathway for metastases and nutrients essential for growth. Vascular endothelial growth factor (VEGF) is a key angiogenic mediator that stimulates endothelial cell proliferation and regulates vascular permeability. Highly proliferative tumors, such as those that are negative for the estrogen, progesterone, and HER2/neu receptors have enhanced angiogenesis that supports rapid growth and early metastases and have been found to have high levels of VEGF. Drugs developed to inhibit the angiogenic process may be particularly effective in triple-negative breast cancer. Subset analyses have demonstrated efficacy with combinations of the VEGF antibody bevacizumab in combination with chemotherapy and, to a limited degree, with other antiangiogenic agents. Many targeted biologic agents in development inhibit angiogenesis including those that inhibit the mammalian target of rapamycin, fibroblast growth factor, Notch, hypoxic inducible factor, 2-methoxyestradiol, insulin like growth factor, matrix metalloproteinase, and others. Ongoing studies are focusing on the effects of these agents in triple-negative disease, and there is an urgent need to identify markers that can predict response to specific targeted therapy. PMID:20164688

  6. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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 enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  7. Multifunctional gold nanostars for molecular imaging and cancer therapy

    PubMed Central

    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 enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy (PDT). This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed. PMID:26322306

  8. Molecular Imaging of Proteases in Cancer

    PubMed Central

    Yang, Yunan; Hong, Hao; Zhang, Yin; Cai, Weibo

    2010-01-01

    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. PMID:20234801

  9. Chain elongation analog of resveratrol as potent cancer chemoprevention agent.

    PubMed

    Kang, Yan-Fei; Qiao, Hai-Xia; Xin, Long-Zuo; Ge, Li-Ping

    2016-09-01

    Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism. PMID:27160168

  10. Radiolabelled D2 agonists as prolactinoma imaging agents

    SciTech Connect

    Otto, C.A.

    1991-12-31

    Research conducted in this terminal year of support centered on three distinct areas: mAChR ligand localization in pancreas and the effect of Ca{sup +2} on localization, continuation of assessment of quaternized and neutral mAChR ligands for possible use as PET myocardial imaging agents, and initiation of a study to determine the relationship of the nAChR receptor to the cellular receptor for measles virus. Several tables and figures illustrating the results are included.

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

    PubMed

    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. PMID:25723091

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

    PubMed Central

    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

  13. Metabolic PET Imaging in Cancer Detection and Therapy Response

    PubMed Central

    Zhu, Aizhi; Lee, Daniel; Shim, Hyunsuk

    2010-01-01

    Positron emission tomography (PET) is a noninvasive imaging technique that provides a functional or metabolic assessment of normal tissue or disease conditions. 18F-fluorodeoxyglucose PET imaging (FDG-PET) is widely used clinically for tumor imaging due to increased glucose metabolism in most types of tumors, and has been shown to improve the diagnosis and subsequent treatment of cancers. In this chapter, we review its use in cancer diagnosis, staging, restaging, and assessment of response to treatment. In addition, other metabolic PET imaging agents in research or clinical trial stages are discussed, including amino acid analogs based on increased protein synthesis, and choline, which is based on increased membrane lipid synthesis. Amino acid analogs and choline are more specific to tumor cells than FDG, so they play an important role in differentiating cancers from benign conditions and in the diagnosis of cancers with low FDG uptake or high background FDG uptake. For decades, researchers have shown that tumors have altered metabolic profiles and display elevated uptake of glucose, amino acids, and lipids, which can be used for cancer diagnosis and monitoring of the therapeutic response with excellent signal-to-noise ratios. PMID:21362516

  14. Multiparametric magnetic resonance imaging of prostate cancer.

    PubMed

    Hedgire, Sandeep S; Oei, Tamara N; McDermott, Shaunagh; Cao, Kai; Patel M, Zena; Harisinghani, Mukesh G

    2012-07-01

    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. PMID:23599562

  15. Applications of nanomedicine in breast cancer detection, imaging, and therapy.

    PubMed

    Saadeh, Yamaan; Leung, Tiffany; Vyas, Arpita; Chaturvedi, Lakshmi Shankar; Perumal, Omathanu; Vyas, Dinesh

    2014-01-01

    Worldwide, breast cancer remains as one of the most common cancer diagnosis and cause of cancer related death among women. Fortunately, nanomedicine has brought forth new potential and hope in breast cancer research. The extremely small size of nanoparticles makes it advantageous and potentially superior to use in tumor detection and imaging. One of the more extensively studied particles is quantum dots, semiconductor crystals which are capable of enhanced labeling and imaging of cancer cells. In addition, due to serious toxicity of chemotherapeutic agents, nano-formulations of breast cancer chemotherapy are under investigation and development. This may provide easier administering route and reduced frequency of drugs. With the use of nanoparticles, drug delivery can be carried out in a minimally invasive fashion and treatment regimens can be made much more targeted and specific for each patient. In this review article, we provide an overview on the role nanomedicine has played in breast cancer and mention some of the latest diagnostic and treatment modalities researched to date.

  16. Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

    PubMed Central

    Joshi, Bishnu P.; Wang, Thomas D.

    2010-01-01

    Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

  17. A naturally occurring contrast agent for OCT imaging of smokers' lung

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Bagnaninchi, Pierre O.; Whiteman, Suzanne C.; Gey van Pittius, Daniel; El Haj, Alicia J.; Spiteri, Monica A.; Wang, Ruikang K.

    2005-08-01

    Optical coherence tomography (OCT) offers great potential for clinical applications in terms of its cost, safety and real-time imaging capability. Improvement of its resolution for revealing sub-layers or sub-cellular components within a tissue will further widen its application. In this study we report that carbon pigment, which is frequently present in the lungs of smokers, could be used as a contrast agent to improve the OCT imaging of lung tissue. Carbon produced an intense bright OCT image at a relatively deep location. The parallel histopathological section analysis confirmed the presence of carbon pigment in such tissues. The underlying mechanism of the OCT image formation has been discussed based on a model system in which carbon particles were dispersed in agar gel. Calculations and in-depth intensity profiles of OCT revealed that higher refractive index particles with a size close to or smaller than the wavelength would greatly increase backscattering and generate a sharp contrast, while a particle size several times larger than the wavelength would absorb or obstruct the light path. The naturally occurring contrast agent could provide a diagnostic biomarker of lung tissue in smokers. Furthermore, carbon under such circumstances, can be used as an effective exogenous contrast agent, with which specific components or tissues exhibiting early tumour formation can be optically labelled to delineate the location and boundary, providing potential for early cancer detection and its treatment.

  18. Medical Imaging of Oral and Oropharyngeal Cancer.

    PubMed

    Anderson, Susan M

    2015-01-01

    Oral cancer is associated with documented risk factors, yet no comprehensive screening program is in place in the United States for early detection of the disease. Oral cancer often is diagnosed in more advanced stages, resulting in a poor prognosis. Dental practitioners and radiographers play an important role in the management of the disease and in helping to improve the quality of life for people who have oral cancer. This article discusses types of oral and oropharyngeal cancer, their diagnosis, treatment options, and the role of dental imaging in patients with these cancers. PMID:26538220

  19. Near Infrared Imaging of Molecular Beacons in Cancers

    NASA Astrophysics Data System (ADS)

    Chance, Britton

    2001-03-01

    The recent demonstrations of the efficacy of the tumor to background contrast in breast cancer using the tricarbo-cyanine near infrared (NIR) agent with time domain 2-D imaging presages the greater efficacy of site-directed optical contrast agents for early detection of cancers which show contrast (tissue to background) of over 20 fold. Further increases of contrast are obtained with structures that quench the fluorescence until the agent is delivered, recognized, and opened by specific enzymatic activity of the tumor. These are termed ``Molecular Beacons". In order to image the localization of the Beacons, we employ light pen (< 40μ) scanning of the freeze trapped tumor in order to immobilize the tissue, to increase the fluorescence quantum yield and to limit the penetration of the excitation to a thin superficial layer (< 20μ). Precision milling of layers (> 20μ) in LN2 gives the desired 3D high resolution image of the location of the Beacon within in the cancer cell. Since cancer prevention is linked to early detection, the high signal to background obtainable with Molecular Beacons enables the detection of very early subsurface cancers, especially breast and prostate (NIH, UIP). Thus the fluorescent Beacon excites and emits in the NIR window and signals from several cm deep in breast are detected by diffusive wave optical tomography (DWOT). Detection of objects (< 1 mm) is achieved by phased array optical system using 0^O, 180^O 50 MHz modulation of pairs of laser diodes (780 nm) and fluorescence detection (> 800 nm) affording 0.2 mm object detection of even low Beacon concentrations. One, two, and 3-D localization is made possible by one, two, and three orthogonal phase array null planes.

  20. Using lithium as a neuroprotective agent in patients with cancer.

    PubMed

    Khasraw, Mustafa; Ashley, David; Wheeler, Greg; Berk, Michael

    2012-11-02

    Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect.This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.

  1. Graphene-based nanomaterials as molecular imaging agents.

    PubMed

    Garg, Bhaskar; Sung, Chu-Hsun; Ling, Yong-Chien

    2015-01-01

    Molecular imaging (MI) is a noninvasive, real-time visualization of biochemical events at the cellular and molecular level within tissues, living cells, and/or intact objects that can be advantageously applied in the areas of diagnostics, therapeutics, drug discovery, and development in understanding the nanoscale reactions including enzymatic conversions and protein-protein interactions. Consequently, over the years, great advancement has been made in the development of a variety of MI agents such as peptides, aptamers, antibodies, and various nanomaterials (NMs) including single-walled carbon nanotubes. Recently, graphene, a material popularized by Geim & Novoselov, has ignited considerable research efforts to rationally design and execute a wide range of graphene-based NMs making them an attractive platform for developing highly sensitive MI agents. Owing to their exceptional physicochemical and biological properties combined with desirable surface engineering, graphene-based NMs offer stable and tunable visible emission, small hydrodynamic size, low toxicity, and high biocompatibility and thus have been explored for in vitro and in vivo imaging applications as a promising alternative of traditional imaging agents. This review begins by describing the intrinsic properties of graphene and the key MI modalities. After which, we provide an overview on the recent advances in the design and development as well as physicochemical properties of the different classes of graphene-based NMs (graphene-dye conjugates, graphene-antibody conjugates, graphene-nanoparticle composites, and graphene quantum dots) being used as MI agents for potential applications including theranostics. Finally, the major challenges and future directions in the field will be discussed.

  2. Molecular imaging of prostate cancer with PET.

    PubMed

    Jadvar, Hossein

    2013-10-01

    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  3. Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology

    PubMed Central

    Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

    2014-01-01

    Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery. PMID:25250092

  4. Evolution of Imaging in Breast Cancer.

    PubMed

    Garcia, Evelyn M; Crowley, James; Hagan, Catherine; Atkinson, Lisa L

    2016-06-01

    The following topics are discussed in this article. A historical review of the evolution of breast cancer imaging from thermography through digital breast tomosynthesis, molecular breast imaging, and advanced breast magnetic resonance imaging. Discussion of multiple clinical trials, their strengths, and weaknesses. Historical perspective on the Mammography Quality Standards Act and its relationship with development and implementation of the Breast Imaging-Reporting and Data System (BI-RADS). PMID:27029017

  5. Single Institution Feasibility Trials - Cancer Imaging Program

    Cancer.gov

    Within the CIP program, the current R21 mechanism provides potential funding for small, single institution feasibility trials. The current announcement is titled In Vivo Cancer Imaging Exploratory/Developmental Grants.

  6. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    PubMed Central

    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

    2016-01-01

    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. PMID:27283889

  7. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    NASA Astrophysics Data System (ADS)

    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.

  8. Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents.

    PubMed

    Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M Sheikh; Nagaoka, Yutaka; Romero Aburto, Rebeca; Mitcham, Trevor; Ajayan, Pulickel M; Bouchard, Richard R; Sakamoto, Yasushi; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D Sakthi

    2015-05-14

    A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies. PMID:25797920

  9. Magnetic nanoparticles as both imaging probes and therapeutic agents.

    PubMed

    Lacroix, Lise-Marie; Ho, Don; Sun, Shouheng

    2010-01-01

    Magnetic nanoparticles (MNPs) have been explored extensively as contrast agents for magnetic resonance imaging (MRI) or as heating agents for magnetic fluid hyperthermia (MFH) [1]. To achieve optimum operation conditions in MRI and MFH, these NPs should have well-controlled magnetic properties and biological functionalities. Although numerous efforts have been dedicated to the investigations on MNPs for biomedical applications [2-5], the NP optimizations for early diagnostics and efficient therapeutics are still far from reached. Recent efforts in NP syntheses have led to some promising MNP systems for sensitive MRI and efficient MFH applications. This review summarizes these advances in the synthesis of monodisperse MNPs as both contrast probes in MRI and as therapeutic agents via MFH. It will first introduce the nanomagnetism and elucidate the critical parameters to optimize the superparamagnetic NPs for MRI and ferromagnetic NPs for MFH. It will further outline the new chemistry developed for making monodisperse MNPs with controlled magnetic properties. The review will finally highlight the NP functionalization with biocompatible molecules and biological targeting agents for tumor diagnosis and therapy. PMID:20388109

  10. Cancer Differentiating Agent Hexamethylene Bisacetamide Inhibits BET Bromodomain Proteins.

    PubMed

    Nilsson, Lisa M; Green, Lydia C; Muralidharan, Somsundar Veppil; Demir, Dağsu; Welin, Martin; Bhadury, Joydeep; Logan, Derek T; Walse, Björn; Nilsson, Jonas A

    2016-04-15

    Agents that trigger cell differentiation are highly efficacious in treating certain cancers, but such approaches are not generally effective in most malignancies. Compounds such as DMSO and hexamethylene bisacetamide (HMBA) have been used to induce differentiation in experimental systems, but their mechanisms of action and potential range of uses on that basis have not been developed. Here, we show that HMBA, a compound first tested in the oncology clinic over 25 years ago, acts as a selective bromodomain inhibitor. Biochemical and structural studies revealed an affinity of HMBA for the second bromodomain of BET proteins. Accordingly, both HMBA and the prototype BET inhibitor JQ1 induced differentiation of mouse erythroleukemia cells. As expected of a BET inhibitor, HMBA displaced BET proteins from chromatin, caused massive transcriptional changes, and triggered cell-cycle arrest and apoptosis in Myc-induced B-cell lymphoma cells. Furthermore, HMBA exerted anticancer effects in vivo in mouse models of Myc-driven B-cell lymphoma. This study illuminates the function of an early anticancer agent and suggests an intersection with ongoing clinical trials of BET inhibitor, with several implications for predicting patient selection and response rates to this therapy and starting points for generating BD2-selective BET inhibitors. Cancer Res; 76(8); 2376-83. ©2016 AACR. PMID:26941288

  11. Alkylphosphocholine Analogs for Broad-Spectrum Cancer Imaging and Therapy

    PubMed Central

    Weichert, Jamey P.; Clark, Paul A.; Kandela, Irawati K.; Vaccaro, Abram M.; Clarke, William; Longino, Marc A.; Pinchuk, Anatoly N.; Farhoud, Mohammed; Swanson, Kyle I.; Floberg, John M.; Grudzinski, Joseph; Titz, Benjamin; Traynor, Anne M.; Chen, Hong-En; Hall, Lance T.; Pazoles, Christopher J.; Pickhardt, Perry J.; Kuo, John S.

    2015-01-01

    Many solid tumors contain an overabundance of phospholipid ethers relative to normal cells. Capitalizing on this difference, we created cancer-targeted alkylphosphocholine (APC) analogs through structure-activity analyses. Depending on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either a positron emission tomography (PET) imaging (124I) or molecular radiotherapeutic (131I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. 131I-CLR1404 also displayed efficacy (tumor growth suppression and survival extension) in a wide range of human tumor xenograft models. Human PET/CT (computed tomography) and SPECT (single-photon emission computed tomography)/CT imaging in advanced-cancer patients with 124I-CLR1404 or 131I-CLR1404, respectively, demonstrated selective uptake and prolonged retention in both primary and metastatic malignant tumors. Combined application of these chemically identical APC-based radioisosteres will enable personalized dual modality cancer therapy of using molecular 124I-CLR1404 tumor imaging for planning 131I-CLR1404 therapy. PMID:24920661

  12. Fluorescent and scattering contrast agents in a mouse model of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Winkler, Amy M.; Rice, Photini F. S.; Troutman, Timothy S.; Backer, Marina V.; Backer, Joseph M.; Drezek, Rebekah A.; Romanowski, Marek; Barton, Jennifer K.

    2008-02-01

    In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye.

  13. Magnetic nanobeads as potential contrast agents for magnetic resonance imaging.

    PubMed

    Pablico-Lansigan, Michele H; Hickling, William J; Japp, Emily A; Rodriguez, Olga C; Ghosh, Anup; Albanese, Chris; Nishida, Maki; Van Keuren, Edward; Fricke, Stanley; Dollahon, Norman; Stoll, Sarah L

    2013-10-22

    Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-1). Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

  14. Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents

    NASA Astrophysics Data System (ADS)

    Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M. Sheikh; Nagaoka, Yutaka; Romero Aburto, Rebeca; Mitcham, Trevor; Ajayan, Pulickel M.; Bouchard, Richard R.; Sakamoto, Yasushi; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

    2015-04-01

    A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies. Electronic supplementary information (ESI) available: Methodology and additional experimental results. See DOI: 10.1039/c4nr07139e

  15. Multimodal optical imaging for detecting breast cancer

    NASA Astrophysics Data System (ADS)

    Patel, Rakesh; Khan, Ashraf; Wirth, Dennis; Kamionek, Michal; Kandil, Dina; Quinlan, Robert; Yaroslavsky, Anna N.

    2012-06-01

    The goal of the study was to evaluate wide-field and high-resolution multimodal optical imaging, including polarization, reflectance, and fluorescence for the intraoperative detection of breast cancer. Lumpectomy specimens were stained with 0.05 mg/ml aqueous solution of methylene blue (MB) and imaged. Wide-field reflectance images were acquired between 390 and 750 nm. Wide-field fluorescence images were excited at 640 nm and registered between 660 and 750 nm. High resolution confocal reflectance and fluorescence images were excited at 642 nm. Confocal fluorescence images were acquired between 670 nm and 710 nm. After imaging, the specimens were processed for hematoxylin and eosin (H&E) histopathology. Histological slides were compared with wide-field and high-resolution optical images to evaluate correlation of tumor boundaries and cellular morphology, respectively. Fluorescence polarization imaging identified the location, size, and shape of the tumor in all the cases investigated. Averaged fluorescence polarization values of tumor were higher as compared to normal tissue. Statistical analysis confirmed the significance of these differences. Fluorescence confocal imaging enabled cellular-level resolution. Evaluation and statistical analysis of MB fluorescence polarization values registered from single tumor and normal cells demonstrated higher fluorescence polarization from cancer. Wide-field high-resolution fluorescence and fluorescence polarization imaging shows promise for intraoperative delineation of breast cancers.

  16. Improved molecular imaging contrast agent for detection of human thrombus.

    PubMed

    Winter, Patrick M; Caruthers, Shelton D; Yu, Xin; Song, Sheng-Kwei; Chen, Junjie; Miller, Brad; Bulte, Jeff W M; Robertson, J David; Gaffney, Patrick J; Wickline, Samuel A; Lanza, Gregory M

    2003-08-01

    Molecular imaging of microthrombus within fissures of unstable atherosclerotic plaques requires sensitive detection with a thrombus-specific agent. Effective molecular imaging has been previously demonstrated with fibrin-targeted Gd-DTPA-bis-oleate (BOA) nanoparticles. In this study, the relaxivity of an improved fibrin-targeted paramagnetic formulation, Gd-DTPA-phosphatidylethanolamine (PE), was compared with Gd-DTPA-BOA at 0.05-4.7 T. Ion- and particle-based r(1) relaxivities (1.5 T) for Gd-DTPA-PE (33.7 (s*mM)(-1) and 2.48 x 10(6) (s*mM)(-1), respectively) were about twofold higher than for Gd-DTPA-BOA, perhaps due to faster water exchange with surface gadolinium. Gd-DTPA-PE nanoparticles bound to thrombus surfaces via anti-fibrin antibodies (1H10) induced 72% +/- 5% higher change in R(1) values at 1.5 T (deltaR(1) = 0.77 +/- 0.02 1/s) relative to Gd-DTPA-BOA (deltaR(1) = 0.45 +/- 0.02 1/s). These studies demonstrate marked improvement in a fibrin-specific molecular imaging agent that might allow sensitive, early detection of vascular microthrombi, the antecedent to stroke and heart attack.

  17. A versatile clearing agent for multi-modal brain imaging.

    PubMed

    Costantini, Irene; Ghobril, Jean-Pierre; Di Giovanna, Antonino Paolo; Allegra Mascaro, Anna Letizia; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Onofri, Leonardo; Conti, Valerio; Vanzi, Francesco; Sacconi, Leonardo; Guerrini, Renzo; Markram, Henry; Iannello, Giulio; Pavone, Francesco Saverio

    2015-05-07

    Extensive mapping of neuronal connections in the central nervous system requires high-throughput µm-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multi-modal optical techniques. Here, we introduce a versatile brain clearing agent (2,2'-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue.

  18. A versatile clearing agent for multi-modal brain imaging

    PubMed Central

    Costantini, Irene; Ghobril, Jean-Pierre; Di Giovanna, Antonino Paolo; Mascaro, Anna Letizia Allegra; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Onofri, Leonardo; Conti, Valerio; Vanzi, Francesco; Sacconi, Leonardo; Guerrini, Renzo; Markram, Henry; Iannello, Giulio; Pavone, Francesco Saverio

    2015-01-01

    Extensive mapping of neuronal connections in the central nervous system requires high-throughput µm-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multi-modal optical techniques. Here, we introduce a versatile brain clearing agent (2,2′-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue. PMID:25950610

  19. Optical Imaging of Ovarian Cancer Using HER-2 Affibody Conjugated Nanoparticles

    PubMed Central

    Satpathy, Minati; Zielinski, Rafal; Lyakhov, Ilya; Yang, Lily

    2015-01-01

    Computed Tomography (CT), Ultrasound (US), and Magnetic Resonance Imaging (MRI) have been the mainstay of clinical imaging regimens for the detection of ovarian cancer. However, without tumor specific contrast enhancement, these imaging modalities lack specificity and sensitivity in the detection of small primary and disseminated tumors in the peritoneal cavity. Herein, we illustrate a fairly new near infrared (NIR) optical imaging approach developed in our laboratory for the noninvasive detection of ovarian tumors using a HER-2 targeted nanoparticle-based imaging agent in an orthotopic mouse model of ovarian cancer. We used multimodal imaging approaches to detect the disease accurately and rapidly by utilizing a single imaging agent, NIR dye-labeled HER-2 affibody conjugated iron oxide nanoparticles. This agent targets HER-2 receptors, which are overexpressed in ovarian tumors. This chapter outlines materials and methods for the: (1) production of HER-2 targeted nanoparticles; (2) establishment of an orthotopic human ovarian cancer xenograft model; (3) monitoring of tumor growth by bioluminescence imaging; (4) administration of targeted nanoparticles followed by NIR optical imaging for the detection of orthotopic ovarian cancers with targeted accumulation of the nanoparticle imaging probes. PMID:25308269

  20. Nanoarchitectonics in cancer therapy and imaging diagnosis.

    PubMed

    Pandey, Abhijeet P; Girase, Nayandip M; Patil, Mahendra D; Patil, Pravin O; Patil, Dilip A; Deshmukh, Prashant K

    2014-01-01

    Nanoarchitectonics has gained remarkable importance due to the fabrication of various recent nanostructures with the capability of being used in biomedical science, particularly in cancer diagnosis and treatment. These nanosized structures possess unique physical and optical properties that can be exploited for cancer therapeutics, and so nanoarchitectonics is popularly known as nanomedicine. The goal of this review is to discuss the latest findings in nanostructures research including nanocrystals, nanotubes, nanoshells, nanopillars, nanoballs, nanoflowers, nanorods, nanocontainers, nanobelts, nanocages, nanodiscs, nanodots, nanoprisms, nanoplates, nanorings, nanocubes, nanobranches, nanospheres, nanorattles, nanostars, nanotrees, nanowires, nanowalls, nanodiamonds, nanosheets, layered nanostructures, quantum dots, mesoporous nanostructures etc. in the field of cancer therapy and imaging. This review further highlights brief information about use of radionuclide in cancer. Lastly, different nanoformulations that are available in the market or are under clinical trials for cancer therapy and imaging are discussed. PMID:24730301

  1. In Vivo Imaging of Cancer in Zebrafish.

    PubMed

    Ignatius, Myron S; Hayes, Madeline; Langenau, David M

    2016-01-01

    Zebrafish cancer models have greatly advanced our understanding of malignancy in humans. This is made possible due to the unique advantages of the zebrafish model including ex vivo development and large clutch sizes, which enable large-scale genetic and chemical screens. Transparency of the embryo and the creation of adult zebrafish devoid of pigmentation (casper) have permitted unprecedented ability to dynamically visualize cancer progression in live animals. When coupled with fluorescent reporters and transgenic approaches that drive oncogenesis, it is now possible to label entire or subpopulations of cancer cells and follow cancer growth in near real-time. Here, we will highlight aspects of in vivo imaging using the zebrafish and how it has enhanced our understanding of the fundamental aspects of tumor initiation, self-renewal, neovascularization, tumor cell heterogeneity, invasion and metastasis. Importantly, we will highlight the contribution of cancer imaging in zebrafish for drug discovery. PMID:27165356

  2. Nanoarchitectonics in cancer therapy and imaging diagnosis.

    PubMed

    Pandey, Abhijeet P; Girase, Nayandip M; Patil, Mahendra D; Patil, Pravin O; Patil, Dilip A; Deshmukh, Prashant K

    2014-01-01

    Nanoarchitectonics has gained remarkable importance due to the fabrication of various recent nanostructures with the capability of being used in biomedical science, particularly in cancer diagnosis and treatment. These nanosized structures possess unique physical and optical properties that can be exploited for cancer therapeutics, and so nanoarchitectonics is popularly known as nanomedicine. The goal of this review is to discuss the latest findings in nanostructures research including nanocrystals, nanotubes, nanoshells, nanopillars, nanoballs, nanoflowers, nanorods, nanocontainers, nanobelts, nanocages, nanodiscs, nanodots, nanoprisms, nanoplates, nanorings, nanocubes, nanobranches, nanospheres, nanorattles, nanostars, nanotrees, nanowires, nanowalls, nanodiamonds, nanosheets, layered nanostructures, quantum dots, mesoporous nanostructures etc. in the field of cancer therapy and imaging. This review further highlights brief information about use of radionuclide in cancer. Lastly, different nanoformulations that are available in the market or are under clinical trials for cancer therapy and imaging are discussed.

  3. Multiphoton and photothermal imaging of molecular events in cancer

    NASA Astrophysics Data System (ADS)

    Skala, Melissa

    2010-10-01

    Optical techniques are attractive for monitoring disease processes in living tissues because they are relatively cheap, non-invasive and provide a wealth of functional information. Multiphoton microscopy (MPM) and Optical Coherence Tomography (OCT) are two types of three-dimensional optical imaging modalities that have demonstrated great utility in pre-clinical models of disease. These techniques are particularly useful for identifying metabolic and molecular biomarkers in cancer. These biomarkers can be used to identify the mechanisms of tumor growth, and to predict the response of a particular tumor to treatment. Specifically, MPM of the co-enzymes NADH and FAD was used to quantify metabolic changes associated with developing cancers in vivo. This imaging technique exploits intrinsic sources of tissue contrast and thus does not require contrast agents. Ongoing work combines this metabolic imaging technique with vascular imaging to provide a comprehensive picture of oxygen supply and demand with tumor therapy. Molecular signaling represents a third critical component in tumor physiology. To this end we have recently developed photothermal OCT, which combines coherent detection with laser-heated gold nanoparticles to achieve high-resolution molecular contrast at deeper depths than MPM. This multi-functional imaging platform will provide unprecedented insight into oxygen supply and demand, and molecular signaling in response to tumor growth and targeted cancer therapies in pre-clinical models.

  4. Imaging and Endoscopic Approaches to Pancreatic Cancer.

    PubMed

    Rosenthal, Michael H; Lee, Alexander; Jajoo, Kunal

    2015-08-01

    Imaging and endoscopy both play important and complementary roles in the initial diagnosis, staging, monitoring, and symptomatic management of pancreatic cancer. This article provides an overview of the uses of each of the diagnostic modalities, common imaging findings, alternative considerations, and areas of ongoing work in diagnostic imaging. This article also provides details of the uses of endoscopy for diagnosis, staging, and intervention throughout the course of a patient's care. These modalities each play important roles in the complex multidisciplinary care of patients with pancreatic cancer.

  5. Lung cancer screening: from imaging to biomarker.

    PubMed

    Xiang, Dong; Zhang, Bicheng; Doll, Donald; Shen, Kui; Kloecker, Goetz; Freter, Carl

    2013-01-16

    Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein.

  6. Lung cancer screening: from imaging to biomarker

    PubMed Central

    2013-01-01

    Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein. PMID:24252206

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

    PubMed

    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.

  8. Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

    PubMed

    Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

    2016-01-01

    Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer. PMID:26961312

  9. Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

    PubMed

    Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

    2016-01-01

    Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

  10. Molecular photoacoustic tomography of breast cancer using receptor targeted magnetic iron oxide nanoparticles as contrast agents

    PubMed Central

    Xi, Lei; Grobmyer, Stephen R.; Zhou, Guangyin; Qian, Weiping; Yang, Lily; Jiang, Huabei

    2013-01-01

    In this report, we present a breast imaging technique combining high-resolution near-infrared (NIR) light induced photoacoustic tomography (PAT) with NIR dyelabeled amino-terminal fragments of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (NIR830-ATF-IONP) for breast cancer imaging using an orthotopic mouse mammary tumor model. We show that accumulation of the targeted nanoparticles in the tumor led to photoacoustic contrast enhancement due to the high absorption of iron oxide nanoparticles (IONP). NIR fluorescence images were used to validate specific delivery of NIR830-ATF-IONP to mouse mammary tumors. We found that systemic delivery of the targeted IONP produced 4- and 10-fold enhancement in photoacoustic signals in the tumor, compared to the tumor of the mice that received non-targeted IONP or control mice. The use of targeted nanoparticles allowed imaging of tumors located as deep as 3.1 cm beneath the normal tissues. Our study indicates the potential of the combination of photoacoustic tomography and receptor-targeted NIR830-ATF-IONP as a clinical tool that can provide improved specificity and sensitivity for breast cancer detection. In vivo photoacoustic MAP and fluorescence images before and after injection. Micrographs were merged with fluorescence images taken 24 hours post injection with indicated agent (a, e, i). Panels b thru 1. Photoacoustic MAP images were merged with images of blood vessels before injection (b, f, j), and at 5 hours (c, g, k) and 24 hours (d, h, l) post injection. PMID:23125139

  11. Development of Tc-99m Imaging Agents for Abeta Plaques

    SciTech Connect

    Zhi-Ping, Zhuang; Mei-Ping Kung; Catherihne Hou; Hank F. Kung

    2008-09-26

    Development of SPECT imaging agents based on Tc-99m targeting Aβ plaques is useful for diagnosis of Alzheimer’s disease (AD). A stilbene derivative, [11C]SB-13, showing promise in detecting senile plaques present in AD patients has been reported previously1,2. Based on the 4’-amino-stilbene core structure we have added substituted groups through which a chelating group, N2S2, was conjugated. We report herein a series of Tc-99m labeled stilbene derivative conjugated with a TcO[N2S2] core. The syntheses of stilbenes containing a N2S2 chelating ligand are achieved by a scheme shown. Lipophilic 99mTc stilbene complexes were successfully prepared and purified through HPLC. Preliminary results of in vitro labeling of brain sections from transgenic mice showed very promising plaque labeling. These 99mTc stilbene derivatives are warranted for further evaluations as potential imaging agents targeting amyloid plaques.

  12. Fluorescent rhenium-naphthalimide conjugates as cellular imaging agents.

    PubMed

    Langdon-Jones, Emily E; Symonds, Nadine O; Yates, Sara E; Hayes, Anthony J; Lloyd, David; Williams, Rebecca; Coles, Simon J; Horton, Peter N; Pope, Simon J A

    2014-04-01

    A range of biologically compatible, fluorescent rhenium-naphthalimide conjugates, based upon the rhenium fac-tricarbonyl core, has been synthesized. The fluorescent ligands are based upon a N-functionalized, 4-amino-derived 1,8-naphthalimide core and incorporate a dipicolyl amine binding unit to chelate Re(I); the structural variations accord to the nature of the alkylated imide with ethyl ester glycine (L(1)), 3-propanol (L(2)), diethylene glycol (L(3)), and benzyl alcohol (L(4)) variants. The species are fluorescent in the visible region between 505 and 537 nm through a naphthalimide-localized intramolecular charge transfer, with corresponding fluorescent lifetimes of up to 9.8 ns. The ligands and complexes were investigated for their potential as imaging agents for human osteoarthritic cells and protistan fish parasite Spironucleus vortens using confocal fluorescence microscopy. The results show that the specific nature of the naphthalimide structure serves to control the uptake and intracellular localization of these imaging agents. Significant differences were noted between the free ligands and complexes, with the Re(I) complex of L(2) showing hydrogenosomal localization in S. vortens.

  13. Optimal imaging protocols for lung cancer staging: CT, PET, MR imaging, and the role of imaging.

    PubMed

    Paul, Narinder S; Ley, Sebastian; Metser, Ur

    2012-09-01

    Chest radiography, the most commonly performed imaging technique for the detection of lung disease, is limited in accurately detecting early lung cancer. The main imaging modality for the staging of lung cancer is computed tomography (CT), supplemented by positron emission tomography (PET), usually as a hybrid technique in conjunction with CT (PET/CT). Magnetic resonance (MR) imaging is a useful diagnostic tool for specific indications and has the advantage of not using ionizing radiation. This article discusses the optimal imaging protocols for lung cancer staging using CT, PET (PET/CT), and MR imaging, and the role of imaging in patient management.

  14. (Fluorine-18 labeled androgens and progestins: Imaging agents for tumors of the prostate and breast)

    SciTech Connect

    Katzenellenbogen, J.A.

    1990-09-20

    The objective of this project is to develop fluorine-18 labeled steroids which possess high binding affinity and selectivity for androgen and progesterone receptors and can be used as positron-emission tomographic imaging agents for prostate tumors and breast tumors, respectively. These novel diagnostic agents may enable an accurate estimation of tumor dissemination (metastasis of prostate cancer and lymph node involvement of breast cancer) and an in vivo determination of the endocrine responsiveness of these tumors. Thus, they will provide essential information for the selection of alternative therapies (the extent of surgical ablation, radiation and chemotherapy vs hormonal therapy, etc.), thereby improving the management of prostate and breast cancer patients. Specific aims of the program include: synthesize fluorine-substituted progestins from the following high affinity classes: R5020 (promegestone), norgestrel, RU486, and retroprogestins; synthesize fluorine-substituted androgens from the following high affinity classes: mibolerone, R1881 (metribolone) and 2-oxametribolone; evaluate the receptor binding and non-specific binding of these fluorosteroids by in vitro binding assays; develop and optimize fluoride ion substitution reactions suitable for the rapid, efficient, and convenient preparation of these fluorosteroids in high specific activity, F-18 labeled form; and evaluate the target tissue uptake of the F-18 labeled androgens and progestins in experimental animals. We have synthesized several new fluorine-substituted androgens (1--6) over the past year. Their structures and binding affinity for the androgen receptor (RBA) are listed in this paper. 6 refs.

  15. Delivery of imaging and therapeutic agents to tumor using pHLIP

    NASA Astrophysics Data System (ADS)

    Wijesinghe, Dayanjali; Moshnikova, Anna; Rossi, Bethany; Engelman, Donald; Andreev, Oleg; Reshetnyak, Yana

    2012-02-01

    We are developing a novel technology for selective delivery of imaging probes and membrane-impermeable molecules to cancer cells. It is based on action of water-soluble membrane peptide, pHLIP^ (pH [Low] Insertion Peptide), which has ability to insert and fold in cellular membrane at slightly acidic environment, which is a characteristic for various pathological states including cancer. The insertion of the peptide is unidirectional: C-terminus moves inside the cell across membrane, while N-terminus flags outside. Thus pHLIP possess dual delivery capability. Imaging agents (fluorescent, PET, SPECT or MRI) could be attached to the N-terminus of the peptide to mark tumor mass and tumor margins with high precision. At the same time, therapeutic molecules attached to the C-inserting end, could be moved across membrane to reach cytoplasmic target. Among translocated molecules are synthetic cyclic peptides, gene regulation agent (peptide nucleic acid) and phalla- and amanita toxins with hydrophobicity tuned by attachment of fatty acids for optimum delivery. Currently we have family of pHLIP peptides for various applications. The work is supported by NIH grants CA133890 to OAA, DME, YRK.

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

    SciTech Connect

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

    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.

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

    PubMed Central

    Thomas, Reju; Park, In-Kyu; Jeong, Yong Yeon

    2013-01-01

    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. PMID:23912234

  18. Experimental evaluation of a hyperspectral imager for near-infrared fluorescent contrast agent studies

    NASA Astrophysics Data System (ADS)

    Luthman, A. S.; Bohndiek, Sarah E.

    2015-03-01

    Hyperspectral imaging (HSI) systems have the potential to combine morphological and spectral information to provide detailed and high sensitivity readouts in biological and medical applications. As HSI enables simultaneous detection in several spectral bands, the technology has significant potential for use in real-time multiplexed contrast agent studies. Examples include tumor detection in intraoperative and endoscopic imaging as well as histopathology. A multiplexed readout from multiple disease targets, such as cell surface receptors overexpressed in cancer cells, could improve both sensitivity and specificity of tumor identification. Here, we evaluate a commercial, compact, near-infrared HSI sensor that has the potential to enable low cost, video rate HSI for multiplexed fluorescent contrast agent studies in biomedical applications. The hyperspectral imager, based on a monolithically integrated Fabry-Perot etalon, has 70 spectral bands between 600-900 nm, making it ideal for this application. Initial calibration of the imager was performed to determine wavelength band response, quantum efficiency and the effect of F-number on the spectral response. A platform for wide-field fluorescence imaging in reflectance using fluorophore specific LED excitation was then developed. The applicability of the imaging platform for simultaneous readout of multiple fluorophore signals was demonstrated using a dilution series of Alexa Fluor 594 and Alexa Fluor 647, showing that nanomolar fluorophore concentrations can be detected. Our results show that the HSI system can clearly resolve the emission spectra of the two fluorophores in mixtures of concentrations across several orders of magnitude, indicating a high dynamic range performance. We therefore conclude that the HSI sensor tested here is suitable for detecting fluorescence in biomedical imaging applications.

  19. Non-invasive Optical Molecular Imaging for Cancer Detection

    NASA Astrophysics Data System (ADS)

    Luo, Zhen

    ), which can selectively target plasma membrane of cells based on lower extracellular pH. 20 pairs of clinically normal and abnormal biopsies were obtained from consenting patients at UCDMC. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG and Alexa-647 labeled pHLIP was measured non-invasively by widefield imaging and confocal microscope. Uptake of propargyl choline was measured after topical delivery using confocal microscope. The results of all three molecular imagine probes were further correlated with pathological diagnosis. The imaging results of clinical biopsies demonstrated that 2-NBDG, propargyl choline and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. Topical application of the contrast agents generated significantly higher fluorescence signal intensity in all neoplastic tissues as compared to clinically normal biopsies irrespective of the anatomic location or patient. This unpaired comparison across all the cancer patients in this study highlights the specificity of the imaging approach. Furthermore, the results indicated that changes in intracellular glucose, choline metabolism and cancer acidosis are initiated in the early stages of cancer and these changes are correlated with the progression of the disease. In conclusion, these novel optical molecular imaging approaches to measure multiple biomarkers in cancer have significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

  20. Optical imaging for breast cancer prescreening

    PubMed Central

    Godavarty, Anuradha; Rodriguez, Suset; Jung, Young-Jin; Gonzalez, Stephanie

    2015-01-01

    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. PMID:26229503

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

    PubMed

    Van Cutsem, Eric; Verheul, Henk M W; Flamen, Patrik; Rougier, Philippe; Beets-Tan, Regina; Glynne-Jones, Rob; Seufferlein, Thomas

    2016-01-01

    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. PMID:27589804

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

    PubMed Central

    Van Cutsem, Eric; Verheul, Henk M. W.; Flamen, Patrik; Rougier, Philippe; Beets-Tan, Regina; Glynne-Jones, Rob; Seufferlein, Thomas

    2016-01-01

    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. PMID:27589804

  3. Ultra-high sensitivity imaging of cancer using SERRS nanoparticles

    NASA Astrophysics Data System (ADS)

    Kircher, Moritz F.

    2016-05-01

    "Surface-enhanced Raman spectroscopy" (SERS) nanoparticles have gained much attention in recent years for in silico, in vitro and in vivo sensing applications. Our group has developed novel generations of biocompatible "surfaceenhanced resonance Raman spectroscopy" (SERRS) nanoparticles as novel molecular imaging agents. Via rigorous optimization of the different variables contributing to the Raman enhancement, we were able to design SERRS nanoparticles with so far unprecedented sensitivity of detection under in vivo imaging conditions (femto-attomolar range). This has resulted in our ability to visualize, with a single nanoparticle, many different cancer types (after intravenous injection) in mouse models. The cancer types we have tested so far include brain, breast, esophagus, stomach, pancreas, colon, sarcoma, and prostate cancer. All mouse models used are state-of-the-art and closely mimic the tumor biology in their human counterparts. In these animals, we were able to visualize not only the bulk tumors, but importantly also microscopic extensions and locoregional satellite metastases, thus delineating for the first time the true extent of tumor spread. Moreover, the particles enable the detection of premalignant lesions. Given their inert composition they are expected to have a high chance for clinical translation, where we envision them to have an impact in various scenarios ranging from early detection, image-guidance in open or minimally invasive surgical procedures, to noninvasive imaging in conjunction with spatially offset (SESORS) Raman detection devices.

  4. Photoluminescent graphene nanoparticles for cancer phototherapy and imaging.

    PubMed

    Nurunnabi, Md; Khatun, Zehedina; Reeck, Gerald R; Lee, Dong Yun; Lee, Yong-kyu

    2014-08-13

    Graphene-based nanomaterials are of great interest in a wide range of applications in electronics, the environment, and energy as well as in biomedical and bioengineering. Their unique properties make them generally applicable as prognostic, diagnostic, and therapeutic agents in cancer. In this work, we focused on photodynamic and photothermal therapeutic properties of our previously synthesized carboxylated photoluminescent graphene nanodots (cGdots). The cGdots are ∼5 nm in diameter and excited at 655 nm. Our findings reveal that, upon laser irradiation by near-infrared (wavelength 670 nm) sensitizer, electrons of the cGdots starts to vibrate and form electron clouds, thereby generating sufficient heat (>50 °C) to kill the cancer cells by thermal ablation. The generation of singlet oxygen also occurs due to irradiation, thus acting similarly to pheophorbide-A, a well-known photodynamic therapeutic agent. The cGdots kills MDA-MB231 cancer cells (more than 70%) through both photodynamic and photothermal effects. The cGdots were equally effective in the in vivo model of MDA-MB231 xenografted tumor-bearing mice also as observed for 21 days. The cGdot was intravenously injected, and the tumor was irradiated by laser, resulting in final volume of tumor was ∼70% smaller than that of saline-treated tumor. It indicates that the growth rate of cGdot-treated tumor was slower compared to saline-treated tumor. The synthesized cGdots could enable visualization of tumor tissue in mice, thereby illustrating their use as optical imaging agents for detecting cancer noninvasively in deep tissue/organ. Collectively, our findings reveal that multimodal cGdots can be used for phototherapy, through photothermal or photodynamic effects, and for noninvasive optical imaging of deep tissues and tumors simultaneously.

  5. Simultaneous Dual-Nuclei Imaging for Motion Corrected Detection and Quantification of 19F Imaging Agents

    PubMed Central

    Keupp, Jochen; Rahmer, Jürgen; Grässlin, Ingmar; Mazurkewitz, Peter C.; Schaeffter, Tobias; Lanza, Gregory M.; Wickline, Samuel A.; Caruthers, Shelton D.

    2011-01-01

    Fluorine MRI offers broad potential for specific detection and quantification of molecularly targeted agents in diagnosis and therapy planning or monitoring. Because non-proton MRI applications lack morphological information, accompanying proton images are needed to elucidate the spatial tissue context. Furthermore, low concentrations typical of targeted molecular imaging agents require long examinations for signal averaging during which physiological motion may lead to blurring, underestimation in signal quantification, and erroneous localization of the agent distribution. Novel methods for truly-simultaneous acquisition of dual-nuclei MR data are presented that offer efficient and precise anatomical localization of fluorine signals using accurate motion correction based on contemporaneous proton signals. The feasibility of simultaneous dual-nuclei MRI motion correction and corresponding dual-resolution reconstruction, providing nuclei-specific spatial resolution to retrospectively optimize the balance between signal-to-noise ratio and resolution, is shown on a clinical 3T MR system. PMID:21394779

  6. Positrons as imaging agents and probes in nanotechnology

    NASA Astrophysics Data System (ADS)

    Smith, Suzanne V.

    2009-09-01

    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.

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

    PubMed

    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

    2015-08-01

    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 T2-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.

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

    NASA Astrophysics Data System (ADS)

    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

    2015-08-01

    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 T2-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.

  9. Imaging oligometastatic cancer before local treatment.

    PubMed

    Franklin, James M; Sharma, Ricky A; Harris, Adrian L; Gleeson, Fergus V

    2016-09-01

    With the advent of novel treatment strategies to help widen the therapeutic window for patients with oligometastatic cancer, improved biomarkers are needed to reliably define patients who can benefit from these treatments. Multimodal imaging is one such option and should be optimised to comprehensively assess metastatic sites, disease burden, and response to neoadjuvant treatment in each disease setting. These features will probably remain important prognostic biomarkers, and are crucial in planning multidisciplinary treatment. There are opportunities to extract additional phenotypic information from conventional imaging, while novel imaging techniques can also reveal specific aspects of tumour biology. Imaging can both characterise and localise the phenotypic heterogeneity of multiple tumour sites. Novel approaches to existing imaging datasets and correlation with tumour biology will be important in realising the potential of imaging to guide treatment in the oligometastatic setting. In this Personal View, we discuss the current status and future directions of imaging before treatment in patients with extracranial oligometastases. PMID:27599145

  10. Early detection and longitudinal imaging of cancer micrometastases using biofunctionalized rare-earth albumin nanocomposites

    NASA Astrophysics Data System (ADS)

    Zevon, M.; Kantamneni, H.; Ganapathy, V.; Higgins, L.; Mingozzi, M.; Pierce, M.; Riman, R.; Roth, C. M.; Moghe, P. V.

    2016-05-01

    Success of personalized medicine in cancer therapy depends on the ability to identify and molecularly phenotype tumors. Current clinical imaging techniques cannot be integrated with precision molecular medicine at the level of single cells or microlesions due to limited resolution. In this work we use molecularly targeted infrared emitting optical probes to identify and characterize metastatic microlesions prior to their detection with clinically relevant imaging modalities. These contrast agents form the basis of an in vivo optical imaging system capable of resolving internal microlesions, filling a critical unmet need in cancer imaging.

  11. Metabolomic Imaging for Human Prostate Cancer Detection

    PubMed Central

    Wu, Chin-Lee; Jordan, Kate W.; Ratai, Eva M.; Sheng, Jinhua; Adkins, Christen B.; DeFeo, Elita M; Jenkins, Bruce G.; Ying, Leslie; McDougal, W. Scott; Cheng, Leo L.

    2010-01-01

    As current radiological approaches cannot accurately localize prostate cancer in vivo, biopsies are conducted at random within prostates for at-risk patients, leading to high false-negative rates. Metabolomic imaging can map cancer-specific biomolecular profile values onto anatomical structures to direct biopsy. In this preliminary study, we evaluated five prostatectomy-removed whole prostates from biopsy-proven cancer patients on a 7 Tesla human, whole-body magnetic resonance scanner. Localized, multi-cross-sectional, multi-voxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous, intact tissue analyses by a 14 Tesla spectrometer. This calculated Malignancy Index shows linear correlation with lesion size (p<0.013) and demonstrates a 93–97% overall accuracy for detecting the presence of prostate cancer lesions. PMID:20371475

  12. Optical Coherence Tomography in Cancer Imaging

    NASA Astrophysics Data System (ADS)

    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.

  13. A highly fluorescent AIE-active theranostic agent with anti-tumor activity to specific cancer cells

    NASA Astrophysics Data System (ADS)

    Zhao, Yueyue; Kwok, Ryan T. K.; Lam, Jacky W. Y.; Tang, Ben Zhong

    2016-06-01

    A tetraphenylethene derivative with a structure resembling Tamoxifen is designed and synthesized as a theranostic agent for cell imaging and anti-breast cancer therapy. Its high brightness, excellent photostability and long-term cell tracing properties enable elucidation of its working mechanism and hence provide new insights into drug development.A tetraphenylethene derivative with a structure resembling Tamoxifen is designed and synthesized as a theranostic agent for cell imaging and anti-breast cancer therapy. Its high brightness, excellent photostability and long-term cell tracing properties enable elucidation of its working mechanism and hence provide new insights into drug development. Electronic supplementary information (ESI) available: Detailed synthesis and characterization of TPE-OH and TPE-TMX PL spectra of TPE-TMX fluorescent photographs of TPE-TMX taken under UV irradiation; various concentrations of TPE-TMX with different incubation times. See DOI: 10.1039/c5nr08782a

  14. Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Feng, Yi

    Macromolecular contrast agents have been shown to be superior to small molecular weight contrast agents for MRI in blood pool imaging, tumor diagnosis and grading. However, none has been approved by the FDA because they circulate in the bloodstream much longer than small molecular weight contrast agents and result in high tissue accumulation of toxic Gd(III) ions. Biodegradable macromolecular contrast agents (BMCA) were invented to alleviate the toxic accumulation. They have a cleavable disulfide bond based backbone that can be degraded in vivo and excreted out of the body via renal filtration. Furthermore, the side chain of the backbone can be modified to achieve various degradation rates. Three BMCA, (Gd-DTPA)-cystamine copolymers (GDCC), Gd-DTPA cystine copolymers (GDCP), and Gd-DTPA cystine diethyl ester copolymers (GDCEP), were evaluated as blood pool contrast agents in a rat model. They have excellent blood pool enhancement, preferred pharmacokinetics, and only minimal long-term tissue retention of toxic Gd(III) ions. GDCC and GDCP, the lead agents with desired degradation rates, with molecular weights of 20 KDa and 70 KDa, were chosen for dynamic contrast enhanced MRI (DCE-MRI) to differentiate human prostate tumor models of different malignancy and growth rates. GDCC and GDCP could differentiate these tumor models, providing more accurate estimations of plasma volume, flow leakage rate, and permeability surface area product than a small molecular weight contrast agent Gd-DTPA-BMA when compared to the prototype macromolecular contrast agent albumin-Gd-DTPA. GDCC was favored for its neutral charge side chain and reasonable uptake rate by the tumors. GDCC with a molecular weight of 40 KDa (GDCC-40, above the renal filtration cutoff size) was used to assess the efficacy of two photothermal therapies (interstitial and indocyanine green enhanced). GDCC-40 provided excellent tumor enhancement shortly after its injection. Acute tumor response (4 hr) after therapies

  15. Theranostic Imaging of Cancer Gene Therapy.

    PubMed

    Sekar, Thillai V; Paulmurugan, Ramasamy

    2016-01-01

    Gene-directed enzyme prodrug therapy (GDEPT) is a promising therapeutic approach for treating cancers of various phenotypes. This strategy is independent of various other chemotherapeutic drugs used for treating cancers where the drugs are mainly designed to target endogenous cellular mechanisms, which are different in various cancer subtypes. In GDEPT an external enzyme, which is different from the cellular proteins, is expressed to convert the injected prodrug in to a toxic metabolite, that normally kill cancer cells express this protein. Theranostic imaging is an approach used to directly monitor the expression of these gene therapy enzymes while evaluating therapeutic effect. We recently developed a dual-GDEPT system where we combined mutant human herpes simplex thymidine kinase (HSV1sr39TK) and E. coli nitroreductase (NTR) enzyme, to improve therapeutic efficiency of cancer gene therapy by simultaneously injecting two prodrugs at a lower dose. In this approach we use two different prodrugs such as ganciclovir (GCV) and CB1954 to target two different cellular mechanisms to kill cancer cells. The developed dual GDEPT system was highly efficacious than that of either of the system used independently. In this chapter, we describe the complete protocol involved for in vitro and in vivo imaging of therapeutic cancer gene therapy evaluation. PMID:27424910

  16. Molecularly Targeted Agents as Radiosensitizers in Cancer Therapy—Focus on Prostate Cancer

    PubMed Central

    Alcorn, Sara; Walker, Amanda J.; Gandhi, Nishant; Narang, Amol; Wild, Aaron T.; Hales, Russell K.; Herman, Joseph M.; Song, Danny Y.; DeWeese, Theodore L.; Antonarakis, Emmanuel S.; Tran, Phuoc T.

    2013-01-01

    As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer. PMID:23863691

  17. PET/MR Imaging in Cancers of the Gastrointestinal Tract.

    PubMed

    Paspulati, Raj Mohan; Gupta, Amit

    2016-10-01

    PET/computed tomography (PET/CT) is an established hybrid imaging technique for staging and follow-up of gastrointestinal (GI) tract malignancies, especially for colorectal carcinoma. Dedicated hybrid PET/MR imaging scanners are currently available for clinical use. Although they will not replace regular use of PET/CT, they may have utility in selected cases of GI tract malignancies. The superior soft tissue contrast resolution and depiction of anatomy and the functional information obtained from diffusion-weighted imaging (DWI) provided by MR imaging in PET/MR imaging are advantages over CT of PET/CT for T staging and follow-up of rectal carcinoma and for better characterization of liver lesions. Functional information from DWI and use of liver-specific MR imaging contrast agents are an added advantage in follow-up of liver metastases after systemic and locoregional treatment. New radiotracers will improve the utility of PET/MR imaging in staging and follow-up of tumors, which may not be [18F]-2-fluoro-2-deoxy-d-glucose avid, such as hepatocellular carcinoma and neuroendocrine tumors. PET/MR imaging also has application in selected cases of cholangiocarcinoma, gallbladder cancer, and pancreatic carcinoma for initial staging and follow-up assessment.

  18. PET/MR Imaging in Cancers of the Gastrointestinal Tract.

    PubMed

    Paspulati, Raj Mohan; Gupta, Amit

    2016-10-01

    PET/computed tomography (PET/CT) is an established hybrid imaging technique for staging and follow-up of gastrointestinal (GI) tract malignancies, especially for colorectal carcinoma. Dedicated hybrid PET/MR imaging scanners are currently available for clinical use. Although they will not replace regular use of PET/CT, they may have utility in selected cases of GI tract malignancies. The superior soft tissue contrast resolution and depiction of anatomy and the functional information obtained from diffusion-weighted imaging (DWI) provided by MR imaging in PET/MR imaging are advantages over CT of PET/CT for T staging and follow-up of rectal carcinoma and for better characterization of liver lesions. Functional information from DWI and use of liver-specific MR imaging contrast agents are an added advantage in follow-up of liver metastases after systemic and locoregional treatment. New radiotracers will improve the utility of PET/MR imaging in staging and follow-up of tumors, which may not be [18F]-2-fluoro-2-deoxy-d-glucose avid, such as hepatocellular carcinoma and neuroendocrine tumors. PET/MR imaging also has application in selected cases of cholangiocarcinoma, gallbladder cancer, and pancreatic carcinoma for initial staging and follow-up assessment. PMID:27593246

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Confocal microendoscopy: Characterization of imaging bundles, fluorescent contrast agents, and early clinical results

    NASA Astrophysics Data System (ADS)

    Udovich, Joshua Anthony

    Ovarian cancer is the fifth leading cause of cancer related deaths among women. Early detection improves the chances of survival following diagnosis, and new imaging modalities have the potential to reduce deaths due to this disease. The confocal microendoscope (CME) is a non-destructive in-vivo imaging device for visualization of the ovaries that operates in real-time. Two components of the CME system are evaluated in this paper, and initial results from an ongoing clinical trial are presented. Fiber-optic imaging bundles are used in the CME imaging catheter to relay images over distances of up to 20 feet. When detecting fluorescent signals from investigated tissue, any fluorescence in the system can potentially reduce contrast in images. The emission and transmission properties of three commercially available fiber optic imaging bundles were evaluated. Emission maps of fluorescence from bundles were generated at multiple excitation wavelengths to determine the profile and amount of fluorescence present in bundles manufactured by Sumitomo, Fujikura, and Schott. Results are also presented that show the variation of transmittance as a function of illumination angle in these bundles. Users of high-resolution fiber-optic imaging bundles should be aware of these properties and take them into account during system design. Contrast is improved in images obtained with the CME through the application of topical dyes. Acridine orange (AO) and SYTO 16 are two fluorescent stains that are used to show the size, shape, and distribution of cell nuclei. Unfortunately, little is known about the effects of these dyes on living tissues. This study was undertaken to evaluate the effects of dye treatment on peritoneal tissues in mice. Seventy-five Balb/c mice were split into five groups of fifteen and given peritoneal injections of dye or saline. The proportions of negative outcomes for the control and test groups were compared using confidence intervals and the Fisher's exact test

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

    PubMed Central

    Lee, Haisung; Sung, Dongkyung; Kim, Jinhoon; Kim, Byung-Tae; Wang, Tuntun; An, Seong Soo A; Seo, Soo-Won; Yi, Dong Kee

    2015-01-01

    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. PMID:26357472

  2. Metallic nanoparticles as optoacoustic contrast agents for medical imaging

    NASA Astrophysics Data System (ADS)

    Conjusteau, Andre; Ermilov, Sergey A.; Lapotko, Dmitri; Liao, Hongwei; Hafner, Jason; Eghtedari, Mohammad; Motamedi, Massoud; Kotov, Nicholas; Oraevsky, Alexander A.

    2006-02-01

    A contrast agent for optoacoustic imaging and laser therapy of early tumors is being developed based on gold nanocolloids strongly absorbing visible and near-infrared light. The optoacoustic signals obtained from gold nanospheres and gold nanorods solutions are studied. In the case of 100 nm nanospheres as an example, a sharp increase in the total area under the curve of the optoacoustic signal is observed when the laser fluence is increased beyond a threshold value of about 0.1 J/cm2. The change in the optoacoustic signal profile is attributed to the formation of water vapor bubbles around heated nanoparticles, as evidenced via thermoacoustic microscopy experiments. It has been determined that, surprisingly, gold nanoparticles fail to generate detectable nanobubbles upon irradiation at the laser fluence of ~2 mJ/cm2, which heats the nanoparticles up to 374°C, the critical temperature of water. Only when the estimated temperature of the particle reaches about 10,000°C, a marked increase of the optoacoustic pressure amplitude and a changed profile of the optoacoustic signals indicate nanobubble formation. A nanoparticle based contrast agent is the most effective if it can be activate by laser pulses with low fluence attainable in the depth of tissue. With this goal in mind, we develop targeting protocols that form clusters of gold nanocolloid in the target cells in order to lower the bubble formation threshold below the level of optical fluence allowed for safe laser illumination of skin. Experiments and modeling suggest that formation of clusters of nanocolloids may improve the sensitivity of optoacoustic imaging in the detection of early stage tumors.

  3. Image-based brachytherapy for cervical cancer.

    PubMed

    Vargo, John A; Beriwal, Sushil

    2014-12-10

    Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes. Advantages of image-based brachytherapy include: improved tumor coverage (especially for large volume disease), decreased dose to critical organs (especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging (MRI), computed tomography (CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. For practical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE (an international study of MRI-guided brachytherapy in locally advanced cervical

  4. Cancer and Pregnancy: Parallels in Growth, Invasion, and Immune Modulation and Implications for Cancer Therapeutic Agents

    PubMed Central

    Holtan, Shernan G.; Creedon, Douglas J.; Haluska, Paul; Markovic, Svetomir N.

    2009-01-01

    Many proliferative, invasive, and immune tolerance mechanisms that support normal human pregnancy are also exploited by malignancies to establish a nutrient supply and evade or edit the host immune response. In addition to the shared capacity for invading through normal tissues, both cancer cells and cells of the developing placenta create a microenvironment supportive of both immunologic privilege and angiogenesis. Systemic alterations in immunity are also detectable, particularly with respect to a helper T cell type 2 polarization evident in advanced cancers and midtrimester pregnancy. This review summarizes the similarities between growth and immune privilege in cancer and pregnancy and identifies areas for further investigation. Our PubMed search strategy included combinations of terms such as immune tolerance, pregnancy, cancer, cytokines, angiogenesis, and invasion. We did not place any restrictions on publication dates. The knowledge gained from analyzing similarities and differences between the physiologic state of pregnancy and the pathologic state of cancer could lead to identification of new potential targets for cancer therapeutic agents. PMID:19880689

  5. Circular polarization terahertz imaging of nonmelanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Martin, Jillian P.

    The use of terahertz (THz) radiation for imaging human tissue and delineating tumor margins has become an appealing topic in the biomedical field because THz radiation is non-ionizing and has the demonstrated ability to differentiate between cancerous and normal tissue without the need for exogenous contrast agents. Previously, a reflective continuous-wave (CW) THz imaging system utilizing a linear polarization-sensitive detection technique was demonstrated and used to delineate tumor margins for nonmelanoma skin cancers [1, 2] and determine reflectivity differences between normal and cancerous colon tissue [3 - 5]. This detection technique involves illuminating ex vivo tissue samples with linearly polarized light and collecting the signal remitted by the sample after passing through an analyzing wire grid polarizer oriented with its transmission axis perpendicular to the linear polarization incident on the sample. By collecting the cross-polarization signal, the strong Fresnel surface reflections from the sample holder interfaces are eliminated and predominantly signal from within the tissue volume is obtained. The aim of the proposed research is to enhance this polarization-sensitive detection technique by incorporating circular polarization illumination and detection channels. This technique has been demonstrated at optical wavelengths [6], where the scattering of light within the tissue volume has been extensively studied; however, it has yet to be implemented using THz radiation. In addition, this detection technique has the potential to demonstrate increased contrast between cancerous and normal tissue, and experimental results may shed light on the mechanism behind the observed contrast.

  6. Cancer detection by quantitative fluorescence image analysis.

    PubMed

    Parry, W L; Hemstreet, G P

    1988-02-01

    Quantitative fluorescence image analysis is a rapidly evolving biophysical cytochemical technology with the potential for multiple clinical and basic research applications. We report the application of this technique for bladder cancer detection and discuss its potential usefulness as an adjunct to methods used currently by urologists for the diagnosis and management of bladder cancer. Quantitative fluorescence image analysis is a cytological method that incorporates 2 diagnostic techniques, quantitation of nuclear deoxyribonucleic acid and morphometric analysis, in a single semiautomated system to facilitate the identification of rare events, that is individual cancer cells. When compared to routine cytopathology for detection of bladder cancer in symptomatic patients, quantitative fluorescence image analysis demonstrated greater sensitivity (76 versus 33 per cent) for the detection of low grade transitional cell carcinoma. The specificity of quantitative fluorescence image analysis in a small control group was 94 per cent and with the manual method for quantitation of absolute nuclear fluorescence intensity in the screening of high risk asymptomatic subjects the specificity was 96.7 per cent. The more familiar flow cytometry is another fluorescence technique for measurement of nuclear deoxyribonucleic acid. However, rather than identifying individual cancer cells, flow cytometry identifies cellular pattern distributions, that is the ratio of normal to abnormal cells. Numerous studies by others have shown that flow cytometry is a sensitive method to monitor patients with diagnosed urological disease. Based upon results in separate quantitative fluorescence image analysis and flow cytometry studies, it appears that these 2 fluorescence techniques may be complementary tools for urological screening, diagnosis and management, and that they also may be useful separately or in combination to elucidate the oncogenic process, determine the biological potential of tumors

  7. Single Walled Carbon Nanohorns as Photothermal Cancer Agents

    SciTech Connect

    Whitney, John; Sarkar, Saugata; Zhang, Jianfei; Do, Thao; Manson, Mary kyle; Campbell, Tom; Puretzky, Alexander A; Rouleau, Christopher M; More, Karren Leslie; Geohegan, David B; Rylander, Christopher; Dorn, Harry C; Rylander, Nichole M

    2011-01-01

    Nanoparticles have significant potential as selective photo-absorbing agents for laser based cancer treatment. This study investigates the use of single walled carbon nanohorns (SWNHs) as thermal enhancers when excited by near infrared (NIR) light for tumor cell destruction. Absorption spectra of SWNHs in deionized water at concentrations of 0, 0.01, 0.025, 0.05, 0.085, and 0.1 mg/ml were measured using a spectrophotometer for the wavelength range of 200-1,400 nm. Mass attenuation coefficients were calculated using spectrophotometer transmittance data. Cell culture media containing 0, 0.01, 0.085, and 0.333 mg/ml SWNHs was laser irradiated at 1,064 nm wavelength with an irradiance of 40 W/cm{sup 2} for 0-5 minutes. Temperature elevations of these solutions during laser irradiation were measured with a thermocouple 8 mm away from the incident laser beam. Cell viability of murine kidney cancer cells (RENCA) was measured 24 hours following laser treatment with the previously mentioned laser parameters alone or with SWNHs. Cell viability as a function of radial position was determined qualitatively using trypan blue staining and bright field microscopy for samples exposed to heating durations of 2 and 6 minutes alone or with 0.085 mg/ml SWNHs. A Beckman Coulter Vi-Cell instrument quantified cell viability of samples treated with varying SWNH concentration (0, 0.01, 0.085, and 0.333 mg/ml) and heating durations of 0-6 minutes. Spectrophotometer measurements indicated inclusion of SWNHs increased light absorption and attenuation across all wavelengths. Utilizing SWNHs with laser irradiation increased temperature elevation compared to laser heating alone. Greater absorption and higher temperature elevations were observed with increasing SWNH concentration. No inherent toxicity was observed with SWNH inclusion. A more rapid and substantial viability decline was observed over time in samples exposed to SWNHs with laser treatment compared with samples experiencing laser

  8. Imaging Localized Prostate Cancer: Current Approaches and New Developments

    PubMed Central

    Turkbey, Baris; Albert, Paul S.; Kurdziel, Karen; Choyke, Peter L.

    2012-01-01

    OBJECTIVE Prostate cancer is the most common noncutaneous malignancy among men in the Western world. Imaging has recently become more important in the diagnosis, local staging, and treatment follow-up of prostate cancer. In this article, we review conventional and functional imaging methods as well as targeted imaging approaches with novel tracers used in the diagnosis and staging of prostate cancer. CONCLUSION Although prostate cancer is the second leading cause of cancer death in men, imaging of localized prostate cancer remains limited. Recent developments in imaging technologies, particularly MRI and PET, may lead to significant improvements in lesion detection and staging. PMID:19457807

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

    PubMed Central

    Akhtar, Muammad Saeed; Imran, Muhammad Babar; Nadeem, Muhammad Afzal; Shahid, Abubaker

    2012-01-01

    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. PMID:22675369

  10. Novel paramagnetic contrast agents for molecular imaging and targeted drug delivery.

    PubMed

    Lanza, Gregory M; Winter, Patrick; Caruthers, Shelton; Schmeider, Anne; Crowder, Kathy; Morawski, Anne; Zhang, Huiying; Scott, Michael J; Wickline, Samuel A

    2004-12-01

    Molecular biology and genomic sciences are revealing the early biological signatures for many diseases. In response, the Molecular Imaging community is rapidly developing contrast agents to visualize the nascent pathological changes and to concomitantly deliver treatment directly to the site of disease. The evaluation, development and use of these new agents require a complementary understanding of contrast chemistry and imaging techniques. The fundamental issues surrounding magnetic contrast agent development, rational drug delivery, MR molecular imaging, and their interdependence are elucidated.

  11. Recent advances in breast cancer imaging.

    PubMed

    Newman, J

    1999-01-01

    Mammography is the best technique currently available for early detection of breast cancer, but it has limitations. Several new techniques are under investigation that may provide valuable complementary images. This article discusses some of the most promising adjuncts to film-screen mammography, including digital mammography, ultrasound of the breast, breast MR, scintimammography and sentinel node lymphoscintigraphy.

  12. Fluorescence lifetime imaging of skin cancer

    NASA Astrophysics Data System (ADS)

    Patalay, Rakesh; Talbot, Clifford; Munro, Ian; Breunig, Hans Georg; König, Karsten; Alexandrov, Yuri; Warren, Sean; Neil, Mark A. A.; French, Paul M. W.; Chu, Anthony; Stamp, Gordon W.; Dunsby, Chris

    2011-03-01

    Fluorescence intensity imaging and fluorescence lifetime imaging microscopy (FLIM) using two photon microscopy (TPM) have been used to study tissue autofluorescence in ex vivo skin cancer samples. A commercially available system (DermaInspect®) was modified to collect fluorescence intensity and lifetimes in two spectral channels using time correlated single photon counting and depth-resolved steady state measurements of the fluorescence emission spectrum. Uniquely, image segmentation has been used to allow fluorescence lifetimes to be calculated for each cell. An analysis of lifetime values obtained from a range of pigmented and non-pigmented lesions will be presented.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Noninvasive Imaging of Cardiovascular Injury Related to the Treatment of Cancer

    PubMed Central

    Kongbundansuk, Suwat; Hundley, W. Gregory

    2014-01-01

    The introduction of multiple treatments for cancer, including chemotherapeutic agents and radiation therapy, has significantly reduced cancer-related morbidity and mortality. However, these therapies can promote a variety of toxicities, among the most severe being the ones involving the cardiovascular system. Currently, for many surviving cancer patients, cardiovascular (CV) events represent the primary cause of morbidity and mortality. Recent data suggests that CV injury occurs early during cancer treatment, creating a substrate for subsequent cardiovascular events. Researchers have investigated the utility of noninvasive imaging strategies to detect the presence of CV injury during and after completion of cancer treatment because it starts early during cancer therapy, often preceding the development of chemotherapy or cancer therapeutics related cardiac dysfunction. In this state of the art article, we review the utility of current clinical and investigative CV noninvasive modalities for the identification and characterization of cancer treatment-related CV toxicity. PMID:25124015

  15. Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles.

    PubMed

    Phillips, William T; Bao, Ande; Brenner, Andrew J; Goins, Beth A

    2014-09-30

    One of the major limitations of current cancer therapy is the inability to deliver tumoricidal agents throughout the entire tumor mass using traditional intravenous administration. Nanoparticles carrying beta-emitting therapeutic radionuclides that are delivered using advanced image-guidance have significant potential to improve solid tumor therapy. The use of image-guidance in combination with nanoparticle carriers can improve the delivery of localized radiation to tumors. Nanoparticles labeled with certain beta-emitting radionuclides are intrinsically theranostic agents that can provide information regarding distribution and regional dosimetry within the tumor and the body. Image-guided thermal therapy results in increased uptake of intravenous nanoparticles within tumors, improving therapy. In addition, nanoparticles are ideal carriers for direct intratumoral infusion of beta-emitting radionuclides by convection enhanced delivery, permitting the delivery of localized therapeutic radiation without the requirement of the radionuclide exiting from the nanoparticle. With this approach, very high doses of radiation can be delivered to solid tumors while sparing normal organs. Recent technological developments in image-guidance, convection enhanced delivery and newly developed nanoparticles carrying beta-emitting radionuclides will be reviewed. Examples will be shown describing how this new approach has promise for the treatment of brain, head and neck, and other types of solid tumors.

  16. Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles✩

    PubMed Central

    Phillips, William T.; Bao, Ande; Brenner, Andrew J.; Goins, Beth A.

    2015-01-01

    One of the major limitations of current cancer therapy is the inability to deliver tumoricidal agents throughout the entire tumor mass using traditional intravenous administration. Nanoparticles carrying beta-emitting therapeutic radionuclides that are delivered using advanced image-guidance have significant potential to improve solid tumor therapy. The use of image-guidance in combination with nanoparticle carriers can improve the delivery of localized radiation to tumors. Nanoparticles labeled with certain beta-emitting radionuclides are intrinsically theranostic agents that can provide information regarding distribution and regional dosimetry within the tumor and the body. Image-guided thermal therapy results in increased uptake of intravenous nanoparticles within tumors, improving therapy. In addition, nanoparticles are ideal carriers for direct intratumoral infusion of beta-emitting radionuclides by convection enhanced delivery, permitting the delivery of localized therapeutic radiation without the requirement of the radionuclide exiting from the nanoparticle. With this approach, very high doses of radiation can be delivered to solid tumors while sparing normal organs. Recent technological developments in image-guidance, convection enhanced delivery and newly developed nanoparticles carrying beta-emitting radionuclides will be reviewed. Examples will be shown describing how this new approach has promise for the treatment of brain, head and neck, and other types of solid tumors. PMID:25016083

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed

    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

  20. Chemopreventive Agent Development Staff | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  1. Chemopreventive Agent Development Funding Opportunities | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  2. Active Chemopreventive Agent Development Grants | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  3. Chemopreventive Agent Development Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  4. Multi-modal imaging and cancer therapy using lanthanide oxide nanoparticles: current status and perspectives.

    PubMed

    Park, J Y; Chang, Y; Lee, G H

    2015-01-01

    Biomedical imaging is an essential tool for diagnosis and therapy of diseases such as cancers. It is likely true that medicine has developed with biomedical imaging methods. Sensitivity and resolution of biomedical imaging methods can be improved with imaging agents. Furthermore, it will be ideal if imaging agents could be also used as therapeutic agents. Therefore, one dose can be used for both diagnosis and therapy of diseases (i.e., theragnosis). This will simplify medical treatment of diseases, and will be also a benefit to patients. Mixed (Ln(1x)Ln(2y)O3, x + y = 2) or unmixed (Ln2O3) lanthanide (Ln) oxide nanoparticles (Ln = Eu, Gd, Dy, Tb, Ho, Er) are potential multi-modal imaging and cancer therapeutic agents. The lanthanides have a variety of magnetic and optical properties, useful for magnetic resonance imaging (MRI) and fluorescent imaging (FI), respectively. They also highly attenuate X-ray beam, useful for X-ray computed tomography (CT). In addition gadolinium-157 ((157)Gd) has the highest thermal neutron capture cross section among stable radionuclides, useful for gadolinium neutron capture therapy (GdNCT). Therefore, mixed or unmixed lanthanide oxide nanoparticles can be used for multi-modal imaging methods (i.e., MRI-FI, MRI-CT, CT-FI, and MRICT- FI) and cancer therapy (i.e., GdNCT). Since mixed or unmixed lanthanide oxide nanoparticles are single-phase and solid-state, they can be easily synthesized, and are compact and robust, which will be beneficial to biomedical applications. In this review physical properties of the lanthanides, synthesis, characterizations, multi-modal imagings, and cancer therapy of mixed and unmixed lanthanide oxide nanoparticles are discussed.

  5. Hybrid graphene/Au activatable theranostic agent for multimodalities imaging guided enhanced photothermal therapy.

    PubMed

    Gao, Shi; Zhang, Liwen; Wang, Guohao; Yang, Kai; Chen, Minglong; Tian, Rui; Ma, Qingjie; Zhu, Lei

    2016-02-01

    Photothermal therapy (PTT) has been increasingly investigated. However, there are still challenges in strategies that can further enhance photoconversion efficiency and improve photothermal tumor ablation effect of current nanomaterials. Herein, we developed a fluorescent/photoacoustic imaging guided PTT agent by seeding Gold (Au) nanoparticles onto graphene oxide (GO). Near infrared dye (Cy5.5) labeled-matrix metalloproteinase-14 (MMP-14) substrate (CP) was conjugated onto the GO/Au complex (GA) forming tumor targeted theranostic probe (CPGA), whereCy5.5 fluorescent signal is quenched by Surface Plasmon Resonance (SPR) capacity from both GO and Au, yet it can boost strong fluorescence signals after degradation by MMP-14. The photothermal effect of GA hybrid was found significantly elevated compared with Au or GO alone. After intravenous administration of CPGA into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.64 ± 0.51 for optical imaging and 2.5 ± 0.27 for PA imaging). The tumors were then irradiated with a laser, and an excellent tumor inhibition was observedwithoutrecurrence. Our studies further encourage applications of the hybrid nanocomposite for image-guided enhanced PTT in biomedical applications, especially in cancer theranostics. PMID:26691399

  6. Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Shan, Liang; Gu, Xinbin; Wang, Paul

    2013-09-01

    Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

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

    PubMed Central

    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

  8. Imaging probe for breast cancer localization

    NASA Astrophysics Data System (ADS)

    Soluri, A.; Scafè, R.; Capoccetti, F.; Burgio, N.; Schiaratura, A.; Pani, R.; Pellegrini, R.; Cinti, M. N.; Mechella, M.; Amanti, A.; David, V.; Scopinaro, F.

    2003-01-01

    High spatial resolution, small Field Of View (FOV), fully portable scintillation cameras are lower cost and obviously lower weight than large FOV, not transportable Anger gamma cameras. Portable cameras allow easy transfer of the detector, thus of radioisotope imaging, where the bioptical procedure takes place. In this paper we describe a preliminary experience on radionuclide Breast Cancer (BC) imaging with a 22.8×22.8 mm 2 FOV minicamera, already used by our group for sentinel node detection with the name of Imaging Probe (IP). In this work IP BC detection was performed with the aim of guiding biopsy, in particular open biopsy, or to help or modify fine needle or needle addressing when main driving method was echography or digital radiography. The IP prototype weight was about 1 kg. This small scintillation camera is based on the compact Position Sensitive Photomultiplier Tube Hamamatsu R7600-00-C8, coupled to a CsI(Tl) scintillation array 2.6×2.6×5.0 mm 3 crystal-pixel size. Spatial resolution of the IP was 2.5 mm Full-Width at Half-Maximum at laboratory tests. IP was provided with acquisition software allowing quick change of pixels number on the computer acquisition frame and an on-line image-smoothing program. Both these programs were developed in order to allow nuclear physicians to quickly get target source when the patient was anesthetized in the operator room, with sterile conditions. 99mTc Sestamibi (MIBI) was injected at the dose of 740 MBq 1 h before imaging and biopsy to 14 patients with suspicious or known BC. Scintigraphic images were acquired before and after biopsy in each patient. Operator was allowed to take into account scintigraphic images as well as previously performed X-ray mammograms and echographies. High-resolution IP images were able to guide biopsy toward cancer or washout zones of the cancer, that are thought to be chemoresistant in 7 patients out of 10. Four patients, in whom IP and MIBI were not able to guide biopsy, did not show

  9. Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic Resonance Imaging.

    PubMed

    Zhang, Kunchi; Liu, Min; Tong, Xiaoyan; Sun, Na; Zhou, Lu; Cao, Yi; Wang, Jine; Zhang, Hailu; Pei, Renjun

    2015-09-14

    A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

  10. Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer

    PubMed Central

    Bothwell, Katelyn D.; Folaron, Margaret; Seshadri, Mukund

    2016-01-01

    Vascular disrupting agents (VDAs) represent a relatively distinct class of agents that target established blood vessels in tumors. In this study, we examined the preclinical activity of the second-generation VDA OXi4503 against human head and neck squamous cell carcinoma (HNSCC). Studies were performed in subcutaneous and orthotopic FaDu-luc HNSCC xenografts established in immunodeficient mice. In the subcutaneous model, bioluminescence imaging (BLI) along with tumor growth measurements was performed to assess tumor response to therapy. In mice bearing orthotopic tumors, a dual modality imaging approach based on BLI and magnetic resonance imaging (MRI) was utilized. Correlative histologic assessment of tumors was performed to validate imaging data. Dynamic BLI revealed a marked reduction in radiance within a few hours of OXi4503 administration compared to baseline levels. However, this reduction was transient with vascular recovery observed at 24 h post treatment. A single injection of OXi4503 (40 mg/kg) resulted in a significant (p < 0.01) tumor growth inhibition of subcutaneous FaDu-luc xenografts. MRI revealed a significant reduction (p < 0.05) in volume of orthotopic tumors at 10 days post two doses of OXi4503 treatment. Corresponding histologic (H&E) sections of Oxi4503 treated tumors showed extensive areas of necrosis and hemorrhaging compared to untreated controls. To the best of our knowledge, this is the first report, on the activity of Oxi4503 against HNSCC. These results demonstrate the potential of tumor-VDAs in head and neck cancer. Further examination of the antivascular and antitumor activity of Oxi4503 against HNSCC alone and in combination with chemotherapy and radiation is warranted. PMID:26751478

  11. Alkylating agents and immunotoxins exert synergistic cytotoxic activity against ovarian cancer cells. Mechanism of action.

    PubMed Central

    Lidor, Y J; O'Briant, K C; Xu, F J; Hamilton, T C; Ozols, R F; Bast, R C

    1993-01-01

    Alkylating agents can be administered in high dosage to patients with ovarian cancer using autologous bone marrow support, but drug-resistant tumor cells can still persist. Immunotoxins provide reagents that might eliminate drug resistant cells. In the present study, concurrent treatment with alkylators and immunotoxins proved superior to treatment with each agent alone. Toxin immunoconjugates prepared from different monoclonal antibodies and recombinant ricin A chain (rRTA) inhibited clonogenic growth of ovarian cancer cell lines in limiting dilution assays. When alkylating agents and toxin conjugates were used in combination, the addition of the immunotoxins to cisplatin, or to cisplatin and thiotepa, produced synergistic cytotoxic activity against the OVCA 432 and OVCAR III cell lines. Studies performed to clarify the mechanism of action showed that cisplatin and thiotepa had no influence on internalization and binding of the 317G5-rRTA immunotoxin. Intracellular uptake of [195m]Pt-cisplatin was not affected by the immunoconjugate and thiotepa. The combination of the 317G5-rRTA and thiotepa, as well as 317G5-rRTA alone, increased [195m]Pt cisplatin-DNA adduct levels. The immunotoxin alone and in combination with the alkylators decreased intracellular glutathione levels and reduced glutathione-S-transferase activity. Repair of DNA damage induced by the combination of alkylators and 317G5-rRTA was significantly reduced when compared to repair after damage with alkylators alone. These findings suggest that immunotoxins affect levels and activity of enzymes required for the prevention and repair of alkylator damage. Images PMID:8227359

  12. Development of Iron Doped Silicon Nanoparticles as Bimodal Imaging Agents

    PubMed Central

    Singh, Mani P.; Atkins, Tonya M.; Muthuswamy, Elayaraja; Kamali, Saeed; Tu, Chuqiao; Louie, Angelique Y.; Kauzlarich, Susan M.

    2012-01-01

    We demonstrate the synthesis of water-soluble allylamine terminated Fe doped Si (SixFe) nanoparticles as bimodal agents for optical and magnetic imaging. The preparation involves the synthesis of a single source iron containing precursor, Na4Si4 with x% Fe (x = 1, 5, 10), and its subsequent reaction with NH4Br to produce hydrogen terminated SixFe nanoparticles. The hydrogen-capped nanoparticles are further terminated with allylamine via thermal hydrosilylation. Transmission electron microscopy (TEM) indicates that the average particle diameter is ~3.0±1.0 nm. The Si5Fe nanoparticles show strong photoluminescence quantum yield in water (~ 10 %) with significant T2 contrast (r2/r1value of 4.31). Electron paramagnetic resonance (EPR) and Mössbauer spectroscopies indicate that iron in the nanoparticles is in the +3 oxidation state. Analysis of cytotoxicity using the resazurin assay on HepG2 liver cells indicates that the particles have minimal toxicity. PMID:22616623

  13. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    SciTech Connect

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  14. Biodegradable Porous Silicon Nanomaterials for Imaging and Treatment of Cancer

    NASA Astrophysics Data System (ADS)

    Gu, Luo

    Cancer is the second leading cause of death, claiming ˜0.56 million lives in the U.S. every year following heart diseases (˜0.62 million). From 1991 to 2007, mortality associated with heart diseases decreased 39%; by contrast, the death rate of cancer only decreased by 17% in spite of intensive research and improved therapeutics. The stagnation of conventional medicine and the complexity of cancer demand new therapeutic strategies. As an emerging approach, the use of nanomaterials as cancer diagnostic and therapeutic agents has shown promising results due to their unique physical and chemical properties. To date, more than two dozen nanoparticle-based products have been approved for clinical use and they show advantages over conventional therapeutics. However, translation of many other nanomaterials has been impeded due to concerns over toxicity and biodegradability. This dissertation presents the development of biodegradable luminescent porous silicon nanomaterials and their potential applications for imaging and treatment of cancer. After a brief introduction to nanomedicine and the biomedical applications of porous silicon, Chapter 2 presents a method of making silicon nanoparticles with porous structure and intrinsic luminescence (LPSiNPs). The low toxicity and biodegradability of LPSiNPs are demonstrated in vitro with human cancer cells and in vivo with mouse model. The in vivo clearance of intravenously injected LPSiNPs is studied by tracking the emission of the nanoparticles with fluorescence imaging. Chapter 3 presents a diagnostic application of LPSiNPs. Time-gated fluorescence imaging of tumors using LPSiNPs with long emission lifetime is developed. This technique can effectively eliminate interference from short-lived tissue autofluorescence and improve the detection sensitivity. Chapter 4--6 demonstrate the therapeutic applications of porous silicon nanomaterials. In Chapter 4, magnetically-guided delivery of anticancer drug to cancer cells in vitro

  15. Novel agents for castration-resistant prostate cancer: Early experience and beyond.

    PubMed

    Fujimoto, Naohiro

    2016-02-01

    Androgen deprivation therapy is the initial treatment for men with advanced prostate cancer. Almost all these patients eventually develop progressive castration-resistant prostate cancer despite an initial favorable response. Docetaxel was the first agent to show a survival benefit in patients with castration-resistant prostate cancer. After cancer progression on docetaxel, patients with castration-resistant prostate cancer had few therapeutic options. A better understanding of the mechanisms of resistance to androgen deprivation therapy has led to the development of novel agents with distinct mechanisms of action. Prospective, large-scale clinical trials have shown overall survival benefits with the hormonal agents abiraterone acetate and enzalutamide, the immunotherapeutic agent sipuleucel T, the chemotherapeutic agent cabazitaxel, and bone-targeted Ra-223. Although these agents provided clinical benefit, treatment for castration-resistant prostate cancer remains a major clinical challenge. We recognize many questions, such as methods to select patients for specific treatments, optimal sequencing and drug combinations, and means to overcome drug resistance. There is an urgent need to answer these questions and to establish better treatment strategies. The development of biomarkers that are predictive of treatment results is also required. The present article reviews new castration-resistant prostate cancer treatments, and discusses possible resistant mechanisms as well as potential drug combinations and optimal sequencing.

  16. New Agents for Prevention of Ultraviolet-Induced Nonmelanoma Skin Cancer

    PubMed Central

    Camp, William L.; Turnham, Jennifer W.; Athar, Mohammad; Elmets, Craig A.

    2012-01-01

    With the incidence of nonmelanoma skin cancer on the rise, current prevention methods, such as the use of sunscreens, have yet to prove adequate to reverse this trend. There has been considerable interest in identifying compounds that will inhibit or reverse the biochemical changes required for skin cancers to develop, either by pharmacologic intervention or by dietary manipulation. By targeting different pathways identified as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or the addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer. PMID:21540016

  17. Non-cancer effects of chemical agents on children's health.

    PubMed

    Röösli, Martin

    2011-12-01

    This paper provides an overview about the non-cancer health effects for children from relevant chemical agents in our environment. In addition, a meta-analysis was conducted on the association between sudden infant death syndrome (SIDS) and maternal smoking during pregnancy as well as postnatal exposure to environmental tobacco smoke (ETS). In children, birth deformities, neurodevelopment, reproductive outcomes and respiratory system are mainly affected by chemical exposures. According to recent systematic reviews, evidence is sufficient for cognitive impairments caused by low lead exposure levels. Evidence for neurotoxicity from prenatal methylmercury exposure is sufficient for high exposure levels and limited for low levels. Prenatal exposure to polychlorinated biphenyls (PCB) and related toxicants results in cognitive and motor deficits. Maternal smoking during pregnancy is a risk factor for preterm birth, foetal growth deficit and SIDS. The meta-analytic pooled risk estimate for SIDS based on 15 studies is 2.94 (95% confidence interval: 2.43-3.57). Postnatal exposure to ETS was found to increase the SIDS risk by a factor of 1.72 (95% CI: 1.28-2.30) based on six studies which took into account maternal smoking during pregnancy. Additionally, postnatal ETS exposure causes acute respiratory infections, ear problems, respiratory symptoms, more severe asthma, and it slows lung growth. These health effects are also of concern for postnatal exposure to ambient and indoor air pollution. Children differ from adults with respect to several aspects which are relevant for assessing their health risk. Thus, independent evaluation of toxicity in childhood populations is essential. PMID:21906619

  18. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  19. Smart Plasmonic Glucose Nanosensors as Generic Theranostic Agents for Targeting-Free Cancer Cell Screening and Killing.

    PubMed

    Chen, Limei; Li, Haijuan; He, Haili; Wu, Haoxi; Jin, Yongdong

    2015-07-01

    Fast and accurate identification of cancer cells from healthy normal cells in a simple, generic way is very crucial for early cancer detection and treatment. Although functional nanoparticles, like fluorescent quantum dots and plasmonic Au nanoparticles (NPs), have been successfully applied for cancer cell imaging and photothermal therapy, they suffer from the main drawback of needing time-consuming targeting preparation for specific cancer cell detection and selective ablation. The lack of a generic and effective method therefore limits their potential high-throughput cancer cell preliminary screening and theranostic applications. We report herein a generic in vitro method for fast, targeting-free (avoiding time-consuming preparations of targeting moiety for specific cancer cells) visual screening and selective killing of cancer cells from normal cells, by using glucose-responsive/-sensitive glucose oxidase-modified Ag/Au nanoshells (Ag/Au-GOx NSs) as a smart plasmonic theranostic agent. The method is generic to some extent since it is based on the distinct localized surface plasmon resonance (LSPR) responses (and colors) of the smart nanoprobe with cancer cells (typically have a higher glucose uptake level) and normal cells.

  20. Liver-specific agents for contrast-enhanced MRI: role in oncological imaging

    PubMed Central

    Thian, Yee Liang; Riddell, Angela M.

    2013-01-01

    Abstract Liver-specific magnetic resonance (MR) contrast agents are increasingly used in evaluation of the liver. They are effective in detection and morphological characterization of lesions, and can be useful for evaluation of biliary tree anatomy and liver function. The typical appearances and imaging pitfalls of various tumours at MR imaging performed with these agents can be understood by the interplay of pharmacokinetics of these contrast agents and transporter expression of the tumour. This review focuses on the applications of these agents in oncological imaging. PMID:24434892

  1. A cationic gadolinium contrast agent for magnetic resonance imaging of cartilage.

    PubMed

    Freedman, Jonathan D; Lusic, Hrvoje; Wiewiorski, Martin; Farley, Michelle; Snyder, Brian D; Grinstaff, Mark W

    2015-06-30

    A new cationic gadolinium contrast agent is reported for delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC). The agent partitions into the glycosaminoglycan rich matrix of articular cartilage, based on Donnan equilibrium theory, and its use enables imaging of the human cadaveric metacarpal phalangeal joint.

  2. Engineered knottin peptides: a new class of agents for imaging integrin expression in living subjects.

    PubMed

    Kimura, Richard H; Cheng, Zhen; Gambhir, Sanjiv Sam; Cochran, Jennifer R

    2009-03-15

    There is a critical need for molecular imaging agents to detect cell surface integrin receptors that are present in human cancers. Previously, we used directed evolution to engineer knottin peptides that bind with high affinity ( approximately 10 to 30 nmol/L) to integrin receptors that are overexpressed on the surface of tumor cells and the tumor neovasculature. To evaluate these peptides as molecular imaging agents, we site-specifically conjugated Cy5.5 or (64)Cu-1,4,7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) to their N termini, and used optical and positron emission tomography (PET) imaging to measure their uptake and biodistribution in U87MG glioblastoma murine xenograft models. NIR fluorescence and microPET imaging both showed that integrin binding affinity plays a strong role in the tumor uptake of knottin peptides. Tumor uptake at 1 hour postinjection for two high-affinity (IC(50), approximately 20 nmol/L) (64)Cu-DOTA-conjugated knottin peptides was 4.47% +/- 1.21% and 4.56% +/- 0.64% injected dose/gram (%ID/g), compared with a low-affinity knottin peptide (IC(50), approximately 0.4 mumol/L; 1.48 +/- 0.53%ID/g) and c(RGDyK) (IC(50), approximately 1 mumol/L; 2.32 +/- 0.55%ID/g), a low-affinity cyclic pentapeptide under clinical development. Furthermore, (64)Cu-DOTA-conjugated knottin peptides generated lower levels of nonspecific liver uptake ( approximately 2%ID/g) compared with c(RGDyK) ( approximately 4%ID/g) 1 hour postinjection. MicroPET imaging results were confirmed by in vivo biodistribution studies. (64)Cu-DOTA-conjugated knottin peptides were stable in mouse serum, and in vivo metabolite analysis showed minimal degradation in the blood or tumor upon injection. Thus, engineered integrin-binding knottin peptides show great potential as clinical diagnostics for a variety of cancers.

  3. Ultrasonic imaging techniques for breast cancer detection.

    SciTech Connect

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

    2006-01-01

    Improving the resolution and specificity of current ultrasonic imaging technology can enhance its relevance to detection of early-stage breast cancers. Ultrasonic evaluation of breast lesions is desirable because it is quick, inexpensive, and does not expose the patient to potentially harmful ionizing radiation. 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 mortality, morbidity, and remission percentages. In this work, a novel ultrasonic imaging reconstruction method that exploits straight-ray migration is described. This technique, commonly used in seismic imaging, accounts for scattering more accurately than standard ultrasonic approaches, thus providing superior image resolution. A breast phantom with various inclusions is imaged using a pulse-echo approach. The data are processed using the ultrasonic migration method and results are compared to standard linear ultrasound and to x-ray computed tomography (CT) scans. For an ultrasonic frequency of 2.25 MHz, imaged inclusions and features of approximately 1mm are resolved, although better resolution is expected with minor modifications. 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 briefly discussed.

  4. A targeted approach to cancer imaging and therapy

    NASA Astrophysics Data System (ADS)

    Li, Chun

    2014-02-01

    Nanoparticle-based imaging plays a crucial role in cancer diagnosis and treatment. Here, we discuss the modalities used for molecular imaging of the tumour microenvironment and image-guided interventions including drug delivery, surgery and ablation therapy.

  5. Positron emission tomography imaging of prostate cancer

    PubMed Central

    Hong, Hao; Zhang, Yin; Sun, Jiangtao; Cai, Weibo

    2009-01-01

    Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. Positron emission tomography (PET), a non-invasive, sensitive, and quantitative imaging technique, can facilitate personalized management of PCa patients. There are two critical needs for PET imaging of PCa, early detection of primary lesions and accurate imaging of PCa bone metastasis, the predominant cause of death in PCa. Since the most widely used PET tracer in the clinic, 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG), does not meet these needs, a wide variety of PET tracers have been developed for PCa imaging which span an enormous size range from small molecules to intact antibodies. In this review, we will first summarize small molecule-based PET tracers for PCa imaging, which measure certain biological events such as cell membrane metabolism, fatty acid synthesis, and receptor expression. Next, we will discuss radiolabeled amino acid derivatives (e.g. methionine, leucine, tryptophan, and cysteine analogs), which are primarily based on the increased amino acid transport of PCa cells. Peptide-based tracers for PET imaging of PCa, mostly based on the bombesin peptide and its derivatives which bind to the gastrin-releasing peptide receptor, will then be presented in detail. We will also cover radiolabeled antibodies and antibody fragments (e.g. diabodies and minibodies) for PET imaging of PCa, targeting integrin αvβ3, EphA2, the epidermal growth factor receptor, or the prostate stem cell antigen. Lastly, we will identify future directions for the development of novel PET tracers for PCa imaging, which may eventually lead to personalized management of PCa patients. PMID:19946787

  6. Segmentation of prostate cancer tissue microarray images

    NASA Astrophysics Data System (ADS)

    Cline, Harvey E.; Can, Ali; Padfield, Dirk

    2006-02-01

    Prostate cancer is diagnosed by histopathology interpretation of hematoxylin and eosin (H and E)-stained tissue sections. Gland and nuclei distributions vary with the disease grade. The morphological features vary with the advance of cancer where the epithelial regions grow into the stroma. An efficient pathology slide image analysis method involved using a tissue microarray with known disease stages. Digital 24-bit RGB images were acquired for each tissue element on the slide with both 10X and 40X objectives. Initial segmentation at low magnification was accomplished using prior spectral characteristics from a training tissue set composed of four tissue clusters; namely, glands, epithelia, stroma and nuclei. The segmentation method was automated by using the training RGB values as an initial guess and iterating the averaging process 10 times to find the four cluster centers. Labels were assigned to the nearest cluster center in red-blue spectral feature space. An automatic threshold algorithm separated the glands from the tissue. A visual pseudo color representation of 60 segmented tissue microarray image was generated where white, pink, red, blue colors represent glands, epithelia, stroma and nuclei, respectively. The higher magnification images provided refined nuclei morphology. The nuclei were detected with a RGB color space principle component analysis that resulted in a grey scale image. The shape metrics such as compactness, elongation, minimum and maximum diameters were calculated based on the eigenvalues of the best-fitting ellipses to the nuclei.

  7. Molecular Imaging of Biomarkers in Breast Cancer

    PubMed Central

    Ulaner, Gary A.; Riedl, Chris C.; Dickler, Maura N.; Jhaveri, Komal; Pandit-Taskar, Neeta; Weber, Wolfgang

    2016-01-01

    The success of breast cancer therapy is ultimately defined by clinical endpoints such as survival. It is valuable to have biomarkers that can predict the most efficacious therapies or measure response to therapy early in the course of treatment. Molecular imaging has a promising role in complementing and overcoming some of the limitations of traditional biomarkers by providing the ability to perform noninvasive, repeatable whole-body assessments. The potential advantages of imaging biomarkers are obvious and initial clinical studies have been promising, but proof of clinical utility still requires prospective multicenter clinical trials. PMID:26834103

  8. Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration.

    PubMed

    Takebe, Naoko; Ahmed, Mansoor M; Vikram, Bhadrasain; Bernhard, Eric J; Zwiebel, James; Norman Coleman, C; Kunos, Charles A

    2016-10-01

    A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next-step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation-agent development initiatives.

  9. Early-phase Development of Cancer Prevention Agents, Challenges and Opportunities

    PubMed Central

    Perloff, Marjorie; Steele, Vernon E.

    2013-01-01

    Chemoprevention is the administration of agents (drugs, biologics, dietary supplements, or nutrients) to reduce the risk of developing cancer or prevent the recurrence of cancer. The National Cancer Institute, Division of Cancer Prevention (NCI, DCP) is a major sponsor of cancer preventive preclinical and clinical research. As such, it has developed a comprehensive drug development program specifically designed to meet the requirements needed for cancer preventive drugs to achieve initial regulatory approval. Clinical development of cancer prevention agents presents unique challenges not encountered with most cancer therapeutic agents. To meet these challenges, NCI, DCP has implemented new approaches and programs, including Phase 0 clinical trial designs and microdose studies. In addition, the PREVENT Cancer Program was recently implemented by NCI, DCP to offer a formalized structure for moving drugs forward in the prevention pipeline using a continue/not continue decision process. Likewise, DCP has implemented a clinical trials Consortium to further develop these agents. These and other approaches will be discussed in this commentary. PMID:23466485

  10. Fluorescence imaging of early lung cancer

    NASA Astrophysics Data System (ADS)

    Lam, Stephen; MacAulay, Calum E.; Le Riche, Jean C.; Ikeda, Norihiko; Palcic, Branko

    1995-01-01

    The performance of a fluorescence imaging device was compared with conventional white-light bronchoscopy in 100 patients with lung cancer, 46 patients with resected State I nonsmall cell lung cancer, 10 patients with head and neck cancer, and 67 volunteers who had smoked at least one pack of cigarettes per day for twenty-five years or more. Using differences in tissue autofluorescence between premalignant, malignant and normal tissues, fluorescence bronchoscopy was found to detect more than twice as many moderate-severe dysplasia and carcinoma in situ sites than conventional white-light bronchoscopy. The use of fluorescence imaging to detect small peripheral lung nodules was investigated in a micro metastatic lung model of mice implanted with Lewis lung tumor cells. Fluorescence imaging was found to be able to detect small malignant lung lesions. The use of (delta) -aminolevulinic acid (ALA) to enhance fluorescence detection of CIS was investigated in a patient after oral administration of 60 mg/kg of ALA four hours prior to bronchoscopy, although ALA enhanced the tumor's visibility, multiple sites of false positive fluorescence were observed in areas of inflammation or metaplasia.

  11. Hyperspectral imaging of skin and lung cancers

    NASA Astrophysics Data System (ADS)

    Zherdeva, Larisa A.; Bratchenko, Ivan A.; Alonova, Marina V.; Myakinin, Oleg O.; Artemyev, Dmitry N.; Moryatov, Alexander A.; Kozlov, Sergey V.; Zakharov, Valery P.

    2016-04-01

    The problem of cancer control requires design of new approaches for instrumental diagnostics, as the accuracy of cancer detection on the first step of diagnostics in clinics is slightly more than 50%. In this study, we present a method of visualization and diagnostics of skin and lung tumours based on registration and processing of tissues hyperspectral images. In a series of experiments registration of hyperspectral images of skin and lung tissue samples is carried out. Melanoma, basal cell carcinoma, nevi and benign tumours are studied in skin ex vivo and in vivo experiments; adenocarcinomas and squamous cell carcinomas are studied in ex vivo lung experiments. In a series of experiments the typical features of diffuse reflection spectra for pathological and normal tissues were found. Changes in tissues morphology during the tumour growth lead to the changes of blood and pigments concentration, such as melanin in skin. That is why tumours and normal tissues maybe differentiated with information about spectral response in 500-600 nm and 600 - 670 nm areas. Thus, hyperspectral imaging in the visible region may be a useful tool for cancer detection as it helps to estimate spectral properties of tissues and determine malignant regions for precise resection of tumours.

  12. Aerospace technology transfer to breast cancer imaging.

    PubMed

    Winfield, D L

    1997-01-01

    In the United States in 1996, an estimated 44,560 women died of breast cancer, and 184,300 new cases were diagnosed. Advances in space technology are now making significant improvements in the imaging technologies used in managing this important foe. The first of these spinoffs, a digital spot mammography system used to perform stereotactic fine-needle breast biopsy, uses a backside-thinned CCD developed originally for the Space Telescope Imaging Spectrometer. This paper describes several successful biomedical applications which have resulted from collaborative technology transfer programs between the National Aeronautics and Space Administration (NASA), the National Cancer Institute (NCI), and the U.S. Dept. of Health and Human Services Office on Women's Health (OWH). These programs have accelerated the introduction of direct digital mammography by two years. In follow-on work, RTI is now assisting the HHS Office on Women's Health to identify additional opportunities for transfer of aerospace, defense, and intelligence technologies to image-guided detection, diagnosis, and treatment of breast cancer. The technology identification and evaluation effort culminated in a May 1997 workshop, and the formative technology development partnerships are discussed.

  13. Aerospace technology transfer to breast cancer imaging.

    PubMed

    Winfield, D L

    1997-01-01

    In the United States in 1996, an estimated 44,560 women died of breast cancer, and 184,300 new cases were diagnosed. Advances in space technology are now making significant improvements in the imaging technologies used in managing this important foe. The first of these spinoffs, a digital spot mammography system used to perform stereotactic fine-needle breast biopsy, uses a backside-thinned CCD developed originally for the Space Telescope Imaging Spectrometer. This paper describes several successful biomedical applications which have resulted from collaborative technology transfer programs between the National Aeronautics and Space Administration (NASA), the National Cancer Institute (NCI), and the U.S. Dept. of Health and Human Services Office on Women's Health (OWH). These programs have accelerated the introduction of direct digital mammography by two years. In follow-on work, RTI is now assisting the HHS Office on Women's Health to identify additional opportunities for transfer of aerospace, defense, and intelligence technologies to image-guided detection, diagnosis, and treatment of breast cancer. The technology identification and evaluation effort culminated in a May 1997 workshop, and the formative technology development partnerships are discussed. PMID:11541150

  14. Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

    PubMed

    Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

    2015-01-01

    Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future.

  15. Magnetic resonance imaging using gadolinium-based contrast agents.

    PubMed

    Mitsumori, Lee M; Bhargava, Puneet; Essig, Marco; Maki, Jeffrey H

    2014-02-01

    The purpose of this article was to review the basic properties of available gadolinium-based magnetic resonance contrast agents, discuss their fundamental differences, and explore common and evolving applications of gadolinium-based magnetic resonance contrast throughout the body excluding the central nervous system. A more specific aim of this article was to explore novel uses of these gadolinium-based contrast agents and applications where a particular agent has been demonstrated to behave differently or be better suited for certain applications than the other contrast agents in this class.

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

    PubMed Central

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

    2014-01-01

    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. PMID:26579381

  17. 99Tcm-LL1: a potential new bone marrow imaging agent.

    PubMed

    Juweid, M; Dunn, R M; Sharkey, R M; Rubin, A D; Hansen, H J; Goldenberg, D M

    1997-02-01

    LL1, a monoclonal antibody (MAb) to HLA Class-II-like antigen (li determinant) on the surface of B-lymphocytes, monocytes and histiocytes, was evaluated as an agent for bone marrow imaging. Six patients with diverse diseases (non-Hodgkin's lymphoma, n = 2; multiple myeloma, n = 1; polycythaemia vera, n = 1; lung cancer, n = 1; breast cancer, n = 1) were given low protein doses (< 1 mg) of 99Tcm (30 mCi) labelled Fab' of LL1. 99Tcm-sulphur colloid (SC) imaging was performed in three patients for comparison. Both planar and single photon emission tomographic images were acquired using Sopha gamma cameras. As early as 2 h post-MAb injection, excellent bone marrow images were achieved in all patients, demonstrating both normal or hyperproliferative marrow, as well as 'cold' bone marrow abnormalities such as radiation defects or cancer metastases. Similar to SC, relatively high uptake of LL1 was found in the liver and spleen. However, the bone marrow-to-liver and -spleen uptake ratios were approximately 19-fold higher (0.75 vs 0.04) and 6-fold higher (1.23 vs 0.22), respectively, with LL1 than with SC. The higher bone marrow uptake allowed clearly superior visualization of the thoracic spine when compared to SC. The mean T1/2 of blood and whole-body clearance were 0.4 and 66 h, respectively. The highest radiation absorbed doses (in cGy mCi-1) were observed in the spleen (0.47 +/- 0.24), kidneys (0.25 +/- 0.09) and liver (0.14 +/- 0.04). The bone marrow dose was only 0.05 +/- 0.02 cGy mCi-1. These results indicate that bone marrow imaging with 99Tcm-LL1 is feasible, and that LL1 may be a suitable alternative to SC because of better visualization of the lower thoracic spine. Potential applications include the improved detection of bone marrow metastases of solid tumours and the assessment of haematological disorders. PMID:9076770

  18. Three-photon imaging of ovarian cancer

    NASA Astrophysics Data System (ADS)

    Barton, Jennifer K.; Amirsolaimani, Babak; Rice, Photini; Hatch, Kenneth; Kieu, Khanh

    2016-02-01

    Optical imaging methods have the potential to detect ovarian cancer at an early, curable stage. Optical imaging has the disadvantage that high resolution techniques require access to the tissue of interest, but miniature endoscopes that traverse the natural orifice of the reproductive tract, or access the ovaries and fallopian tubes through a small incision in the vagina wall, can provide a minimally-invasive solution. We have imaged both rodent and human ovaries and fallopian tubes with a variety of endoscope-compatible modalities. The recent development of fiber-coupled femtosecond lasers will enable endoscopic multiphoton microscopy (MPM). We demonstrated two- and three-photon excited fluorescence (2PEF, 3PEF), and second- and third-harmonic generation microscopy (SHG, THG) in human ovarian and fallopian tube tissue. A study was undertaken to understand the mechanisms of contrast in these images. Six patients (normal, cystadenoma, and ovarian adenocarcinoma) provided ovarian and fallopian tube biopsies. The tissue was imaged with three-dimensional optical coherence tomography, multiphoton microscopy, and frozen for histological sectioning. Tissue sections were stained with hematoxylin and eosin, Masson's trichrome, and Sudan black. Approximately 1 μm resolution images were obtained with an excitation source at 1550 nm. 2PEF signal was absent. SHG signal was mainly from collagen. 3PEF and THG signal came from a variety of sources, including a strong signal from fatty connective tissue and red blood cells. Adenocarcinoma was characterized by loss of SHG signal, whereas cystic abnormalities showed strong SHG. There was limited overlap of two- and three- photon signals, suggesting that three-photon imaging can provide additional information for early diagnosis of ovarian cancer.

  19. Trends in Imaging after Thyroid Cancer Diagnosis

    PubMed Central

    Banerjee, Mousumi; Muenz, Daniel G.; Worden, Francis P.; Haymart, Megan R.

    2015-01-01

    Background The largest growth in differentiated thyroid cancer (DTC) diagnosis is in low-risk cancers. Trends in imaging after DTC diagnosis are understudied. Hypothesizing a reduction in imaging utilization due to rising low-risk disease, we evaluated post-diagnosis imaging patterns over time and patient characteristics that are associated with likelihood of imaging. Methods Using the Surveillance Epidemiology and End Results-Medicare database, we identified patients diagnosed with localized, regional or distant DTC between 1991 and 2009. We reviewed Medicare claims for neck ultrasound, I-131 scan, or PET scan within 3 years post-diagnosis. Using regression analyses we evaluated trends of imaging utilization. Multivariable logistic regression was used to estimate the likelihood of imaging based on patient characteristics. Results 23,669 patients were included. Patients diagnosed during 2001-2009, compared to 1991-2000, were more likely to have localized disease (p<0.001) and tumors less than 1cm (p<0.001). Use of neck ultrasound and I-131 scan increased in patients with localized disease (p=<0.001 and p=0.003, respectively), regional disease (p<0.001 and p<0.001), and distant metastasis (p=0.001 and p=0.015). Patients diagnosed after 2000 were more likely to undergo neck ultrasound (OR 2.15, 95% CI 2.02-2.28) and I-131 scan (OR 1.44, 95% CI 1.35-1.54). PET scan use from 2005-2009, compared to 1996-2004, increased 32.4-fold (p=<0.001) in localized patients, 13.1-fold (p<0.001) in regional disease patients, and 33.4-fold (p<0.001) in patients with distant DTC. Conclusion Despite a rise in low-risk disease, the use of post-diagnosis imaging increased in all stages of disease. The largest growth was in use of PET scan after 2004. PMID:25565063

  20. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor

  1. About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

    Cancer.gov

    The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and negative predictive values of preclinical models for clinical development. |

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Synergistic Effects of Dietary Natural Products as Anti-Prostate Cancer Agents.

    PubMed

    Vue, Bao; Zhang, Sheng; Chen, Qiao-Hong

    2015-12-01

    This review is to describe synergistic effects of various combinations of dietary natural products including curcumin, quercetin, soybean isoflavones, silibinin, and EGCG that have potential for the treatment of prostate cancer. These data can provide valuable insights into the future rational design and development of synergistic and/or hybrid agents for potential treatment of prostate cancer. PMID:26882694

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

    DOEpatents

    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.

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

    DOEpatents

    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. Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy.

    PubMed

    Zhang, Liwen; Gao, Shi; Zhang, Fan; Yang, Kai; Ma, Qingjie; Zhu, Lei

    2014-12-23

    Photothermal therapy (PTT) is an emerging treatment modality that is under intensive preclinical investigations for the treatment of various medical conditions, including cancer. However, the lack of targeting function of PTT agents hampers its clinical application. An effective and nontoxic delivery vehicle that can carry PTT agents into tumor areas is still needed urgently. In this study, we developed a multifunctional nanocomposite by loading copper sulfide (CuS) into Cy5.5-conjugated hyaluronic acid nanoparticles (HANP), obtaining an activatable Cy5.5-HANP/CuS (HANPC) nanocomposite. In this system, Cy5.5 fluorescent signal is quenched by CuS inside the particle until the whole nanocomposite is degraded by hyaluronidase present in tumor, giving strong fluorescence signals delineating the tumor. Importantly, CuS with strong NIR absorbance appears to be an excellent contrast agent for photoacoustic (PA) imaging and an effective PTT agent. After intravenous administration of HANPC into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.25±0.25 for optical imaging and 3.8±0.42 for PA imaging). The tumors were then irradiated with a laser, and a good tumor inhibition rate (89.74% on day 5) was observed. Our studies further encourage application of this HA-based multifunctional nanocomposite for image-guided PTT in biomedical applications, especially in cancer theranostics. PMID:25402600

  7. Targeted Aucore-Agshell nanorods as a dual-functional contrast agent for photoacoustic imaging and photothermal therapy

    PubMed Central

    Shi, Yiwen; Peng, Dong; Wang, Kun; Chai, Xinyu; Ren, Qiushi; Tian, Jie; Zhou, Chuanqing

    2016-01-01

    Optimizing contrast enhancement is essential for producing specific signals in biomedical imaging and therapy. The potential of using Aucore-Agshell nanorods (Au@Ag NRs) as a dual-functional theranostic contrast agent is demonstrated for effective cancer imaging and treatments. Due to its strong NIR absorption and high efficiency of photothermal conversion, effects of both photoacoustic tomography (PAT) and photothermal therapy (PTT) are enhanced significantly. The PAT signal grows by 45.3% and 82% in the phantom and in vivo experiments, respectively, when compared to those using Au NRs. In PTT, The maximum increase of tissue temperature treated with Au@Ag NRs is 22.8 °C, twice that with Au NRs. Results of the current study show the feasibility of using Au@Ag NRs for synergetic PAT with PTT. And it will enhance the potential application on real-time PAT guided PTT, which will greatly benefit the customized PTT treatment of cancer. PMID:27231624

  8. X ray imaging microscope for cancer research

    NASA Technical Reports Server (NTRS)

    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.

  9. Integrin inhibitors as a therapeutic agent for ovarian cancer.

    PubMed

    Sawada, Kenjiro; Ohyagi-Hara, Chifumi; Kimura, Tadashi; Morishige, Ken-Ichirou

    2012-01-01

    Ovarian cancer is a deadly disease, with a cure rate of only 30%. Despite aggressive treatments, relapse remains almost inevitable in patients with advanced-stage disease. In recent years, great progress has been made towards targeting integrins in cancer treatment, and clinical studies with various integrin inhibitors have demonstrated their effectiveness in blocking cancer progression. Given that the initial critical step of ovarian cancer metastasis is the attachment of cancer cells onto the peritoneum or omentum, in addition to the proven positive clinical results of anti-angiogenic therapy, targeting integrins is likely to be one of the most feasible approaches. This paper summarizes the current understanding of the integrin biology in ovarian cancer metastasis and the various therapeutic approaches attempted with integrin inhibitors. Although no integrin inhibitors have shown favorable results so far, integrin-targeted therapies continue to be a promising approach to be explored for further clinical investigation.

  10. Integrin Inhibitors as a Therapeutic Agent for Ovarian Cancer

    PubMed Central

    Sawada, Kenjiro; Ohyagi-Hara, Chifumi; Kimura, Tadashi; Morishige, Ken-ichirou

    2012-01-01

    Ovarian cancer is a deadly disease, with a cure rate of only 30%. Despite aggressive treatments, relapse remains almost inevitable in patients with advanced-stage disease. In recent years, great progress has been made towards targeting integrins in cancer treatment, and clinical studies with various integrin inhibitors have demonstrated their effectiveness in blocking cancer progression. Given that the initial critical step of ovarian cancer metastasis is the attachment of cancer cells onto the peritoneum or omentum, in addition to the proven positive clinical results of anti-angiogenic therapy, targeting integrins is likely to be one of the most feasible approaches. This paper summarizes the current understanding of the integrin biology in ovarian cancer metastasis and the various therapeutic approaches attempted with integrin inhibitors. Although no integrin inhibitors have shown favorable results so far, integrin-targeted therapies continue to be a promising approach to be explored for further clinical investigation. PMID:22235205

  11. Ultrasound Molecular Imaging of Tumor Angiogenesis with an Integrin Targeted Microbubble Contrast Agent

    PubMed Central

    Anderson, Christopher R.; Hu, Xiaowen; Tlaxca, Jose; Decleves, Anne-Emilie; Houghtaling, Robert; Sharma, Kumar; Lawrence, Michael; Ferrara, Katherine; Rychak, Joshua J.

    2010-01-01

    Rationale and Objectives Ultrasound molecular imaging is an emerging technique for sensitive detection of intravascular targets. Molecular imaging of angiogenesis has strong potential for both clinical use and as a research tool in tumor biology and the development of anti-angiogenic therapies. Our objective is to develop a robust microbubble (MB) ultrasound contrast agent platform to which targeting ligands can be conjugated by biocompatible, covalent conjugation chemistry, and to develop a pure low mechanical index imaging processing method and corresponding quantifying method. The microbubbles and the imaging methods were evaluated in a mouse model of breast cancer in vivo. Materials and Methods We utilized a cyclic RGD (cRGD) pentapeptide containing a terminal cysteine group conjugated to the surface of MB bearing pyridyldithio-propionate (PDP) for targeting αvβ3 integrins. As negative controls, MB without a ligand or MB bearing a scrambled sequence (cRAD) were prepared. To enable characterization of peptides bound to MB surfaces, the cRGD peptide was labeled with FITC and detected by plate fluorometry, flow cytometry, and fluorescence microscopy. Targeted adhesion of cRGD-MB was demonstrated in an in vitro flow adhesion assay against recombinant murine αvβ3 integrin protein and αvβ3 integrin-expressing endothelial cells (bEnd.3). The specificity of cRGD-MB for αvβ3 integrin was demonstrated by treating bEnd.3 EC with a blocking antibody. A murine model of mammary carcinoma was used to assess targeted adhesion and ultrasound molecular imaging in vivo. The targeted microbubbles were visualized using a low mechanical index contrast imaging pulse sequence, and quantified by intensity normalization and two-dimensional Fourier transform analysis, Results The cRGD ligand concentration on the MB surface was ~8.2 × 106 molecules/MB. At a wall shear stress of 1.0 dynes/cm2, cRGD-MB exhibited 5-fold higher adhesion to immobilized recombinant αvβ3 integrin

  12. Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy.

    PubMed

    Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

    2016-01-01

    Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics. PMID:27446485

  13. Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy

    PubMed Central

    Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

    2016-01-01

    Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics. PMID:27446485

  14. Nanoparticles for cancer imaging: The good, the bad, and the promise.

    PubMed

    Chapman, Sandra; Dobrovolskaia, Marina; Farahani, Keyvan; Goodwin, Andrew; Joshi, Amit; Lee, Hakho; Meade, Thomas; Pomper, Martin; Ptak, Krzysztof; Rao, Jianghong; Singh, Ravi; Sridhar, Srinivas; Stern, Stephan; Wang, Andrew; Weaver, John B; Woloschak, Gayle; Yang, Lily

    2013-10-01

    Recent advances in molecular imaging and nanotechnology are providing new opportunities for biomedical imaging with great promise for the development of novel imaging agents. The unique optical, magnetic, and chemical properties of materials at the scale of nanometers allow the creation of imaging probes with better contrast enhancement, increased sensitivity, controlled biodistribution, better spatial and temporal information, multi-functionality and multi-modal imaging across MRI, PET, SPECT, and ultrasound. These features could ultimately translate to clinical advantages such as earlier detection, real time assessment of disease progression and personalized medicine. However, several years of investigation into the application of these materials to cancer research has revealed challenges that have delayed the successful application of these agents to the field of biomedical imaging. Understanding these challenges is critical to take full advantage of the benefits offered by nano-sized imaging agents. Therefore, this article presents the lessons learned and challenges encountered by a group of leading researchers in this field, and suggests ways forward to develop nanoparticle probes for cancer imaging. Published by Elsevier Ltd. PMID:25419228

  15. X-ray fluorescence microscopy demonstrates preferential accumulation of a vanadium-based magnetic resonance imaging contrast agent in murine colonic tumors.

    PubMed

    Mustafi, Devkumar; Ward, Jesse; Dougherty, Urszula; Bissonnette, Marc; Hart, John; Vogt, Stefan; Karczmar, Gregory S

    2015-01-01

    Contrast agents that specifically enhance cancers on magnetic resonance imaging (MRI) will allow earlier detection. Vanadium-based chelates (VCs) selectively enhance rodent cancers on MRI, suggesting selective uptake of VCs by cancers. Here we report x-ray fluorescence microscopy (XFM) of VC uptake by murine colon cancer. Colonic tumors in mice treated with azoxymethane/dextran sulfate sodium were identified by MRI. Then a gadolinium-based contrast agent and a VC were injected intravenously; mice were sacrificed and colons sectioned. VC distribution was sampled at 120 minutes after injection to evaluate the long-term accumulation. Gadolinium distribution was sampled at 10 minutes after injection due to its rapid washout. XFM was performed on 72 regions of normal and cancerous colon from five normal mice and four cancer-bearing mice. XFM showed that all gadolinium was extracellular, with similar concentrations in colon cancers and normal colon. In contrast, the average VC concentration was twofold higher in cancers versus normal tissue (p < .002). Cancers also contained numerous "hot spots" with intracellular VC concentrations sixfold higher than the concentration in normal colon (p < .0001). No hot spots were detected in normal colon. This is the first direct demonstration that VCs selectively accumulate in cancer cells and thus may improve cancer detection.

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

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?

    PubMed

    Apetoh, L; Ladoire, S; Coukos, G; Ghiringhelli, F

    2015-09-01

    Recent clinical trials revealed the impressive efficacy of immunological checkpoint blockade in different types of metastatic cancers. Such data underscore that immunotherapy is one of the most promising strategies for cancer treatment. In addition, preclinical studies provide evidence that some cytotoxic drugs have the ability to stimulate the immune system, resulting in anti-tumor immune responses that contribute to clinical efficacy of these agents. These observations raise the hypothesis that the next step for cancer treatment is the combination of cytotoxic agents and immunotherapies. The present review aims to summarize the immune-mediated effects of chemotherapeutic agents and their clinical relevance, the biological and clinical features of immune checkpoint blockers and finally, the preclinical and clinical rationale for novel therapeutic strategies combining anticancer agents and immune checkpoint blockers.

  19. Multimeric Near IR-MR Contrast Agent for Multimodal In Vivo Imaging.

    PubMed

    Harrison, Victoria S R; Carney, Christiane E; MacRenaris, Keith W; Waters, Emily A; Meade, Thomas J

    2015-07-22

    Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety. One agent contains a PEG linker and the other a short alkyl linker. These agents label cells with extraordinary efficacy and can be detected in vivo using both imaging modalities. Biodistribution of the PEGylated agent shows observable fluorescence in xenograft MCF7 tumors and renal clearance by MR imaging.

  20. Antibodies to human papillomavirus and to other genital infectious agents and invasive cervical cancer risk.

    PubMed

    Jha, P K; Beral, V; Peto, J; Hack, S; Hermon, C; Deacon, J; Mant, D; Chilvers, C; Vessey, M P; Pike, M C

    1993-05-01

    Human papillomaviruses (HPVs) play an important part in the development of cervical cancer, but the role of other infectious agents, such as herpes simplex virus (HSV), is not clear. We assayed serum samples collected from 219 women with cervical cancer and from 387 controls for antibody to infectious agents. HPV 16-E7 and/or HPV 18-E7 antibodies were significantly related to cervical cancer risk (RR 1.9, 95% CI 1.2-3.2). Antibodies to HSV types 1 and 2, Chlamydia trachomatis, and to multiple infectious agents were associated with cervical cancer when seroprevalence rates in all cases and controls were compared, but when HPV-seropositive cases and controls were compared these associations were weaker and non-significant. This finding suggests that past infections with sexually transmitted infections other than HPV may be surrogate markers of exposure to HPV, and of no separate aetiological significance.

  1. Strigolactone analogs act as new anti-cancer agents in inhibition of breast cancer in xenograft model

    PubMed Central

    Mayzlish-Gati, Einav; Laufer, Dana; Grivas, Christopher F; Shaknof, Julia; Sananes, Amiram; Bier, Ariel; Ben-Harosh, Shani; Belausov, Eduard; Johnson, Michael D; Artuso, Emma; Levi, Oshrat; Genin, Ola; Prandi, Cristina; Khalaila, Isam; Pines, Mark; Yarden, Ronit I; Kapulnik, Yoram; Koltai, Hinanit

    2015-01-01

    Strigolactones (SLs) are a novel class of plant hormones. Previously, we found that analogs of SLs induce growth arrest and apoptosis in breast cancer cell lines. These compounds also inhibited the growth of breast cancer stem cell enriched-mammospheres with increased potency. Furthermore, strigolactone analogs inhibited growth and survival of colon, lung, prostate, melanoma, osteosarcoma and leukemia cancer cell lines. To further examine the anti-cancer activity of SLs in vivo, we have examined their effects on growth and viability of MDA-MB-231 tumor xenografts model either alone or in combination with paclitaxel. We show that strigolactone act as new anti-cancer agents in inhibition of breast cancer in xenograft model. In addition we show that SLs affect the integrity of the microtubule network and therefore may inhibit the migratory phenotype of the highly invasive breast cancer cell lines that were examined. PMID:26192476

  2. Severe systemic reaction to diphosphonate bone imaging agents: skin testing to predict allergic response and a safe alternative agent

    SciTech Connect

    Ramos-Gabatin, A.; Orzel, J.A.; Maloney, T.R.; Murnane, J.E.; Borchert, R.D.

    1986-09-01

    We describe a severe systemic reaction which occurred in a patient on two occasions after i.v. injection of chemically related diphosphonate bone imaging agents. Skin testing showed reactivity to multiple commercially available diphosphonate compounds but no significant response to pyrophosphates. A subsequent pyrophosphate bone scan resulted in no adverse reaction. Severe systemic reactions to diphosphonates can occur, skin testing may prove useful in evaluating allergic reactions, and pyrophosphates appear to be a safe alternative agent in patients proven or suspected allergic to diphosphonates.

  3. Infrared imager requirements for breast cancer detection.

    PubMed

    González, Francisco Javier

    2007-01-01

    Infrared imaging was introduced into medicine in the late 1950s, early studies suggested there were applications of the technology in areas as diverse as detection of breast cancer and malfunctions of the nervous system, however the early instrumentation was not sensitive enough to detect the subtle changes in temperature needed to accurately detect and monitor disease. In recent years the sensitivity of infrared instruments has greatly improved. In this paper the bioheat transfer equation is solved for a simplified model of a female breast and a cancerous tumor in order to quantify the minimum size of a tumor or the maximum depth of a certain sized tumor that a modern state-of-the-art imager can detect. Finite Element simulations showed that current state-of-the-art imagers are capable of detecting 3 cm tumors located deeper than 7 cm from the skin surface and tumors smaller than 0.5 cm can be detected if they are close to the surface of the skin.

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

    SciTech Connect

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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 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.

  6. ER maleate is a novel anticancer agent in oral cancer: implications for cancer therapy

    PubMed Central

    Fu, Guodong; Somasundaram, Raj Thani; Jessa, Fatima; Srivastava, Gunjan; MacMillan, Christina; Witterick, Ian; Walfish, Paul G.; Ralhan, Ranju

    2016-01-01

    ER maleate [10-(3-Aminopropyl)-3, 4-dimethyl-9(10H)-acridinone maleate] identified in a kinome screen was investigated as a novel anticancer agent for oral squamous cell carcinoma (OSCC). Our aim was to demonstrate its anticancer effects, identify putative molecular targets and determine their clinical relevance and investigate its chemosensitization potential for platinum drugs to aid in OSCC management. Biologic effects of ER maleate were determined using oral cancer cell lines in vitro and oral tumor xenografts in vivo. mRNA profiling, real time PCR and western blot revealed ER maleate modulated the expression of polo-like kinase 1 (PLK1) and spleen tyrosine kinase (Syk). Their clinical significance was determined in oral SCC patients by immunohistochemistry and correlated with prognosis by Kaplan-Meier survival and multivariate Cox regression analyses. ER maleate induced cell apoptosis, inhibited proliferation, colony formation, migration and invasion in oral cancer cells. Imagestream analysis revealed cell cycle arrest in G2/M phase and increased polyploidy, unravelling deregulation of cell division and cell death. Mechanistically, ER maleate decreased expression of PLK1 and Syk, induced cleavage of PARP, caspase9 and caspase3, and increased chemosensitivity to carboplatin; significantly suppressed tumor growth and increased antitumor activity of carboplatin in tumor xenografts. ER maleate treated tumor xenografts showed reduced PLK1 and Syk expression. Clinical investigations revealed overexpression of PLK1 and Syk in oral SCC patients that correlated with disease prognosis. Our in vitro and in vivo findings provide a strong rationale for pre-clinical efficacy of ER maleate as a novel anticancer agent and chemosensitizer of platinum drugs for OSCC. PMID:26934445

  7. Differential effects of depleting agents on cytoplasmic and nuclear non-protein sulphydryls: a fluorescence image cytometry study.

    PubMed Central

    Thomas, M.; Nicklee, T.; Hedley, D. W.

    1995-01-01

    The intracellular distribution of glutathione (GSH) was measured by a quantitative image cytometry method, using the sulphydryl-reactive agent mercury orange. This readily forms fluorescent adducts with GSH and other non-protein sulphydryls (NPSH), but reacts much more slowly with protein sulphydryls. Under optimum staining conditions mean integrated mercury orange fluorescence per cell was closely correlated with a standard biochemical assay for GSH. Use of the DNA dye DAPI as a counterstain allowed measurement of nuclear NPSH. The mean nuclear-cytoplasmic ratio was 0.57 +/- 0.05. Isolation of nuclei under aqueous conditions resulted in the loss of approximately 90% of mercury orange fluorescence, compared with nuclear fluorescence from intact cells, suggesting that background labelling of protein sulphydryls or other macromolecules is low. Depletion of GSH with N-ethylmaleimide or diethylmaleate decreased mercury orange fluorescence in the nucleus and cytoplasm to a similar extent. In contrast, mercury orange fluorescence in the nucleus was much more resistant to DL-buthionine-S,R-sulphoximine (BSO) depletion than that in the cytoplasm. This finding is compatible with a distinct pool of GSH in the nucleus that is comparatively resistant to BSO depletion. Alternatively, the retention of fluorescence in the nucleus following GSH depletion by BSO treatment might be due to accumulation of cysteine. These findings have implications for cancer treatment since the level of NPSH in the nucleus might be a more important determinant of resistance to DNA-damaging agents than that in cytoplasm. The image cytometry method described here is quantitative, allows a measure of tumour cell heterogeneity and can be applied to small biopsy samples obtained by fine-needle aspiration. Thus it appears suitable for prospective clinical studies in cancer patients, and for monitoring the effects of GSH-depleting agents used as adjuncts to cancer chemotherapy or radiotherapy. Images Figure

  8. Engineered iron-oxide-based nanoparticles as enhanced T1 contrast agents for efficient tumor imaging.

    PubMed

    Zhou, Zijian; Wang, Lirong; Chi, Xiaoqin; Bao, Jianfeng; Yang, Lijiao; Zhao, Wenxiu; Chen, Zhong; Wang, Xiaomin; Chen, Xiaoyuan; Gao, Jinhao

    2013-04-23

    We report the design and synthesis of small-sized zwitterion-coated gadolinium-embedded iron oxide (GdIO) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects. The combination of spin-canting effects and the collection of gadolinium species within small-sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect. For example, GdIO nanoparticles with a diameter of ∼4.8 nm exhibited a high r1 relaxivity of 7.85 mM(-1)·S(-1) and a low r2/r1 ratio of 5.24. After being coated with zwitterionic dopamine sulfonate molecules, the 4.8 nm GdIO nanoparticles showed a steady hydrodynamic diameter (∼5.2 nm) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption. This study provides a valuable strategy for the design of highly sensitive iron-oxide-based T1 contrast agents with relatively long circulation half-lives (∼50 min), efficient tumor passive targeting (SKOV3, human ovarian cancer xenograft tumor as a model), and the possibility of rapid renal clearance after tumor imaging.

  9. Bone-targeted agents: preventing skeletal complications in prostate cancer.

    PubMed

    Morgans, Alicia K; Smith, Matthew R

    2012-11-01

    In men, prostate cancer is the most common non-cutaneous malignancy and the second most common cause of cancer death. Skeletal complications occur at various points during the disease course, either due to bone metastases directly, or as an unintended consequence of androgen deprivation therapy (ADT). Bone metastases are associated with pathologic fractures, spinal cord compression, and bone pain and can require narcotics or palliative radiation for pain relief. ADT results in bone loss and fragility fractures. This review describes the biology of bone metastases, skeletal morbidity, and recent advances in bone-targeted therapies to prevent skeletal complications of prostate cancer.

  10. [Comparative imaging of cancers of the tongue].

    PubMed

    Maradji-Melia, P; Bruneton, J N; Balu-Maestro, C; Marcy, P Y; Dubruque, F; Dassonville, O

    1993-05-01

    In a comparative study of 18 cases of tongue cancer examined with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI), the authors assess the advantages and disadvantages of each technique. MRI seems to be more effective for the detection of small lesions, the examination of the mobile part of the tongue, in case of dental artifacts, for the study of regional extension and to screen recurrence. CT retains its indications for large tumors in patients who are in a poor general condition, tired, and cannot stand lengthy examinations. Ultrasonography remains the first-intention examination in all cases because of its indisputable superiority for lymph node examination.

  11. Molecular Imaging of Prostate Cancer: A Concise Synopsis

    PubMed Central

    Jadvar, Hossein

    2009-01-01

    Prostate cancer is the most common malignancy in men and continues to be a major public health problem. Imaging of prostate cancer remains particularly challenging owing to disease heterogeneity. Molecular imaging can provide unprecedented opportunities for deciphering the molecular mechanisms that are involved in the development and natural progression of prostate cancer from a localized process to the hormone-refractory metastatic disease. Such understanding will be the key for targeted imaging and therapy and for predicting and evaluating treatment response and prognosis. In this article, we review briefly the contribution of multimodality molecular imaging methods for the in vivo characterization of the pathophysiology of prostate cancer. PMID:19397851

  12. A near-infrared phthalocyanine dye-labeled agent for integrin αvβ6-targeted theranostics of pancreatic cancer.

    PubMed

    Gao, Duo; Gao, Liquan; Zhang, Chenran; Liu, Hao; Jia, Bing; Zhu, Zhaohui; Wang, Fan; Liu, Zhaofei

    2015-06-01

    Integrin αvβ6 is widely upregulated in variant malignant cancers but is undetectable in normal organs, making it a promising target for cancer diagnostic imaging and therapy. Using streptavidin-biotin chemistry, we synthesized an integrin αvβ6-targeted near-infrared phthalocyanine dye-labeled agent, termed Dye-SA-B-HK, and investigated whether it could be used for cancer imaging, optical imaging-guided surgery, and phototherapy in pancreatic cancer mouse models. Dye-SA-B-HK specifically bound to integrin αvβ6 in vitro and in vivo with high receptor binding affinity. Using small-animal optical imaging, we detected subcutaneous and orthotopic BxPC-3 human pancreatic cancer xenografts in vivo. Upon optical image-guidance, the orthotopically growing pancreatic cancer lesions could be successfully removed by surgery. Using light irradiation, Dye-SA-B-HK manifested remarkable antitumor effects both in vitro and in vivo. (18)F-FDG positron emission tomography (PET) imaging and ex vivo fluorescence staining validated the observed decrease in proliferation of treated tumors by Dye-DA-B-HK phototherapy. Tissue microarray results revealed overexpression of integrin αvβ6 in over 95% cases of human pancreatic cancer, indicating that theranostic application of Dye-DA-B-HK has clear translational potential. Overall, the results of this study demonstrated that integrin αvβ6-specific Dye-SA-B-HK is a promising theranostic agent for the management of pancreatic cancer.

  13. State-of-the-Art Treatment and Novel Agents in Local and Distant Recurrences of Cervical Cancer.

    PubMed

    Tempfer, Clemens B; Beckmann, Matthias W

    2016-01-01

    Depending on the stage at initial presentation, cervical cancer will recur in 25-61% of women. Typical manifestations of recurrent cervical cancer include the central pelvis and the pelvic side walls as well as retroperitoneal lymph node basins in the pelvis and the para-aortic region, and - more rarely - supraclavicular lymph nodes. There are no typical symptoms of recurrent cervical cancer. Women with suspected recurrence after cervical cancer based on gynecological examination or organ-specific symptoms must undergo imaging studies and - if technically feasible - biopsy with histological verification, especially in cases of distant metastases, in order to rule out a second primary. Radiotherapy-naïve women should be treated with salvage radiochemotherapy with curative intention. For women with previous radiotherapy, surgery in the form of hysterectomy, local resection, or pelvic exenteration is the treatment of choice. Pelvic exenteration can lead to cure in selected patients, but at the price of a high rate of complications and significant morbidity and mortality. If complete surgical resection is not feasible or if the woman is not a candidate for surgery, chemotherapy with palliative intent should be offered. Patients with recurrent disease outside the pelvis are candidates for systemic chemotherapy. Several agents have shown to be active in this situation, either in single-agent or combination regimens. Platinum-containing regimens have a superior efficacy over non-platinum regimens and bevacizumab may be added to chemotherapy. PMID:27614445

  14. Classification and basic properties of contrast agents for magnetic resonance imaging.

    PubMed

    Geraldes, Carlos F G C; Laurent, Sophie

    2009-01-01

    A comprehensive classification of contrast agents currently used or under development for magnetic resonance imaging (MRI) is presented. Agents based on small chelates, macromolecular systems, iron oxides and other nanosystems, as well as responsive, chemical exchange saturation transfer (CEST) and hyperpolarization agents are covered in order to discuss the various possibilities of using MRI as a molecular imaging technique. The classification includes composition, magnetic properties, biodistribution and imaging applications. Chemical compositions of various classes of MRI contrast agents are tabulated, and their magnetic status including diamagnetic, paramagnetic and superparamagnetic are outlined. Classification according to biodistribution covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting strategies of molecular, macromolecular and particulate carriers are also illustrated.

  15. Cancer Imaging at the Crossroads of Precision Medicine: Perspective From an Academic Imaging Department in a Comprehensive Cancer Center.

    PubMed

    Van den Abbeele, Annick D; Krajewski, Katherine M; Tirumani, Sree Harsha; Fennessy, Fiona M; DiPiro, Pamela J; Nguyen, Quang-Dé; Harris, Gordon J; Jacene, Heather A; Lefever, Greg; Ramaiya, Nikhil H

    2016-04-01

    The authors propose one possible vision for the transformative role that cancer imaging in an academic setting can play in the current era of personalized and precision medicine by sharing a conceptual model that is based on experience and lessons learned designing a multidisciplinary, integrated clinical and research practice at their institution. The authors' practice and focus are disease-centric rather than imaging-centric. A "wall-less" infrastructure has been developed, with bidirectional integration of preclinical and clinical cancer imaging research platforms, enabling rapid translation of novel cancer drugs from discovery to clinical trial evaluation. The talents and expertise of medical professionals, scientists, and staff members have been coordinated in a horizontal and vertical fashion through the creation of Cancer Imaging Consultation Services and the "Adopt-a-Radiologist" campaign. Subspecialized imaging consultation services at the hub of an outpatient cancer center facilitate patient decision support and management at the point of care. The Adopt-a-Radiologist campaign has led to the creation of a novel generation of imaging clinician-scientists, fostered new collaborations, increased clinical and academic productivity, and improved employee satisfaction. Translational cancer research is supported, with a focus on early in vivo testing of novel cancer drugs, co-clinical trials, and longitudinal tumor imaging metrics through the imaging research core laboratory. Finally, a dedicated cancer imaging fellowship has been developed, promoting the future generation of cancer imaging specialists as multidisciplinary, multitalented professionals who are trained to effectively communicate with clinical colleagues and positively influence patient care.

  16. Dehydroascorbic acid as an anti-cancer agent.

    PubMed

    Toohey, John I

    2008-05-18

    Three discoveries together point the way to a potential treatment for cancer. In 1982, Poydock and colleagues found that dehydroascorbic acid has the remarkable ability to eliminate the aggressive mouse tumours, L1210, P388, Krebs sarcoma, and Ehrlich carcinoma. In 1993, Jakubowski found that cancer cells (but not normal cells) contain measurable quantities of homocysteine thiolactone. Recently, the author found that dehydroascorbic acid reacts with homocysteine thiolactone converting it to the toxic compound, 3-mercaptopropionaldehyde. Taken together, these findings suggest that rapidly-dividing tumour cells make unusually large amounts of homocysteine thiolactone and that administered dehydroascorbic acid enters the cells and converts the thiolactone to mercaptopropionaldehyde which kills the cancer cells. The effectiveness of dehydroascorbic acid might be further increased by combining it with methionine and/or methotrexate to increase the homocysteine concentration in cancer cells.

  17. Targeted Agents Active Against Breast Cancer: Q&A

    Cancer.gov

    ALTTO was a clinical trial designed to determine whether the combination of the monoclonal antibody trastuzumab (Herceptin) and the drug lapatinib (Tykerb) was more effective in treating HER2/ErbB2-positive breast cancer when combined with chemotherapy.

  18. Metal-oxo containing polymer nanobeads as potential contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Pablico, Michele Huelar

    Magnetic resonance imaging (MRI) has greatly revolutionized the way diseases are detected and treated, as it is a non-invasive imaging modality solely based on the interaction of radiowaves and hydrogen nuclei in the presence of an external magnetic field. It is widely used today for the diagnosis of diseases as it offers an efficient method of mapping structure and function of soft tissues in the body. Most MRI examinations utilize paramagnetic materials known as contrast agents, which enhance the MR signal by decreasing the longitudinal (T1) and transverse (T2) relaxation times of the surrounding water protons in biological systems. This results into increased signal intensity differences thereby allowing better interpretation and analysis of pathological tissues. Contrast agents function by lowering the T1 or lowering the T2, resulting into bright and dark contrasts, respectively. The most common MRI contrast agents that are in clinical use today are gadolinium chelates and superparamagnetic iron oxide nanoparticles, both of which have their own advantages in terms of contrast enhancement properties. In the past few years, however, there has been interest in utilizing metal-containing clusters for MRI contrast enhancement as these materials bridge the gap between the constrained structure and magnetic properties of the gadolinium chelates with the superparamagnetic behavior of the iron oxide nanoparticles. Recently, metallic clusters containing Mn and Fe metal centers have received increased attention mainly because of their potential for high spin states and benign nature. In the quest to further develop novel imaging agents, this research has focused on investigating the use of metal-oxo clusters as potential contrast agents for MRI. The primary goal of this project is to identify clusters that meet the following criteria: high paramagnetic susceptibility, water-soluble, stable, cheap, contain environmentally benign metals, and easily derivatized. This work is

  19. Response to microtubule-interacting agents in primary epithelial ovarian cancer cells

    PubMed Central

    2013-01-01

    Background Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Methods Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated. Results All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. Conclusions The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients’ specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings. PMID:23574945

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    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 sliding 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.

  1. Challenges in Clinical Prostate Cancer: Role of Imaging

    PubMed Central

    Kelloff, Gary J.; Choyke, Peter; Coffey, Donald S.

    2010-01-01

    Objective This article reviews a recent 2-day workshop on prostate cancer and imaging technology that was conducted by the Cancer Imaging Program of the National Cancer Institute. The workshop dealt with research trends and avenues for improving imaging and applications across the clinical spectrum of the disease. Conclusion After a summary of prostate cancer incidence and mortality, four main clinical challenges in prostate cancer treatment and management—diagnostic accuracy; risk stratification, initial staging, active surveillance, and focal therapy; prostate-specific antigen relapse after radiation therapy or radical prostatectomy; and assessing response to therapy in advanced disease—were discussed by the 55-member panel. The overarching issue in prostate cancer is distinguishing lethal from nonlethal disease. New technologies and fresh uses for established procedures make imaging effective in both assessing and treating prostate cancer. PMID:19457806

  2. A New F-18 Labeled PET Agent For Imaging Alzheimer's Plaques

    SciTech Connect

    Kulkarni, Padmakar V.; Hao Guiyang; Arora, Veera; Long, Michael; Slavine, Nikolai; Chiguru, Srinivas; Qu Baoxi; Sun Xiankai; Bennett, Michael; Antich, Peter P.; Bonte, Frederick J.; Vasdev, Neil

    2011-06-01

    Amyloid plaques and neurofibrillary tangles are hallmarks of Alzheimer's disease (AD). Advances in development of imaging agents have focused on targeting amyloid plaques. Notable success has been the development of C-11 labeled PIB (Pittsburgh Compound) and a number of studies have demonstrated the utility of this agent. However, the short half life of C-11 (t1/2: 20 min), is a limitation, thus has prompted the development of F-18 labeled agents. Most of these agents are derivatives of amyloid binding dyes; Congo red and Thioflavin. Some of these agents are in clinical trials with encouraging results. We have been exploring new class of agents based on 8-hydroxy quinoline, a weak metal chelator, targeting elevated levels of metals in plaques. Iodine-123 labeled clioquinol showed affinity for amyloid plaques however, it had limited brain uptake and was not successful in imaging in intact animals and humans. We have been successful in synthesizing F-18 labeled 8-hydroxy quinoline. Small animal PET/CT imaging studies with this agent showed high (7-10% ID/g), rapid brain uptake and fast washout of the agent from normal mice brains and delayed washout from transgenic Alzheimer's mice. These promising results encouraged us in further evaluation of this class of compounds for imaging AD plaques.

  3. Diagnostic imaging techniques in thyroid cancer

    SciTech Connect

    Friedman, M.; Toriumi, D.M.; Mafee, M.F.

    1988-02-01

    With the refinement of fine-needle aspiration, the specific applications of thyroid imaging techniques need to be reevaluated for efficiency and cost containment. No thyroid imaging test should be routinely obtained. Radionuclide scanning is most beneficial in evaluating the functional status of thyroid nodules when fine-needle aspiration is inadequate, the findings are benign, or when there is no discrete nodule that is palpated in an enlarged gland. When fine-needle aspiration is unavailable or unreliable, radionuclide scanning becomes a first-line diagnostic tool. Ultrasonography should be used primarily for identifying a solid component of a cystic nodule, determining the size of nodules on thyroxine suppression that are not easily palpable, or for performing guided fine-needle aspiration. Computerized tomography and magnetic resonance imaging both have a definite role in the evaluation of thyroid tumors. Magnetic resonance imaging is superior to computerized tomography for the evaluation of metastatic, retrotracheal, or mediastinal involvement of large thyroid tumors or goiters. Careful selection of the diagnostic techniques will ensure more accurate diagnosis and reduce unnecessary patient costs in the treatment of thyroid cancer.

  4. Luminescence Enhanced Eu(3+)/Gd(3+) Co-Doped Hydroxyapatite Nanocrystals as Imaging Agents In Vitro and In Vivo.

    PubMed

    Xie, Yunfei; He, Wangmei; Li, Fang; Perera, Thalagalage Shalika Harshani; Gan, Lin; Han, Yingchao; Wang, Xinyu; Li, Shipu; Dai, Honglian

    2016-04-27

    Biocompatible, biodegradable, and luminescent nano material can be used as an alternative bioimaging agent for early cancer diagnosis, which is crucial to achieve successful treatment. Hydroxyapatite (HAP) nanocyrstals have good biocompatibility and biodegradability, and can be used as an excellent host for luminescent rare earth elements. In this study, based on the energy transfer from Gd(3+) to Eu(3+), the luminescence enhanced imaging agent of Eu/Gd codoping HAP (HAP:Eu/Gd) nanocrystals are obtained via coprecipitation with plate-like shape and no change in crystal phase composition. The luminescence can be much elevated (up to about 120%) with a nonlinear increase versus Gd doping content, which is due to the energy transfer ((6)PJ of Gd(3+) → (5)HJ of Eu(3+)) under 273 nm and the possible combination effect of the cooperative upconversion and the successive energy transfer under 394 nm, respectively. Results demonstrate that the biocompatible HAP:Eu/Gd nanocrystals can successfully perform cell labeling and in vivo imaging. The intracellular HAP:Eu/Gd nanocrystals display good biodegradability with a cumulative degradation of about 65% after 72 h. This biocompatible, biodegradable, and luminescence enhanced HAP:Eu/Gd nanocrystal has the potential to act as a fluorescent imaging agent in vitro and in vivo. PMID:27043792

  5. Weakly supervised histopathology cancer image segmentation and classification.

    PubMed

    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.

  6. Nanoparticle-Based Systems for T1-Weighted Magnetic Resonance Imaging Contrast Agents

    PubMed Central

    Zhu, Derong; Liu, Fuyao; Ma, Lina; Liu, Dianjun; Wang, Zhenxin

    2013-01-01

    Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T1-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T1-weighted MRI/computed X-ray tomography (CT) and T1-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality. PMID:23698781

  7. Isonitrile radionuclide complexes for labelling and imaging agents

    SciTech Connect

    Jones, A.G.; Abrams, M.J.; Davison, A.

    1984-06-05

    A coordination complex of an isonitrile ligand and radionuclide such as Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, is useful as a diagnostic agent for labelling liposomes or vesicles, and selected living cells containing lipid membranes, such as blood clots, myocardial tissue, gall bladder tissue, etc.

  8. Isonitrile radionuclide complexes for labelling and imaging agents

    DOEpatents

    Jones, Alun G.; Davison, Alan; Abrams, Michael J.

    1984-06-04

    A coordination complex of an isonitrile ligand and radionuclide such as Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, is useful as a diagnostic agent for labelling liposomes or vesicles, and selected living cells containing lipid membranes, such as blood clots, myocardial tissue, gall bladder tissue, etc.

  9. F18 Fluoromisonidazole for Imaging Tumor Hypoxia: Imaging the Microenvironment for Personalized Cancer Therapy

    PubMed Central

    Rajendran, JG; Krohn, KA

    2014-01-01

    Hypoxia in solid tumors is one of the seminal mechanisms for developing aggressive trait and treatment resistsance in solid tumors. This evolutionarily conserved biological mechanism along with de-repression of cellular functions in cancer, although resulting in many challenges, provide us with opportunities to use these adversities to our advantage. Our ability to use molecular imaging to characterize therapeutic targets such as hypoxia and apply this information for therapeutic interventions is growing rapidly. Evaluation of hypoxia and its biological ramifications to effectively plan appropriate therapy that can overcome the cure-limiting effects of hypoxia provides an objective means for treatment selection and planning. FMISO PET imaging of tumor hypoxia continues to be the lead radiopharmaceutical for the evaluation, prognostication and quantification of hypoxia, one of the key elements of the tumor microenvironment. FMISO is less confounded by blood flow and, although the images have less contrast than FDG PET, its uptake after 2 hours is an accurate reflection of inadequate regional Po2 at the time of radiopharmaceutical administration. By virtue of extensive clinical utilization, FMISO remains the lead candidate for imaging and quantifying hypoxia. The past decade has seen significant technological advances in investigating hypoxia imaging in radiation treatment planning and in providing us with the ability to individualize radiation delivery and target volume coverage. The presence of widespread hypoxia in the tumor can be effectively targeted with a systemic hypoxic cell cytotoxin or other agents that are more effective with diminished PO2, either alone or in combination. Molecular imaging in general and hypoxia imaging in particular will likely become an important in vivo imaging biomarker of the future, complementing the traditional direct tissue sampling methods by providing a snap shot of a primary tumor and metastatic disease and in following

  10. Radioiodinated glucose analogues for use as imaging agents

    DOEpatents

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1988-01-01

    A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

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

    PubMed Central

    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. Cucurbit[8]uril Regulated Activatable Supramolecular Photosensitizer for Targeted Cancer Imaging and Photodynamic Therapy.

    PubMed

    Wang, Xiao-Qiang; Lei, Qi; Zhu, Jing-Yi; Wang, Wen-Jing; Cheng, Qian; Gao, Fan; Sun, Yun-Xia; Zhang, Xian-Zheng

    2016-09-01

    Activatable photosensitizers (aPSs) have emerged as promising photodynamic therapy (PDT) agents for simultaneous imaging and selective ablation of cancer. However, traditional synthetic aPSs are limited by complex design and tedious synthesis. Here, aPS regulated by cucurbit[8]uril (CB[8]) for targeted cancer imaging and PDT is reported. This system is based on the host-guest interaction between biotinylated toluidine blue (TB-B) and CB[8] to form 2TB-B@CB[8]. Moreover, a facile strategy to turn off/on the fluorescence and photodynamic activity of TB-B is developed through the reversible assembly/disassembly of 2TB-B@CB[8]. This established system can achieve selective accumulation in tumor, light-up cancer imaging, and enhanced anticancer behavior. Therefore, this work provides a novel and promising strategy for the aPS build via simple and facile regulation of supramolecular chemistry. PMID:27513690

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

    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.

  14. Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration.

    PubMed

    Takebe, Naoko; Ahmed, Mansoor M; Vikram, Bhadrasain; Bernhard, Eric J; Zwiebel, James; Norman Coleman, C; Kunos, Charles A

    2016-10-01

    A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next-step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation-agent development initiatives. PMID:27619249

  15. First pharmacophore-based identification of androgen receptor down-regulating agents: discovery of potent anti-prostate cancer agents.

    PubMed

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Chopra, Pankaj; Maheshwari, Neha; Gediya, Lalji K; Vasaitis, Tadas S; Bruno, Robert D; Clement, Omoshile O; Njar, Vincent C O

    2007-05-15

    A qualitative 3D pharmacophore model (a common feature based model or Catalyst HipHop algorithm) was developed for well-known natural product androgen receptor down-regulating agents (ARDAs). The four common chemical features identified included: one hydrophobic group, one ring aromatic group, and two hydrogen bond acceptors. This model served as a template in virtual screening of the Maybridge and NCI databases that resulted in identification of six new ARDAs (EC(50) values 17.5-212 microM). Five of these molecules strongly inhibited the growth of human prostate LNCaP cells. These novel compounds may be used as leads to develop other novel anti-prostate cancer agents. PMID:17383188

  16. First pharmacophore-based identification of androgen receptor down-regulating agents: discovery of potent anti-prostate cancer agents.

    PubMed

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Chopra, Pankaj; Maheshwari, Neha; Gediya, Lalji K; Vasaitis, Tadas S; Bruno, Robert D; Clement, Omoshile O; Njar, Vincent C O

    2007-05-15

    A qualitative 3D pharmacophore model (a common feature based model or Catalyst HipHop algorithm) was developed for well-known natural product androgen receptor down-regulating agents (ARDAs). The four common chemical features identified included: one hydrophobic group, one ring aromatic group, and two hydrogen bond acceptors. This model served as a template in virtual screening of the Maybridge and NCI databases that resulted in identification of six new ARDAs (EC(50) values 17.5-212 microM). Five of these molecules strongly inhibited the growth of human prostate LNCaP cells. These novel compounds may be used as leads to develop other novel anti-prostate cancer agents.

  17. Macromolecular Imaging Agents Containing Lanthanides: Can Conceptual Promise Lead to Clinical Potential?

    PubMed Central

    Bryson, Joshua; Reineke, Jeffrey W.; Reineke, Theresa M.

    2012-01-01

    Macromolecular magnetic resonance imaging (MRI) contrast agents are increasingly being used to improve the resolution of this noninvasive diagnostic technique. All clinically-approved T1 contrast agents are small molecule chelates of gadolinium [Gd(III)] that affect bound water proton relaxivity. Both the small size and monomeric nature of these agents ultimately limits the image resolution enhancement that can be achieved for both contrast enhancement and pharmacokinetic/biodistribution reasons. The multimeric nature of macromolecules, such as polymers, dendrimers, and noncovalent complexes of small molecule agents with proteins, have been shown to significantly increase the image contrast and resolution due to their large size and ability to incorporate multiple Gd(III) chlelation sites. Also, macromolecular agents are advantageous as they have the ability to be designed to be nontoxic, hydrophilic, easily purified, aggregation-resistant, and have controllable three-dimensional macromolecular structure housing the multiple lanthanide chelation sites. For these reasons, large molecule diagnostics have the ability to significantly increase the relaxivity of water protons within the targeted tissues and thus the image resolution for many diagnostic applications. The FDA approval of a contrast agent that consists of a reversible, non-covalent coupling of a small Gd(III) chelate with serum albumin for blood pool imaging (marketed under the trade names of Vasovist and Ablivar) proved to be one of the first diagnostic agent to capitalize on these benefits from macromolecular association in humans. However, much research and development is necessary to optimize the safety of these unique agents for in vivo use and potential clinical development. To this end, recent work in the field of polymer, dendrimer, and noncovalent complex-based imaging agents are reviewed herein and the future outlook of this field is discussed. PMID:23467737

  18. Carbon nanomaterials: multi-functional agents for biomedical fluorescence and Raman imaging.

    PubMed

    Bartelmess, J; Quinn, S J; Giordani, S

    2015-07-21

    Carbon based nanomaterials have emerged over the last few years as important agents for biomedical fluorescence and Raman imaging applications. These spectroscopic techniques utilize either fluorescently labelled carbon nanomaterials or the intrinsic photophysical properties of the carbon nanomaterial. In this review article we present the utilization and performance of several classes of carbon nanomaterials, namely carbon nanotubes, carbon nanohorns, carbon nanoonions, nanodiamonds and different graphene derivatives, which are currently employed for in vitro as well as in vivo imaging in biology and medicine. A variety of different approaches, imaging agents and techniques are examined and the specific properties of the various carbon based imaging agents are discussed. Some theranostic carbon nanomaterials, which combine diagnostic features (i.e. imaging) with cell specific targeting and therapeutic approaches (i.e. drug delivery or photothermal therapy), are also included in this overview.

  19. Small animal imaging platform for quantitative assessment of short-wave infrared-emitting contrast agents

    NASA Astrophysics Data System (ADS)

    Hu, Philip; Mingozzi, Marco; Higgins, Laura M.; Ganapathy, Vidya; Zevon, Margot; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.; Pierce, Mark C.

    2015-03-01

    We report the design, calibration, and testing of a pre-clinical small animal imaging platform for use with short-wave infrared (SWIR) emitting contrast agents. Unlike materials emitting at visible or near-infrared wavelengths, SWIR-emitting agents require detection systems with sensitivity in the 1-2 μm wavelength region, beyond the range of commercially available small animal imagers. We used a collimated 980 nm laser beam to excite rare-earth-doped NaYF4:Er,Yb nanocomposites, as an example of a SWIR emitting material under development for biomedical imaging applications. This beam was raster scanned across the animal, with fluorescence in the 1550 nm wavelength region detected by an InGaAs area camera. Background adjustment and intensity non-uniformity corrections were applied in software. The final SWIR fluorescence image was overlaid onto a standard white-light image for registration of contrast agent uptake with respect to anatomical features.

  20. Image-guided synergistic photothermal therapy using photoresponsive imaging agent-loaded graphene-based nanosheets.

    PubMed

    Miao, Wenjun; Shim, Gayong; Kim, Gunwoo; Lee, Soondong; Lee, Hee-Jung; Kim, Young Bong; Byun, Youngro; Oh, Yu-Kyoung

    2015-08-10

    We report the image-guided synergistic photothermal antitumor effects of photoresponsive near-infrared (NIR) imaging agent, indocyanine green (ICG), by loading onto hyaluronic acid-anchored, reduced graphene oxide (HArGO) nanosheets. Loading of ICG onto either rGO (ICG/rGO) or HArGO (ICG/HArGO) substantially improved the photostability of photoresponsive ICG upon NIR irradiation. After 1min of irradiation, the NIR absorption peak of ICG almost disappeared whereas the peak of ICG on rGO or HArGO was retained even after 5min of irradiation. Compared with plain rGO, HArGO provided greater cellular delivery of ICG and photothermal tumor cell-killing effects upon laser irradiation in CD44-positive KB cells. The temperature of cell suspensions treated with ICG/HArGO was 2.4-fold higher than that of cells treated with free ICG. Molecular imaging revealed that intravenously administered ICG/HArGO accumulated in KB tumor tissues higher than ICG/rGO or free ICG. Local temperatures in tumor tissues of laser-irradiated KB cell-bearing nude mice were highest in those intravenously administered ICG/HArGO, and were sufficient to trigger thermal-induced complete tumor ablation. Immunohistologically stained tumors also showed the highest percentages of apoptotic cells in the group treated with ICG/HArGO. These results suggest that photoresponsive ICG-loaded HArGO nanosheets could serve as a potential theranostic nano-platform for image-guided and synergistic photothermal antitumor therapy.

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

    PubMed

    Azmi, Asfar S; Sarkar, Fazlul H; Hadi, S M

    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

  2. Multispectral fluorescence imaging of human ovarian and fallopian tube tissue for early-stage cancer detection

    NASA Astrophysics Data System (ADS)

    Tate, Tyler H.; Baggett, Brenda; Rice, Photini F. S.; Koevary, Jennifer Watson; Orsinger, Gabriel V.; Nymeyer, Ariel C.; Welge, Weston A.; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth D.; Chambers, Setsuko K.; Utzinger, Urs; Barton, Jennifer Kehlet

    2016-05-01

    With early detection, 5-year survival rates for ovarian cancer exceed 90%, yet no effective early screening method exists. Emerging consensus suggests over 50% of the most lethal form of the disease originates in the fallopian tube. Twenty-eight women undergoing oophorectomy or debulking surgery provided informed consent for the use of surgical discard tissue samples for multispectral fluorescence imaging. Using multiple ultraviolet and visible excitation wavelengths and emissions bands, 12 fluorescence and 6 reflectance images of 47 ovarian and 31 fallopian tube tissue samples were recorded. After imaging, each sample was fixed, sectioned, and stained for pathological evaluation. Univariate logistic regression showed cancerous tissue samples had significantly lower intensity than noncancerous tissue for 17 image types. The predictive power of multiple image types was evaluated using multivariate logistic regression (MLR) and quadratic discriminant analysis (QDA). Two MLR models each using two image types had receiver operating characteristic curves with area under the curve exceeding 0.9. QDA determined 56 image type combinations with perfect resubstituting using as few as five image types. Adaption of the system for future in vivo fallopian tube and ovary endoscopic imaging is possible, which may enable sensitive detection of ovarian cancer with no exogenous contrast agents.

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

    PubMed Central

    Khodarahmi, Ghadamali; Asadi, Parvin; Hassanzadeh, Farshid; Khodarahmi, Elham

    2015-01-01

    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. PMID:26941815

  4. Multi-agent systems: effective approach for cancer care information management.

    PubMed

    Mohammadzadeh, Niloofar; Safdari, Reza; Rahimi, Azin

    2013-01-01

    Physicians, in order to study the causes of cancer, detect cancer earlier, prevent or determine the effectiveness of treatment, and specify the reasons for the treatment ineffectiveness, need to access accurate, comprehensive, and timely cancer data. The cancer care environment has become more complex because of the need for coordination and communication among health care professionals with different skills in a variety of roles and the existence of large amounts of data with various formats. The goals of health care systems in such a complex environment are correct health data management, providing appropriate information needs of users to enhance the integrity and quality of health care, timely access to accurate information and reducing medical errors. These roles in new systems with use of agents efficiently perform well. Because of the potential capability of agent systems to solve complex and dynamic health problems, health care system, in order to gain full advantage of E- health, steps must be taken to make use of this technology. Multi-agent systems have effective roles in health service quality improvement especially in telemedicine, emergency situations and management of chronic diseases such as cancer. In the design and implementation of agent based systems, planning items such as information confidentiality and privacy, architecture, communication standards, ethical and legal aspects, identification opportunities and barriers should be considered. It should be noted that usage of agent systems only with a technical view is associated with many problems such as lack of user acceptance. The aim of this commentary is to survey applications, opportunities and barriers of this new artificial intelligence tool for cancer care information as an approach to improve cancer care management. PMID:24460364

  5. Phase-Change Contrast Agents for Imaging and Therapy

    PubMed Central

    Sheeran, Paul S.; Dayton, Paul A.

    2016-01-01

    Phase-change contrast agents (PCCAs) for ultrasound-based applications have resulted in novel ways of approaching diagnostic and therapeutic techniques beyond what is possible with microbubble contrast agents and liquid emulsions. When subjected to sufficient pressures delivered by an ultrasound transducer, stabilized droplets undergo a phase-transition to the gaseous state and a volumetric expansion occurs. This phenomenon, termed acoustic droplet vaporization, has been proposed as a means to address a number of in vivo applications at the microscale and nanoscale. In this review, the history of PCCAs, physical mechanisms involved, and proposed applications are discussed with a summary of studies demonstrated in vivo. Factors that influence the design of PCCAs are discussed, as well as the need for future studies to characterize potential bioeffects for administration in humans and optimization of ultrasound parameters. PMID:22352770

  6. High-Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

    SciTech Connect

    Werner, Eric J.; Datta, Ankona; Jocher, Christoph J.; Raymond, Kenneth N.

    2008-01-15

    The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.

  7. Multifunctional Nanoprobes for Cancer Cell Targeting, Imaging and Anticancer Drug Delivery

    NASA Astrophysics Data System (ADS)

    Linkov, Pavel; Laronze-Cochard, Marie; Sapi, Janos; Sidorov, Lev N.; Nabiev, Igor

    The diagnosis and treatment of cancer have been greatly improved with recent developments in bio-nanotechnology, including engineering of multifunctional probes. One of the promising nanoscale tools for cancer imaging is fluorescent quantum dots (QDs), whose small size and unique optical properties allow them to penetrate into cells and ensure highly sensitive optical diagnosis of cancer at the cellular level. Furthermore, novel multi-functional probes have been developed in which QDs are conjugated with one or several functional molecules, including targeting moieties and therapeutic agents. Here, the strategy for engineering novel nanocarriers for controlled nucleus-targeted antitumor drug delivery and real-time imaging by single- or two-photon microscopy is described. A triple multifunctional nanoprobe is being developed that consists of a nitrogen-based heterocyclic derivative, an anticancer agent interacting with a DNA in living cells; a recognized molecule serving as a vector responsible for targeted delivery of the probe into cancer cells; and photoluminescent QDs providing the imaging capability of the probe. Subsequent optimization of the multifunctional nanoprobe will offer new possibilities for cancer diagnosis and treatment.

  8. Prostate-specific membrane antigen as a target for cancer imaging and therapy

    PubMed Central

    KIESS, A. P.; BANERJEE, S. R.; MEASE, R. C.; ROWE, S. P.; RAO, A.; FOSS, C. A.; CHEN, Y.; YANG, X.; CHO, S. Y.; NIMMAGADDA, S.; POMPER, M. G.

    2016-01-01

    The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers. PMID:26213140

  9. Diagnosis of colon cancer using frequency domain fluorescence imaging technique

    NASA Astrophysics Data System (ADS)

    Dinish, U. S.; Gulati, P.; Murukeshan, V. M.; Seah, L. K.

    2007-03-01

    Early detection and treatment of colon cancer has been associated with better disease prognosis. Conventional and reported optical techniques have limitations in detecting early stages of colon cancer growth. In this paper, a homodyne signal processing assisted frequency domain (FD) fluorescence imaging methodology is proposed for the early diagnosis of colon cancer. Simulated phantom tissues representing the biopsy samples at different stages of colon cancer growth are prepared and used for the imaging study. Selective imaging of healthy and diseased sites simulated in the samples was achieved even for fluorescence emissions having close lifetimes and wavelength values. Possible extension of the methodology for in vivo investigations is also discussed.

  10. Novel imaging strategies for upper gastrointestinal tract cancers.

    PubMed

    Mortensen, Michael Bau

    2015-03-01

    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 to detect microscopic cancer dissemination.

  11. Biocompatible PEGylated Fe3O4 Nanoparticles as Photothermal Agents for Near-Infrared Light Modulated Cancer Therapy

    PubMed Central

    Yuan, Gang; Yuan, Yongjie; Xu, Kan; Luo, Qi

    2014-01-01

    In accordance with the World Cancer Report, cancer has become the leading cause of mortality worldwide, and various therapeutic strategies have been developed at the same time. In the present study, biocompatible magnetic nanoparticles were designed and synthesized as high-performance photothermal agents for near-infrared light mediated cancer therapy in vitro. Via a facile one-pot solvothermal method, well-defined PEGylated magnetic nanoparticles (PEG–Fe3O4) were prepared with cheap inhesion as a first step. Due to the successful coating of PEG molecules on the surface of PEG–Fe3O4, these nanoparticles exhibited excellent dispersibility and dissolvability in physiological condition. Cytotoxicity based on MTT assays indicated these nanoparticles revealed high biocompatibility and low toxicity towards both Hela cells and C6 cells. After near-infrared (NIR) laser irradiation, the viabilities of C6 cells were effectively suppressed when incubated with the NIR laser activated PEG–Fe3O4. In addition, detailed photothermal anti-cancer efficacy was evaluated via visual microscope images, demonstrating that our PEG–Fe3O4 were promising for photothermal therapy of cancer cells. PMID:25329618

  12. Biocompatible PEGylated Fe₃O₄ nanoparticles as photothermal agents for near-infrared light modulated cancer therapy.

    PubMed

    Yuan, Gang; Yuan, Yongjie; Xu, Kan; Luo, Qi

    2014-01-01

    In accordance with the World Cancer Report, cancer has become the leading cause of mortality worldwide, and various therapeutic strategies have been developed at the same time. In the present study, biocompatible magnetic nanoparticles were designed and synthesized as high-performance photothermal agents for near-infrared light mediated cancer therapy in vitro. Via a facile one-pot solvothermal method, well-defined PEGylated magnetic nanoparticles (PEG-Fe3O4) were prepared with cheap inhesion as a first step. Due to the successful coating of PEG molecules on the surface of PEG-Fe3O4, these nanoparticles exhibited excellent dispersibility and dissolvability in physiological condition. Cytotoxicity based on MTT assays indicated these nanoparticles revealed high biocompatibility and low toxicity towards both Hela cells and C6 cells. After near-infrared (NIR) laser irradiation, the viabilities of C6 cells were effectively suppressed when incubated with the NIR laser activated PEG-Fe3O4. In addition, detailed photothermal anti-cancer efficacy was evaluated via visual microscope images, demonstrating that our PEG-Fe3O4 were promising for photothermal therapy of cancer cells. PMID:25329618

  13. High-Accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems.

    PubMed

    Ito, Koichi; Noro, Kazumasa; Yanagisawa, Yukari; Sakamoto, Maya; Mori, Shiro; Shiga, Kiyoto; Kodama, Tetsuya; Aoki, Takafumi

    2015-12-01

    An accurate method for detecting contrast agents using diagnostic ultrasound imaging systems is proposed. Contrast agents, such as microbubbles, passing through a blood vessel during ultrasound imaging are detected as blinking signals in the temporal axis, because their intensity value is constantly in motion. Ultrasound contrast agents are detected by evaluating the intensity variation of a pixel in the temporal axis. Conventional methods are based on simple subtraction of ultrasound images to detect ultrasound contrast agents. Even if the subject moves only slightly, a conventional detection method will introduce significant error. In contrast, the proposed technique employs spatiotemporal analysis of the pixel intensity variation over several frames. Experiments visualizing blood vessels in the mouse tail illustrated that the proposed method performs efficiently compared with conventional approaches. We also report that the new technique is useful for observing temporal changes in microvessel density in subiliac lymph nodes containing tumors. The results are compared with those of contrast-enhanced computed tomography.

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Improving the Outcome for Children With Cancer: Development of Targeted New Agents

    PubMed Central

    Adamson, Peter C.

    2015-01-01

    The outcome for children with cancer has improved significantly over the past 60 years, with greater than 80% of patients today becoming 5-year survivors. Despite this progress, cancer remains the leading cause of death from disease in children in the United States, and significant short-term and long-term treatment toxicities continue to impact the majority of children with cancer. The development of targeted new agents offers the prospect of potentially more effective and less toxic treatment for children. More than a decade since imatinib mesylate was introduced into the treatment of children with Philadelphia chromosomepositive acute lymphoblastic leukemia, transforming its outcome, a range of targeted agents has undergone study in pediatric cancer patients. Early lessons learned from these studies include a better understanding of the adverse event profile of these drugs in children, the challenge of developing pediatric-specific formulations, and the continued reliance on successful development for adult cancer indications on pediatric drug development. The collaborative research infrastructure for children with cancer in the United States is well positioned to advance novel treatments into clinical investigations for a spectrum of rare and ultra-rare childhood cancers. A greater investment of resources in target discovery and validation can help drive much needed development of new, more effective treatments for children with cancer. PMID:25754421

  16. Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development †

    PubMed Central

    Newman, David J.; Cragg, Gordon M.

    2014-01-01

    The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743), Eribulin (a synthetic derivative based on the structure of halichondrin B), and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin) as a warhead, have been approved for use in humans (Adcetris®). In this review, we show the compounds derived from marine sources that are currently in clinical trials against cancer. We have included brief discussions of the approved agents, where they are in trials to extend their initial approved activity (a common practice once an agent is approved), and have also included an extensive discussion of the use of auristatin derivatives as warheads, plus an area that has rarely been covered, the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies. PMID:24424355

  17. Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging

    PubMed Central

    Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G.

    2015-01-01

    Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early-stage cancer diagnosis. Gadolinium (Gd) (III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high x-ray attenuation coefficient, is an ideal contrast agent candidate for x-ray based CT imaging. Gd metal organic framework (MOF) nanoparticles with tunable size, high Gd (III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multi-modal imaging probes. PMID:26147906

  18. Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging.

    PubMed

    Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G

    2015-08-19

    Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early stage cancer diagnosis. Gadolinium (Gd)(III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high X-ray attenuation coefficient, is an ideal contrast agent candidate for X-ray-based CT imaging. Gd metal-organic framework (MOF) nanoparticles with tunable size, high Gd(III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multimodal imaging probes.

  19. Double layered hydroxides as potential anti-cancer drug delivery agents.

    PubMed

    Riaz, Ufana; Ashraf, S M

    2013-04-01

    The emergence of nanotechnology has changed the scenario of the medical world by revolutionizing the diagnosis, monitoring and treatment of cancer. This nanotechnology has been proved miraculous in detecting cancer cells, delivering chemotherapeutic agents and monitoring treatment from non-specific to highly targeted killing of tumor cells. In the past few decades, a number of inorganic materials have been investigated such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide, and layered double hydroxide (LDH) for examining their efficacy in targeting drug delivery. The reason behind the selection of these inorganic materials was their versatile and unique features efficient in drug delivery, such as wide availability, rich surface functionality, good biocompatibility, potential for target delivery, and controlled release of the drug from these inorganic nanomaterials. Although, the drug-LDH hybrids are found to be quite instrumental because of their application as advanced anti-cancer drug delivery systems, there has not been much research on them. This mini review is set to highlight the advancement made in the use of layered double hydroxides (LDHs) as anti-cancer drug delivery agents. Along with the advantages of LDHs as anti-cancer drug delivery agents, the process of interaction of some of the common anti-cancer drugs with LDH has also been discussed.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Effects of nonlinear propagation in ultrasound contrast agent imaging.

    PubMed

    Tang, Meng-Xing; Kamiyama, Naohisa; Eckersley, Robert J

    2010-03-01

    This paper investigates two types of nonlinear propagation and their effects on image intensity and contrast-to-tissue ratio (CTR) in contrast ultrasound images. Previous studies have shown that nonlinear propagation can occur when ultrasound travels through tissue and microbubble clouds, making tissue farther down the acoustic path appear brighter in pulse inversion (PI) images, thus reducing CTR. In this study, the effect of nonlinear propagation through tissue or microbubbles on PI image intensity and CTR are compared at low mechanical index. A combination of simulation and experiment with SonoVue microbubbles were performed using a microbubble dynamics model, a laboratory ultrasound system and a clinical prototype scanner. The results show that, close to the bubble resonance frequency, nonlinear propagation through a bubble cloud of a few centimeter thickness with a modest concentration (1:10000 dilution of SonoVue microbubbles) is much more significant than through tissue-mimicking material. Consequently, CTR in regions distal to the imaging probe is greatly reduced for nonlinear propagation through the bubble cloud, with as much as a 12-dB reduction compared with nonlinear propagation through tissue-mimicking material. Both types of nonlinear propagation cause only a small change in bubble PI signals at the bubble resonance frequency. When the driving frequency increases beyond bubble resonance, nonlinear propagation through bubbles is greatly reduced in absolute values. However because of a greater reduction in nonlinear scattering from bubbles at higher frequencies, the corresponding CTR is much lower than that at bubble resonance frequency.

  2. MOLECULAR IMAGING OF PROSTATE CANCER: translating molecular biology approaches into the clinical realm

    PubMed Central

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

    2016-01-01

    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 behavior which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterizes this disease has lead 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 tumor detection alone to distinguishing patients with indolent tumors that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumors that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualization 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. PMID:25693661

  3. Plant Polyphenols as Chemopreventive Agents for Lung Cancer.

    PubMed

    Amararathna, Madumani; Johnston, Michael R; Rupasinghe, H P Vasantha

    2016-01-01

    Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases. PMID:27548149

  4. Plant Polyphenols as Chemopreventive Agents for Lung Cancer

    PubMed Central

    Amararathna, Madumani; Johnston, Michael R.; Rupasinghe, H. P. Vasantha

    2016-01-01

    Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases. PMID:27548149

  5. Nanoparticles as magnetic resonance imaging contrast agents for vascular and cardiac diseases

    PubMed Central

    Chen, Wei; Cormode, David P.; Fayad, Zahi A.; Mulder, Willem J. M.

    2011-01-01

    Advances in nanoparticle contrast agents for molecular imaging have made magnetic resonance imaging a promising modality for noninvasive visualization and assessment of vascular and cardiac disease processes. This review provides a description of the various nanoparticles exploited for imaging cardiovascular targets. Nanoparticle probes detecting inflammation, apoptosis, extracellular matrix, and angiogenesis may provide tools for assessing the risk of progressive vascular dysfunction and heart failure. The utility of nanoparticles as multimodal probes and/or theranostic agents has also been investigated. Although clinical application of these nanoparticles is largely unexplored, the potential for enhancing disease diagnosis and treatment is considerable. PMID:20967875

  6. Research into europium complexes as magnetic resonance imaging contrast agents (Review)

    PubMed Central

    HAN, GUOCAN; DENG, YANGWEI; SUN, JIHONG; LING, JUN; SHEN, ZHIQUAN

    2015-01-01

    Europium (Eu) is a paramagnetic lanthanide element that possesses an outstanding luminescent property. Eu complexes are ideal fluorescence imaging (FI) agents. Eu2+ has satisfactory relaxivity and optical properties, and can realize magnetic resonance (MRI)-FI dual imaging applications when used with appropriate cryptands that render it oxidatively stable. By contrast, based on the chemical exchange saturation transfer (CEST) mechanism, Eu3+ complexes can provide enhanced MRI sensitivity when used with optimal cryptands, incorporated into polymeric CEST agents or blended with Gd3+. Eu complexes are promising in MRI-FI dual imaging applications and have a bright future. PMID:26136858

  7. Imaging of Isotopically Enhanced Molecular Targeting Agents Final Report

    SciTech Connect

    Quong, J N

    2004-02-19

    The goal of this project is to develop experimental and computational protocols to use SIMS to image the chemical composition of biological samples, focusing on optimizing sample preparation protocols and developing multivariate data analysis methods. Our results on sample preparation, molecular imaging, and multivariate analysis have been presented at several meeting abstracts (UCRL151797ABS, UCRL151797ABSREV1, UCRL151426ABS, UCRL201277, UCRL154757). A refereed paper describing our results for sample preparation and molecular imaging of various endogenous biomolecules as well as the mutagen PhIP has been accepted for publication (UCRL-JC-151797). We are also preparing two additional papers describing our multivariate analysis methods to analyze spectral data. As these papers have not been submitted, their content is included in this final report.

  8. Breast cancer imaging by microwave-induced thermoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Xu, Minghua; Ku, Geng; Jin, Xing; Wang, Lihong V.; Fornage, Bruno D.; Hunt, Kelly K.

    2005-04-01

    We report a preliminary study of breast cancer imaging by microwave-induced thermoacoustic tomography. In this study, we built a prototype of breast cancer imager based on a circular scan mode. A 3-GHz 0.3~0.5-μs microwave is used as the excitation energy source. A 2.25-MHz ultrasound transducer scans the thermoacoustic signals. All the measured data is transferred to a personal computer for imaging based on our proposed back-projection reconstruction algorithms. We quantified the line spread function of the imaging system. It shows the spatial resolution of our experimental system reaches 0.5 mm. After phantom experiments demonstrated the principle of this technique, we moved the imaging system to the University of Texas MD Anderson Cancer Center to image the excised breast cancer specimens. After the surgery performed by the physicians at the Cancer Center, the excised breast specimen was placed in a plastic cylindrical container with a diameter of 10 cm; and it was then imaged by three imaging modalities: radiograph, ultrasound and thermoacoustic imaging. Four excised breast specimens have been tested. The tumor regions have been clearly located. This preliminary study demonstrated the potential of microwave-induced thermoacoustic tomography for applications in breast cancer imaging.

  9. Radionuclide imaging and treatment of thyroid cancer.

    PubMed

    Wang, Xiu Juan; Li, XianFeng; Ren, Yuan

    2016-01-01

    Over the past decades, the diagnostic methods and therapeutic tools for thyroid cancer (TC) have been greatly improved. In addition to the classical method of ingestion of radioactive iodine-131 (I131) and subsequent I123 and I124 positron emission tomography (PET) in therapy and examination, I124 PET-based 3-dimensional imaging, Ga68-labeled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-octreotide (DOTANOC) PET/computed tomography (CT), Tc99m tetrofosmin, pre-targeted radioimmunotherapy, and peptide receptor radionuclide therapy have all been used clinically. These novel methods are useful in diagnosis and therapy of TC, but also have unavoidable adverse effects. In this review, we will discuss the development of nuclear medicine in TC examination and treatment. PMID:27100499

  10. Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging.

    PubMed

    De Jesus, Elizabeth; Keating, Jane J; Kularatne, Sumith A; Jiang, Jack; Judy, Ryan; Predina, Jarrod; Nie, Shuming; Low, Philip; Singhal, Sunil

    2015-01-01

    Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes. Materials. HeLa and KB cells lines were used for in vitro and in vivo comparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution. In vivo experiments were then performed in mice. Results. The peak excitation and emission wavelengths of EC17 and OTL38 were 470/520 nm and 774/794 nm, respectively. In vitro, OTL38 required increased incubation time compared to EC17 for maximum fluorescence; however, peak signal-to-background ratio (SBR) was 1.4-fold higher compared to EC17 within 60 minutes (p < 0.001). Additionally, the SBR for detecting smaller quantity of cells was improved with OTL38. In vivo, the mean improvement in SBR of tumors visualized using OTL38 compared to EC17 was 3.3 fold (range 1.48-5.43). Neither dye caused noticeable toxicity in animal studies. Conclusions. In preclinical testing, OTL38 appears to have superior sensitivity and brightness compared to EC17. This coincides with the accepted belief that near infrared (NIR) dyes tend to have less autofluorescence and scattering issues than visible wavelength fluorochromes. PMID:26491562

  11. Recent progress of imaging agents for Parkinson's disease.

    PubMed

    Wu, Xiaoai; Cai, Huawei; Ge, Ran; Li, Lin; Jia, Zhiyun

    2014-12-01

    Parkinson's disease (PD) is a common progressive, neurodegenerative brain disease that is promoted by mitochondrial dysfunction, oxidative stress, protein aggregation and proteasome dysfunction in the brain. Compared with computer tomography (CT) or magnetic resonance imaging (MRI), non-invasive nuclear radiopharmaceuticals have great significance for the early diagnosis of PD due to their high sensitivity and specificity in atypical and preclinical cases. Based on the development of coordination chemistry and chelator design, radionuclides may be delivered to lesions by attaching to PD-related transporters and receptors, such as dopamine, serotonin, and others. In this review, we comprehensively detailed the current achievements in radionuclide imaging in Parkinson's disease. PMID:25977680

  12. Recent Progress of Imaging Agents for Parkinson's Disease

    PubMed Central

    Wu, Xiaoai; Cai, Huawei; Ge, Ran; Li, Lin; Jia, Zhiyun

    2014-01-01

    Parkinson's disease (PD) is a common progressive, neurodegenerative brain disease that is promoted by mitochondrial dysfunction, oxidative stress, protein aggregation and proteasome dysfunction in the brain. Compared with computer tomography (CT) or magnetic resonance imaging (MRI), non-invasive nuclear radiopharmaceuticals have great significance for the early diagnosis of PD due to their high sensitivity and specificity in atypical and preclinical cases. Based on the development of coordination chemistry and chelator design, radionuclides may be delivered to lesions by attaching to PD-related transporters and receptors, such as dopamine, serotonin, and others. In this review, we comprehensively detailed the current achievements in radionuclide imaging in Parkinson’s disease. PMID:25977680

  13. Photoacoustic imaging with an acoustic lens detects prostate cancer cells labeled with PSMA-targeting near-infrared dye-conjugates

    NASA Astrophysics Data System (ADS)

    Dogra, Vikram; Chinni, Bhargava; Singh, Shalini; Schmitthenner, Hans; Rao, Navalgund; Krolewski, John J.; Nastiuk, Kent L.

    2016-06-01

    There is an urgent need for sensitive and specific tools to accurately image early stage, organ-confined human prostate cancers to facilitate active surveillance and reduce unnecessary treatment. Recently, we developed an acoustic lens that enhances the sensitivity of photoacoustic imaging. Here, we report the use of this device in conjunction with two molecular imaging agents that specifically target the prostate-specific membrane antigen (PSMA) expressed on the tumor cell surface of most prostate cancers. We demonstrate successful imaging of phantoms containing cancer cells labeled with either of two different PSMA-targeting agents, the ribonucleic acid aptamer A10-3.2 and a urea-based peptidomimetic inhibitor, each linked to the near-infrared dye IRDye800CW. By specifically targeting cells with these agents linked to a dye chosen for optimal signal, we are able to discriminate prostate cancer cells that express PSMA.

  14. N-( sup 18 F)fluoroacetyl-D-glucosamine: A potential agent for cancer diagnosis

    SciTech Connect

    Fujiwara, T.; Kubota, K.; Sato, T.; Matsuzawa, T.; Tada, M.; Iwata, R.; Itoh, M.; Hatazawa, J.; Sato, K.; Fukuda, H. )

    1990-10-01

    Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N-({sup 18}F)fluoroacetyl-D-glucosamine ({sup 18}F-FAG), which is a structural analog of N-acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that {sup 18}F-FAG has potential as a new agent for tumor imaging.

  15. Dynamic infrared imaging for skin cancer screening

    NASA Astrophysics Data System (ADS)

    Godoy, Sebastián E.; Ramirez, David A.; Myers, Stephen A.; von Winckel, Greg; Krishna, Sanchita; Berwick, Marianne; Padilla, R. Steven; Sen, Pradeep; Krishna, Sanjay

    2015-05-01

    Dynamic thermal imaging (DTI) with infrared cameras is a non-invasive technique with the ability to detect the most common types of skin cancer. We discuss and propose a standardized analysis method for DTI of actual patient data, which achieves high levels of sensitivity and specificity by judiciously selecting pixels with the same initial temperature. This process compensates the intrinsic limitations of the cooling unit and is the key enabling tool in the DTI data analysis. We have extensively tested the methodology on human subjects using thermal infrared image sequences from a pilot study conducted jointly with the University of New Mexico Dermatology Clinic in Albuquerque, New Mexico (ClinicalTrials ID number NCT02154451). All individuals were adult subjects who were scheduled for biopsy or adult volunteers with clinically diagnosed benign condition. The sample size was 102 subjects for the present study. Statistically significant results were obtained that allowed us to distinguish between benign and malignant skin conditions. The sensitivity and specificity was 95% (with a 95% confidence interval of [87.8% 100.0%]) and 83% (with a 95% confidence interval of [73.4% 92.5%]), respectively, and with an area under the curve of 95%. Our results lead us to conclude that the DTI approach in conjunction with the judicious selection of pixels has the potential to provide a fast, accurate, non-contact, and non-invasive way to screen for common types of skin cancer. As such, it has the potential to significantly reduce the number of biopsies performed on suspicious lesions.

  16. Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents.

    PubMed

    Cragg, Gordon M; Pezzuto, John M

    2016-01-01

    Throughout history, natural products have played a dominant role in the treatment of human ailments. For example, the legendary discovery of penicillin transformed global existence. Presently, natural products comprise a large portion of current-day pharmaceutical agents, most notably in the area of cancer therapy. Examples include Taxol, vinblastine, and camptothecin. These structurally unique agents function by novel mechanisms of action; isolation from natural sources is the only plausible method that could have led to their discovery. In addition to terrestrial plants as sources for starting materials, the marine environment (e.g., ecteinascidin 743, halichondrin B, and dolastatins), microbes (e.g., bleomycin, doxorubicin, and staurosporin), and slime molds (e.g., epothilone B) have yielded remarkable cancer chemotherapeutic agents. Irrespective of these advances, cancer remains a leading cause of death worldwide. Undoubtedly, the prevention of human cancer is highly preferable to treatment. Cancer chemoprevention, the use of vaccines or pharmaceutical agents to inhibit, retard, or reverse the process of carcinogenesis, is another important approach for easing this formidable public health burden. Similar to cancer chemotherapeutic agents, natural products play an important role in this field. There are many examples, including dietary phytochemicals such as sulforaphane and phenethyl isothiocyanate (cruciferous vegetables) and resveratrol (grapes and grape products). Overall, natural product research is a powerful approach for discovering biologically active compounds with unique structures and mechanisms of action. Given the unfathomable diversity of nature, it is reasonable to suggest that chemical leads can be generated that are capable of interacting with most or possibly all therapeutic targets. PMID:26679767

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

    NASA Astrophysics Data System (ADS)

    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

  18. Synchronous gynecologic cancer and the use of imaging for diagnosis.

    PubMed

    Boaventura, Camila Silva; Galvão, José Lucas Scarpinetti; Soares, Giovanna Milanes Bego; Bitencourt, Almir Galvão Vieira; Chojniak, Rubens; Bringel, Shenia Lauanna Rezende; Brot, Louise De

    2016-04-01

    Endometrial and cervical cancers are the most prevalent gynecologic neoplasms. While endometrial cancer occurs in older women, cervical cancer is more prevalente in young subjects. The most common clinical manifestation in these two gynecological cancers is vaginal bleeding. In the first case, diagnosis is made based on histological and imaging evaluation of the endometrium, while cervical cancers are diagnosed clinically, according to the International Federation of Gynecology and Obstetrics (FIGO). The authors present a case of synchronous gynecological cancer of the endometrium and cervix diagnosed during staging on MRI and confirmed by histological analysis of the surgical specimen. PMID:27167539

  19. Near-infrared fluorescence imaging of cancer mediated by tumor hypoxia and HIF1α/OATPs signaling axis.

    PubMed

    Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Shi, Changhong; Li, Qinlong; Hu, Peizhen; Chen, Yi-Ting; Dou, Xiaoliang; Sahu, Divya; Li, Wei; Harada, Hiroshi; Zhang, Yi; Wang, Ruoxiang; Zhau, Haiyen E; Chung, Leland W K

    2014-09-01

    Near-infrared fluorescence (NIRF) imaging agents are promising tools for noninvasive cancer imaging. Here, we explored the mechanistic properties of a specific group of NIR heptamethine carbocyanines including MHI-148 dye we identified and synthesized, and demonstrated these dyes to achieve cancer-specific imaging and targeting via a hypoxia-mediated mechanism. We found that cancer cells and tumor xenografts exhibited hypoxia-dependent MHI-148 dye uptake in vitro and in vivo, which was directly mediated by hypoxia-inducible factor 1α (HIF1α). Microarray analysis and dye uptake assay further revealed a group of hypoxia-inducible organic anion-transporting polypeptides (OATPs) responsible for dye uptake, and the correlation between OATPs and HIF1α was manifested in progressive clinical cancer specimens. Finally, we demonstrated increased uptake of MHI-148 dye in situ in perfused clinical tumor samples with activated HIF1α/OATPs signaling. Our results establish these NIRF dyes as potential tumor hypoxia-dependent cancer-targeting agents and provide a mechanistic rationale for continued development of NIRF imaging agents for improved cancer detection, prognosis and therapy.

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

    SciTech Connect

    Cuneo, Kyle C.; Mito, Jeffrey K.; Javid, Melodi P.; Ferrer, Jorge M.; Kim, Yongbaek; Lee, W. David; Bawendi, Moungi G.; Brigman, Brian E.; Kirsch, David G.

    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.

  1. In vivo detection of copper ions by magnetic resonance imaging using a prion-based contrast agent.

    PubMed

    Makino, Satoshi; Umemoto, Tomohiro; Yamada, Hiroshi; Yezdimer, Eric M; Tooyama, Ikuo

    2012-10-01

    Abnormal distributions of transition metals inside the body are potential diagnostic markers for several diseases, including Alzheimer's disease, Parkinson's disease, Wilson's disease, and cancer. In this article, we demonstrate that P57/Gd, a novel prion-based contrast agent, can selectively image tissues with excessive copper accumulation using magnetic resonance imaging (MRI). P57/Gd selectivity binds copper(II) over other physiologically relevant cations such as zinc, iron, manganese, and calcium. To simulate a metabolic copper disorder, we treated mice with an intraperitoneal injection of a CuSO(4) solution to induce a renal copper overload. The MRI signal intensities from the renal cortex and medulla of copper spiked animals that were administered P57/Gd were found to correlate with the ex vivo copper concentrations determined by inductively coupled plasma mass spectrometry.

  2. Autofluorescence spectroscopy and imaging for cancer detection in the larynx

    NASA Astrophysics Data System (ADS)

    Lin, Kan; Zheng, Wei; Huang, Zhiwei

    2009-11-01

    Autofluorescence imaging has shown high sensitivity for early diagnosis and detection of cancer in humans. However, it has a limitation in diagnostic specificity due to high false positive rates. In this work, we apply an integrated fluorescence spectroscopy and endoscopic imaging technique for real-time tissue measurements. The results show that the combined autofluorescence imaging and spectroscopy has the potential for improving laryngeal cancer diagnosis and detection.

  3. Quantum dots targeted to vascular endothelial growth factor receptor 2 as a contrast agent for the detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Carbary-Ganz, Jordan L.; Barton, Jennifer K.; Utzinger, Urs

    2014-08-01

    We successfully labeled colorectal cancer in vivo using quantum dots targeted to vascular endothelial growth factor receptor 2 (VEGFR2). Quantum dots with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. The resulting QD655-VEGFR2 contrast agent was applied in vivo to the colon of azoxymethane (AOM) treated mice via lavage and allowed to incubate. The colons were then excised, cut longitudinally, opened to expose the lumen, and imaged en face using a fluorescence stereoscope. The QD655-VEGFR2 contrast agent produced a significant increase in contrast between diseased and undiseased tissues, allowing for fluorescence-based visualization of the diseased areas of the colon. Specificity was assessed by observing insignificant contrast increase when labeling colons of AOM-treated mice with quantum dots bioconjugated to isotype control antibodies, and by labeling the colons of saline-treated control mice. This contrast agent has a great potential for in vivo imaging of the colon through endoscopy.

  4. ADVANCES IN IMAGING TECHNOLOGIES IN THE EVALUATION OF HIGH-GRADE BLADDER CANCER

    PubMed Central

    Zlatev, Dimitar V.; Altobelli, Emanuela; Liao, Joseph C.

    2015-01-01

    Bladder cancer is a heterogeneous disease that ranges from low-grade variant with an indolent course, to high-grade subtype with a recurrent, progressive, and potentially lethal outcome. Accurate assessment for individualized treatment depends critically on the diagnostic accuracy of white light cystoscopy. Despite its central role, white light cystoscopy has several well-documented shortcomings including difficult flat lesion detection, imprecise tumor delineation that limits complete resection, differentiation between inflammation and malignancy, and grade and stage determination. As the limitations of white light cystoscopy contribute to the risk of cancer persistence, recurrence, and progression, there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Optical imaging technologies have emerged as an adjunct to white light cystoscopy with the goal to guide more effective treatment by improving cancer detection and patient stratification on the basis of grade and stage. Photodynamic diagnosis and narrow band imaging are macroscopic imaging modalities similar to white light cystoscopy, but provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography are microscopic imaging technologies that enable real-time high resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection. PMID:25882557

  5. Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review.

    PubMed

    Craig, Sonya E L; Wright, James; Sloan, Andrew E; Brady-Kalnay, Susann M

    2016-06-01

    The median life expectancy after a diagnosis of glioblastoma is 15 months. Although chemotherapeutics may someday cure glioblastoma by killing the highly dispersive malignant cells, the most important contribution that clinicians can currently offer to improve survival is by maximizing the extent of resection and providing concurrent chemo-radiation, which has become standard. Strides have been made in this area with the advent and implementation of methods of improved intraoperative tumor visualization. One of these techniques, optical fluorescent imaging with targeted molecular imaging agents, allows the surgeon to view fluorescently labeled tumor tissue during surgery with the use of special microscopy, thereby highlighting where to resect and indicating when tumor-free margins have been obtained. This advantage is especially important at the difficult-to-observe margins where tumor cells infiltrate normal tissue. Targeted fluorescent agents also may be valuable for identifying tumor versus nontumor tissue. In this review, we briefly summarize nontargeted fluorescent tumor imaging agents before discussing several novel targeted fluorescent agents being developed for glioma imaging in the context of fluorescent-guided surgery or live molecular navigation. Many of these agents are currently undergoing preclinical testing. As the agents become available, however, it is necessary to understand the strengths and weaknesses of each. PMID:26915698

  6. Prostate cancer: multiparametric MR imaging for detection, localization, and staging.

    PubMed

    Hoeks, Caroline M A; Barentsz, Jelle O; Hambrock, Thomas; Yakar, Derya; Somford, Diederik M; Heijmink, Stijn W T P J; Scheenen, Tom W J; Vos, Pieter C; Huisman, Henkjan; van Oort, Inge M; Witjes, J Alfred; Heerschap, Arend; Fütterer, Jurgen J

    2011-10-01

    This review presents the current state of the art regarding multiparametric magnetic resonance (MR) imaging of prostate cancer. Technical requirements and clinical indications for the use of multiparametric MR imaging in detection, localization, characterization, staging, biopsy guidance, and active surveillance of prostate cancer are discussed. Although reported accuracies of the separate and combined multiparametric MR imaging techniques vary for diverse clinical prostate cancer indications, multiparametric MR imaging of the prostate has shown promising results and may be of additional value in prostate cancer localization and local staging. Consensus on which technical approaches (field strengths, sequences, use of an endorectal coil) and combination of multiparametric MR imaging techniques should be used for specific clinical indications remains a challenge. Because guidelines are currently lacking, suggestions for a general minimal protocol for multiparametric MR imaging of the prostate based on the literature and the authors' experience are presented. Computer programs that allow evaluation of the various components of a multiparametric MR imaging examination in one view should be developed. In this way, an integrated interpretation of anatomic and functional MR imaging techniques in a multiparametric MR imaging examination is possible. Education and experience of specialist radiologists are essential for correct interpretation of multiparametric prostate MR imaging findings. Supportive techniques, such as computer-aided diagnosis are needed to obtain a fast, cost-effective, easy, and more reproducible prostate cancer diagnosis out of more and more complex multiparametric MR imaging data. PMID:21931141

  7. Towards a framework for agent-based image analysis of remote-sensing data

    PubMed Central

    Hofmann, Peter; Lettmayer, Paul; Blaschke, Thomas; Belgiu, Mariana; Wegenkittl, Stefan; Graf, Roland; Lampoltshammer, Thomas Josef; Andrejchenko, Vera

    2015-01-01

    Object-based image analysis (OBIA) as a paradigm for analysing remotely sensed image data has in many cases led to spatially and thematically improved classification results in comparison to pixel-based approaches. Nevertheless, robust and transferable object-based solutions for automated image analysis capable of analysing sets of images or even large image archives without any human interaction are still rare. A major reason for this lack of robustness and transferability is the high complexity of image contents: Especially in very high resolution (VHR) remote-sensing data with varying imaging conditions or sensor characteristics, the variability of the objects’ properties in these varying images is hardly predictable. The work described in this article builds on so-called rule sets. While earlier work has demonstrated that OBIA rule sets bear a high potential of transferability, they need to be adapted manually, or classification results need to be adjusted manually in a post-processing step. In order to automate these adaptation and adjustment procedures, we investigate the coupling, extension and integration of OBIA with the agent-based paradigm, which is exhaustively investigated in software engineering. The aims of such integration are (a) autonomously adapting rule sets and (b) image objects that can adopt and adjust themselves according to different imaging conditions and sensor characteristics. This article focuses on self-adapting image objects and therefore introduces a framework for agent-based image analysis (ABIA). PMID:27721916

  8. EGFR Targeted Theranostic Nanoemulsion For Image-Guided Ovarian Cancer Therapy

    PubMed Central

    Ganta, Srinivas; Singh, Amit; Kulkarni, Praveen; Keeler, Amanda W.; Piroyan, Aleksandr; Sawant, Rupa R.; Patel, Niravkumar R.; Davis, Barbara; Ferris, Craig; O’Neal, Sara; Zamboni, William; Amiji, Mansoor M.; Coleman, Timothy P.

    2015-01-01

    Purpose Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-apoptotic agent, C6-ceramide. Methods The surface of the nanoemulsion is annotated with an endothelial growth factor receptor (EGFR) binding peptide to improve targeting ability and gadolinium to provide diagnostic capability for image-guided therapy of EGFR overexpressing ovarian cancers. A high shear microfludization process was employed to produce the formulation with particle size below 150 nm. Results Pharmacokinetic study showed a prolonged blood platinum and gadolinium levels with nanoemulsions in nu/nu mice. The theranostic nanoemulsions also exhibited less toxicity and enhanced the survival time of mice as compared to an equivalent cisplatin treatment. Conclusions Magnetic resonance imaging (MRI) studies indicate the theranostic nanoemulsions were effective contrast agents and could be used to track accumulation in a tumor. The MRI study additionally indicate that significantly more EGFR-targeted theranostic nanoemulsion accumulated in a tumor than non-targeted nanoemulsuion providing the feasibility of using a targeted theranostic agent in conjunction with MRI to image disease loci and quantify the disease progression. PMID:25732960

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

    PubMed Central

    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. PMID:25955231

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

    PubMed

    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. PMID:22692028

  11. Gold nano-rods as a targeting contrast agent for photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Agarwal, A.; Huang, S.-W.; Day, K. C.; O'Donnell, M.; Day, M.; Kotov, N.; Ashkenazi, S.

    2007-02-01

    We have studied the potential of gold nanorods to target cancer cells and provide contrast for photoacoustic imaging. The elongated "rod" shape of these nanoparticles provides a mechanism to tune their plasmon peak absorption wavelength. The absorption peak is shifted to longer wavelengths by increasing the aspect ratio of the rods. Particles 15 nm in diameter and 45 nm long were prepared using a seed mediated growth method. Their plasmon absorption peak was designed to be at 800 nm for increased penetration depth into biological tissue. They were conjugated with a specific antibody to target prostate cancer cells. We have applied photoacoustics to image a prostate cell culture targeted by conjugated gold particles. Images confirm the efficiency of conjugated particle binding to the targeted cell membranes. Photoacoustic detection of a single cell layer is demonstrated. To evaluate the applicability of the technique to clinical prostate cancer detection, we have imaged phantom objects mimicking a real tissue with small (2 mm size) inclusions of nanoparticle gel solution. Our photoacoustic imaging setup is based on a modified commercial ultrasonic scanner which makes it attractive for fast implementation in cancer diagnosis in clinical application. In addition, the setup allows for dual mode operation where a photoacoustic image is superimposed on a conventional B-mode ultrasound image. Dual mode operation is demonstrated by imaging a mouse with gold nanorod gel solution implanted in its hind limb.

  12. Sea Cucumbers Metabolites as Potent Anti-Cancer Agents.

    PubMed

    Janakiram, Naveena B; Mohammed, Altaf; Rao, Chinthalapally V

    2015-05-12

    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.

  13. Sea Cucumbers Metabolites as Potent Anti-Cancer Agents

    PubMed Central

    Janakiram, Naveena B.; Mohammed, Altaf; Rao, Chinthalapally V.

    2015-01-01

    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. PMID:25984989

  14. Amphetamines and