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Sample records for cancer imaging agents

  1. A multimodal nano agent for image-guided cancer surgery.

    PubMed

    Zheng, Jinzi; Muhanna, Nidal; De Souza, Raquel; Wada, Hironobu; Chan, Harley; Akens, Margarete K; Anayama, Takashi; Yasufuku, Kazuhiro; Serra, Stefano; Irish, Jonathan; Allen, Christine; Jaffray, David

    2015-10-01

    Intraoperative imaging technologies including computed tomography and fluorescence optical imaging are becoming routine tools in the cancer surgery operating room. They constitute an enabling platform for high performance surgical resections that assure local control while minimizing morbidity. New contrast agents that can increase the sensitivity and visualization power of existing intraoperative imaging techniques will further enhance their clinical benefit. We report here the development, detection and visualization of a dual-modality computed tomography and near-infrared fluorescence nano liposomal agent (CF800) in multiple preclinical animal models of cancer. We describe the successful application of this agent for combined preoperative computed tomography based three-dimensional surgical planning and intraoperative target mapping (>200 Hounsfield Units enhancement), as well as near-infrared fluorescence guided resection (>5-fold tumor-to-background ratio). These results strongly support the clinical advancement of this agent for image-guided surgery with potential to improve lesion localization, margin delineation and metastatic lymph node detection. PMID:26218742

  2. MULTIFUNCTIONAL SYNTHETIC POLY(L-GLUTAMIC ACID)-BASED CANCER THERAPEUTIC AND IMAGING AGENTS

    PubMed Central

    Melancon, Marites P.

    2012-01-01

    Modern polymer chemistry has led to the generation of a number of biocompatible synthetic polymers have been increasingly studied as efficient carriers for drugs and imaging agents. Synthetic biocompatible polymers have been used to improve the efficacy of both small-molecular-weight therapeutics and imaging agents. Furthermore, multiple targeted anticancer agents and/or imaging reporters can be attached to a single polymer chain, allowing multifunctional and/or multimodality therapy and molecular imaging. Having both an anticancer drug and an imaging reporter in a single polymer chain allows noninvasive real-time visualization of the pharmacokinetics of polymeric drug delivery systems, which can uncover and explain the complicated mechanisms of in vivo drug delivery and their correlation to pharmacodynamics. This review examines use of the synthetic biocompatible polymer poly(L-glutamic acid) (PG) as an efficient carrier of cancer therapeutics and imaging agents. This review will summarize and update our recent research on use of PG as a platform for drug delivery and molecular imaging, including recent clinical findings with respect to PG-paclitaxel (PG-TXL); the combination of PG-TXL with radiotherapy; mechanisms of action of PG-TXL; and noninvasive visualization of in vivo delivery of polymeric conjugates with contrast-enhanced magnetic resonance imaging (MRI), optical imaging, and multimodality imaging. PMID:21303613

  3. 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.

  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. 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

  6. 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.

  7. Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer

    PubMed Central

    Wang, Xinning; Huang, Steve S.; Heston, Warren D.W.; Guo, Hong; Wang, Bing-Cheng; Basilion, James P.

    2015-01-01

    Prostate cancer is the most common noncutaneous malignancy affecting men in North America. Radical prostatectomy remains a definitive treatment for prostate cancer. However, prostate surgeries are still performed “blindly” with the extent of tumor infiltration past the margins of the surgery only being determined postoperatively. An imaging modality that can be used during surgery is needed to help define the tumor margins. With its abundant expression in prostate cancer, prostate-specific membrane antigen (PSMA) is an ideal target for detection of prostate cancer. The purpose of this study was to develop PSMA-targeted near-infrared (NIR) optical imaging probes for intraoperative visualization of prostate cancer. We synthesized a high-affinity PSMA ligand (PSMA-1) with low molecular weight and further labeled it with commercially available NIR dyes IRDy800 and Cy5.5. PSMA-1 and PSMA-1–NIR conjugates had binding affinities better than the parent ligand Cys-CO-Glu. Selective binding was measured for each of the probes in both in vitro and in vivo studies using competitive binding and uptake studies. Interestingly, the results indicated that the pharmacokinetics of the probes was dependent of the fluorophore conjugated to the PSMA-1 ligand and varied widely. These data suggest that PSMA-targeted probes have the potential to be further developed as contrast agents for clinical intraoperative fluorescence-guided surgery. PMID:25239933

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

    PubMed Central

    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.

    2015-01-01

    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 Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ 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. PMID:25971726

  9. Time-resolved spectroscopy and near infrared imaging enhanced by receptor-targeted contrast agents for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Pu, Y.; Wang, W. B.; Tang, G. C.; Achilefu, S.; Alfano, R. R.

    2011-03-01

    Time-resolved spectroscopy and near infrared imaging enhanced by receptor-targeted contrast agents for prostate cancer detection will be presented. Two contrast agents, Cybesin and Cytate, were investigated using time-resolved spectroscopy in aqueous solution and cancerous and normal prostate tissues. The time evolution of the fluorescent dipole in solution was studied using a system of first-order linear differential equations containing two main parameters: the decay rate of emission and the rate of one orthogonal emission component transferring to another. An analytical polarization model was developed and used to extract rotational times and fluorescence anisotropies of the contrast agents in prostate tissues. The differences of rotational times and polarization anisotropies were observed for Cybesin (Cytate) in cancerous and normal prostate tissue, which reflect preferred bond of contrast agents and cancerous tissue cells. The conjugation of Cybesin (Cytate) to prostate cancerous cells offers high contrast between normal and cancerous tissues.

  10. 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.

  11. Two-photon luminescence imaging of cancerous tissue using gold nanorods as bright contrast agents

    NASA Astrophysics Data System (ADS)

    Durr, Nicholas J.; Holfeld, Benjamin A.; Larson, Timothy; Smith, Danielle K.; Korgel, Brian A.; Sokolova, Konstantin; Ben-Yakar, Adela

    2007-07-01

    We demonstrate the use of gold nanorods as molecularly targeted contrast agents for two-photon luminescence (TPL) imaging of cancerous cells 150 µm deep inside a tissue phantom. We synthesized gold nanorods of 50 nm x 15 nm size with a longitudinal surface plasmon resonance of 760 nm. Gold nanorods were conjugated to antibodies against epidermal growth factor receptor (EGFR) and labeled to A431 human epithelial skin cancer cells in a collagen matrix tissue phantom. Using a 1.4 NA oil immersion objective lens, we found that excitation power needed for similar emission intensity in TPL imaging of labeled cells was up to 64 times less than that needed for two-photon autofluorescence (TPAF) imaging of unlabeled cells, which would correspond to a more than 4,000 times increase in emission intensity under equal excitation energy. However, the aberrations due to refractive index mismatch of the immersion oil and the sample limit imaging depth to 75 µm. Using a 0.95 NA water immersion objective lens, we observe robust two-photon emission signal from gold nanorods in the tissue phantoms from at depths of up to 150 µm. Furthermore, the increase in excitation energy required to maintain a constant emission signal intensity as imaging depth was increased was the same in both labeled and unlabeled phantom, suggesting that at the concentrations used, the addition of gold nanorods did not appreciably increase the bulk scattering coefficient of the sample. The remarkable TPL brightness of gold nanorods in comparison to TPAF signal makes them an attractive contrast agent for early detection of cutaneous melanoma.

  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. Radiolabeled liposome imaging determines an indication for liposomal anticancer agent in ovarian cancer mouse xenograft models.

    PubMed

    Ito, Ken; Hamamichi, Shusei; Asano, Makoto; Hori, Yusaku; Matsui, Junji; Iwata, Masao; Funahashi, Yasuhiro; Umeda, Izumi O; Fujii, Hirofumi

    2016-01-01

    Liposomal anticancer agents can effectively deliver drugs to tumor lesions, but their therapeutic effects are enhanced in only limited number of patients. Appropriate biomarkers to identify responder patients to these liposomal agents will improve their treatment efficacies. We carried out pharmacological and histopathological analyses of mouse xenograft models bearing human ovarian cancers (Caov-3, SK-OV-3, KURAMOCHI, and TOV-112D) to correlate the therapeutic effects of doxorubicin-encapsulated liposome (Doxil(®) ) and histological characteristics linked to the enhanced permeability and retention effect. We next generated (111) In-encapsulated liposomes to examine their capacities to determine indications for Doxil(®) treatment by single-photon emission computed tomography (SPECT)/CT imaging. Antitumor activities of Doxil(®) were drastically enhanced in Caov-3, moderately in SK-OV-3, and minimally in KURAMOCHI and TOV-112D when compared to doxorubicin. Microvessel density and vascular perfusion were high in Caov-3 and SK-OV-3, indicating a close relation with the enhanced antitumor effects. Next, (111) In-encapsulated liposomes were given i.v. to the animals. Their tumor accumulation and area under the curve values over 72 h were high in Caov-3, relatively high in SK-OV-3, and low in two other tumors. Importantly, as both Doxil(®) effects and liposomal accumulation varied in the SK-OV-3 group, we individually obtained SPECT/CT images of SK-OV-3-bearing mouse (n = 11) before Doxil(®) treatment. Clear correlation between liposomal tumor accumulation and effects of Doxil(®) was confirmed (R(2) = 0.73). Taken together, our experiments definitely verified that enhanced therapeutic effects through liposomal formulations of anticancer agents depend on tumor accumulation of liposomes. Tumor accumulation of the radiolabeled liposomes evaluated by SPECT/CT imaging is applicable to appropriately determine indications for liposomal antitumor agents. PMID:26509883

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

    PubMed

    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

  18. 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

  19. 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

  20. A novel functional CT contrast agent for molecular imaging of cancer

    NASA Astrophysics Data System (ADS)

    Li, Ji; Chaudhary, Ahmed; Chmura, Steven J.; Pelizzari, Charles; Rajh, Tijana; Wietholt, Christian; Kurtoglu, Metin; Aydogan, Bulent

    2010-08-01

    The purpose of this study was to investigate the feasibility of using a 2-deoxy-d-glucose (2-DG) labeled gold nanoparticle (AuNP-2-DG) as a functionally targeted computed tomography (CT) contrast agent to obtain high-resolution metabolic and anatomic information of tumor in a single CT scan. Gold nanoparticles (AuNPs) were fabricated and were conjugated with 1-DG or 2-DG. 1-DG provides an excellent comparison since it is known to interfere with the ability of the glucose transporter to recognize the sugar moiety. The human alveolar epithelial cancer cell line, A-549, was chosen for the in vitro cellular uptake assay. Three groups of cell samples were incubated with the 1-DG or 2-DG labeled AuNP and the unlabeled AuNP. Following the incubation, the cells were washed with sterile phosphate buffered saline to remove the excess AuNPs and spun using a centrifuge. The cell pellets were imaged using a microCT scanner immediately after the centrifugation. Internalization of AuNP-2-DG is verified using transmission electron microscopy imaging. Significant contrast enhancement in the cell samples incubated with the AuNP-2-DG with respect to the cell samples incubated with the unlabeled AuNP and the AuNP-1-DG was observed in multiple CT slices. Results from our in vitro experiments suggest that the AuNP-2-DG may be used as a functional CT contrast agent to provide high-resolution metabolic and anatomic information in a single CT scan. These results justify further in vitro and in vivo experiments to study the feasibility of using the AuNP-2-DG as a functional CT contrast agent in radiation therapy settings.

  1. "Smart" gold nanoparticles for photoacoustic imaging: an imaging contrast agent responsive to the cancer microenvironment and signal amplification via pH-induced aggregation.

    PubMed

    Song, Jaejung; Kim, Jeesu; Hwang, Sekyu; Jeon, Mansik; Jeong, Sanghwa; Kim, Chulhong; Kim, Sungjee

    2016-07-01

    'Smart' gold nanoparticles can respond to mild acidic environments, rapidly form aggregates, and shift the absorption to red and near-infrared. They were used as a photoacoustic imaging agent responsive to the cancer microenvironment, and have demonstrated the cancer-specific accumulation at the cellular level and an amplified signal which is twice higher than the control in vivo. PMID:27292365

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

    PubMed Central

    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 (tBuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that tBuBipyGd-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. PMID:25565804

  3. MR Molecular Imaging of Prostate Cancer with a Peptide Targeted Contrast Agent in a Mouse Orthotopic Prostate Cancer Model

    PubMed Central

    Tan, Mingqian; Burden-Gulley, Susan M.; Li, Wen; Wu, Xueming; Lindner, Daniel; Brady-Kalnay, Susann M.; Gulani, Vikas; Lu, Zheng-Rong

    2014-01-01

    Purpose To study the effectiveness of a peptide targeted nanoglobular Gd-DOTA complexes for MR molecular imaging of prostate cancer in a mouse orthotopic PC-3 prostate cancer model. Methods A CLT1 (CGLIIQKNEC) peptide targeted generation 2 nanoglobular Gd-DOTA monoamide conjugate [CLT1-G2-(Gd-DOTA)] was used for imaging fibrin-fibronectin complexes in prostate tumor using a non-specific peptide KAREC modified conjugate, KAREC-G2-(Gd-DOTA) as a control. Cy5 conjugates of CLT1 and KAREC were synthesized for binding studies. Orthotopic PC-3 prostate tumors were established in the prostate of athymic male nude mice. MRI study was performed on a Bruker 7T animal scanner. Results CLT1 peptide showed specific binding in the prostate tumor with no binding in normal tissues. The control peptide had little binding in both normal and tumor tissues. CLT1-G2-(Gd-DOTA) resulted in stronger contrast enhancement in the tumor tissue than the KAREC-G2-(Gd-DOTA). CLT1-G2-(Gd-DOTA) generated approximately 100% increase in contrast-to-noise ratio (CNR) in the tumor as compared to precontrast CNR at 1 minute post-injection, while the control agent KAREC-G2-(Gd-DOTA) only resulted in 8% CNR increase. Conclusion CLT1-G2-(Gd-DOTA) is a promising molecular MRI contrast agent for fibrin-fibronectin complexes in the tumor stroma. It has a potential for the diagnosis and assessing prognosis of malignant tumors with MRI. PMID:22139536

  4. A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

    PubMed

    Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

    2016-04-01

    The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID:26874280

  5. Cancer Imaging

    MedlinePlus

    ... I/II Trials CIP ARRA-Funded Clinical Trials Informatics The Cancer Imaging Archive TCGA Imaging Genomics Quantitative Imaging Network LIDC-IDRI Imaging Informatics Resources News & Events News and Announcements Events – Meetings ...

  6. Quasi-Cubic Magnetite/Silica Core-Shell Nanoparticles as Enhanced MRI Contrast Agents for Cancer Imaging

    PubMed Central

    Cowell, Simon F.; Garg, Ashish; Eu, Peter; Bhargava, Suresh K.; Bansal, Vipul

    2011-01-01

    Development of magnetic resonance imaging (MRI) contrast agents that can be readily applied for imaging of biological tissues under clinical settings is a challenging task. This is predominantly due to the expectation of an ideal MR agent being able to be synthesized in large quantities, possessing longer shelf life, reasonable biocompatibility, tolerance against its aggregation in biological fluids, and high relaxivity, resulting in better contrast during biological imaging. Although a repertoire of reports address various aforementioned issues, the previously reported results are far from optimal, which necessitates further efforts in this area. In this study, we demonstrate facile large-scale synthesis of sub-100 nm quasi-cubic magnetite and magnetite/silica core-shell (Mag@SiO2) nanoparticles and their applicability as a biocompatible T2 contrast agent for MRI of biological tissues. Our study suggests that silica-coated magnetite nanoparticles reported in this study can potentially act as improved MR contrast agents by addressing a number of aforementioned issues, including longer shelf life and stability in biological fluids. Additionally, our in vitro and in vivo studies clearly demonstrate the importance of silica coating towards improved applicability of T2 contrast agents for cancer imaging. PMID:21747962

  7. 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

  8. Hybrid plasmonic magnetic nanoparticles as molecular specific agents for MRI/optical imaging and photothermal therapy of cancer cells

    NASA Astrophysics Data System (ADS)

    Larson, Timothy A.; Bankson, James; Aaron, Jesse; Sokolov, Konstantin

    2007-08-01

    Nanoparticles which consist of a plasmonic layer and an iron oxide moiety could provide a promising platform for development of multimodal imaging and therapy approaches in future medicine. However, the feasibility of this platform has yet to be fully explored. In this study we demonstrated the use of gold-coated iron oxide hybrid nanoparticles for combined molecular specific MRI/optical imaging and photothermal therapy of cancer cells. The gold layer exhibits a surface plasmon resonance that provides optical contrast due to light scattering in the visible region and also presents a convenient surface for conjugating targeting moieties, while the iron oxide cores give strong T2 (spin-spin relaxation time) contrast. The strong optical absorption of the plasmonic gold layer also makes these nanoparticles a promising agent for photothermal therapy. We synthesized hybrid nanoparticles which specifically target epidermal growth factor receptor (EGFR), a common biomarker for many epithelial cancers. We demonstrated molecular specific MRI and optical imaging in MDA-MB-468 breast cancer cells. Furthermore, we showed that receptor-mediated aggregation of anti-EGFR hybrid nanoparticles allows selective destruction of highly proliferative cancer cells using a nanosecond pulsed laser at 700 nm wavelength, a significant shift from the peak absorbance of isolated hybrid nanoparticles at 532 nm.

  9. 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

  10. 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

  11. 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.

  12. 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

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

    PubMed

    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

    2016-07-01

    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 Gd(3+) contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd(3+) 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. PMID:26961235

  14. 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

  15. Introducing Infectious Agents and Cancer

    PubMed Central

    Buonaguro, Franco M; Lewis, George K; Pelicci, PierGiuseppe

    2006-01-01

    Infectious Agents and Cancer is a new open access, peer-reviewed, online journal, which encompasses all aspects of basic, clinical and translational research that provide an insight into the association between chronic infections and cancer. PMID:23509916

  16. 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

  17. 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. PMID:26093124

  18. 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.

  19. 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

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

    PubMed Central

    Hawrysz, Daniel J; Sevick-Muraca, Eva M

    2000-01-01

    Abstract The use of near-infrared (NIR) light to interrogate deep tissues has enormous potential for molecular-based imaging when coupled with NIR excitable dyes. More than a decade has now passed since the initial proposals for NIR optical tomography for breast cancer screening using time-dependent measurements of light propagation in the breast. Much accomplishment in the development of optical mammography has been demonstrated, most recently in the application of time-domain, frequency-domain, and continuous-wave measurements that depend on endogenous contrast owing to angiogenesis and increased hemoglobin absorbance for contrast. Although exciting and promising, the necessity of angiogenesis-mediated absorption contrast for diagnostic optical mammography minimizes the potential for using NIR techniques to assess sentinel lymph node staging, metastatic spread, and multifocality of breast disease, among other applications. In this review, we summarize the progress made in the development of optical mammography, and focus on the emerging work underway in the use of diagnostic contrast agents for the molecular-based, diagnostic imaging of breast. PMID:11191107

  1. Targeting and in vivo imaging of non-small-cell lung cancer using nebulized multimodal contrast agents.

    PubMed

    Bianchi, Andrea; Dufort, Sandrine; Lux, François; Fortin, Pierre-Yves; Tassali, Nawal; Tillement, Olivier; Coll, Jean-Luc; Crémillieux, Yannick

    2014-06-24

    One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this work, we evaluated the potential of optimized lung MRI techniques and nebulized ultrasmall multimodal gadolinium-based contrast agents [ultrasmall rigid platforms (USRPs)] as a completely noninvasive approach for non-small-cell lung cancer (NSCLC) in vivo detection. A mouse model of NSCLC expressing the luciferase gene was developed. Ultrashort echo-time free-breathing MRI acquisitions were performed before and after i.v. or intrapulmonary administration of the nanoparticles to identify and segment the tumor. After orotracheal or i.v. administration of USRPs, an excellent colocalization of the position the tumor with MRI, bioluminescence and fluorescence reflectance imaging, and histology was observed in all mice. Significantly higher signal enhancements and contrast-to-noise ratios were observed with orotracheal administration using lower doses, reducing the toxicity issues and the interobserver variability in tumor detection. The observations suggested the existence of an unknown original mechanism (different from the enhanced permeability and retention effect) responsible for this phenomenon. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify, and longitudinally monitor the development of submillimetric NSCLCs. The absence of ionizing radiation and high resolution MRI, along with the complete noninvasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge this is the first time that the advantages of an orotracheal administration route are demonstrated for the investigation of the pathomorphological changes due to NSCLCs. PMID:24927562

  2. Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo.

    PubMed

    Cohen, Allison S; Patek, Renata; Enkemann, Steven A; Johnson, Joseph O; Chen, Tingan; Toloza, Eric; Vagner, Josef; Morse, David L

    2016-02-17

    In the United States, lung cancer is the leading cause of cancer death and ranks second in the number of new cases annually among all types of cancers. Better methods or tools for diagnosing and treating this disease are needed to improve patient outcomes. The delta-opioid receptor (δOR) is reported to be overexpressed in lung cancers and not expressed in normal lung. Thus, we decided to develop a lung cancer-specific imaging agent targeting this receptor. We have previously developed a δOR-targeted fluorescent imaging agent based on a synthetic peptide antagonist (Dmt-Tic) conjugated to a Cy5 fluorescent dye. In this work, we describe the synthesis of Dmt-Tic conjugated to a longer wavelength near-infrared fluorescent (NIRF) dye, Li-cor IR800CW. Binding affinity of Dmt-Tic-IR800 for the δOR was studied using lanthanide time-resolved fluorescence (LTRF) competitive binding assays in cells engineered to overexpress the δOR. In addition, we identified lung cancer cell lines with high and low endogenous expression of the δOR. We confirmed protein expression in these cell lines using confocal fluorescence microscopy imaging and used this technique to estimate the cell-surface receptor number in the endogenously expressing lung cancer cell lines. The selectivity of Dmt-Tic-IR800 for imaging of the δOR in vivo was shown using both engineered cell lines and endogenously expressing lung cancer cells in subcutaneous xenograft models in mice. In conclusion, the δOR-specific fluorescent probe developed in this study displays excellent potential for imaging of lung cancer. PMID:26488422

  3. 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

  4. 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.

  5. New agents for prostate cancer.

    PubMed

    Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

    2014-09-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

  6. Early detection of colonic dysplasia by magnetic resonance molecular imaging with a contrast agent raised against the colon cancer marker MUC5AC.

    PubMed

    Rossez, Yannick; Burtea, Carmen; Laurent, Sophie; Gosset, Pierre; Léonard, Renaud; Gonzalez, Walter; Ballet, Sébastien; Raynal, Isabelle; Rousseaux, Olivier; Dugué, Timothée; Vander Elst, Luce; Michalski, Jean-Claude; Muller, Robert N; Robbe-Masselot, Catherine

    2016-05-01

    Human gastric mucin MUC5AC is secreted in the colonic mucus of cancer patients and is a specific marker of precancerous lesions called aberrant crypt foci. Using MUC5AC as a specific marker can improve sensitivity in the detection of early colorectal cancer. Here we demonstrated that the accumulation of MUC5AC in xenograft and mouse stomach can be detected by magnetic resonance imaging (MRI). We used ultrasmall particles of iron oxide (USPIOs) conjugated with disulfide constrained heptapeptide that were identified using a screening phage display. To accomplish this, we employed positive selection of the phage display library on MUC5AC purified from fresh human colonic adenomas in combination with negative selection of the phage library on purified human MUC2, which is predominantly found in normal colorectal tissues. This conjugate was tested on human colorectal cancer cell lines that were either able or unable to secrete MUC5AC, both in vitro and in vivo. MUC5AC-USPIO contrast agent and USPIOs alone were not detected in cell lines unable to secrete MUC5AC. A combination of MRI and microscopy studies was performed to detect a specific accumulation of the contrast agent in vivo. Thus, the MUC5AC contrast agent enabled non-invasive detection of precancerous lesions and colorectal cancer, highlighting its potential use in diagnostics, in the early detection of colorectal cancer recurrences after treatment and in mechanistic studies implicating MUC5AC. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26762591

  7. 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

  8. 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

  9. 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

  10. Multi-modality PET-CT imaging of breast cancer in an animal model using nanoparticle x-ray contrast agent and 18F-FDG

    NASA Astrophysics Data System (ADS)

    Badea, C. T.; Ghaghada, K.; Espinosa, G.; Strong, L.; Annapragada, A.

    2011-03-01

    Multi-modality PET-CT imaging is playing an important role in the field of oncology. While PET imaging facilitates functional interrogation of tumor status, the use of CT imaging is primarily limited to anatomical reference. In an attempt to extract comprehensive information about tumor cells and its microenvironment, we used a nanoparticle xray contrast agent to image tumor vasculature and vessel 'leakiness' and 18F-FDG to investigate the metabolic status of tumor cells. In vivo PET/CT studies were performed in mice implanted with 4T1 mammary breast cancer cells.Early-phase micro-CT imaging enabled visualization 3D vascular architecture of the tumors whereas delayedphase micro-CT demonstrated highly permeable vessels as evident by nanoparticle accumulation within the tumor. Both imaging modalities demonstrated the presence of a necrotic core as indicated by a hypo-enhanced region in the center of the tumor. At early time-points, the CT-derived fractional blood volume did not correlate with 18F-FDG uptake. At delayed time-points, the tumor enhancement in 18F-FDG micro-PET images correlated with the delayed signal enhanced due to nanoparticle extravasation seen in CT images. The proposed hybrid imaging approach could be used to better understand tumor angiogenesis and to be the basis for monitoring and evaluating anti-angiogenic and nano-chemotherapies.

  11. 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

  12. Nanoparticles as image enhancing agents for ultrasonography

    NASA Astrophysics Data System (ADS)

    Liu, Jun; Levine, Andrea L.; Mattoon, John S.; Yamaguchi, Mamoru; Lee, Robert J.; Pan, Xueliang; Rosol, Thomas J.

    2006-05-01

    Nanoparticles have drawn great attention as targeted imaging and/or therapeutic agents. The small size of the nanoparticles allows them to target cells that are beyond capillary vasculature, such as cancer cells. We investigated the effect of solid nanoparticles for enhancing ultrasonic grey scale images in tissue phantoms and mouse livers in vivo. Silica nanospheres (100 nm) were dispersed in agarose at 1-2.5% mass concentration and imaged by a high-resolution ultrasound imaging system (transducer centre frequency: 30 MHz). Polystyrene particles of different sizes (500-3000 nm) and concentrations (0.13-0.75% mass) were similarly dispersed in agarose and imaged. Mice were injected intravenously with nanoparticle suspensions in saline. B-mode images of the livers were acquired at different time points after particle injection. An automated computer program was used to quantify the grey scale changes. Ultrasonic reflections were observed from nanoparticle suspensions in agarose gels. The image brightness, i.e., mean grey scale level, increased with particle size and concentration. The mean grey scale of mouse livers also increased following particle administration. These results indicated that it is feasible to use solid nanoparticles as contrast enhancing agents for ultrasonic imaging.

  13. 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

  14. pH-controlled gas-generating mineralized nanoparticles: a theranostic agent for ultrasound imaging and therapy of cancers.

    PubMed

    Min, Kyung Hyun; Min, Hyun Su; Lee, Hong Jae; Park, Dong Jin; Yhee, Ji Young; Kim, Kwangmeyung; Kwon, Ick Chan; Jeong, Seo Young; Silvestre, Oscar F; Chen, Xiaoyuan; Hwang, Yu-Shik; Kim, Eun-Cheol; Lee, Sang Cheon

    2015-01-27

    We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release simultaneously with CO2 bubble generation at the acidic tumoral environment. The DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers. PMID:25559896

  15. 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

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

    PubMed

    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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Multifunctional PLGA Nanobubbles as Theranostic Agents: Combining Doxorubicin and P-gp siRNA Co-Delivery Into Human Breast Cancer Cells and Ultrasound Cellular Imaging.

    PubMed

    Yang, Hong; Deng, Liwei; Li, Tingting; Shen, Xue; Yan, Jie; Zuo, Liangming; Wu, Chunhui; Liu, Yiyao

    2015-12-01

    Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. One of the effective approaches to overcome MDR is to use nanoparticle-mediated the gene silence of chemotherapeutic export proteins by RNA interference to increase drug accumulation in drug resistant cancer cells. In this work, a new co-delivery system, DOX-PLGA/PEI/P-gp shRNA nanobubbles (NBs) around 327 nm, to overcome doxorubicin (DOX) resistance in MCF-7 human breast cancer was designed and developed. Positively charged polyethylenimine (PEI) were modified onto the surface of DOX-PLGA NBs through DCC/NHS crosslinking, and could efficiently condense P-gp shRNA into DOX-PLGA/PEI NBs at vector/shRNA weight ratios of 70:1 and above. An in vitro release profile demonstrated an efficient DOX release (more than 80%) from DOX-PLGA/PEI NBs at pH 4.4, suggesting a pH-responsive drug release for the multifunctionalized NBs. Cellular experimental results further showed that DOX-PLGA/PEI/P-gp shRNA NBs could facilitate cellular uptake of DOX into cells and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The IC50 of DOX-PLGA NBs against MCF-7/ADR cells was 2-fold lower than that of free DOX. The increased cellular uptake and nuclear accumulation of DOX delivered by DOX-PLGA/PEI/P-gp shRNA NBs in MCF-7/ADR cells was confirmed by fluorescence microscopy and fluorescence spectrophotometry, and might be owning to the down-regulation of P-gp and reduced the efflux of DOX. The cellular uptake mechanism of DOX-PLGA/PEI/P-gp shRNA NBs indicated that the macropinocytosis was one of the pathways for the uptake of NBs by MCF-7/ADR cells, which was also an energy-dependent process. Furthermore, the in vitro cellular ultrasound imaging suggested that the employment of the DOX-PLGA/PEI/P-gp shRNA NBs could efficiently enhance ultrasound imaging of cancer cells. These results demonstrated

  2. 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

  3. First clinical experience with the magnetic resonance imaging contrast agent and superoxide dismutase mimetic mangafodipir as an adjunct in cancer chemotherapy-a translational study.

    PubMed

    Karlsson, Jan Olof G; Adolfsson, Karin; Thelin, Bo; Jynge, Per; Andersson, Rolf Gg; Falkmer, Ursula G

    2012-02-01

    Preclinical research suggests that the clinically approved magnetic resonance imaging contrast agent mangafodipir may protect against adverse events (AEs) caused by chemotherapy, without interfering negatively with the anticancer efficacy. The present translational study tested if pretreatment with mangafodipir lowers AEs during curative (adjuvant) FOLFOX6 chemotherapy in stage III colon cancer (Dukes' C). The study was originally scheduled to include 20 patients, but because of the unforeseen withdrawal of mangafodipir from the market, the study had to be closed after 14 patients had been included. The withdrawal of mangafodipir was purely based on commercial considerations from the producer and not on any safety concerns. The patients were treated throughout the first 3 of 12 scheduled cycles. Patients were randomized to a 5-minute infusion of either mangafodipir or placebo (7 in each group). AEs were evaluated according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events and the Sanofi-NCI criteria. The primary end points were neutropenia and neurosensory toxicity. There were four AEs of grade 3 (severe) and one AE of grade 4 (life threatening) in four patients in the placebo group, whereas there were none in the mangafodipir group (P < .05). Of the grade 3 and 4 events, two were neutropenia and one was neurosensory toxicity. Furthermore, white blood cell count was statistically, significantly higher in the mangafodipir group than in the placebo group (P < .01) after treatment with FOLFOX. This small feasibility study seems to confirm what has been demonstrated preclinically, namely, that pretreatment with mangafodipir lowers AEs during adjuvant 5-fluorouracil plus oxaliplatin-based chemotherapy in colon cancer patients. PMID:22348174

  4. 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

  5. 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.

  6. Functional Imaging for Prostate Cancer: Therapeutic Implications

    PubMed Central

    Aparici, Carina Mari; Seo, Youngho

    2012-01-01

    Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

  7. 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.

  8. Imaging in oral cancers

    PubMed Central

    Arya, Supreeta; Chaukar, Devendra; Pai, Prathamesh

    2012-01-01

    Oral cavity squamous cell cancers form a significant percentage of the cancers seen in India. While clinical examination allows direct visualization, it cannot evaluate deep extension of disease. Cross-sectional imaging has become the cornerstone in the pretreatment evaluation of these cancers and provides accurate information about the extent and depth of disease that can help decide the appropriate management strategy and indicate prognosis. Early cancers are treated with a single modality, either surgery or radiotherapy while advanced cancers are offered a combination of surgery, radiotherapy and chemotherapy. Imaging can decide resectability, help plan the precise extent of resection, and indicate whether organ conservation therapy should be offered. Quality of life issues necessitate preservation of form and function and pretreatment imaging helps plan appropriate reconstruction and counsel patients regarding lifestyle changes. Oral cavity has several subsites and the focus of the review is squamous cancers of the gingivobuccal region, oral tongue and retromolar trigone as these are most frequently encountered in the subcontinent. References for this review were identified by searching Medline and PubMed databases. Only articles published in English language literature were selected. This review aims to familiarize the radiologist with the relevant anatomy of the oral cavity, discuss the specific issues that influence prognosis and management at the above subsites, the optimal imaging methods, the role of imaging in accurately staging these cancers and in influencing management. A checklist for reporting will emphasize the information to be conveyed by the radiologist. PMID:23599568

  9. Ultrasound Imaging Beyond the Vasculature with New Generation Contrast Agents

    PubMed Central

    Perera, Reshani H.; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan

    2015-01-01

    Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 μm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer. PMID:25580914

  10. 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

  11. 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

  12. Dietary flavonoids as cancer prevention agents.

    PubMed

    Yao, Hua; Xu, Weizheng; Shi, Xianglin; Zhang, Zhuo

    2011-01-01

    Dietary agents identified from fruits and vegetables contribute to keeping balanced cell proliferation and preventing cell carcinogenesis. Dietary flavonoids, combined with other components such as various vitamins, play an important role in cancer prevention. Flavonoids act on reactive oxygen species, cell signal transduction pathways related to cellular proliferation, apoptosis, and angiogenesis. Many studies demonstrate that flavonoids are responsible for chemoprevention, although mechanisms of action remain to be investigated. Overall, exciting data show that dietary flavonoids could be considered as a useful cancer preventive approach. This review summarizes recent advancements on potential cancer preventive effects and mechanic insight of dietary flavonoids. PMID:21424974

  13. 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

  14. Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging

    PubMed Central

    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

  15. 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

  16. 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

  17. 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

  18. Agent Orange Linked to Bladder Cancer, Thyroid Problems, Panel Says

    MedlinePlus

    ... 157716.html Agent Orange Linked to Bladder Cancer, Thyroid Problems, Panel Says Herbicide was used during Vietnam ... the herbicide Agent Orange and bladder cancer and thyroid problems among U.S. military personnel exposed to the ...

  19. Alternate dosing schedules for cancer chemopreventive agents.

    PubMed

    Lazzeroni, Matteo; DeCensi, Andrea

    2016-02-01

    Pharmacologic interventions for cancer risk reduction involve the chronic administration of synthetic or natural agents to reduce or delay the occurrence of malignancy. Despite the strong evidence for a favorable risk-benefit ratio for a number of agents in several common malignancies such as breast and prostate cancer, the public's attitude toward cancer chemoprevention remains ambivalent, with the issue of toxicity associated with drugs being perceived as the main barrier to widespread use of preventive therapy by high-risk subjects. Among the strategies to overcome such obstacles to preventive therapies, two novel and potentially safer modes of administering agents are discussed in this paper. The first strategy is to lower the dose of drugs that are in common use in the adjuvant setting based on the notion that prevention of cancer cells from developing should require a lower dose than eradicating established tumor cells. A second approach is to adopt an intermittent administration similar to what is used in the chemotherapy setting in an attempt to minimize risks while retaining benefits. This article provides a detailed discussion of the principles and future development of these two approaches in the direction of a precision preventive medicine. PMID:26970130

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Modular strategies for PET imaging agents

    SciTech Connect

    Hooker, , J.M.

    2010-03-01

    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.

  7. [Breast cancer imaging].

    PubMed

    Canale, Sandra; Balleyguier, Corinne; Dromain, Clarisse

    2013-12-01

    Imaging of breast cancer is multimodal. Mammography uses X-rays, the development of digital mammography has improved its quality and enabled implementations of new technologies such astomosynthesis (3D mammography) or contrast-enhanced digital mammography. Ultrasound is added to mammography when there is need to improve detection in high-density breast, to characterize an image, or guide apuncture or biopsy. Breast MRI is the most sensitive imaging modality. It detects a possible tumor angiogenesis by highlighting an early and intense contrast uptake. This method has an excellent negative predictive value, but its lack of specificity (false positives) can be problematic, thus it has to be prescribed according to published standards. An imaging breast screening report must be concluded by the BI-RADS lexicon classification of the ACR and recommendations about monitoring or histological verification. PMID:24579332

  8. 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

  9. 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).

  10. Contrast dispersion imaging for cancer localization.

    PubMed

    Mischi, Massimo; Wijkstra, Hessel

    2014-01-01

    Cancer growth is associated with angiogenic processes in many types of cancer. Several imaging strategies have therefore been developed that target angiogenesis as a marker for cancer localization. To this end, intravascular and extravascular tissue perfusion is typically assessed by dynamic contrast enhanced (DCE) ultrasound (US) and MRI. All the proposed strategies, however, overlook important changes in the microvascular architecture that result from angiogenic processes. To overcome these limitations, we have recently introduced a new imaging strategy that analyzes the intravascular dispersion kinetics of contrast agents spreading through the microvasculature. Contrast dispersion is mainly determined by microvascular multi-path trajectories, reflecting the underlying microvascular architecture. This paper reviews the results obtained for prostate cancer localization by US and MRI dispersion imaging, also presenting the latest new developments and future perspectives. PMID:25570935

  11. Development and Characterization of an Antibody-Labeled Super-Paramagnetic Iron Oxide Contrast Agent Targeting Prostate Cancer Cells for Magnetic Resonance Imaging

    PubMed Central

    Bates, David; Abraham, Suraj; Campbell, Michael; Zehbe, Ingeborg; Curiel, Laura

    2014-01-01

    In this study we developed, characterized and validated in vitro a functional superparagmagnetic iron-oxide based magnetic resonance contrast agent by conjugating a commercially available iron oxide nanoparticle, Molday ION Rhodamine-B Carboxyl (MIRB), with a deimmunized mouse monoclonal antibody (muJ591) targeting prostate-specific membrane antigen (PSMA). This functional contrast agent is intended for the specific and non-invasive detection of prostate cancer cells that are PSMA positive, a marker implicated in prostate tumor progression and metastasis. The two-step carbodiimide reaction used to conjugate the antibody to the nanoparticle was efficient and we obtained an elemental iron content of 1958±611 per antibody. Immunofluorescence microscopy and flow cytometry showed that the conjugated muJ591:MIRB complex specifically binds to PSMA-positive (LNCaP) cells. The muJ591:MIRB complex reduced cell adhesion and cell proliferation on LNCaP cells and caused apoptosis as tested by Annexin V assay, suggesting anti-tumorigenic characteristics. Measurements of the T2 relaxation time of the muJ591:MIRB complex using a 400 MHz Innova NMR and a multi-echo spin-echo sequence on a 3T MRI (Achieva, Philips) showed a significant T2 relaxation time reduction for the muJ591:MIRB complex, with a reduced T2 relaxation time as a function of the iron concentration. PSMA-positive cells treated with muJ591:MIRB showed a significantly shorter T2 relaxation time as obtained using a 3T MRI scanner. The reduction in T2 relaxation time for muJ591:MIRB, combined with its specificity against PSMA+LNCaP cells, suggest its potential as a biologically-specific MR contrast agent. PMID:24819929

  12. Demethylating Agents in the Treatment of Cancer

    PubMed Central

    Howell, Paul M.; Liu, Zixing; Khong, Hung T.

    2010-01-01

    Gene silencing resulting from aberrant DNA methylation can lead to tumorigenesis. Therefore, drugs that inhibit or interfere with DNA methylation have been used to reactivate and induce silenced gene re-expression in malignancies. Two demethylating agents, azacitidine and decitabine, are approved for the treatment of myelodysplastic syndromes (MDS) by the U.S. Food and Drug Administration (FDA), and are now considered the standard of care in MDS. In this review, we discuss clinical data, including clinical benefits and toxicities, which led to the approval of azacitidine and decitabine. We also summarize findings from clinical trials that used these two demethylating agents in the treatment of solid tumors. Lastly, we discuss some limitations in the use of azacitidine and decitabine in cancer therapy.

  13. 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.

  14. A review of cancer chemopreventive agents.

    PubMed

    Levi, M S; Borne, R F; Williamson, J S

    2001-09-01

    In the late 20(th) century, the treatment of cancer began to include its prevention. Today, compounds exist that will lower the risk of developing certain types of cancer. This has been demonstrated in studies where chemically induced tumor growth has been slowed or reversed. Anti-inflammatory compounds having chemopreventive activity are piroxicam, sulindac, aspirin, celecoxib and curcumin. The selective estrogen receptor modulators, tamoxifen and raloxifene, are beneficial in the prevention of estrogen dependent tumors. Retinoids, vitamin A derivatives, such as targretin and fenretinide are useful in the prevention of tumors. Compounds containing sulfur, such as sulforaphane and oltipraz, are even useful as radioprotective agents. The steroid dehydroepiandosterone can inhibit experimental carcinogenesis. All of these chemical classes provide a start for the medicinal chemist to design more effective chemopreventive agents. The biomarkers used to determine the chemopreventive activity of new compounds are quite often activities of enzymes. The identification of those individuals at high risk is still in its infancy and presents a troubling dilemma. PMID:11562271

  15. 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

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

    PubMed

    Sinharay, Sanhita; Pagel, Mark D

    2016-06-12

    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 (13)C to detect the agent with outstanding sensitivity. These hyperpolarized (13)C 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

  17. 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.

  18. Angiogenesis and antiangiogenic agents in cervical cancer

    PubMed Central

    Tomao, Federica; Papa, Anselmo; Rossi, Luigi; Zaccarelli, Eleonora; Caruso, Davide; Zoratto, Federica; Benedetti Panici, Pierluigi; Tomao, Silverio

    2014-01-01

    Standard treatment of cervical cancer (CC) consists of surgery in the early stages and of chemoradiation in locally advanced disease. Metastatic CC has a poor prognosis and is usually treated with palliative platinum-based chemotherapy. Current chemotherapeutic regimens are associated with significant adverse effects and only limited activity, making identification of active and tolerable novel targeted agents a high priority. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer. The dominant role of angiogenesis in CC seems to be directly related to human papillomavirus-related inhibition of p53 and stabilization of hypoxia-inducible factor-1α. Both of these mechanisms are able to increase expression of vascular endothelial growth factor (VEGF). Activation of VEGF promotes endothelial cell proliferation and migration, favoring formation of new blood vessels and increasing permeability of existing blood vessels. Since bevacizumab, a recombinant humanized monoclonal antibody binding to all isoforms of VEGF, has been demonstrated to significantly improve survival in gynecologic cancer, some recent clinical research has explored the possibility of using novel therapies directed toward inhibition of angiogenesis in CC too. Here we review the main results from studies concerning the use of antiangiogenic drugs that are being investigated for the treatment of CC. PMID:25506227

  19. Optical imaging with dynamic contrast agents.

    PubMed

    Wei, Qingshan; Wei, Alexander

    2011-01-24

    Biological imaging applications often employ molecular probes or nanoparticles for enhanced contrast. However, resolution and detection are still often limited by the intrinsic heterogeneity of the sample, which can produce high levels of background that obscure the signals of interest. Herein, we describe approaches to overcome this obstacle based on the concept of dynamic contrast: a strategy for elucidating signals by the suppression or removal of background noise. Dynamic contrast mechanisms can greatly reduce the loading requirement of contrast agents, and may be especially useful for single-probe imaging. Dynamic contrast modalities are also platform-independent, and can enhance the performance of sophisticated biomedical imaging systems or simple optical microscopes alike. Dynamic contrast is performed in two stages: 1) a signal modulation scheme to introduce time-dependent changes in amplitude or phase, and 2) a demodulation step for signal recovery. Optical signals can be coupled with magnetic nanoparticles, photoswitchable probes, or plasmon-resonant nanostructures for modulation by magnetomotive, photonic, or photothermal mechanisms, respectively. With respect to image demodulation, many of the strategies developed for signal processing in electronics and communication technologies can also be applied toward the editing of digital images. The image-processing step can be as simple as differential imaging, or may involve multiple reference points for deconvolution by using cross-correlation algorithms. Periodic signals are particularly amenable to image demodulation strategies based on Fourier transform; the contrast of the demodulated signal increases with acquisition time, and modulation frequencies in the kHz range are possible. Dynamic contrast is an emerging topic with considerable room for development, both with respect to molecular or nanoscale probes for signal modulation, and also to methods for more efficient image processing and editing. PMID

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

    PubMed Central

    Winter, Patrick M.

    2014-01-01

    Perfluorocarbon nanoparticles offer a biologically inert, highly stable, and nontoxic platform that can be specifically designed to accomplish a range of molecular imaging and drug delivery functions in vivo. The particle surface can be decorated with targeting ligands to direct the agent to a variety of biomarkers that are associated with diseases such as cancer, cardiovascular disease, obesity, and thrombosis. The surface can also carry a high payload of imaging agents, ranging from paramagnetic metals for MRI, radionuclides for nuclear imaging, iodine for CT, and florescent tags for histology, allowing high sensitivity mapping of cellular receptors that may be expressed at very low levels in the body. In addition to these diagnostic imaging applications, the particles can be engineered to carry highly potent drugs and specifically deposit them into cell populations that display biosignatures of a variety of diseases. The highly flexible and robust nature of this combined molecular imaging and drug delivery vehicle has been exploited in a variety of animal models to demonstrate its potential impact on the care and treatment of patients suffering from some of the most debilitating diseases. PMID:25024867

  1. 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.

  2. 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

  3. Application of GFP imaging in cancer

    PubMed Central

    Hoffman, Robert M.

    2014-01-01

    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 follow the dynamics of metastatic cancer to be followed in real time in individual animals. Non-invasive imaging of cancer cells expressing fluorescent proteins has enabled 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 allow visualization of the nuclear–cytoplasmic dynamics of cancer cells in vivo, mitosis, apoptosis, cell-cycle position and differential behavior of nucleus and cytoplasm such as occurs during cancer-cell deformation and extravasation. Recent applications of the technology described here include linking fluorescent proteins with cell-cycle-specific proteins (FUCCI) 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, enabling the new field of in vivo cell biology using fluorescent proteins. PMID:25686095

  4. 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

  5. Colon cancer - Series (image)

    MedlinePlus

    Colon cancer is the third most common cancer in the United States. Risk factors include a diet low ... The treatment of colon cancer depends on the stage of the disease. Stage I cancer is limited to the inner lining of the colon; ...

  6. 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. PMID:26984362

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Fluorescent nanoparticle probes for imaging of cancer.

    PubMed

    Santra, Swadeshmukul; Malhotra, Astha

    2011-01-01

    Fluorescent nanoparticles (FNPs) have received immense popularity in cancer imaging in recent years because of their attractive optical properties. In comparison to traditional organic-based fluorescent dyes and fluorescent proteins, FNPs offer much improved sensitivity and photostability. FNPs in certain size range have a strong tendency to enter and retain in solid tumor tissue with abnormal (leaky) vasculature--a phenomenon known as Enhanced Permeation and Retention (EPR) effect, advancing their use for in vivo tumor imaging. Furthermore, large surface area of FNPs and their usual core-shell structure offer a platform for designing and fabricating multimodal/multifunctional nanoparticles (MMNPs). For effective cancer imaging, often the optical imaging modality is integrated with other nonoptical-based imaging modalities such as MRI, X-ray, and PET, thus creating multimodal nanoparticle (NP)-based imaging probes. Such multimodal NP probes can be further integrated with therapeutic drug as well as cancer targeting agent leading to multifunctional NPs. Biocompatibility of FNPs is an important criterion that must be seriously considered during FNP design. NP composition, size, and surface chemistry must be carefully selected to minimize potential toxicological consequences both in vitro and in vivo. In this article, we will mainly focus on three different types of FNPs: dye-loaded NPs, quantum dots (Qdots), and phosphores; briefly highlighting their potential use in translational research. PMID:21480546

  13. 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

  14. Chemopreventive Agent Development | Division of Cancer Prevention

    Cancer.gov

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

  15. 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.

  16. NO-NSAIDs and cancer: promising novel agents.

    PubMed

    Rigas, B; Kalofonos, H; Lebovics, E; Vagenakis, A G

    2003-05-01

    Three potential applications of NO-donating NSAIDs in human cancer include their use: as chemopreventive agents; against already developed cancers (chemotherapy); and for the control of cancer symptoms, notably cancer pain. The evidence to date of greater safety and enhanced efficacy of NO-donating NSAIDs underscores their potential to prevent colon cancer and overcome the limitations of traditional NSAIDs. NO-donating NSAIDs affect several pathways critical to colon carcinogenesis and this may explain in part their greater efficacy in colon cancer prevention as assessed in preclinical models. PMID:12846441

  17. Optical imaging-guided cancer therapy with fluorescent nanoparticles

    PubMed Central

    Jiang, Shan; Gnanasammandhan, Muthu Kumara; Zhang, Yong

    2010-01-01

    The diagnosis and treatment of cancer have been greatly improved with the recent developments in nanotechnology. One of the promising nanoscale tools for cancer diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs, quantum dots and upconversion NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. Furthermore, the emerging development of novel multi-functional NPs, which can be conjugated with several functional molecules simultaneously including targeting moieties, therapeutic agents and imaging probes, provides new potentials for clinical therapies and diagnostics and undoubtedly will play a critical role in cancer therapy. In this article, we review the types and characteristics of fluorescent NPs, in vitro and in vivo imaging of cancer using fluorescent NPs and multi-functional NPs for imaging-guided cancer therapy. PMID:19759055

  18. 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

  19. 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

  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. 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

  2. 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

  3. Imaging ‘the lost tribe’: a review of adolescent cancer imaging. Part 2: imaging of complications of cancer treatment

    PubMed Central

    Zerizer, I.

    2009-01-01

    Abstract Adolescent cancers are treated with a host of chemotherapy agents, radiotherapy and stem cell transplantation. The complications of these treatments may contribute significantly to the morbidity and mortality in this age group, with imaging playing a role in identifying some of these complications. This second article reviews the imaging of acute and early complications relating to adolescent cancer treatment, many of which may also be seen in the treatment of paediatric patients. Late effects involving endocrine and reproductive systems or psychosocial considerations are not discussed in this paper, although these are clearly important issues in long-term survivors. PMID:19933021

  4. 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

  5. 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

  6. Imaging of liver cancer

    PubMed Central

    Ariff, Ben; Lloyd, Claire R; Khan, Sameer; Shariff, Mohamed; Thillainayagam, Andrew V; Bansi, Devinder S; Khan, Shahid A; Taylor-Robinson, Simon D; Lim, Adrian KP

    2009-01-01

    Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identification and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality. PMID:19294758

  7. CT and MR Imaging Diagnosis and Staging of Hepatocellular Carcinoma: Part II. Extracellular Agents, Hepatobiliary Agents, and Ancillary Imaging Features

    PubMed Central

    Choi, Jin-Young; Lee, Jeong-Min

    2014-01-01

    Computed tomography (CT) and magnetic resonance (MR) imaging play critical roles in the diagnosis and staging of hepatocellular carcinoma (HCC). The second article of this two-part review discusses basic concepts of diagnosis and staging, reviews the diagnostic performance of CT and MR imaging with extracellular contrast agents and of MR imaging with hepatobiliary contrast agents, and examines in depth the major and ancillary imaging features used in the diagnosis and characterization of HCC. © RSNA, 2014 PMID:25247563

  8. 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

  9. Gold nanoparticles as novel agents for cancer therapy.

    PubMed

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

    2012-02-01

    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

  10. 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

  11. 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 ...

  12. 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

  13. 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. PMID:22289255

  14. Phytoconstituents as apoptosis inducing agents: strategy to combat cancer.

    PubMed

    Kumar, Manish; Kaur, Varinder; Kumar, Subodh; Kaur, Satwinderjeet

    2016-08-01

    Advancement in the field of cancer molecular biology has aided researchers to develop various new chemopreventive agents which can target cancer cells exclusively. Cancer chemopreventive agents have proficiency to inhibit, reverse and delay process of carcinogenesis during its early and later course. Chemopreventive agents can act as antioxidative, antimutagenic/antigenotoxic, anti-inflammatory agents or via aiming various molecular targets in a cell to induce cell death. Apoptosis is a kind of cell death which shows various cellular morphological alterations such as cell shrinkage, blebbing of membrane, chromatin condensation, DNA fragmentation, formation of apoptotic bodies etc. Nowadays, apoptosis is being one of the new approaches for the identification and development of novel anticancer therapies. For centuries, plants are known to play part in daily routine from providing food to management of human health. In the last two decades, diverse phytochemicals and various botanical formulations have been characterized as agents that possess potential to execute cancer cells via inducing apoptosis. Data obtained from the research carried out globally pointed out that natural products are the potential candidates which have capability to combat cancer. In the present review, we surveyed literature on natural products which throws light on the mechanism through which these phytochemicals induce apoptosis in cancer cells. PMID:26239338

  15. 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.

  16. 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

  17. Delivery of gene silencing agents for breast cancer therapy

    PubMed Central

    2013-01-01

    The discovery of RNA interference has opened the door for the development of a new class of cancer therapeutics. Small inhibitory RNA oligos are being designed to specifically suppress expression of proteins that are traditionally considered nondruggable, and microRNAs are being evaluated to exert broad control of gene expression for inhibition of tumor growth. Since most naked molecules are not optimized for in vivo applications, the gene silencing agents need to be packaged into delivery vehicles in order to reach the target tissues as their destinations. Thus, the selection of the right delivery vehicles serves as a crucial step in the development of cancer therapeutics. The current review summarizes the status of gene silencing agents in breast cancer and recent development of candidate cancer drugs in clinical trials. Nanotechnology-based delivery vectors for the formulation and packaging of gene silencing agents are also described. PMID:23659575

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  19. Molecular Imaging of Prostate Cancer

    PubMed Central

    Fox, Josef J.; Schöder, Heiko; Larson, Steven M.

    2015-01-01

    Purpose of review Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Recent findings Several PET tracers are active in early and late stage prostate cancer in humans. F18-FDG, C11/F18-choline and F18-sodium fluoride (NaF) have been studied most extensively. There is a growing body of literature supporting to the utility of choline in early stage prostate cancer. FDG and NaF are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-Fluoro-dihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel AR-targeted therapies. Anti-PSMA PET tracers are in the early stages of clinical development. Summary Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer. PMID:22617062

  20. Medical applications of nanoparticles in biological imaging, cell labeling, antimicrobial agents, and anticancer nanodrugs.

    PubMed

    Singh, Ravina; Nalwa, Hari Singh

    2011-08-01

    This article reviews the applications of nanotechnology in the fields of medical and life sciences. Nanoparticles have shown promising applications from diagnosis to treatment of various types of diseases including cancer. In this review, we discuss the applications of nanostructured materials such as nanoparticles, quantum dots, nanorods, nanowires, and carbon nanotubes in diagnostics, biomarkers, cell labeling, contrast agents for biological imaging, antimicrobial agents, drug delivery systems, and anticancer nanodrugs for treatment of cancer and other infectious diseases. The adverse affects of nanoparticles on human skin from daily use in cosmetics and general toxicology of nanoscale materials are also reviewed. PMID:21870454

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

    PubMed

    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

    2014-10-15

    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 a 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 noninvasive clinical imaging. Furthermore, the approach compares favorably with accepted and emerging clinical standards, including PET with [(18)F]fluorodeoxyglucose and [(18)F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. PMID:25145668

  2. 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.

  3. 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

  4. 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

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

    PubMed Central

    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

    2013-01-01

    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. PMID:24220641

  6. 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). PMID:23432005

  7. 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.

  8. 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.

  9. Childhood cancers: what is a possible role of infectious agents?

    PubMed Central

    2013-01-01

    The etiology of childhood cancers has been studied for more than 40 years. However, most if not all cancers occurring in children are attributed to unknown causes. This review is focused on the role of infections in cancer development and progression in children. The main infectious agents include human herpesviruses, polyoma viruses, and human papilloma viruses. It is known that infections can lead to carcinogenesis through various mechanisms, and most likely act in addition to genetic and environmental factors. Given the importance of the infectious etiology of childhood cancers, clinical implications and possible prevention strategies are discussed. PMID:24321500

  10. Prostate Cancer MR Imaging

    NASA Astrophysics Data System (ADS)

    Fütterer, Jurgen J.

    With a total of 192,280 new cases predicted for 2009, prostate cancer (PC) now accounts for 25% of all new male cancers diagnosed in the United States [1]. Furthermore, in their lifetime, one in six men will be clinically diagnosed with having PC, although many more men are found to have histological evidence of PC at autopsy [2,3,4]. Presently, approximately 1 in 10 men will die of PC [5,6]. The ever-aging population and wider spread use of the blood prostate-specific antigen (PSA) test [7,8], as well as the tendency to apply lower cut-off levels for this test [9], will further increase the diagnosis of this disease [10].

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Grafting of [(64)Cu]-TPPF20 porphyrin complex on Functionalized nano-porous MCM-41 silica as a potential cancer imaging agent.

    PubMed

    Fazaeli, Yousef; Feizi, Shahzad; Jalilian, Amir R; Hejrani, Ali

    2016-06-01

    Mesoporous silica, MCM-41, functionalized with 3-aminopropyltriethoxysilane (APTES) was investigated as a potential drug delivery system, using [(64)Cu]-5, 10, 15, 20-tetrakis penta fluorophenyl porphyrin complex. [(64)Cu]-TPPF20 complex was grafted on functionalized MCM-41. The product was characterized by paper chromatography, FTIR spectroscopy, low angle X-ray diffraction, CHN and TGA/DTA analyses and atomic force microscopy. The biological evaluations of the grafted complex, [(64)Cu]-TPPF20@NH2-MCM-41, were done in Fibrosarcoma tumor-bearing Sprague-Dawley rats using scarification studies and Sopha DST-XL Dual-Head SPECT system. The actual loading amount of aminopropyl groups was found about 1.6mmol per gram of final silica. The specific activity of the final compound was found to be 3Ci/g. Amine functionalized MCM-41 was found to be a good platform for theranostic radiopharmaceuticals such as copper-64 complexes. Considering the accumulation of the tracer in tumor cells, fast wash-out from normal tissues, the short half-life copper-64 and less imposed radiation doses to patients, [(64)Cu]-TPPF20@NH2-MCM-41 can potentially be a suitable candidate for tumor imaging applications and future PET studies. PMID:26974487

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Selenium as a cancer preventive agent

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most epidemiological studies have shown inverse associations of selenium (Se) status and cancer risk. Almost all experimental animal studies have shown that supranutritional exposures of Se can reduce tumor yield. Each of the limited number of clinical intervention trials conducted to date has found...

  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. Botanical agents for the treatment of nonmelanoma skin cancer.

    PubMed

    Millsop, Jillian W; Sivamani, Raja K; Fazel, Nasim

    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

  5. 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

  6. 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

  7. 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

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

    PubMed

    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. PMID:25985096

  9. 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.

  10. 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.

  11. 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

  12. Novel therapeutic agents in the treatment of metastatic colorectal cancer

    PubMed Central

    Pai, Sachin Gopalkrishna; Fuloria, Jyotsna

    2016-01-01

    Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers (mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well. PMID:26798440

  13. 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

  14. 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

  15. 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.

  16. Selective imaging of adherent targeted ultrasound contrast agents

    PubMed Central

    Zhao, S; Kruse, D E; Ferrara, K W; Dayton, P A

    2007-01-01

    The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles from tissue and from freely circulating microbubbles, each of which would otherwise obscure signal from molecularly targeted adherent agents. The methods are based on a harmonic signal model of the returned echoes over a train of pulses. The first method utilizes an ‘image–push–image’ pulse sequence where adhesion of contrast agents is rapidly promoted by acoustic radiation force and the presence of adherent agents is detected by the signal change due to targeted microbubble adhesion. The second method rejects tissue echoes using a spectral high-pass filter. Free agent signal is suppressed by a pulse-to-pulse low-pass filter in both methods. An overlay of the adherent and/or flowing contrast agents on B-mode images can be readily created for anatomical reference. Contrast-to-tissue ratios from adherent microbubbles exceeding 30 dB and 20 dB were achieved for the two methods proposed, respectively. The performance of these algorithms is compared, emphasizing the significance and potential applications in ultrasonic molecular imaging. PMID:17404455

  17. 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

  18. Beer constituents as potential cancer chemopreventive agents.

    PubMed

    Gerhäuser, Clarissa

    2005-09-01

    Beer is a complex alcoholic beverage made from barley (malt), hop, water and yeast. Phenolic constituents of beer are derived from malt (70-80%) and hop (20-30%). Structural classes include simple phenols, benzoic- and cinnamic acid derivatives, coumarins, catechins, di-, tri- and oligomeric proanthocyanidins, (prenylated) chalcones and flavonoids as well as alpha- and iso-alpha-acids derived from hop. Compounds belonging to different structural classes have distinct profiles of biological activity in in vitro test systems, and in combination might lead to enhanced effects. Scientific evidence has accumulated over the past 10 years pointing to the cancer preventive potential of selected hop-derived beer constituents, i.e., prenylflavonoids including xanthohumol and isoxanthohumol, and hop bitter acids. Chemopreventive activities observed with these compounds relevant to inhibition of carcinogenesis at the initiation, promotion and progression phases, as well as results from in vivo studies on metabolism, bioavailability and efficacy are summarised in this review. PMID:15953717

  19. 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

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

    PubMed

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

    2013-09-01

    Paradigm shifts in surgery arise when surgeons are empowered to perform surgery faster, better and less expensively than current standards. Optical imaging that exploits invisible near-infrared (NIR) fluorescent light (700-900 nm) has the potential to improve cancer surgery outcomes, minimize the time patients are under anaesthesia and lower health-care costs largely by way of its improved contrast and depth of tissue penetration relative to visible light. Accordingly, the past few years have witnessed an explosion of proof-of-concept clinical trials in the field. In this Review, we introduce the concept of NIR fluorescence imaging for cancer surgery, examine the clinical trial literature to date and outline the key issues pertaining to imaging system and contrast agent optimization. Although NIR seems to be superior to many traditional imaging techniques, its incorporation into routine care of patients with cancer depends on rigorous clinical trials and validation studies. PMID:23881033

  1. Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance

    PubMed Central

    Mallidi, Srivalleesha; Luke, Geoffrey P.; Emelianov, Stanislav

    2011-01-01

    Imaging modalities play an important role in the clinical management of cancer, including screening, diagnosis, treatment planning, and therapy monitoring. Owing to increased research efforts in the past two decades, photoacoustic imaging – a non-ionizing, non-invasive technique capable of visualizing optical absorption properties of tissue at reasonable depth, with spatial resolution of ultrasound – has emerged. Ultrasound-guided photoacoustics is regarded for its ability to provide in vivo morphological and functional information about the tumor within the surrounding tissue. With the recent advent of targeted contrast agents, photoacoustics is capable of in vivo molecular imaging, thus facilitating further molecular and cellular characterization of cancer. This review examines the role of photoacoustics and photoacoustic-augmented imaging techniques in comprehensive cancer detection, diagnosis and treatment guidance. PMID:21324541

  2. 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

  3. 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.

  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. 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

  6. Bone imaging in prostate cancer.

    PubMed

    Dotan, Zohar A

    2008-08-01

    Bone metastases of solid tumors are common, and about 80% of them occur in patients with breast, lung or prostate cancer. Bone metastases can be suspected clinically and by laboratory tests; however, a final diagnosis relies on radiographic evidence. Bone metastases of prostate cancer usually have osteoblastic characteristics, manifested by pathological bone resorption and formation. Conventional bone scans (e.g. with (99m)Tc-labeled methylene diphosphonate) are preferred to plain-film radiography for surveillance of the entire skeleton. Radiologic diagnosis of bone metastases, particularly in patients with low burden of disease, is difficult because noncancerous bone lesions that mimic cancer are common. Conventional bone scans are limited by their low sensitivity and high false-negative rate (up to 40%) compared with advanced bone-imaging modalities such as PET, PET-CT and MRI, which might assist or replace conventional scanning methods. The correct diagnosis of bone involvement in prostate cancer is crucial to assess the effects of therapy on the primary tumor, the patient's prognosis, and the efficacy of bone-specific treatments that can reduce future bone-associated morbidity. In addition, predictive tools such as nomograms enable the identification of patients at risk of bone involvement during the course of their disease. Such tools may limit treatment costs by avoidance of unnecessary tests and might reduce both short-term and long-term complication rates. PMID:18682719

  7. Imaging targeted-agent binding in vivo with two probes

    NASA Astrophysics Data System (ADS)

    Pogue, Brian W.; Samkoe, Kimberley S.; Hextrum, Shannon; O'Hara, Julia A.; Jermyn, Michael; Srinivasan, Subhadra; Hasan, Tayyaba

    2010-05-01

    An approach to quantitatively image targeted-agent binding rate in vivo is demonstrated with dual-probe injection of both targeted and nontargeted fluorescent dyes. Images of a binding rate constant are created that reveal lower than expected uptake of epidermal growth factor in an orthotopic xenograft pancreas tumor (2.3×10-5 s-1), as compared to the normal pancreas (3.4×10-5 s-1). This approach allows noninvasive assessment of tumor receptor targeting in vivo to determine the expected contrast, spatial localization, and efficacy in therapeutic agent delivery.

  8. 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.

  9. 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

  10. 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.

  11. Viscous optical clearing agent for in vivo optical imaging

    NASA Astrophysics Data System (ADS)

    Deng, Zijian; Jing, Lijia; Wu, Ning; lv, Pengyu; Jiang, Xiaoyun; Ren, Qiushi; Li, Changhui

    2014-07-01

    By allowing more photons to reach deeper tissue, the optical clearing agent (OCA) has gained increasing attention in various optical imaging modalities. However, commonly used OCAs have high fluidity, limiting their applications in in vivo studies with oblique, uneven, or moving surfaces. In this work, we reported an OCA with high viscosity. We measured the properties of this viscous OCA, and tested its successful performances in the imaging of a living animal's skin with two optical imaging modalities: photoacoustic microscopy and optical coherence tomography. Our results demonstrated that the viscous OCA has a great potential in the study of different turbid tissues using various optical imaging modalities.

  12. 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

  13. Coevolving feature extraction agents for target recognition in SAR images

    NASA Astrophysics Data System (ADS)

    Bhanu, Bir; Krawiec, Krzysztof

    2003-09-01

    This paper describes a novel evolutionary method for automatic induction of target recognition procedures from examples. The learning process starts with training data containing SAR images with labeled targets and consists in coevolving the population of feature extraction agents that cooperate to build an appropriate representation of the input image. Features extracted by a team of cooperating agents are used to induce a machine learning classifier that is responsible for making the final decision of recognizing a target in a SAR image. Each agent (individual) contains feature extraction procedure encoded according to the principles of linear genetic programming (LGP). Like 'plain' genetic programming, in LGP an agent's genome encodes a program that is executed and tested on the set of training images during the fitness calculation. The program is a sequence of calls to the library of parameterized operations, including, but not limited to, global and local image processing operations, elementary feature extraction, and logic and arithmetic operations. Particular calls operate on working variables that enable the program to store intermediate results, and therefore design complex features. This paper contains detailed description of the learning and recognition methodology outlined here. In experimental part, we report and analyze the results obtained when testing the proposed approach for SAR target recognition using MSTAR database.

  14. 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).

  15. 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

  16. Recombinant mumps virus as a cancer therapeutic agent.

    PubMed

    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 21(st) 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

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

    PubMed

    Thoppil, Roslin J; Bishayee, Anupam

    2011-09-27

    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

  18. 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

  19. Ovulation inducing agents and cancer risk: review of literature.

    PubMed

    Impicciatore, Gianna Gabriella; Tiboni, Gian Mario

    2011-09-01

    Over the past decades, the use of ovulation inducing drugs has been increasing. A possible causal link between fertility treatments (especially clomiphene citrate and gonadotrophins) and various types of malignancies, including cancers of female reproductive system, thyroid cancer and melanoma, has been postulated. The majority of the available studies on this subject suffers from methodological limitations, including the small number of outcomes, short and incomplete follow-up, and inability to control for potential confounders. Concerning ovarian cancer, while early studies led to the suggestion of an association between ovulation inducing agents and increased risk of malignancies, the majority of data do not support a causal link. An increased risk was recently observed in women giving birth after in vitro fertilization (IVF), but it appeared to be consequential to the infertile status rather than the effect of fertility drugs. More controversial are the results concerning breast cancer with some investigations suggesting an increased risk after exposure to ovulation inducing agents, especially clomiphene citrate, whereas others not supporting this concept. A possible trend towards an increased risk has been reported by some authors for endometrial cancer. Altogether, current data should be thus regarded as a signal for the need of further studies rather than being definitive in them. PMID:22129320

  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. Activatable Molecular Probes for Cancer Imaging

    PubMed Central

    Lee, Seulki; Xie, Jin; Chen, Xiaoyuan

    2013-01-01

    The development of highly sensitive and specific molecular probes for cancer imaging still remains a daunting challenge. Recently, interdisciplinary research at the interface of imaging sciences and bionanoconjugation chemistry has generated novel activatable imaging probes that can provide high-resolution imaging with ultra-low background signals. Activatable imaging probes are designed to amplify output imaging signals in response to specific biomolecular recognition or environmental changes in real time. This review introduces and highlights the unique design strategies and applications of various activatable imaging probes in cancer imaging. PMID:20388112

  2. 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

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

    PubMed Central

    Blagosklonny, Mikhail V

    2013-01-01

    Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are involved in both cancer and aging). In cancer, intrinsic and acquired resistance, tumor heterogeneity, adaptation, and genetic instability of cancer cells all hinder cancer-directed therapy. But for anti-aging applications, these hurdles are irrelevant. For example, since anti-aging interventions should be aimed at normal postmitotic cells, no selection for resistance is expected. At low doses, certain agents may decelerate aging and age-related diseases. Importantly, deceleration of aging can in turn postpone cancer, which is an age-related disease. PMID:24345884

  4. Imaging considerations for a technetium-99m myocardial perfusion agent

    SciTech Connect

    English, R.J.; Jones, A.G.; Davison, A.; Lister-James, J.; Campbell, S.; Holman, B.L.

    1986-03-01

    Myocardial perfusion imaging with /sup 201/Tl chloride suffers from a number of physical, geometric, and dosimetric constraints that could be diminished if an agent labeled with /sup 99m/Tc were available. The cationic complex /sup 99m/Tc hexakis-(t-butylisonitrile)technetium(I) ((/sup 99m/Tc)TBI) has been shown to concentrate in the myocardial tissue of both animals and humans, with preliminary clinical studies demonstrating a number of technical attributes not possible with /sup 201/Tl. Technetium-99m-TBI is a promising myocardial imaging agent that may permit high quality planar, gated, and tomographic imaging of both myocardial ischemia and infarction with reduced imaging times and improved resolution.

  5. 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

  6. 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

  7. Multispectral image analysis of forest (grassland) fire based on agent

    NASA Astrophysics Data System (ADS)

    Guan, Jiaying; Li, Deren; Guan, Zequn

    2001-09-01

    Now the developing research of Agent can help operators to do the routine assignments, by which we can economize the precious resources and improve the real-time image analysis of the computers. This paper firstly makes a brief introduction of the Agent conception. Then we make some discussions about the multispectral images of a certain area, which is based on the concept of Agent. The main objects of this paper are inspections of forest (grassland) fire. The purpose of this paper is to propose three stages with which Agent could monitor the wildly areas and make decision automatically, without operators' intervention. First stage, if the value of pixels are more than a given threshold, Agent will give the operators an alarm and notify the operators that there are something happened; Second stage, analyze data and self-learning; Third stage, according to the database and knowledge database, Agents make decisions. As the decisions will be influenced by many factors, so some models, such as heat sources model, weather model, fire model, vegetation model are needed.

  8. 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

  9. Dual-frequency transducer for nonlinear contrast agent imaging.

    PubMed

    Guiroy, Axel; Novell, Anthony; Ringgaard, Erling; Lou-Moeller, Rasmus; Grégoire, Jean-Marc; Abellard, André-Pierre; Zawada, Tomasz; Bouakaz, Ayache; Levassort, Franck

    2013-12-01

    Detection of high-order nonlinear components issued from microbubbles has emerged as a sensitive method for contrast agent imaging. Nevertheless, the detection of these high-frequency components, including the third, fourth, and fifth harmonics, remains challenging because of the lack of transducer sensitivity and bandwidth. In this context, we propose a new design of imaging transducer based on a simple fabrication process for high-frequency nonlinear imaging. The transducer is composed of two elements: the outer low-frequency (LF) element was centered at 4 MHz and used in transmit mode, whereas the inner high-frequency (HF) element centered at 14 MHz was used in receive mode. The center element was pad-printed using a lead zirconate titanate (PZT) paste. The outer element was molded using a commercial PZT, and curved porous unpoled PZT was used as backing. Each piezoelectric element was characterized to determine the electromechanical performance with thickness coupling factor around 45%. After the assembly of the two transducer elements, hydrophone measurements (electroacoustic responses and radiation patterns) were carried out and demonstrated a large bandwidth (70% at -3 dB) of the HF transducer. Finally, the transducer was evaluated for contrast agent imaging using contrast agent microbubbles. The results showed that harmonic components (up to the sixth harmonic) of the microbubbles were successfully detected. Moreover, images from a flow phantom were acquired and demonstrated the potential of the transducer for high-frequency nonlinear contrast imaging. PMID:24297028

  10. 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.

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

    PubMed

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

    2013-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds. PMID:23983210

  12. 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

  13. 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

  14. 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

  15. Optimized Near-IR fluorescent agents for in vivo imaging of Btk expression

    PubMed Central

    Kim, Eunha; Yang, Katherine S.; Kohler, Rainer H.; Dubach, John M.; Mikula, Hannes; Weissleder, Ralph

    2016-01-01

    Bruton’s tyrosine kinase (Btk) is intricately involved in anti-apototic signaling pathways in cancer and in regulating innate immune response. A number of Btk inhibitors are in development for use in treating B-cell malignancies and certain immunologic diseases. To develop robust companion imaging diagnostics for in vivo use, we set up to explore the effects of red wavelength fluorochrome modifications of two highly potent irreversible Btk inhibitors, Ibrutinib and AVL-292. Surprisingly, we found that subtle chemical differences in the fluorochrome had considerable effects on target localization. Based on iterative designs, we developed a single optimized version with superb in vivo imaging characteristics enabling single cell Btk imaging in vivo. This agent (Ibrutinib-SiR-COOH) is expected to be valuable chemical tool in deciphering Btk biology in cancer and host cells in vivo. PMID:26017814

  16. 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

  17. Palladium nanosheets as highly stable and effective contrast agents for in vivo photoacoustic molecular imaging

    NASA Astrophysics Data System (ADS)

    Nie, Liming; Chen, Mei; Sun, Xiaolian; Rong, Pengfei; Zheng, Nanfeng; Chen, Xiaoyuan

    2014-01-01

    A stable and efficient contrast agent is highly desirable for photoacoustic (PA) imaging applications. Recently gold nanostructures have been widely reported and studied for PA imaging and photothermal therapy. However, the structures of the nonspherical gold nanoparticles are easily destroyed after laser irradiation and thus may fail to complete the intended tasks. In this study, we propose to apply palladium nanosheets (PNSs), with strong optical absorption in the near-infrared (NIR) region, as a new class of exogenous PA contrast agents. PA and ultrasound (US) images were acquired sequentially by a portable and fast photoacoustic tomography (PAT) system with a hand-held transducer. Significant and long-lasting imaging enhancement in SCC7 head and neck squamous cell carcinoma was successfully observed in mice by PAT over time after tail vein administration of PNSs. The morphology and functional perfusion of the tumors were delineated in PA images due to the nanoparticle accumulation. PAT of the main organs was also conducted ex vivo to trace the fate of PNSs, which was further validated by inductively coupled plasma atomic emission spectrometry (ICP-AES). No obvious toxic effect was observed by in vitro MTT assay and ex vivo histological examination 7 days after PNS administration. With the combination of a portable imaging instrument and signal specificity, PNSs might be applied as stable and effective agents for photoacoustic cancer detection, diagnosis and treatment guidance.

  18. Magnetic resonance imaging of prostate cancer.

    PubMed

    Guneyli, Serkan; Erdem, Cemile Zuhal; Erdem, Lutfi Oktay

    2016-01-01

    Prostate cancer is one of the causes of cancer-related deaths. Multiparametric magnetic resonance imaging (MRI) provides the best soft tissue resolution and plays an important role in the management of prostate cancer patients. It is the recommended imaging modality for patients with prostate cancer, and it is clinically indicated for diagnosis, staging, tumor localization, detection of tumor aggressiveness, follow-up, and MRI-guided interventions. Multiparametric MRI includes T1- and high-resolution T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced MRI. We evaluated MR images of patients with prostate cancer who underwent multiparametric endorectal MRI on a 3.0-T scanner and presented demonstrative images. PMID:27317204

  19. 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

  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. 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.

  2. 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

  3. 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). PMID:26118960

  4. 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

  5. MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent

    PubMed Central

    Zhou, Zhuxian; Qutaish, Mohammed; Han, Zheng; Schur, Rebecca M.; Liu, Yiqiao; Wilson, David L.; Lu, Zheng-Rong

    2015-01-01

    Metastasis is the primary cause of death in breast cancer patients. Early detection of high-risk breast cancer, including micrometastasis, is critical in tailoring appropriate and effective interventional therapies. Increased fibronectin expression, a hallmark of epithelial-to-mesenchymal transition, is associated with high-risk breast cancer and metastasis. We have previously developed a penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala)-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agent, CREKA-Tris(Gd-DOTA)3 (Gd-DOTA (4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecyl gadolinium), which binds to fibrin–fibronectin complexes that are abundant in the tumour microenvironment of fast-growing breast cancer. Here we assess the capability of CREKA-Tris(Gd-DOTA)3 to detect micrometastasis with MRI in co-registration with high-resolution fluorescence cryo-imaging in female mice bearing metastatic 4T1 breast tumours. We find that CREKA-Tris(Gd-DOTA)3 provides robust contrast enhancement in the metastatic tumours and enables the detection of micrometastases of size <0.5 mm, extending the detection limit of the current clinical imaging modalities. These results demonstrate that molecular MRI with CREKA-Tris(Gd-DOTA)3 may facilitate early detection of high-risk breast cancer and micrometastasis in the clinic. PMID:26264658

  6. Thermoacoustic imaging and spectroscopy for enhanced cancer diagnostics

    NASA Astrophysics Data System (ADS)

    Bauer, Daniel Ryan

    Early detection of cancer is paramount for improved patient survival. This dissertation presents work developing imaging techniques to improve cancer diagnostics and detection utilizing light and microwave induced thermoacoustic imaging. In the second chapter, the well-established pre-clinical mouse window chamber model is interfaced with simultaneously acquired high-resolution pulse echo (PE) ultrasound and photoacoustic (PA) imaging. Co-registered PE and PA imaging, coupled with developed image segmentation algorithms, are used to quantitatively track and monitor the size, shape, heterogeneity, and neovasculature of the tumor microenvironment during a month long study. Average volumetric growth was 5.35 mm3/day, which correlated well with two dimensional results from fluorescent imaging (R = 0.97, p < 0.01). Spectroscopic PA imaging is also employed to probe the assumed oxygenation status of the tumor vasculature. The window chamber model combined with high-resolution PE and PA imaging could form a powerful testbed for characterizing cancers and evaluating new contrast and therapeutic agents. The third chapter utilizes a clinical ultrasound array to facilitate fast volumetric spectroscopic PA imaging to detect and discriminate endogenous absorbers (i.e. oxy/deoxygenated hemoglobin) as well as exogenous PA contrast agents (i.e. gold nanorods, fluorophores). In vivo spatiotemporal tracking of administered gold nanorods is presented, with the contrast agent augmenting the PA signal 18 dB. Furthermore, through the use of spectral unmixing algorithms, the relative concentrations of multiple endogenous and exogenous co-localized absorbers were reconstructed in tumor bearing mice. The concentration of Alexaflour647 was calculated to increase nearly 20 dB in the center of a prostate tumor after a tail-vein injection of the contrast agent. Additionally, after direct subcutaneous injections of two different gold nanorods into a breast tumor, the concentration of each

  7. 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. PMID:25626064

  8. 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.

  9. 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. PMID:26218920

  10. 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

  11. Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.

    PubMed

    Pan, Ying; Volkmer, Jens-Peter; Mach, Kathleen E; Rouse, Robert V; Liu, Jen-Jane; Sahoo, Debashis; Chang, Timothy C; Metzner, Thomas J; Kang, Lei; van de Rijn, Matt; Skinner, Eila C; Gambhir, Sanjiv S; Weissman, Irving L; Liao, Joseph C

    2014-10-29

    A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer. PMID:25355698

  12. 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

  13. Triple Negative Breast Cancer: Role of Specific Chemotherapy Agents

    PubMed Central

    Isakoff, Steven J.

    2010-01-01

    Cytotoxic chemotherapy remains the mainstay of treatment for triple negative breast cancer (TNBC) despite the promise of new targeted and biologic agents. Many studies have shown significant benefit of chemotherapy in the neoadjuvant, adjuvant and metastatic treatment of TNBC. Neoadjuvant chemotherapy studies have consistently reported higher response rates in TNBC than non-TNBC, and pathologic complete response has been shown to predict improved long term outcomes for TNBC. Although the specific adjuvant regimens that may be most effective for TNBC are still being determined, third generation chemotherapy regimens utilizing dose dense or metronomic polychemotherapy are among the most effective tools presently available. The role of specific chemotherapy agents in the treatment of TNBC remains incompletely defined and warrants careful review to ensure the most effective therapy is delivered while minimizing unnecessary toxicity. Platinum agents have seen renewed interest in TNBC based on a growing body of preclinical and clinical data suggesting encouraging activity. Taxanes and anthracyclines are active in TNBC and remain important agents, but have not shown specific benefit over non-TNBC. Capecitabine has limited reported data in TNBC, but some reports suggest differential activity in TNBC compared to hormone receptor positive breast cancer. TNBC is itself a heterogeneous group in which subgroups such as BRCA1 mutation carriers may have particular sensitivity to platinum agents and relatively less sensitivity to taxanes. Therefore, the identification of additional molecular biomarkers to predict response to specific chemotherapy is required to further improve treatment strategies with the current menu of chemotherapy options and future combinations with targeted therapies. PMID:20164691

  14. 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.

  15. 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

  16. 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

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

    PubMed

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

    2016-07-01

    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. PMID:26781935

  18. Near Infrared Heptamethine Cyanine Dye-Mediated Cancer Imaging*

    PubMed Central

    Yang, Xiaojian; Shi, Chunmeng; Tong, Rong; Qian, Weiping; Zhau, Haiyen E.; Wang, Ruoxiang; Zhu, Guodong; Cheng, Jianjun; Yang, Vincent W.; Cheng, Tianmin; Henary, Maged; Strekowski, Lucjan; Chung, Leland W.K.

    2010-01-01

    Purpose Near-infrared (NIR) fluorescence imaging has great potential for noninvasive in vivo imaging of tumors. In this study, we demonstrate the preferential uptake and retention of two hepatamethine cyanine dyes, IR-783 and MHI-148, in tumor cells and tissues. Experimental Design IR-783 and MHI-148 were investigated for their ability to accumulate in human cancer cells, tumor xenografts and spontaneous mouse tumors in transgenic animals. Time- and concentration-dependent dye uptake and retention in normal and cancer cells and tissues were compared, and subcellular localization of the dyes and mechanisms of the dye uptake and retention in tumor cells were evaluated using organelle-specific tracking dyes and bromosulfophthalein (BSP), a competitive inhibitor of organic anion transporting peptides (OATPs). These dyes were used to detect human cancer metastases in a mouse model and differentiate cancer cells from normal cells in blood. Results These NIR hepatamethine cyanine dyes were retained in cancer cells but not normal cells, in tumor xenografts, and in spontaneous tumors in transgenic mice. They can be used to detect cancer metastasis and cancer cells in blood with a high degree of sensitivity. The dyes were found to concentrate in the mitochondria and lysosomes of cancer cells, probably through OATPs since the dye uptake and retention in cancer cells can be blocked completely by BSP. These dyes, when injected to mice, did not cause systemic toxicity. Conclusions These two heptamethine cyanine dyes are promising imaging agents for human cancers and can be further exploited to improve cancer detection, prognosis and treatment. PMID:20410058

  19. 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

  20. Promising oncolytic agents for metastatic breast cancer treatment

    PubMed Central

    Cody, James J; Hurst, Douglas R

    2015-01-01

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

  1. Urinary bladder cancer: role of MR imaging.

    PubMed

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

    2012-01-01

    Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. PMID:22411938

  2. 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.

  3. 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

  4. 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. PMID:25662491

  5. Octapod iron oxide nanoparticles as high-performance T₂ contrast agents for magnetic resonance imaging.

    PubMed

    Zhao, Zhenghuan; Zhou, Zijian; Bao, Jianfeng; Wang, Zhenyu; Hu, Juan; Chi, Xiaoqin; Ni, Kaiyuan; Wang, Ruifang; Chen, Xiaoyuan; Chen, Zhong; Gao, Jinhao

    2013-01-01

    Spherical superparamagnetic iron oxide nanoparticles have been developed as T2-negative contrast agents for magnetic resonance imaging in clinical use because of their biocompatibility and ease of synthesis; however, they exhibit relatively low transverse relaxivity. Here we report a new strategy to achieve high transverse relaxivity by controlling the morphology of iron oxide nanoparticles. We successfully fabricate size-controllable octapod iron oxide nanoparticles by introducing chloride anions. The octapod iron oxide nanoparticles (edge length of 30 nm) exhibit an ultrahigh transverse relaxivity value (679.3 ± 30 mM(-1) s(-1)), indicating that these octapod iron oxide nanoparticles are much more effective T2 contrast agents for in vivo imaging and small tumour detection in comparison with conventional iron oxide nanoparticles, which holds great promise for highly sensitive, early stage and accurate detection of cancer in the clinic. PMID:23903002

  6. 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

  7. Near Infrared Resonant Gold / Gold Sulfide Nanoparticles as a Photothermal Cancer Therapeutic Agent

    PubMed Central

    Gobin, André M.; Watkins, Emily M.; Quevedo, Elizabeth; Colvin, Vicki L.; West, Jennifer L.

    2010-01-01

    The development and optimization of near-infrared (nIR) absorbing nanoparticles for use as photothermal cancer therapeutic agents has been ongoing. We have previously reported on larger layered gold / silica nanoshells (~140 nm) for combined therapy and imaging applications. This work exploits the properties of smaller gold / gold sulfide (GGS) nIR absorbing nanoparticles (~35–55 nm) that provide higher absorption (98% absorption & 2% scattering for GGS versus 70% absorption & 30% scattering for gold/silica nanoshells) as well as potentially better tumor penetration. In this work we demonstrate ability to ablate tumor cells in vitro, and efficacy for photothermal cancer therapy, where in an in vivo model we show significantly increased long-term, tumor-free survival. Further, enhanced circulation and bio-distribution is observed in vivo. This class of nIR absorbing nanoparticles has potential to improve upon photothermal tumor ablation for cancer therapy. PMID:20183810

  8. 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.

  9. 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

  10. 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

  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. 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. 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

  15. 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.

  16. 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.

  17. Molecular magnetic resonance imaging in cancer.

    PubMed

    Haris, Mohammad; Yadav, Santosh K; Rizwan, Arshi; Singh, Anup; Wang, Ena; Hariharan, Hari; Reddy, Ravinder; Marincola, Francesco M

    2015-01-01

    The ability to identify key biomolecules and molecular changes associated with cancer malignancy and the capacity to monitor the therapeutic outcome against these targets is critically important for cancer treatment. Recent developments in molecular imaging based on magnetic resonance (MR) techniques have provided researchers and clinicians with new tools to improve most facets of cancer care. Molecular imaging is broadly described as imaging techniques used to detect molecular signature at the cellular and gene expression levels. This article reviews both established and emerging molecular MR techniques in oncology and discusses the potential of these techniques in improving the clinical cancer care. It also discusses how molecular MR, in conjunction with other structural and functional MR imaging techniques, paves the way for developing tailored treatment strategies to enhance cancer care. PMID:26394751

  18. Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen.

    PubMed

    Wang, Xinning; Tsui, Brian; Ramamurthy, Gopolakrishnan; Zhang, Ping; Meyers, Joseph; Kenney, Malcolm E; Kiechle, Jonathan; Ponsky, Lee; Basilion, James P

    2016-08-01

    Prostatectomy has been the mainstay treatment for men with localized prostate cancer. Surgery, however, often can result in major side effects, which are caused from damage and removal of nerves and muscles surrounding the prostate. A technology that can help surgeons more precisely identify and remove prostate cancer resulting in a more complete prostatectomy is needed. Prostate-specific membrane antigen (PSMA), a type II membrane antigen highly expressed in prostate cancer, has been an attractive target for imaging and therapy. The objective of this study is to develop low molecular weight PSMA-targeted photodynamic therapy (PDT) agents, which would provide image guidance for prostate tumor resection and allow for subsequent PDT to eliminate unresectable or remaining cancer cells. On the basis of our highly negatively charged, urea-based PSMA ligand PSMA-1, we synthesized two PSMA-targeting PDT conjugates named PSMA-1-Pc413 and PSMA-1-IR700. In in vitro cellular uptake experiments and in vivo animal imaging experiments, the two conjugates demonstrated selective and specific uptake in PSMA-positive PC3pip cells/tumors, but not in PSMA-negative PC3flu cells/tumors. Further in vivo photodynamic treatment proved that the two PSMA-1-PDT conjugates can effectively inhibit PC3pip tumor progression. The two PSMA-1-PDT conjugates reported here may have the potential to aid in the detection and resection of prostate cancers. It may also allow for the identification of unresectable cancer tissue and PDT ablation of such tissue after surgical resection with potentially less damage to surrounding tissues. Mol Cancer Ther; 15(8); 1834-44. ©2016 AACR. PMID:27297866

  19. 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.

  20. 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

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

    PubMed

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

    2012-01-01

    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. PMID:23121766

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Preclinical efficacy of the oncolytic measles virus expressing the sodium iodide symporter in iodine non-avid anaplastic thyroid cancer: a novel therapeutic agent allowing noninvasive imaging and radioiodine therapy.

    PubMed

    Reddi, H V; Madde, P; McDonough, S J; Trujillo, M A; Morris, J C; Myers, R M; Peng, K W; Russell, S J; McIver, B; Eberhardt, N L

    2012-09-01

    Anaplastic thyroid cancer is an extremely aggressive disease resistant to radioiodine treatment because of loss of sodium iodide symporter (NIS) expression. To enhance prognosis of this fatal cancer, we validated the preclinical efficacy of measles virus (MV)-NIS, the vaccine strain of the oncolytic MV (MV-Edm), modified to include the NIS gene. Western blotting analysis confirmed that a panel of eight anaplastic thyroid cancer (ATC)-derived cell lines do not express NIS protein, but do express CD46, the MV receptor. In vitro cell death assays and in vivo xenograft studies demonstrate the oncolytic efficacy of MV-NIS in BHT-101 and KTC-3, ATC-derived cell lines. Radioactive iodine uptake along with single-photon emission computed tomography (SPECT)-computed tomography imaging of KTC-3 xenografts after (99)Tc(m) administration confirmed NIS expression in vitro and in vivo, respectively, after virus treatment. Adjuvant administration of RAI, to MV-NIS-treated KTC-3 tumors showed a trend for increased tumor cell killing. As current treatment for ATC is only palliative, and MV-NIS is currently Food and Drug Administration approved for human clinical trials in myeloma, our data indicate that targeting ATC with MV-NIS could prove to be a novel therapeutic strategy for effective treatment of iodine-resistant ATC and will expedite its testing in clinical trials for this aggressive disease. PMID:22790962

  7. Molecular-Genetic Imaging of Cancer

    PubMed Central

    Minn, Il; Menezes, Mitchell E.; Sarkar, Siddik; Yarlagadda, Keerthi; Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.; Pomper, Martin G.

    2015-01-01

    Molecular-genetic imaging of cancer using nonviral delivery systems has great potential for clinical application as a safe, efficient, noninvasive tool for visualization of various cellular processes including detection of cancer, and its attendant metastases. In recent years, significant effort has been expended in overcoming technical hurdles to enable clinical adoption of molecular-genetic imaging. This chapter will provide an introduction to the components of molecular-genetic imaging and recent advances on each component leading to safe, efficient clinical applications for detecting cancer. Combination with therapy, namely, generating molecular-genetic theranostic constructs, will provide further impetus for clinical translation of this promising technology. PMID:25287688

  8. 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

  9. 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.

  10. 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. PMID:25857851

  11. Antibiofouling polymer coated gold nanoparticles as a dual modal contrast agent for X-ray and photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Huang, Guojia; Yuan, Yi; Xing, Da

    2011-01-01

    X-ray is one of the most useful diagnostic tools in hospitals in terms of frequency of use and cost, while photoacoustic (PA) imaging is a rapidly emerging non-invasive imaging technology that integrates the merits of high optical contrast with high ultrasound resolution. In this study, for the first time, we used gold nanoparticles (GNPs) as a dual modal contrast agent for X-ray and PA imaging. Soft gelatin phantoms with embedded tumor simulators of GNPs in various concentrations are clearly shown in both X-ray and PA imaging. With GNPs as a dual modal contrast agent, X-ray can fast detect the position of tumor and provide morphological information, whereas PA imaging has important potential applications in the image guided therapy of superficial tumors such as breast cancer, melanoma and Merkel cell carcinoma.

  12. Toward carbon nanotube-based imaging agents for the clinic.

    PubMed

    Hernández-Rivera, Mayra; Zaibaq, Nicholas G; Wilson, Lon J

    2016-09-01

    Among the many applications for carbon nanotubes (CNTs), their use in medicine has drawn special attention due to their potential for a variety of therapeutic and diagnostic applications. As progress toward clinical applications continues, monitoring CNTs in vivo will be essential to evaluate their biodistribution, potential toxicity, therapeutic activity, and any physiological changes that the material may induce in specific tissues. There are many different imaging modalities to visualize and track CNTs in vivo, yet only a few are full-body penetrating, a central characteristic that widens their clinical utility. In order to visualize CNTs, chemical modification is often required for the material to be used as a platform to carry imaging agents compatible with one or more of the clinical imaging techniques. Here, we focus on the most recent work involving the use of CNTs as imaging agents for the non-invasive, full-body penetrating clinical modalities of MRI, PET, SPECT, and X-ray CT. The synthesis and modification of the CNT materials are discussed, as well as relevant preclinical studies. PMID:27294540

  13. Terahertz polarization imaging for colon cancer detection

    NASA Astrophysics Data System (ADS)

    Doradla, Pallavi; Alavi, Karim; Joseph, Cecil S.; Giles, Robert H.

    2014-03-01

    Continuous wave terahertz (THz) imaging has the potential to offer a safe, noninvasive medical imaging modality for delineating colorectal cancer. The terahertz reflectance measurements of fresh 3 - 5 mm thick human colonic excisions were acquired using a continuous-wave polarization imaging technique. A CO2 optically pumped Far- Infrared molecular gas laser operating at 584 GHz was used to illuminate the colon tissue, while the reflected signals were detected using a liquid Helium cooled silicon bolometer. Both co-polarized and cross-polarized remittance from the samples was collected using wire grid polarizers in the experiment. The experimental analysis of 2D images obtained from THz reflection polarization imaging techniques showed intrinsic contrast between cancerous and normal regions based on increased reflection from the tumor. Also, the study demonstrates that the cross-polarized terahertz images not only correlates better with the histology, but also provide consistent relative reflectance difference values between normal and cancerous regions for all the measured specimens.

  14. 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.

  15. 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

  16. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging.

    PubMed

    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

  17. In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation.

    PubMed

    Cao, Jian; Campbell, James; Liu, Li; Mason, Ralph P; Lippert, Alexander R

    2016-05-01

    Tissue oxygenation is a driving parameter of the tumor microenvironment, and hypoxia can be a prognostic indicator of aggressiveness, metastasis, and poor response to therapy. Here, we report a chemiluminescence imaging (CLI) agent based on the oxygen-dependent reduction of a nitroaromatic spiroadamantane 1,2-dioxetane scaffold. Hypoxia ChemiLuminescent Probe 2 (HyCL-2) responds to nitroreductase with ∼170-fold increase in luminescence intensity and high selectivity for enzymatic reductase versus other small molecule reductants. HyCL-2 can image exogenous nitroreductase in vitro and in vivo in living mice, and total luminescent intensity is increased by ∼5-fold under low oxygen conditions. HyCL-2 is demonstrated to report on tumor oxygenation during an oxygen challenge in H1299 lung tumor xenografts grown in a murine model as independently confirmed using multispectral optoacoustic tomography (MSOT) imaging of hemoglobin oxygenation. PMID:27054463

  18. 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.

  19. Molecular nanomagnets as contrast agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Rodríguez, Elisenda; Roig, Anna; Molins, Elies; Arús, Carles; Cabañas, Miquel; Quintero, María Rosa; Cerdán, Sebastián; Sanfeliu, Coral

    2003-03-01

    Magnetic resonance imaging (MRI) is a non-invasive technique used in medicine to produce high quality images of human body slices. In order to enhance the contrast between different organs or to reveal altered portions of them such necrosis or tumors, the administration of a contrast agent is highly convenient. Currently Gd-DTPA, a paramagnetic complex, is the most widely administered compound. In this context, we have assayed molecular nanomagnets as MRI contrast agents. The complex [(tacn)_6Fe_8(μ_3-O)_2(μ_2-OH)_12]Br_8·9H_2O^1(Fe8 in brief) has been evaluated and shorter relaxation times, T1 and T_2, have been obtained for Fe8 than those obtained for the commercial Gd-DTPA. No toxic effects have been observed at concentrations up to 1 mM of Fe8 in cultured cells. Phantom studies with T_1-weighted MRI at 9.4 Tesla suggest that Fe8 can have potentiality as T_1-contrast agent. ^1Wieghardt K Angew Chem Intl Ed Engl 23 1 (1984) 77

  20. Plant polyphenolics as anti-invasive cancer agents.

    PubMed

    Bracke, M E; Vanhoecke, B W A; Derycke, L; Bolca, S; Possemiers, S; Heyerick, A; Stevens, C V; De Keukeleire, D; Depypere, H T; Verstraete, W; Williams, C A; McKenna, S T; Tomar, S; Sharma, D; Prasad, A K; DePass, A L; Parmar, V S

    2008-02-01

    Because invasion is, either directly or via metastasis formation, the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. We have established a screening program for potentially anti-invasive compounds. The assay is based on organotypic confronting cultures between human invasive cancer cells and a fragment of normal tissue in three dimensions. Anti-invasive agents appeared to be heterogeneous with regard to their chemical nature, but plant alkaloids, polyphenolics and some of their synthetic congeners were well represented. Even within this group, active compounds were quite diverse: (+)-catechin, tangeretin, xanthohumol and other prenylated chalcones, 3,7-dimethoxyflavone, a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin. The data gathered in this system are now applied in two projects. Firstly, structure-activity relationships are explored with computer models using an artificial neural network approach, based on quantitative structural descriptors. The aim of this study is the prediction and design of optimally efficient anti-invasive compounds. Secondly, the metabolism of orally ingested plant polyphenolics by colonic bacteria is studied in a simulator of the human intestinal microbial ecosystem (SHIME) and in human intervention trials. This method should provide information on the final bioavailability of the active compounds in the human body, with regard to microbial metabolism, and the feasibility of designing pre- or probiotics that increase the generation of active principles for absorption in the gastro-intestinal tract. The final and global aim of all these studies is to predict, synthesize and apply in vivo molecules with an optimal anti-invasive, and hence an anti-metastatic activity against cancer. PMID:18288920

  1. 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

  2. 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

  3. 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

  4. Breast cancer histopathology image analysis: a review.

    PubMed

    Veta, Mitko; Pluim, Josien P W; van Diest, Paul J; Viergever, Max A

    2014-05-01

    This paper presents an overview of methods that have been proposed for the analysis of breast cancer histopathology images. This research area has become particularly relevant with the advent of whole slide imaging (WSI) scanners, which can perform cost-effective and high-throughput histopathology slide digitization, and which aim at replacing the optical microscope as the primary tool used by pathologist. Breast cancer is the most prevalent form of cancers among women, and image analysis methods that target this disease have a huge potential to reduce the workload in a typical pathology lab and to improve the quality of the interpretation. This paper is meant as an introduction for nonexperts. It starts with an overview of the tissue preparation, staining and slide digitization processes followed by a discussion of the different image processing techniques and applications, ranging from analysis of tissue staining to computer-aided diagnosis, and prognosis of breast cancer patients. PMID:24759275

  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. New approaches for imaging and therapy of solid cancer.

    PubMed

    Sollini, M; Boni, R; Traino, A C; Lazzeri, E; Pasqualetti, F; Modeo, L; Mariani, G; Petrini, M; Erba, P A

    2015-06-01

    Radionuclide therapy is a systemic treatment that aims to deliver cytotoxic radiation to cancer cells. Due to their properties, antibodies have been considered as suitable agent for the delivery of therapeutic radioisotopes, radioimmunotherapy (RIT). This article gives an overview of new approaches for imaging and therapy of solid cancer with particular attention to strategies to enhance treatment success. Examples of increased antibody uptake by targeting stromal constituent of tumor microenvironment such as fibronectin (FN) an important tumor-associated angiogenesis targeting agent, with specifically designed antibody format will be provided. Strategies oriented to identify patients most likely to benefit from RIT including identification of radiosensitivity profiles, in vivo target identification by teragnostic approach and better prediction of dosimetric estimates would be presents. Combination regimens such as with chemo-radiotherapy and immunotherapy would be also discussed as an approach to enhance RIT success. PMID:25693421

  7. 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

  8. Screening CEST contrast agents using ultrafast CEST imaging.

    PubMed

    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. PMID:26969814

  9. 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

  10. Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy.

    PubMed

    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

    2014-06-11

    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 ((124)I) or molecular radiotherapeutic ((131)I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. (131)I-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 (124)I-CLR1404 or (131)I-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 (124)I-CLR1404 tumor imaging for planning (131)I-CLR1404 therapy. PMID:24920661

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

    PubMed Central

    Liu, Guanshu; Li, Yuguo; Sheth, Vipul R.; Pagel, Mark D.

    2016-01-01

    The measurement of extracellular pH (pHe) has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance imaging (MRI) contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST) was designed to measure tumor pHe throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb3+-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid,10-o-aminoanilide (Yb-DO3A-oAA) suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST) effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pHe measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer. PMID:22418027

  12. 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.

  13. 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

    2015-01-01

    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

  14. 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

  15. Fluoro-pegylated (FPEG) Imaging Agents Targeting Aβ Aggregates

    PubMed Central

    Stephenson, Karin A.; Chandra, Rajesh; Zhuang, Zhi-Ping; Hou, Catherine; Oya, Shunichi; Kung, Mei-Ping; Kung, Hank F.

    2008-01-01

    A novel approach of producing positron emission tomography (PET) imaging agents through the formation of bioconjugates based on pegylation-fluorination strategy resulting in fluoro-pegylated (FPEG) molecules is reported. This approach offers a simple and easy method by which to incorporate 18F in the target molecule without appreciable increase in the lipophilicity. After 18F labeling this convenient approach leads to PET imaging probes binding to Aβ aggregates in the brain (an important factor associated with Alzheimer’s disease) using the known core structures, such as [2-(4-dimethylaminophenyl)-vinyl]-benzoxazol (3′) or 2-phenylbenzothiazole (4). This approach appears to be effective in some core structures, but it cannot be uniformly applied to all structures. PMID:17226978

  16. 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.

  17. 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.

  18. 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

  19. Development of molecularly targeted agents and immunotherapies in small cell lung cancer.

    PubMed

    Sharp, Adam; Bhosle, Jaishree; Abdelraouf, Fatma; Popat, Sanjay; O'Brien, Mary; Yap, Timothy A

    2016-06-01

    Small cell lung cancer (SCLC) is a smoking-induced malignancy with multiple toxin-associated mutations, which accounts for 15% of all lung cancers. It remains a clinical challenge with a rapid doubling time, early dissemination and poor prognosis. Despite multiple clinical trials in SCLC, platinum-based chemotherapy remains the mainstay of treatment in the first line advanced disease setting; good initial responses are nevertheless inevitably followed by disease relapse and survival ultimately remains poor. There are currently no molecularly targeted agents licenced for use in SCLC. Advances in sequencing the cancer genome and other high-throughput profiling technologies have identified aberrant pathways and mechanisms implicated in SCLC development and progression. Novel anti-tumour therapeutics that impact these putative targets are now being developed and investigated in SCLC. In this review, we discuss novel anti-tumour agents assessed in SCLC with reference to the complex molecular mechanisms implicated in SCLC development and progression. We focus on novel DNA damage response inhibitors, immune checkpoint modulators and antibody-drug conjugates that have shown promise in SCLC, and which may potentially transform treatment strategies in this disease. Finally, we envision the future management of SCLC and propose a biomarker-driven translational treatment paradigm for SCLC that incorporates next generation sequencing studies with patient tumours, circulating plasma DNA and functional imaging. Such modern strategies have the potential to transform the management and improve patient outcomes in SCLC. PMID:27060747

  20. Multimodal-Imaging-Guided Cancer Phototherapy by Versatile Biomimetic Theranostics with UV and γ-Irradiation Protection.

    PubMed

    Lin, Jing; Wang, Min; Hu, Hao; Yang, Xiangyu; Wen, Bronte; Wang, Zhantong; Jacobson, Orit; Song, Jibin; Zhang, Guofeng; Niu, Gang; Huang, Peng; Chen, Xiaoyuan

    2016-05-01

    A versatile biomimetic theranostic agent based on magnetic melanin nanoparticles is developed for positron-emission tomography/magnetic resonance/photoacoustic/photothermal multimodal-imaging-guided cancer photothermal therapy and UV and γ-irradiation protection. PMID:26928972

  1. Recent Development of Silica Nanoparticles as Delivery Vectors for Cancer Imaging and Therapy

    PubMed Central

    Wu, Xu; Wu, Min; Xiaojun Zhao, Julia

    2013-01-01

    In spite of significant advances in early detection and combined treatments, a number of cancers are often diagnosed at advanced stages and thereby carry a poor prognosis. Developing novel prognostic biomarkers and targeted therapies may offer alternatives for cancer diagnosis and treatment. Recent rapid development of nanomaterials, such as silica based nanoparticles (SiNPs), can just render such a promise. In this article, we attempt to summarize the recent progress of SiNPs in tumor research as a novel delivery vector. SiNP-assisted imaging techniques are used in cancer diagnosis both in vitro and in vivo. Meanwhile, SiNP-mediated drug delivery can efficiently treat tumor by carrying chemotherapeutic agents, photosensitizers, photothermal agents, siRNA, and gene therapeutic agents. Finally, SiNPs that contain at least two different functional agents may be more powerful for both tumor imaging and therapy. PMID:24028896

  2. Dual-function fluorescent probe for cancer imaging and therapy.

    PubMed

    Cui, Hongjing; Wang, Ran; Zhou, Ying; Shu, Chang; Song, Fengjuan; Zhong, Wenying

    2016-05-01

    To date, several fluorescent probes modified by a single targeting agent have been explored. However, studies on the preparation of dual-function quantum dot (QD) fluorescent probes with dual-targeting action and a therapeutic effect are rare. Here, a dual-targeting CdTe/CdS QD fluorescent probe with a bovine serum albumin-glycyrrhetinic acid conjugate and arginine-glycine-aspartic acid was successfully prepared that could induce the apoptosis of liver cancer cells and showed enhanced targeting in in vitro cell imaging. Therefore, the as-prepared fluorescent probe in this work is an efficient diagnostic tool for the simultaneous detection of liver cancer and breast cancer cells. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26387677

  3. Microtubule-stabilizing agents: New drug discovery and cancer therapy.

    PubMed

    Zhao, Ying; Mu, Xin; Du, Guanhua

    2016-06-01

    Microtubule-stabilizing agents (MSAs) have been highly successful in the treatment of cancer in the past 20years. To date, three classes of MSAs have entered the clinical trial stage or have been approved for clinical anticancer chemotherapy, and more than 10 classes of novel structural MSAs have been derived from natural resources. The microtubule typically contains two MSA-binding sites: the taxoid site and the laulimalide/peloruside site. All defined MSAs are known to bind at either of these sites, with subtle but significant differences. MSAs with different binding sites may produce a synergistic effect. Although having been extensively applied in the clinical setting, paclitaxel and other approved MSAs still pose many challenges such as multidrug resistance, low bioavailability, poor solubility, high toxicity, and low passage through the blood-brain barrier. A variety of studies focus on the structure-activity relationship in order to improve the pharmaceutical properties of these agents. Here, the mechanisms of action, advancements in pharmacological research, and clinical developments of defined MSAs during the past decade are discussed. The latest discovered MSAs are also briefly introduced in this review. The increasing number of natural MSAs indicates the potential discovery of more novel, natural MSAs with different structural bases, which will further promote the development of anticancer chemotherapy. PMID:26706241

  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. PMID:26226904

  5. Lung cancer screening: from imaging to biomarker.

    PubMed

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

    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

  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. Controlling RNA Expression in Cancer Using Iron Oxide Nanoparticles Detectable by MRI and In Vivo Optical Imaging.

    PubMed

    Medarova, Zdravka; Balcioglu, Mustafa; Yigit, Mehmet V

    2016-01-01

    Herein, we describe a protocol for the preparation of iron oxide nanoparticle-based contrast agents and drug delivery vehicles for noninvasive cancer imaging and therapy. In the first part of the chapter we describe the details of the contrast agent synthesis, functionalization, and characterization. In the second part we describe the methods for tumor imaging using the synthesized particles with noninvasive T2-weighted magnetic resonance imaging (MRI) and in vivo near infrared optical imaging. PMID:26530923

  8. 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.

  9. Honokiol: a novel natural agent for cancer prevention and therapy.

    PubMed

    Arora, S; Singh, S; Piazza, G A; Contreras, C M; Panyam, J; Singh, A P

    2012-12-01

    Honokiol (3',5-di-(2-propenyl)-1,1'-biphenyl-2,4'-diol) is a bioactive natural product derived from Magnolia spp. Recent studies have demonstrated anti-inflammatory, anti-angiogenic, anti-oxidative and anticancer properties of honokiol in vitro and in preclinical models. Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR), which have great relevance during cancer initiation and progression. Furthermore, pharmacokinetic profile of honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials. In this review, we discuss recent data describing the molecular targets of honokiol and its anti-cancer activities against various malignancies in pre-clinical models. Evaluation of honokiol in clinical trials will be the next step towards its possible human applications. PMID:22834827

  10. 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.

  11. NOVEL ALKYLPHOSPHOCHOLINE ANALOGS FOR BROAD SPECTRUM CANCER IMAGING AND THERAPY

    PubMed Central

    Kuo, John S.; Weichert, Jamey P.; Clark, Paul A.; Kandela, Irawati K.; Vacaro, Abram; Clark, William; Longino, Marc; Pinchuk, Anatoly; Farhoud, Mohammed; Swanson, Kyle I.; Floberg, John; Traynor, Anne; Hall, Lance T.; Pazoles, Christopher

    2014-01-01

    BACKGROUND: We present in vitro and in vivo imaging and therapeutic studies using a novel alkylphosphocholine (APC)-based molecular scaffold (CLR1404) that combines selective targeting of cancer (including cancer stem cells) with broad-spectrum activity against many different cancer types. CLR1404 APC analogs were created to exploit the finding that phospholipid ethers selectively accumulate in many cancers versus normal cells. METHODS: Depending on the iodine isotope used, radioiodinated CLR1404 is either a PET imaging (124I) or molecular radiotherapeutic agent (131I), with fluorescence analogs created by replacing iodide with various fluorophores. Standard tissue culture, xenograft and molecular biology protocols were used for these studies. RESULTS: CLR1404 displayed preferential uptake and retention in cancer and cancer stem cells compared to normal cells in vitro and in vivo. After 24 hours, selective uptake of fluorescent or radioiodinated CLR1404 analogs by multiple human cancer cell lines in vitro compared to patient-matched normal human fibroblasts was observed (2.3-2.8x). CLR1404 showed highly specific labeling of both human patient-matched glioblastoma stem cells and serum-cultured glioblastoma cells (3x over minimal labeling of control normal human astrocytes and neural stem cells). Lipid raft disruption reduced in vitro CLR1404 analog uptake.In vivo, CLR1404 analogs displayed prolonged tumor-selective retention in 55 different rodent and human cancer models (including triple-negative breast, lung, pancreatic, colorectal, prostate, renal, melanoma, GBM). Tumor accumulation was seen by 24 hours with continued normal tissue clearance between 48-120 hours. In vivo cancer stem cell labeling was also demonstrated. CLR1404 analogs do not visualize inflammatory or premalignant lesions (unlike currently used 18F-fluorodeoxy glucose (FDG)-PET tumor imaging).131I-CLR1404 also displayed therapeutic efficacy (tumor growth suppression, survival extension) especially

  12. 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.

  13. 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

  14. Nuclear and optical dual-labelled imaging agents. Design and challenges.

    PubMed

    Singh, G; Gott, M D; Pietzsch, H-J; Stephan, H

    2016-04-12

    Over the last two decades, molecular imaging has been established as a valuable technology, aiming at visualization and characterization of biochemical processes on a molecular level in isolated cells, tissues and higher organisms. Within the wide scope of the various imaging techniques, dual-labelled modalities for nuclear (PET, SPECT) and near-infrared fluorescence (NIRF) imaging show promise owing to their comparable detection sensitivity. Novel materials offer excellent prospects for the development of new non-invasive strategies of early diagnosis and efficient monitoring of therapeutic treatments. In the field of cancer medicine, the combination of different imaging techniques such as PET/SPECT and OI for tracking down tumours and metastases, and subsequent image-guided surgery for tumour resection is particularly attractive. This review focuses on the development of promising dual-labelled agents to be applied in bimodal nuclear/optical imaging, combining radionuclides and fluorescent dyes. The discussion encompasses modular ligands as well as nanoscale systems, including antibodies and their fragments. PMID:27067792

  15. Hybrid anisotropic nanostructures for dual-modal cancer imaging and image-guided chemo-thermo therapies.

    PubMed

    Zhang, Ruiping; Cheng, Kai; Antaris, Alexander L; Ma, Xiaowei; Yang, Min; Ramakrishnan, Sindhuja; Liu, Guifeng; Lu, Alex; Dai, Hongjie; Tian, Mei; Cheng, Zhen

    2016-10-01

    The multimodality theranostic system, which can integrate two or more different therapeutic modalities and multimodal imaging agents into a nanoentity, shows great promising prospects for the cancer treatment. Herein, we developed an efficient and novel strategy to synthesize hybrid anisotropic nanoparticles (HANs) with intrinsic multimodal theranostic capability [chemotherapy, photothermal therapy, magnetic resonance imaging (MRI), and photoacoustic imaging (PAI)]. For the first time, under the guidance of MRI and PAI, the chemotherapy and thermotherapy induced by administration of multifunctional hybrid nanoprobes were applied simultaneously to the treatment of colon cancer-bearing mice in vivo. PMID:27394161

  16. 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. PMID:25054687

  17. 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

  18. 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

  19. 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.

  20. 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.

  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. 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

  3. 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.

  4. 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. PMID:26177713

  5. 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

  6. 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.

  7. Uptake of myocardial imaging agents by rejected hearts

    SciTech Connect

    Bergsland, J.; Carr, E.A.; Carroll, M.; Wright, J.W.; Feldman, M.J.; Massucci, J.; Bhayana, J.N.; Gona, J.M.

    1985-09-01

    Technetium 99 m pyrophosphate, Gallium 67 and Thallium 201 uptakes were measured in heterotopically transplanted rat hearts. Five days after transplantation, Technetium 99 m pyrophosphate, and Gallium 67 uptakes were significantly higher in allogeneic grafts than in syngeneic grafts. At an early stage of rejection (three days after transplantation), only Technetium 99 m pyrophosphate uptake in the left ventricle of allogeneic grafts showed a significant difference (p less than 0.04). At five days, Thallium 201 uptake was significantly lower in allo- than syngeneic grafts. There was a positive correlation between radionuclide uptake and histologic degree of rejection for Technetium 99 m pyrophosphate and Gallium 67 while Thallium 201 uptake correlated negatively. Analysis of variance revealed that hearts with no or minimal rejection had statistically different uptakes than hearts with mild to moderate rejection. These results suggest that uptake of imaging agents might be useful in the diagnosis of rejection of the transplanted heart.

  8. 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

  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. 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

  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. T-oligo as an anticancer agent in colorectal cancer

    PubMed Central

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

    2016-01-01

    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. PMID:24632202

  14. 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

  15. 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

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

    PubMed

    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

  17. Magnetic resonance imaging for lung cancer screen.

    PubMed

    Wang, Yi-Xiang J; Lo, Gladys G; Yuan, Jing; Larson, Peder E Z; Zhang, Xiaoliang

    2014-09-01

    Lung cancer is the leading cause of cancer related death throughout the world. Lung cancer is an example of a disease for which a large percentage of the high-risk population can be easily identified via a smoking history. This has led to the investigation of lung cancer screening with low-dose helical/multi-detector CT. Evidences suggest that early detection of lung cancer allow more timely therapeutic intervention and thus a more favorable prognosis for the patient. The positive relationship of lesion size to likelihood of malignancy has been demonstrated previously, at least 99% of all nodules 4 mm or smaller are benign, while noncalcified nodules larger than 8 mm diameter bear a substantial risk of malignancy. In the recent years, the availability of high-performance gradient systems, in conjunction with phased-array receiver coils and optimized imaging sequences, has made MR imaging of the lung feasible. It can now be assumed a threshold size of 3-4 mm for detection of lung nodules with MRI under the optimal conditions of successful breath-holds with reliable gating or triggering. In these conditions, 90% of all 3-mm nodules can be correctly diagnosed and that nodules 5 mm and larger are detected with 100% sensitivity. Parallel imaging can significantly shorten the imaging acquisition time by utilizing the diversity of sensitivity profile of individual coil elements in multi-channel radiofrequency receive coil arrays or transmit/receive coil arrays to reduce the number of phase encoding steps required in imaging procedure. Compressed sensing technique accelerates imaging acquisition from dramatically undersampled data set by exploiting the sparsity of the images in an appropriate transform domain. With the combined imaging algorithm of parallel imaging and compressed sensing and advanced 32-channel or 64-channel RF hardware, overall imaging acceleration of 20 folds or higher can then be expected, ultimately achieve free-breathing and no ECG gating acquisitions

  18. Magnetic resonance imaging for lung cancer screen

    PubMed Central

    Lo, Gladys G.; Yuan, Jing; Larson, Peder E. Z.

    2014-01-01

    Lung cancer is the leading cause of cancer related death throughout the world. Lung cancer is an example of a disease for which a large percentage of the high-risk population can be easily identified via a smoking history. This has led to the investigation of lung cancer screening with low-dose helical/multi-detector CT. Evidences suggest that early detection of lung cancer allow more timely therapeutic intervention and thus a more favorable prognosis for the patient. The positive relationship of lesion size to likelihood of malignancy has been demonstrated previously, at least 99% of all nodules 4 mm or smaller are benign, while noncalcified nodules larger than 8 mm diameter bear a substantial risk of malignancy. In the recent years, the availability of high-performance gradient systems, in conjunction with phased-array receiver coils and optimized imaging sequences, has made MR imaging of the lung feasible. It can now be assumed a threshold size of 3-4 mm for detection of lung nodules with MRI under the optimal conditions of successful breath-holds with reliable gating or triggering. In these conditions, 90% of all 3-mm nodules can be correctly diagnosed and that nodules 5 mm and larger are detected with 100% sensitivity. Parallel imaging can significantly shorten the imaging acquisition time by utilizing the diversity of sensitivity profile of individual coil elements in multi-channel radiofrequency receive coil arrays or transmit/receive coil arrays to reduce the number of phase encoding steps required in imaging procedure. Compressed sensing technique accelerates imaging acquisition from dramatically undersampled data set by exploiting the sparsity of the images in an appropriate transform domain. With the combined imaging algorithm of parallel imaging and compressed sensing and advanced 32-channel or 64-channel RF hardware, overall imaging acceleration of 20 folds or higher can then be expected, ultimately achieve free-breathing and no ECG gating acquisitions

  19. Image-based brachytherapy for cervical cancer

    PubMed Central

    Vargo, John A; Beriwal, Sushil

    2014-01-01

    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

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

    PubMed Central

    2013-01-01

    Background Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients. Methods We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl2 (L)] and [PdCl2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl2 (L)] and [PdCl2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo. Results CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl2 (L)] induced DNA double-strand breaks. Conclusion These results indicate that [PdCl2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications. PMID:23672493

  1. Development of a calcium-sensing receptor molecular imaging agent

    PubMed Central

    Yusof, Adlina Mohd; Kothandaraman, Shankaran; Zhang, Xiaoli; Saji, Motoyasu; Ringel, Matthew D.; Tweedle, Michael F.; Phay, John E.

    2015-01-01

    Background Calcium-sensing receptor (CaSR) is expressed by parathyroid cells and thyroid C-cells (from which medullary thyroid carcinoma [MTC] is derived). A molecular imaging agent localizing to the CaSR could improve the detection of parathyroids and MTC preoperatively or intraoperatively. We synthesized a novel compound containing a fluorine residue for potential future labeling and demonstrated that the compound inhibited CaSR function in vitro. Methods We synthesized compound M, a derivative of a known calcilytic compound, Calhex-231. Human embryonic kidney cells transfected with green-fluorescent protein-tagged CaSR or control vector were preincubated with compound M before the addition of calcium. Immunoblotting for total mitogen-activated protein kinase (MAPK: ERK1/2), activated MAPK (phosphorylated ERK1/2), and glyceraldehyde 3-phosphate dehydrogenase was performed. Results Synthesis of compound M was confirmed by mass spectrometry. Inhibition of the MAPK signaling pathway by compound M was demonstrated in a dose-dependent manner by a decrease in phosphorylated ERK1/2 with no change in total ERK1/2 levels. Compound M inhibited MAPK signaling slightly better than the parent compound. Conclusion We have developed a novel molecule which demonstrates functional inhibition of CaSR and has a favorable structure for labeling. This compound appears to be appropriate for further development as a molecular imaging tool to enhance the surgical treatment of parathyroid disease and MTC. PMID:24238055

  2. 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

  3. 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

  4. Radiolabeled Apoptosis Imaging Agents for Early Detection of Response to Therapy

    PubMed Central

    2014-01-01

    Since apoptosis plays an important role in maintaining homeostasis and is associated with responses to therapy, molecular imaging of apoptotic cells could be useful for early detection of therapeutic effects, particularly in oncology. Radiolabeled annexin V compounds are the hallmark in apoptosis imaging in vivo. These compounds are reviewed from the genesis of apoptosis (cell death) imaging agents up to recent years. They have some disadvantages, including slow clearance and immunogenicity, because they are protein-based imaging agents. For this reason, several studies have been conducted in recent years to develop low molecule apoptosis imaging agents. In this review, radiolabeled phosphatidylserine targeted peptides, radiolabeled bis(zinc(II)-dipicolylamine) complex, radiolabeled 5-fluoropentyl-2-methyl-malonic acid (ML-10), caspase-3 activity imaging agents, radiolabeled duramycin, and radiolabeled phosphonium cation are reviewed as promising low-molecular-weight apoptosis imaging agents. PMID:25383382

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Confocal Raman imaging for cancer cell classification

    NASA Astrophysics Data System (ADS)

    Mathieu, Evelien; Van Dorpe, Pol; Stakenborg, Tim; Liu, Chengxun; Lagae, Liesbet

    2014-05-01

    We propose confocal Raman imaging as a label-free single cell characterization method that can be used as an alternative for conventional cell identification techniques that typically require labels, long incubation times and complex sample preparation. In this study it is investigated whether cancer and blood cells can be distinguished based on their Raman spectra. 2D Raman scans are recorded of 114 single cells, i.e. 60 breast (MCF-7), 5 cervix (HeLa) and 39 prostate (LNCaP) cancer cells and 10 monocytes (from healthy donors). For each cell an average spectrum is calculated and principal component analysis is performed on all average cell spectra. The main features of these principal components indicate that the information for cell identification based on Raman spectra mainly comes from the fatty acid composition in the cell. Based on the second and third principal component, blood cells could be distinguished from cancer cells; and prostate cancer cells could be distinguished from breast and cervix cancer cells. However, it was not possible to distinguish breast and cervix cancer cells. The results obtained in this study, demonstrate the potential of confocal Raman imaging for cell type classification and identification purposes.

  11. 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

  12. Molecular Imaging of CD44-Overexpressing Gastric Cancer in Mice Using T2 MR Imaging.

    PubMed

    Lee, Hwunjae; Yang, Seung-Hyun; Heo, Dan; Son, Heyoung; Haam, Seungjoo; Suh, Jin-Suck; Yang, Jaemoon; Huh, Yong-Min

    2016-01-01

    Novel diagnostic techniques have been developed in many research area using targetable contrast agents with magnetic resonance imaging (MRI) for cancer diagnosis. For cancer diagnosis, the use of MRI with biocompatible targeting moieties and manganese ferrite nanoparticles (MFNPs) is preferred. Thus, we synthesized MFNPs using a thermal decomposition method which enables sensitive T2 or T2 Turbo Spin Echo (TSE) MRI and coated them with hyaluronic acid (HA). The high targeting ability of HA-MFNPs was observed at MKN-45 cells (gastric cancer cell line) which high-expressing CD44 in contrast with MKN-28 cells which low-expressing CD44. We also prepared the gastric cancer mice model using MKN-45 cells which has the stem-like property was implanted into BALB/c nude mice. And then HA-MFNPs of the T2 contrast enhancement effects and targeting ability were investigated by in vivo MR imaging. As a result of these studies, we conclude that HA coated MFNPs can be effectively used as a novel probes for visualizing gastric cancer stem cells. PMID:27398445

  13. Polymeric Nanomedicine for Cancer MR Imaging and Drug Delivery

    PubMed Central

    Khemtong, Chalermchai; Kessinger, Chase W.

    2010-01-01

    Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (<200 nm). Currently, several nanoscopic therapeutic and diagnostic systems have been translated into clinical practices. In this feature article, we will provide an up-to-date review on the development and biomedical applications of nanocomposite materials for cancer diagnosis and therapy. Overview of each functional component, i.e. polymer carriers, MR imaging agents, and therapeutic drugs will be presented. Integration of different functional components will be illustrated in several highlighted examples to demonstrate the synergy of the multifunctional nanomedicine design. PMID:19521593

  14. N3-substituted thymidine bioconjugates for cancer therapy and imaging

    PubMed Central

    Khalil, Ahmed; Ishita, Keisuke; Ali, Tehane; Tjarks, Werner

    2013-01-01

    The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer. Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1. Favorable in vivo biodistribution profiles of 3CTAs led to promising results in preclinical BNCT of rats with intracerebral brain tumors. This review presents an overview on the design, synthesis, and biological evaluation of first- and second-generation 3CTAs. Boronated nucleosides developed prior to 3CTAs for BNCT and non-boronated N3-substituted thymidine conjugates for other areas of cancer therapy and imaging are also described. In addition, basic features of carborane clusters, which are used as boron moieties in the design and synthesis of 3CTAs, and the biological and structural features of TK1-like enzymes, which are the molecular targets of 3CTAs, are discussed. PMID:23617430

  15. 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

  16. Autofluorescence spectroscopic imaging for laryngeal cancer detection

    NASA Astrophysics Data System (ADS)

    Kan, Lin; Zheng, Wei; Huang, Zhiwei

    2008-02-01

    Autofluorescence imaging has shown a high sensitivity for early diagnosis and detection of cancer and precancer in humans, however, this diagnostic technique has a limitation with high false positive rates resulting in a low diagnostic specificity. In this study, we develop an endoscope-based autofluorescence imaging system in combination with spectroscopy measurement system for tissue diagnostics and characterization in the head and neck. The results show that combining the spectroscopy and imaging techniques can improve both the diagnostic sensitivity and specificity for discriminating laryngeal carcinoma from normal tissue.

  17. 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.

  18. Breast Cancer Imaging with Novel PET Tracers.

    PubMed

    Mankoff, David A; Lee, Jean H; Eubank, William B

    2009-10-01

    Whereas (18)F-fluorodeoxyglucose (FDG)-PET/computed tomography has proven to be valuable for breast cancer diagnosis and response evaluation, it is likely that PET radiopharmaceuticals beyond FDG will contribute further to the understanding of breast cancer and thereby further direct breast cancer care. Increasingly specific and quantitative approaches will help direct treatment selection from an ever-expanding and increasing array of targeted breast cancer therapies. This article highlights 4 areas of ongoing research where preliminary patient results look promising: (1) tumor perfusion and angiogenesis, (2) drug delivery and transport, (3) tumor receptor imaging, and (4) early response evaluation. For each area, the biologic background is reviewed and early results are highlighted. PMID:27157306

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

    PubMed

    Vedham, Vidya; Verma, Mukesh; Mahabir, Somdat

    2015-12-01

    There is a growing understanding that several infectious agents are acquired in early life and this is the reason why available vaccines target the new born, infants, and adolescents. Infectious agents are associated with cancer development and it is estimated that about 20% of the world's cancer burden is attributed to infectious agents. There is a growing evidence that certain infectious agents acquired in early life can give rise to cancer development, but estimates of the cancer burden from this early-life acquisition is unknown. In this article, we have selected five cancers (cervical, liver, Burkitt's lymphoma-leukemia, nasopharyngeal carcinoma, and adult T-cell leukemia-lymphoma) and examine their links to infectious agents (HPV, HBV, HCV, EBV, and HTLV-1) acquired in early life. For these agents, the acquisition in early life is from mother-to-child transmission, perinatal contact (with genital tract secretions, amniotic fluids, blood, and breast milk), saliva, sexual intercourse, and blood transfusion. We also discuss prevention strategies, address future directions, and propose mechanisms of action after a long latency period from the time of acquisition of the infectious agent in early life to cancer development. PMID:26377256

  20. 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.

  1. 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

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

    PubMed

    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

  3. 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

  4. Quantitative Imaging in Cancer Evolution and Ecology

    PubMed Central

    Grove, Olya; Gillies, Robert J.

    2013-01-01

    Cancer therapy, even when highly targeted, typically fails because of the remarkable capacity of malignant cells to evolve effective adaptations. These evolutionary dynamics are both a cause and a consequence of cancer system heterogeneity at many scales, ranging from genetic properties of individual cells to large-scale imaging features. Tumors of the same organ and cell type can have remarkably diverse appearances in different patients. Furthermore, even within a single tumor, marked variations in imaging features, such as necrosis or contrast enhancement, are common. Similar spatial variations recently have been reported in genetic profiles. Radiologic heterogeneity within tumors is usually governed by variations in blood flow, whereas genetic heterogeneity is typically ascribed to random mutations. However, evolution within tumors, as in all living systems, is subject to Darwinian principles; thus, it is governed by predictable and reproducible interactions between environmental selection forces and cell phenotype (not genotype). This link between regional variations in environmental properties and cellular adaptive strategies may permit clinical imaging to be used to assess and monitor intratumoral evolution in individual patients. This approach is enabled by new methods that extract, report, and analyze quantitative, reproducible, and mineable clinical imaging data. However, most current quantitative metrics lack spatialness, expressing quantitative radiologic features as a single value for a region of interest encompassing the whole tumor. In contrast, spatially explicit image analysis recognizes that tumors are heterogeneous but not well mixed and defines regionally distinct habitats, some of which appear to harbor tumor populations that are more aggressive and less treatable than others. By identifying regional variations in key environmental selection forces and evidence of cellular adaptation, clinical imaging can enable us to define intratumoral

  5. 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

  6. 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

  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. 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. PMID:26027697

  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. PMID:26212580

  10. On-chip preparation of nanoscale contrast agents towards high-resolution ultrasound imaging.

    PubMed

    Peyman, Sally A; McLaughlan, James R; Abou-Saleh, Radwa H; Marston, Gemma; Johnson, Benjamin R G; Freear, Steven; Coletta, P Louise; Markham, Alexander F; Evans, Stephen D

    2016-02-21

    Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo. However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10(6) particles per s and at high concentration, typically >10(11) particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C4F10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition. PMID:26689151

  11. The Effects of Image and Animation in Enhancing Pedagogical Agent Persona

    ERIC Educational Resources Information Center

    Baylor, Amy L.; Ryu, Jeeheon

    2003-01-01

    The purpose of this experimental study was to test the role of image and animation on: a) learners' perceptions of pedagogical agent persona characteristics (i.e., extent to which agent was person-like, engaging, credible, and instructor-like); b) agent value; and c) performance. The primary analysis consisted of two contrast comparisons: 1)…

  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. 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

  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. 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

  16. Time-Resolved Spectroscopy and Near Infrared Imaging for Prostate Cancer Detection: Receptor-targeted and Native Biomarker

    NASA Astrophysics Data System (ADS)

    Pu, Yang

    Optical spectroscopy and imaging using near-infrared (NIR) light provides powerful tools for non-invasive detection of cancer in tissue. Optical techniques are capable of quantitative reconstructions maps of tissue absorption and scattering properties, thus can map in vivo the differences in the content of certain marker chromophores and/or fluorophores in normal and cancerous tissues (for example: water, tryptophan, collagen and NADH contents). Potential clinical applications of optical spectroscopy and imaging include functional tumor detection and photothermal therapeutics. Optical spectroscopy and imaging apply contrasts from intrinsic tissue chromophores such as water, collagen and NADH, and extrinsic optical contrast agents such as Indocyanine Green (ICG) to distinguish disease tissue from the normal one. Fluorescence spectroscopy and imaging also gives high sensitivity and specificity for biomedical diagnosis. Recent developments on specific-targeting fluorophores such as small receptor-targeted dye-peptide conjugate contrast agent offer high contrast between normal and cancerous tissues hence provide promising future for early tumour detection. This thesis focus on a study to distinguish the cancerous prostate tissue from the normal prostate tissues with enhancement of specific receptor-targeted prostate cancer contrast agents using optical spectroscopy and imaging techniques. The scattering and absorption coefficients, and anisotropy factor of cancerous and normal prostate tissues were investigated first as the basis for the biomedical diagnostic and optical imaging. Understanding the receptors over-expressed prostate cancer cells and molecular target mechanism of ligand, two small ICG-derivative dye-peptides, namely Cypate-Bombesin Peptide Analogue Conjugate (Cybesin) and Cypate-Octreotate Peptide Conjugate (Cytate), were applied to study their clinical potential for human prostate cancer detection. In this work, the steady-state and time

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

    NASA Astrophysics Data System (ADS)

    Cheng, Liang; Wang, Chao; Liu, Zhuang

    2012-12-01

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

  18. 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

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

    PubMed

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

    2014-06-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis. PMID:26579381

  20. 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. |

  1. 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.

  2. 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.

  3. 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

  4. 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. PMID:25453958

  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. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. State-of-the-art imaging of prostate cancer.

    PubMed

    Marko, Jamie; Gould, C Frank; Bonavia, Grant H; Wolfman, Darcy J

    2016-03-01

    Prostate cancer is the most common cancer in men. Modern medical imaging is intimately involved in the diagnosis and management of prostate cancer. Ultrasound is primarily used to guide prostate biopsy to establish the diagnosis of prostate carcinoma. Prostate magnetic resonance imaging uses a multiparametric approach, including anatomic and functional imaging sequences. Multiparametric magnetic resonance imaging can be used for detection and localization of prostate cancer and to evaluate for disease recurrence. Computed tomography and scintigraphic imaging are primarily used to detect regional lymph node spread and distant metastases. Recent advancements in ultrasound, multiparametric magnetic resonance imaging, and scintigraphic imaging have the potential to change the way prostate cancer is diagnosed and managed. This article addresses the major imaging modalities involved in the evaluation of prostate cancer and updates the reader on the state of the art for each modality. PMID:26087969

  9. Radioiodinated fenetylline (captagon): A new potential brain imaging agent

    SciTech Connect

    Biersack, H.J.; Klunenberg, H.; Breuel, H.P.; Reske, S.N.; Reichmann, K.; Winkler, C.

    1984-01-01

    Since about 2 years /sup 123/I-labeled iodamphetamines (IMP) and diamines (HIPDM) have been used for scintigraphic brain investigations. As another possibly useful brain imaging agent we studied radioiodine labeled Fenetylline which is metabolized into amphetamine. Thirty wistar rats were injected 5 ..mu..Ci /sup 125/I-IMP and 2 ..mu..Ci /sup 131/I-Fenetylline each simultaneously. The animals were sacrificed 5,10,15,30,60, and 120 min. p.i. The radioactivity content of tissue specimens (brain, cerebellum, liver, kidney, lung, myocardium, muscle) was measured in a well-counter (% dose/g tissue). In 2 dogs sequential cerebral scintigraphy was performed following the injection of 0.5 mCi /sup 131/I-Fenetylline. Three patients underwent brain SPECT after injection of 6.5 mCi /sup 123/I-Fenetylline. The results can be summarized as follows: after 5/10 min. p.i. Fenetylline-uptake in the brain of rats was 1.0/1.3% compared to 1.3/1.9% (IMP). A fast decrease of cerebral Fenetylline concentration was established after 30 (0.2%) and 60 (0.5%) min. The canine and human sequential scintigraphy revealed a rapid cerebral uptake (maximum after 2-10 min.) suggesting that Fenetylline is concentrated in the brain as a function of cerebral blood flow. From the first clinical findings it appears to be likely that the combined use of /sup 123/I labelled IMP and Fenetylline for SPECT may lead to a more differentiated evaluation of cerebral blood flow and metabolism.

  10. Salinomycin: A Novel Anti-Cancer Agent with Known Anti-Coccidial Activities

    PubMed Central

    Zhou, Shuang; Wang, Fengfei; Wong, Eric T.; Fonkem, Ekokobe; Hsieh, Tze-Chen; Wu, Joseph M.; Wu, Erxi

    2014-01-01

    Salinomycin, traditionally used as an anti-coccidial drug, has recently been shown to possess anti-cancer and anti-cancer stem cell (CSC) effects, as well as activities to overcome multi-drug resistance based on studies using human cancer cell lines, xenograft mice, and in case reports involving cancer patients in pilot clinical trials. Therefore, salinomycin may be considered as a promising novel anti-cancer agent despite its largely unknown mechanism of action. This review summarizes the pharmacologic effects of salinomycin and presents possible mechanisms by which salinomycin exerts its anti-tumorigenic activities. Recent advances and potential complications that might limit the utilization of salinomycin as an anti-cancer and anti-CSC agent are also presented and discussed. PMID:23931281

  11. 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

  12. Towards (99m)Tc-based imaging agents with effective doxorubicin mimetics: a molecular and cellular study.

    PubMed

    Imstepf, S; Pierroz, V; Raposinho, P; Felber, M; Fox, T; Fernandes, C; Gasser, G; Santos, I R; Alberto, R

    2016-08-16

    Doxorubicin is a clinical benchmark drug, which is applied in the treatment of numerous cancers. Known for its accumulation in the nucleus and ability to intercalate into DNA, it targets quickly dividing i.e. hypermitotic cells. Through this mechanism, it could be an ideal structural motif for a new class of imaging agents, given that the new entity approximates the in vitro profile of the parent drug. Here we describe design, synthesis and biological activity of a small array of Doxorubicin-metalloconjugates (M = (99m)Tc, Re). We demonstrate that the conjugates preferably accumulate in the nuclear compartment, tightly bind to DNA and retain an appreciable cytotoxicity. Moreover, the Re conjugates effectively act as inhibitors of the human Topoisomerase II enzyme, which is the widely accepted mechanism of action of the parent drug. Since the conjugates effectively mimic the in vitro behavior of native Doxorubicin, the (99m)Tc compounds are prospective imaging agents. PMID:27097328

  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. 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.

  15. 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.

  16. 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

  17. 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.

  18. Imaging and IGRT in Liver Cancer

    PubMed Central

    Brock, Kristy K.

    2012-01-01

    Imaging for radiation therapy treatment planning and delivery is a critical component of the radiation planning process for liver cancer. Due to the lack of inherent contrast between liver tumors and the surrounding liver, intravenous contrast is required for accurate target delineation on the planning CT. The appropriate phase of contrast is tumor specific, with arterial phase imaging usually used to define hepatocellular carcinoma, and venous phase imaging for vascular thrombosis related to hepatocellular carcinoma and most types of liver metastases. Breathing motion and changes in the liver position day-to-day may be substantial and need to be considered at the time of radiation planning and treatment. Many types of integrated imaging-radiation treatment systems and image guidance strategies are available to produce volumetric and/or planar imaging at the time of treatment delivery to reduce the negative impact of geometric changes that may occur. Image guided radiation therapy (IGRT) can improve the precision of radiation therapy, so that the prescribed doses are more likely to represent those actually delivered. PMID:21939853

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. Novel compounds in the treatment of lung cancer: current and developing therapeutic agents

    PubMed Central

    Bao, Rudi; Chan, Pokman

    2011-01-01

    Lung cancer is the leading cause of cancer-related death in the United States. Though incremental advances have been made in the treatment of this devastating disease during the past decade, new therapies are urgently needed. Traditional cytotoxic agents have been combined with other modalities with improved survival for early-stage patients. Newer cytotoxic agents targeting the same or different mechanisms have been developed at different stages. Optimization of various chemotherapy regimens in different settings is one of the aims of current clinical trials. Some predictive biomarkers (eg, excision repair cross-complementing 1, ERCC1) and histotypes (eg, adenocarcinoma) are found to be associated with resistance/response to some cytotoxic drugs. Another notable advance is the addition of targeted therapy to lung cancer treatment. Targeted agents such as erlotinib and bevacizumab have demonstrated clinical benefits and gained Food and Drug Administration approval for lung cancer. More agents targeting various signaling pathways critical to lung cancer are at different stages of development. Along with the effort of new targeted drug discovery, biomarkers such as epidermal growth factor receptor and anaplastic lymphoma kinase mutations have proven useful for patient selection, and more predictive biomarkers have been actively evaluated in non-small cell lung cancer. The paradigm of lung cancer treatment has shifted towards biomarker-based personalized medicine.

  6. Peptide-conjugated nanoparticles for targeted imaging and therapy of prostate cancer.

    PubMed

    Yeh, Chen-Yun; Hsiao, Jong-Kai; Wang, Yi-Ping; Lan, Chun-Hsin; Wu, Han-Chung

    2016-08-01

    While there has been extensive development of anti-cancer drugs for treatment of prostate cancer, the therapeutic efficacy of such drugs remains inadequate in many cases. Here, we performed in vitro biopanning of the PC3 human prostate carcinoma cell line to select prostate cancer-specific peptides by phage display. We successfully identified specific peptides targeting prostate cancer cells, and their specificity was confirmed by cellular ELISA and flow cytometry. Moreover, we found that the phage clones also recognize other prostate cancer cell lines and surgical specimens from prostate cancer patients. The tumor targeting ability of these phages was validated in a xenograft model, in which high accumulation of targeting phage was observed. To investigate whether selected peptides are able to target tumors and enhance drug delivery into cancer cells, we synthesized peptide-PEGylated lipids and post-inserted them into preformed liposomal doxorubicin and vinorelbine. The results of our cellular uptake and MTT assays indicate that peptide-conjugated liposomes exhibit enhanced drug intracellular delivery and cytotoxicity. The conjugation of targeting peptide to imaging agents, such as quantum dots (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs), results in more precise delivery of these agents to tumor sites. Furthermore, administration of liposomal doxorubicin and vinorelbine conjugated with targeting peptides was found to markedly increase the inhibition of human prostate tumor growth in mouse xenograft and orthotopic models. These results indicate that targeting peptide, SP204, has significant potential for targeted therapy and molecular imaging in prostate cancer. PMID:27209258

  7. Theranostic applications of nanomaterials in cancer: Drug delivery, image-guided therapy and multifunctional platforms

    PubMed Central

    Fernandez-Fernandez, Alicia; Manchanda, Romila

    2011-01-01

    Successful cancer management depends on accurate diagnostics along with specific treatment protocols. Current diagnostic techniques need to be improved to provide earlier detection capabilities, and traditional chemotherapy approaches to cancer treatment are limited by lack of specificity and systemic toxicity. This review highlights advances in nanotechnology that have allowed the development of multifunctional platforms for cancer detection, therapy, and monitoring. Nanomaterials can be used as MRI, optical imaging, and photoacoustic imaging contrast agents. When used as drug carriers, nanoformulations can increase tumor exposure to therapeutic agents and result in improved treatment effects by prolonging circulation times, protecting entrapped drugs from degradation, and enhancing tumor uptake through the EPR effect as well as receptor-mediated endocytosis. Multiple therapeutic agents such as chemotherapy, antiangiogenic, or gene therapy agents can be simultaneously delivered by nanocarriers to tumor sites to enhance the effectiveness of therapy. Additionally, imaging and therapy agents can be co-delivered to provide seamless integration of diagnostics, therapy and follow-up, and different therapeutic modalities such as chemotherapy and hyperthermia can be coadministered to take advantage of synergistic effects. Liposomes, metallic nanoparticles, polymeric nanoparticles, dendrimers, carbon nanotubes, and quantum dots are examples of nanoformulations that can be used as multifunctional platforms for cancer theranostics. Nanomedicine approaches in cancer have great potential for clinically translatable advances that can positively impact the overall diagnostic and therapeutic process, and result in enhanced quality of life for cancer patients. However, a concerted scientific effort is still necessary to fully explore long-term risks, effects, and precautions for safe human use. PMID:21947761

  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. 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

  10. Investigation of gastric cancers in nude mice using X-ray in-line phase contrast imaging

    PubMed Central

    2014-01-01

    Background This paper is to report the new imaging of gastric cancers without the use of imaging agents. Both gastric normal regions and gastric cancer regions can be distinguished by using the principal component analysis (PCA) based on the gray level co-occurrence matrix (GLCM). Methods Human gastric cancer BGC823 cells were implanted into the stomachs of nude mice. Then, 3, 5, 7, 9 or 11 days after cancer cells implantation, the nude mice were sacrificed and their stomachs were removed. X-ray in-line phase contrast imaging (XILPCI), an X-ray phase contrast imaging method, has greater soft tissue contrast than traditional absorption radiography and generates higher-resolution images. The gastric specimens were imaged by an XILPCIs’ charge coupled device (CCD) of 9 μm image resolution. The PCA of the projective images’ region of interests (ROIs) based on GLCM were extracted to discriminate gastric normal regions and gastric cancer regions. Different stages of gastric cancers were classified by using support vector machines (SVMs). Results The X-ray in-line phase contrast images of nude mice gastric specimens clearly show the gastric architectures and the details of the early gastric cancers. The phase contrast computed tomography (CT) images of nude mice gastric cancer specimens are better than the traditional absorption CT images without the use of imaging agents. The results of the PCA of the texture parameters based on GLCM of normal regions is (F1 + F2) > 8.5, but those of cancer regions is (F1 + F2) < 8.5. The classification accuracy is 83.3% that classifying gastric specimens into different stages using SVMs. Conclusions This is a very preliminary feasibility study. With further researches, XILPCI could become a noninvasive method for future the early detection of gastric cancers or medical researches. PMID:25060352

  11. 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

  12. 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.

  13. Multimeric Near IR–MR Contrast Agent for Multimodal In Vivo Imaging

    PubMed Central

    2015-01-01

    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. PMID:26083313

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

    PubMed Central

    Hadaki, Maher; Harrison, Mark

    2013-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed

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

    2014-09-22

    Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based "nanobubble" contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

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

    PubMed Central

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

    2014-01-01

    Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based “nanobubble” contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

  18. Differentiating Between Cancer and Inflammation: A Metabolic-Based Method for Functional Computed Tomography Imaging.

    PubMed

    Motiei, Menachem; Dreifuss, Tamar; Betzer, Oshra; Panet, Hana; Popovtzer, Aron; Santana, Jordan; Abourbeh, Galith; Mishani, Eyal; Popovtzer, Rachela

    2016-03-22

    One of the main limitations of the highly used cancer imaging technique, PET-CT, is its inability to distinguish between cancerous lesions and post treatment inflammatory conditions. The reason for this lack of specificity is that [(18)F]FDG-PET is based on increased glucose metabolic activity, which characterizes both cancerous tissues and inflammatory cells. To overcome this limitation, we developed a nanoparticle-based approach, utilizing glucose-functionalized gold nanoparticles (GF-GNPs) as a metabolically targeted CT contrast agent. Our approach demonstrates specific tumor targeting and has successfully distinguished between cancer and inflammatory processes in a combined tumor-inflammation mouse model, due to dissimilarities in angiogenesis occurring under different pathologic conditions. This study provides a set of capabilities in cancer detection, staging and follow-up, and can be applicable to a wide range of cancers that exhibit high metabolic activity. PMID:26886076

  19. 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

  20. [A new lymph node imaging agent--99mTc-polyphase liposome oleatis (99mTc-plo)].

    PubMed

    Yu, B F

    1988-07-01

    A new lymph node radio-imaging agent, technetium-99m polyphase liposome oleatis (99mTc-plo), has recently been developed. Polyphase liposome oleatis was labelled with radionuclide by stannous chloride method. The labelled rate was 90% or more as technically identified by thin layer chromatography, external gamma-camera imaging and radioautography. In animal experiment, 0.2-0.3 ml (0.2 mci) of the 99mTc-plo was injected subcutaneously into the toes web of rats. After half an hour, the regional lymph nodes of popliteal fossa were visualized very clearly. The imaging figures may keep their distinct shadow up to 24 hours. The tested rabbits were sacrificed 10 hours after 99mTc-plo injection for detecting various kinds of tissue and organ with a scintillation counter. The regional lymph nodes revealed the highest uptake rate of the new agent, 12,116; 1,303; 1,615 times higher than that of the adjacent muscles, liver and spleen, respectively. In clinical experiment, 0.2-0.3 ml (0.5-0.8 mci) of the 99mTc-plo was injected subcutaneously into the toes web of patients. Half an hour later, the lymph nodes of inguinal, external iliac and common iliac regions appeared in sequence. If the new agent is injected perianally, the internal iliac lymph nodes will be seen. No side effect was observed in both types of experiment. This new agent has been tried in rats, rabbits and dogs with similar positive results. The new lymph node imaging technique is simple, safe, reliable and reproducible. This agent, being directed toward the lymph nodes and possessing affinity to cancer cells, is expected to be supplementary method to CT and B-ultrasonography for detecting lymphoid malignancy and lymph node metastasis. PMID:3248482

  1. 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.

  2. Significance of Infectious Agents in Colorectal Cancer Development

    PubMed Central

    Antonic, Vlado; Stojadinovic, Alexander; Kester, Kent E.; Weina, Peter J; Brücher, Björn LDM; Protic, Mladjan; Avital, Itzhak; Izadjoo, Mina

    2013-01-01

    Colorectal cancer (CRC) is a major burden to healthcare systems worldwide accounting for approximately one million of new cancer cases worldwide. Even though, CRC mortality has decreased over the last 20 years, it remains the third most common cause of cancer-related mortality, accounting for approximately 600,000 deaths in 2008 worldwide. A multitude of risk factors have been linked to CRC, including hereditary factors, environmental factors and inflammatory syndromes affecting the gastrointestinal tract. Recently, various pathogens were added to the growing list of risk factors for a number of common epithelial cancers, but despite the multitude of correlative studies, only suggestions remain about the possible relationship between selected viruses and bacteria of interest and the CRC risk. United States military service members are exposed to various risk factors impacting the incidence of cancer development. These exposures are often different from that of many sectors of the civilian population. Thereby, cancer risk identification, screening and early detection are imperative for both the military health care beneficiaries and the population as a whole. In this review, we will focus on several pathogens and their potential roles in development of CRC, highlighting the clinical trials evaluating this correlation and provide our personal opinion about the importance of risk reduction, health promotion and disease prevention for military health care beneficiaries. PMID:23459622

  3. Experimental characterization, comparison and image quality assessment of two ultrasound contrast agents: Optison and Definity

    NASA Astrophysics Data System (ADS)

    Hughes, Amy C.; Day, Steven W.; Linte, Cristian A.; Schwarz, Karl Q.

    2016-04-01

    Microbubble-based contrast agents are commonly used in ultrasound imaging to help differentiate the blood pool from the endocardial wall. It is essential to use an agent which produces high image intensity relative to the surrounding tissue, commonly referred to contrast effect. When exposed to ultrasound waves, microbubbles produce an intense backscatter signal in addition to the contrast produced by the fluctuating size of the microbubbles. However, over time, the microbubble concentration depletes, leading to reduced visual enhancement. The retention time associated with contrast effect varies according to the frequency and power level of the ultrasound wave, as well as the contrast agent used. The primary objective of this study was to investigate and identify the most appropriate image acquisition parameters that render optimal contrast effect for two intravenous contrast agents, Optison™ and Definity™. Several controlled in vitro experiments were conducted using an experimental apparatus that featured a perfused tissue-emulating phantom. A continuous flow of contrast agent was imaged using ultrasound at different frequencies and power levels, while a pulse wave Doppler device was used to monitor the concentration of the contrast agent solution. The contrast effect was determined based on the image intensity inside the flow pipe mimicking the blood-pool relative to the intensity of the surrounding phantom material mimicking cardiac tissue. To identify the combination of parameters that yielded optimal visualization for each contrast agent tested, the contrast effect was assessed at different microbubble concentrations and different ultrasound imaging frequencies and transmission power levels.

  4. Targeting the androgen receptor in prostate and breast cancer – several new agents in development

    PubMed Central

    Proverbs-Singh, Tracy; Feldman, Jarett L.; Morris, Michael J.; Autio, Karen A.; Traina, Tiffany A.

    2016-01-01

    Prostate cancer and breast cancer share similarities as hormone-sensitive cancers with a wide heterogeneity of both phenotype and biology. The androgen receptor (AR) is a hormone receptor involved in both benign and malignant processes. Targeting androgen synthesis and the AR pathway has been and remains central to prostate cancer therapy. Recently, there is increased interest in the role of the AR in breast cancer development and growth, with data suggesting AR co-expression with estrogen, progesterone and human epidermal growth factor receptors, across all intrinsic subtypes of breast cancer. Targeting the AR axis is an evolving field with novel therapies in development which may ultimately be applicable for both tumor types. In this review, we offer an overview of available agents which target the AR axis in both prostate and breast cancer and provide insight into the novel drugs in development for targeting this signaling pathway. PMID:25722318

  5. 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.

  6. 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.

  7. Engineered Iron-Oxide-Based Nanoparticles as Enhanced T1 Contrast Agents for Efficient Tumor Imaging

    PubMed Central

    Zhou, Zijian; Wang, Lirong; Chi, Xiaoqin; Bao, Jianfeng; Yang, Lijiao; Zhao, Wenxiu; Chen, Zhong; Wang, Xiaomin; Chen, Xiaoyuan; Gao, Jinhao

    2013-01-01

    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. PMID:23473444

  8. Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

    PubMed

    Coelho, Bianca Feliciano; de Souza Albernaz, Marta; Iscaife, Alexandre; Moreira Leite, Katia Ramos; de Souza Junqueira, Mara; Bernardes, Emerson Soares; da Silva, Emerson Oliveira; Santos-Oliveira, Ralph

    2015-01-01

    Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radiopharmaceuticals for many years; however, their use as nanoradiopharmaceuticals is very innovative and creates a new way to establish radiopharmacy in this new scenario offered by nanotechnology. In this study we developed and tested nano-MDP-labelled with 99mTc in rats induced with bone cancer metastasis and the results showed that it may work in patients. However, some further experiments are required in order to initiate protocols in humans. PMID:25847010

  9. Targeting cancer stem-like cells using dietary-derived agents - Where are we now?

    PubMed

    Khan, Sameena; Karmokar, Ankur; Howells, Lynne; Thomas, Anne L; Bayliss, Richard; Gescher, Andreas; Brown, Karen

    2016-06-01

    Diet has been linked to an overwhelming proportion of cancers. Current chemotherapy and targeted therapies are limited by toxicity and the development of resistance against these treatments results in cancer recurrence or progression. In vitro evidence indicates that a number of dietary-derived agents have activity against a highly tumorigenic, chemoradiotherapy resistant population of cells within a tumour. This population is associated with cancer recurrence and is therefore clinically significant. Targeting this subpopulation, termed cancer stem-like cells with dietary-derived agents provides a potentially low toxicity strategy to enhance current treatment regimens. In addition, dietary-derived compounds also provide a novel approach to cancer prevention strategies. This review focusses on selected diet-derived agents that have been shown to specifically target cancer stem-like cells using in vivo models, or in clinical trials. Furthermore, the potential limitations of these studies are discussed, and areas of research that need to be addressed to allow successful translation of dietary-derived agents to the clinical arena are highlighted. PMID:27060283

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

    PubMed

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

    2013-03-01

    Quinones are plant-derived secondary metabolites that present some anti-proliferation and anti-metastasis effects in various cancer types both in vitro and in vivo. This review focuses on the anti-cancer prospects of plant-derived quinones, namely, aloe-emodin, juglone, β-lapachol, plumbagin, shikonin, and thymoquinone. We intend to summarize their anti-cancer effects and investigate the mechanism of actions to promote the research and development of anti-cancer agents from quinones. PMID:22931417

  11. Speeding up the Evaluation of New Agents in Cancer

    PubMed Central

    Barthel, Friederike. M.-S.; Sydes, Matthew; Langley, Ruth; Kaplan, Rick; Eisenhauer, Elizabeth; Brady, Mark; James, Nicholas; Bookman, Michael A.; Swart, Ann-Marie; Qian, Wendi; Royston, Patrick

    2008-01-01

    Despite both the increase in basic biologic knowledge and the fact that many new agents have reached various stages of development during the last 10 years, the number of new treatments that have been approved for patients has not increased as expected. We propose the multi-arm, multi-stage trial design as a way to evaluate treatments faster and more efficiently than current standard trial designs. By using intermediate outcomes and testing a number of new agents (and combinations) simultaneously, the new design requires fewer patients. Three trials using this methodology are presented. PMID:18728279

  12. Study of suspending agents for gadolinium(III)-exchanged hectorite. An oral magnetic resonance imaging contrast agent

    SciTech Connect

    Balkus, K.J. Jr.; Shi, J.

    1996-12-25

    Clays modified with paramagnetic ions have been shown to be effective magnetic resonance imaging contrast agents. The efficacy in part relies on the suspension of the small clay particles in aqueous solution. In this study a series of macromolecules were eveluated as suspending agents for Gd(III) ion exchanged hectorite clay in water. The room temperature relaxivities for the Gd-hectorite clays were enhanced by the addition of poly(ethylene oxide), poly(ethylene glycol), cyclodextrins, and cholic acid to aqueous suspensions. Additionally, there was no evidence of free Gd(III) in solution in the presence of these suspending agents. In contrast the combination of alginic acid or poly(sodium 4-styrenesulfonate) with the clays resulted in release of the Gd(III) into solution. Xanthan gum, which is often used as an emulsifier and stabilizer in food products, forms a viscous suspension but also reacts with free Gd(III) ions. 25 refs., 10 figs., 2 tabs.

  13. 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

  14. Microbubble embedded with upconversion nanoparticles as a bimodal contrast agent for fluorescence and ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Jin, Birui; Lin, Min; You, Minli; Zong, Yujin; Wan, Mingxi; Xu, Feng; Duan, Zhenfeng; Lu, Tianjian

    2015-08-01

    Bimodal imaging offers additional imaging signal thus finds wide spread application in clinical diagnostic imaging. Fluorescence/ultrasound bimodal imaging contrast agent using fluorescent dyes or quantum dots for fluorescence signal has emerged as a promising method, which however requires visible light or UV irradiation resulting in photobleaching, photoblinking, auto-fluorescence and limited tissue penetration depth. To surmount these problems, we developed a novel bimodal contrast agent using layer-by-layer assembly of upconversion nanoparticles onto the surface of microbubbles. The resulting microbubbles with average size of 2 μm provide enhanced ultrasound echo for ultrasound imaging and upconversion emission upon near infrared irradiation for fluorescence imaging. The developed bimodal contrast agent holds great potential to be applied in ultrasound target technique for targeted diseases diagnostics and therapy.

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

    PubMed Central

    Gupta, Suneet; Porwal, Rabins

    2016-01-01

    Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images. PMID:27127497

  16. One-Shot Immunomodulatory Nanodiamond Agents for Cancer Immunotherapy.

    PubMed

    Zhang, Yu; Cui, Zhifen; Kong, Huating; Xia, Kai; Pan, Liang; Li, Jiang; Sun, Yanhong; Shi, Jiye; Wang, Lihua; Zhu, Ying; Fan, Chunhai

    2016-04-01

    The use of functional nanodiamonds (fNDs) to deliver CpG oligonucleotides (ODNs) for sustained immunostimulation is reported. It is demonstrated that monotherapy using this immunostimulatory agent significantly suppresses the tumor growth in two murine tumor models. This fND-based nanoagent opens new opportunities for immunotherapy, as well as clinical applications of various types of therapeutic nucleic acids. PMID:26833992

  17. First Pharmacophore-Based Identification of Androgen Receptor Down-regulating Agents: Discovery of Potent Anti-Prostate Cancer Agents

    PubMed Central

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Chopra, Pankaj; Maheshwari, Neha; Gediya, Lalji K; Vasaitis, Tadas S.; Bruno, Robert; Clement, Omoshile O.; Njar, Vincent C. O.

    2007-01-01

    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 6 new ARDAs (EC50 values 17.5 – 212 μM). 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

  18. 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

  19. Imaging for staging and management of thyroid cancer

    PubMed Central

    2008-01-01

    Abstract The management of thyroid cancer has been controversial and, as a result, the routine use of imaging in this disease, especially for pre-operative staging, has lagged behind other head and neck cancers. However, as more is known about the natural history of thyroid cancer, the role of imaging is becoming more established. This review focuses on how imaging now influences the staging and management of the primary cancer, nodal metastases and distant metastases. This is followed by a brief review of the role of imaging in planning post-operative radiotherapy and post-treatment surveillance. PMID:18390389

  20. 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.

  1. RAMP: a bioinformatics framework for researching imaging agents through molecular pathways.

    PubMed

    Khokhlovich, Edward; Wahl, Daniel; Masiello, Anthony; Parisot, Pierre; El-Ghatta, Stefan; Szustakowski, Joseph D; Nirmala, Nanguneri; Tuch, David S

    2013-01-01

    Signaling pathways are the fundamental grammar of cellular communication, yet few frameworks are available to analyze molecular imaging probes in the context of signaling pathways. Such a framework would aid in the design and selection of imaging probes for measuring specific signaling pathways and, vice versa, help illuminate which pathways are being assayed by a given probe. RAMP (Researching imaging Agents through Molecular Pathways) is a bioinformatics framework for connecting signaling pathways and imaging probes using a controlled vocabulary of the imaging targets. RAMP contains signaling pathway data from MetaCore, the Kyoto Encyclopedia of Genes and Genomes, and the Gene Ontology project; imaging probe data from the Molecular Imaging and Contrast Agent Database (MICAD); and tissue protein expression data from The Human Protein Atlas. The RAMP search tool is available at . Examples are presented to demonstrate the utility of RAMP for pathway-based searches of molecular imaging probes. PMID:23348786

  2. Novel cytotoxic and biological agents for prostate cancer: where will the money be in 2005?

    PubMed

    Strother, John M; Beer, Tomasz M; Dreicer, Robert

    2005-04-01

    In 2004, docetaxel-based chemotherapy became the first treatment capable of extending life in androgen-independent prostate cancer. The era of therapeutic nihilism in this disease has thus been put to rest and a broad range of agents is being tested with the goal of improving on the successes of 2004. Lessons learned from other tumour types will need to be applied to prostate cancer in order to harness the bounty of available ideas. Target amplification or activating mutations and not merely the presence of a target are likely to be important to the success of targeted agents. Thus, the promise of the current crop of targeted agents is most likely to be realised when pursued in the context of well-credentialed targets and tested in highly translational clinical trials that are capable not only of assessing tumour response, but also of evaluating the status of the targeted pathway. The most promising agents in clinical development are reviewed. PMID:15808961

  3. 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

  4. Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

    PubMed Central

    Shapiro, Mikhail G; Westmeyer, Gil G; Romero, Philip A; Szablowski, Jerzy O; Küster, Benedict; Shah, Ameer; Otey, Christopher R; Langer, Robert; Arnold, Frances H; Jasanoff, Alan

    2011-01-01

    The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h’s paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets. PMID:20190737

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Determining efficacy of cancer chemopreventive agents using a cell-free system concomitant with DNA adduction.

    PubMed

    Smith, W A; Gupta, R C

    1999-03-10

    The large (>2000) and expanding number of natural and synthetic agents with potential cancer chemopreventive properties renders it economically and physically impossible to test each of these agents for their efficacy in the widely accepted 2-year animal bioassay and clinical trials. Therefore, there is a growing need for relevant short-term screening tests to study these compounds such that only the most efficacious ones undergo extensive long-term studies. We have previously reported in a pilot study that the use of a microsome-mediated test system concomitant with DNA adduction is a pertinent and relevant model for rapidly studying the efficacy and mechanisms of cancer chemopreventive agents. We have extended this study to investigate 26 additional agents for their potential chemopreventive abilities by studying their effects on microsome-mediated benzo[a]pyrene (BP)-DNA adduction. These agents had differential effects on the two major adducts of BP-DNA, i.e., BP-7,8-diol-9,10-epoxide (BPDE)-deoxyguanosine (dG) and 9-OH-BP-dG-derived adducts. These agents were therefore categorized into five classes. Three test agents (ellagic acid, genistein and oltipraz) were strong inhibitors of both adducts. These agents diminished BP-DNA adduction by 65-95% and were categorized as Class I agents. Six other agents (benzyl isocyanate, R(+)-1-phenylethyl isocyanate, linoleic acid ethyl ester, (+)-biotin, indole-3-carboxylic acid and beta-carotene) moderately inhibited both BP-DNA adducts (25-64%); these compounds were identified as Class II agents. Six additional test agents inhibited only one adduct selectively and nine others were ineffective; these agents were categorized as Class III and Class IV, respectively. Interestingly, seven test agents enhanced BPDE-dG or 9-OH-BP-dG or both adducts and were categorized as Class V agents. Four of these Class V agents concomitantly inhibited BPDE-dG while enhancing 9-OH-BP-dG. This emphasizes the importance of studying individual DNA

  10. 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

  11. Acetamides: chemotherapeutic agents for inflammation-associated cancers.

    PubMed

    Rani, Priyanka; Pal, Dilipkumar; Hegde, Rahul Rama; Hashim, Syed Riaz

    2016-08-01

    Now clear evidences are available to support the hypothesis that inflammation accelerates the conditions including events and molecules that reach to various types of cancers. Inflammation is a normal response to infection containing the innate and adaptive immune systems. However, when allowed to continue, unresolved, perturbation of cellular microenvironment takes place; therefore, it leads to adaptations in genes that are linked to cancer. In addition, a lot of data are accessible confirming the concept that tumour microenvironment is orchestrated by various inflammatory cells and goes to neoplastic process and finally invasion, migration and metastasis. However, infiltrations of leucocytes lead to angiogenesis, propagation and invasion. An inflammatory microenvironment that perhaps fostering impact of angiogenesis include cytokines, chemokines, enzymes and growth factors that play key role for expansion and invasion of cancer cells. This insight highlights the pathogenesis of inflammation-associated cancers and also touches and fosters the role of acetamides for the treatment and chemoprevention of carcinomas that are allied with inflammation. PMID:26198312

  12. Imaging approach to hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer.

    PubMed

    Fowler, Kathryn J; Saad, Nael E; Linehan, David

    2015-01-01

    Liver imaging is a highly evolving field with new imaging contrast agents and modalities. Knowledge of the different imaging options and what they have to offer in primary and metastatic liver disease is essential for appropriate diagnosis, staging, and prognosis in patients. This review summarizes the major imaging modalities in liver neoplasms and provides specific discussion of imaging hepatocellular carcinoma, cholangiocarcinoma, and colorectal liver metastases. The final sections provide an overview of presurgical imaging relevant to planning hepatectomies and ablative procedures. PMID:25444467

  13. 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.

  14. 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.

  15. DNA Repair and Cancer Therapy: Targeting APE1/Ref-1 Using Dietary Agents

    PubMed Central

    Raffoul, Julian J.; Heydari, Ahmad R.; Hillman, Gilda G.

    2012-01-01

    Epidemiological studies have demonstrated the cancer protective effects of dietary agents and other natural compounds isolated from fruits, soybeans, and vegetables on neoplasia. Studies have also revealed the potential for these natural products to be combined with chemotherapy or radiotherapy for the more effective treatment of cancer. In this paper we discuss the potential for targeting the DNA base excision repair enzyme APE1/Ref-1 using dietary agents such as soy isoflavones, resveratrol, curcumin, and the vitamins ascorbate and α-tocopherol. We also discuss the potential role of soy isoflavones in sensitizing cancer cells to the effects of radiotherapy. A comprehensive review of the dual nature of APE1/Ref-1 in DNA repair and redox activation of cellular transcription factors, NF-κB and HIF-1α, is also discussed. Further research efforts dedicated to delineating the role of APE1/Ref-1 DNA repair versus redox activity in sensitizing cancer cells to conventional treatment are warranted. PMID:22997517

  16. Multiparametric magnetic resonance imaging: Current role in prostate cancer management.

    PubMed

    Ueno, Yoshiko; Tamada, Tsutomu; Bist, Vipul; Reinhold, Caroline; Miyake, Hideaki; Tanaka, Utaru; Kitajima, Kazuhiro; Sugimura, Kazuro; Takahashi, Satoru

    2016-07-01

    Digital rectal examination, serum prostate-specific antigen screening and transrectal ultrasound-guided biopsy are conventionally used as screening, diagnostic and surveillance tools for prostate cancer. However, they have limited sensitivity and specificity. In recent years, the role of multiparametric magnetic resonance imaging has steadily grown, and is now part of the standard clinical management in many institutions. In multiparametric magnetic resonance imaging, the morphological assessment of T2-weighted imaging is correlated with diffusion-weighted imaging, dynamic contrast-enhanced imaging perfusion and/or magnetic resonance spectroscopic imaging. Multiparametric magnetic resonance imaging is currently regarded as the most sensitive and specific imaging technique for the evaluation of prostate cancer, including detection, staging, localization and aggressiveness evaluation. This article presents an overview of multiparametric magnetic resonance imaging, and discusses the current role of multiparametric magnetic resonance imaging in the different fields of prostate cancer management. PMID:27184019

  17. Content-based image retrieval in the World Wide Web: a web agent for fetching portraits

    NASA Astrophysics Data System (ADS)

    Muenkelt, Olaf; Kaufmann, Oliver; Eckstein, Wolfgang

    1997-01-01

    This article propose a way to automatically retrieve images from the world-wide-web using a semantic description for images and an agent concept for the retrieval of images. The system represents image in a textual way, e.g. look for a portrait of the a specific person, or fetch an image showing a countryside in Southern California. This textual descriptions are fed in search machines, e.g. yahoo, alta- vista. The resulting html documents are seeked for links. The next step subsequently processes each link by fetching the document other the net, converting it to an ascii representation, and performing a full text search by using the image description. This leads to starting points of images which are retrieved via a web-agent. The image descriptions are decomposed in a set of parts containing image operations which are further processed, e.g. a set for representing the background of a portrait tries to find a homogeneous region in the image because this is likely to find in a portrait. Additional operations are performed on the foreground, i.e. the image region which contains e.g. the face of a person. The system is realized using two C++ libraries: one for building up web-agents, LIWA++, and one for processing images, HORUS.

  18. Medicinal plants from Peru: a review of plants as potential agents against cancer.

    PubMed

    Gonzales, Gustavo F; Valerio, Luis G

    2006-09-01

    Natural products have played a significant role in drug discovery and development especially for agents against cancer and infectious disease. An analysis of new and approved drugs for cancer by the United States Food and Drug Administration over the period of 1981-2002 showed that 62% of these cancer drugs were of natural origin. Natural compounds possess highly diverse and complex molecular structures compared to small molecule synthetic drugs and often provide highly specific biological activities likely derived from the rigidity and high number of chiral centers. Ethnotraditional use of plant-derived natural products has been a major source for discovery of potential medicinal agents. A number of native Andean and Amazonian medicines of plant origin are used as traditional medicine in Peru to treat different diseases. Of particular interest in this mini-review are three plant materials endemic to Peru with the common names of Cat's claw (Uncaria tomentosa), Maca (Lepidium meyenii), and Dragon's blood (Croton lechleri) each having been scientifically investigated for a wide range of therapeutic uses including as specific anti-cancer agents as originally discovered from the long history of traditional usage and anecdotal information by local population groups in South America. Against this background, we present an evidence-based analysis of the chemistry, biological properties, and anti-tumor activities for these three plant materials. In addition, this review will discuss areas requiring future study and the inherent limitations in their experimental use as anti-cancer agents. PMID:17017852

  19. Magnetic Resonance Imaging with Hyperpolarized 13C Contrast Agents

    NASA Astrophysics Data System (ADS)

    Gordon, Jeremy W.

    Hyperpolarized 13C substrates offer the potential to non-invasively image metabolism and enzymatic activity. However, hyperpolarization introduces a number of difficulties, and imaging is hampered by non-equilibrium magnetization and the need for spectral encoding. There is therefore a need for fast and RF efficient spectral imaging techniques. This work presents a number of new methods that can be used to improve polarization, increase RF efficiency and improve modeling accuracy in hyperpolarized 13C experiments. In particular, a novel encoding and reconstruction algorithm is presented that can generate spatially and spectrally resolved images with a single RF excitation and echo time. This reconstruction framework increases data acquisition efficiency, enabling accelerated acquisition speed, preserved polarization, and/or improved temporal or spatial resolution. Overall, the methods enumerated in this dissertation have the potential to improve modeling accuracy and to mitigate the conventional tradeoffs between SNR, spatial resolution, and temporal resolution that govern image quality in hyperpolarized 13C experiments.

  20. Gold hybrid nanoparticles for targeted phototherapy and cancer imaging

    NASA Astrophysics Data System (ADS)

    Kirui, Dickson K.; Rey, Diego A.; Batt, Carl A.

    2010-03-01

    Gold and iron oxide hybrid nanoparticles (HNPs) synthesized by the thermal decomposition technique are bio-functionalized with a single chain antibody, scFv, that binds to the A33 antigen present on colorectal cancer cells. The HNP-scFv conjugates are stable in aqueous solution with a magnetization value of 44 emu g - 1 and exhibit strong optical absorbance at 800 nm. Here we test this material in targeting, imaging and selective thermal killing of colorectal cancer cells. Cellular uptake studies showed that A33-expressing cells take up the A33scFv-conjugated HNPs at a rate five times higher than cells that do not express the A33 antigen. Laser irradiation studies showed that approximately 53% of the A33-expressing cells exposed to targeted HNPs are killed after a six-minute laser treatment at 5.1 W cm - 2 using a 808 nm continuous wave laser diode while < 5% of A33-nonexpressing cells are killed. At a higher intensity, 31.5 W cm - 2, the thermal destruction increases to 99 and 40% for A33-expressing cells and A33 nonexpressing cells, respectively, after 6 min exposure. Flow cytometric analyses of the laser-irradiated A33 antigen-expressing cells show apoptosis-related cell death to be the primary mode of cell death at 5.1 W cm - 2, with increasing necrosis-related cell death at higher laser power. These results suggest that this new class of bio-conjugated hybrid nanoparticles can potentially serve as an effective antigen-targeted photothermal therapeutic agent for cancer treatment as well as a probe for magnetic resonance-based imaging.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. F-18 fluoromisonidazole for imaging tumor hypoxia: imaging the microenvironment for personalized cancer therapy.

    PubMed

    Rajendran, Joseph G; Krohn, Kenneth A

    2015-03-01

    Hypoxia in solid tumors is one of the seminal mechanisms for developing aggressive trait and treatment resistance in solid tumors. This evolutionarily conserved biological mechanism along with derepression 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. Fluoromisonidazole (FMISO) continues to be the lead radiopharmaceutical in PET imaging for the evaluation, prognostication, and quantification of tumor 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 oxygen partial pressure 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 oxygen partial pressure, 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

  7. 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

  8. Tumor imaging with novel radiogallium (67/68Ga) labeled agents

    NASA Astrophysics Data System (ADS)

    Kulkarni, P. V.; Antich, P. P.; Constantinescu, A.; Ranney, D. F.; Fernando, J. L.; Xiong, R.; Oz, O.; Parkey, R. W.

    1997-02-01

    Gallium-67 (t1/2: 78 h) has played an important role in tumor imaging. It is produced in a cyclotron and is commercially available for routine clinical use. 68Ga (t1/2: 68 min), a positron emitter, suitable for positron emission tomographic (PET) imaging, is obtained from a generator with long lived parent 68Ge (t1/2: 288 d). Radiogallium has been used mostly, as gallium citrate in imaging studies. Recently, receptor specific agents labeled with gallium have been developed. These include, agents to image somatostatin and folate receptors. We have shown that a new class of agents based on glycosaminoglycoans (GLYCOS) target a variety of tumors. Gallium labeled deferroxamine (DF) bound to sulfated glycosaminoglycans has the ability to rapidly target and permeate a wide variety of solid animal tumors and also undergo rapid blood clearance almost exclusively by the renal route. We have been able to image (within 5 min to 1 hr), prostate adenocarcinoma (AT-1 tumor) grown in surgically prepared pedicles of Copenhagen male rats and breast tumor in pedicles of Fisher female rats. 67Ga labeled agent was used in single photon imaging mode and 68Ga labeled agent was used in PET mode with a small animal PET imaging device built in our laboratory with plastic scintillating optical fibers.

  9. Improving the outcome for children with cancer: Development of targeted new agents.

    PubMed

    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 chromosome-positive 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

  10. 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

  11. 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.

  12. Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents.

    PubMed

    Cassady, J M; Baird, W M; Chang, C J

    1990-01-01

    Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered. PMID:2189947

  13. 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. PMID:23170959

  14. Plant-derived anticancer agents - curcumin in cancer prevention and treatment.

    PubMed

    Creţu, Elena; Trifan, Adriana; Vasincu, Al; Miron, Anca

    2012-01-01

    Nowadays cancer is still a major public health issue. Despite all the progresses made in cancer prevention, diagnosis and treatment, mortality by cancer is on the second place after the one caused by cardiovascular diseases. The high mortality and the increasing incidence of certain cancers (lung, prostate, colorectal) justify a growing interest for the identification of new pharmacological agents efficient in cancer prevention and treatment. In the last fifty years many plant-derived agents (vinblastine, vincristine, vindesine, paclitaxel, docetaxel, topotecan, irinotecan, elliptinium) played a major role in cancer treatment. Other very promising plant-derived anticancer agents (combrestatins, betulinic acid, roscovitine, purvalanols, indirubins) are in clinical or preclinical trials. Curcumin, a liposoluble polyphenolic pigment isolated from the rhizomes of Curcuma longa L. (Zingiberaceae), is another potential candidate for new anticancer drug development. Curcumin has been reported to influence many cell-signaling pathways involved in tumor initiation and proliferation. Curcumin inhibits COX-2 activity, cyclin D1 and MMPs overexpresion, NF-kB, STAT and TNF-alpha signaling pathways and regulates the expression of p53 tumor suppressing gene. Curcumin is well-tolerated but has a reduced systemic bioavailability. Polycurcumins (PCurc 8) and curcumin encapsulated in biodegradable polymeric nanoparticles (NanoCurc) showed higher bioavailability than curcumin together with a significant tumor growth inhibition in both in vitro and in vivo studies. BILITY. PMID:23700916

  15. Superparamagnetic And Paramagnetic MRI Contrast Agents: Application Of Rapid Magnetic Resonance Imaging To Assess Renal Function

    NASA Astrophysics Data System (ADS)

    Carvlin, Mark J.; Renshaw, Perry F.; Arger, Peter; Kundel, Harold L.; Dougherty, Larry; Axel, Leon; Kassab, Eleanor; Moore, Bethanne

    1988-06-01

    The paramagnetic chelate complex, gadolinium-diethylene-triamine-pentaacetic acid, Gd-DTPA, and superparamagnetic particles, such as those composed of dextran coated magnetite, function as magnetic resonance contrast agents by changing the relaxation rates, 1/T1 and 1/T2. The effects that these agents have upon MR signal intensity are determined by: the inherent biophysical properties of the tissue being imaged, the concentration of the contrast agent and the data acquisition scheme (pulse sequence parameters) employed. Following the time course of MR signal change in the first minutes after the injection of contrast agent(s) allows a dynamic assessment of organ functions in a manner analogous to certain nuclear medicine studies. In order to study renal function, sequential MR fast scan images, gradient echo (TR=35/TE=7 msec, flip angle=25 degrees), were acquired, one every 12 seconds, after intravenous injection of Gd-DTPA and/or dextran-magnetite. Gd-DTPA, which is freely filtered at the glomerulus and is neither secreted nor reabsorbed, provides information concerning renal perfusion, glomerular filtration and tubular concentrating ability. Dextran-magnetite (200 A diameter), which is primarily contained within the intravascular space shortly after injection, provides information on blood flow to and distribution within the kidney. The MR signal change observed after administration of contrast agents varied dramatically depending upon the agents injected and the imaging parameters used. Hence a broad range of physiolgic processes may be described using these techniques, i.e. contrast agent enhanced functional MR examinations.

  16. Multi-agent systems and neural networks for automatic target recognition on air images

    NASA Astrophysics Data System (ADS)

    Cozien, Roger F.; Rosenberger, Christophe; Eyherabide, Partrick; Rossettini, Joaquim; Ceyrolle, Arnaud

    2000-08-01

    Our purpose is, in medium term, to detect in air images, characteristic shapes and objects such as airports, industrial plants, planes, tanks, trucks, ... with great accuracy and low rate of mistakes. However, we also want to value whether the link between neural networks and multi-agents systems is relevant and effective. If it appears to be really effective, we hope to use this kind of technology in other fields. That would be an easy and convenient way to depict and to use the agents' knowledge which is distributed and fragmented. After a first phase of preliminary tests to know if agents are able to give relevant information to a neural network, we verify that only a few agents running on an image are enough to inform the network and let it generalize the agents' distributed and fragmented knowledge. In a second phase, we developed a distributed architecture allowing several multi- agents systems running at the same time on different computers with different images. All those agents send information to a 'multi neural networks system' whose job is to identify the shapes detected by the agents. The name we gave to our project is Jarod.

  17. Advanced Imaging Among Health Maintenance Organization Enrollees With Cancer

    PubMed Central

    Loggers, Elizabeth T.; Fishman, Paul A.; Peterson, Do; O'Keeffe-Rosetti, Maureen; Greenberg, Caprice; Hornbrook, Mark C.; Kushi, Lawrence H.; Lowry, Sarah; Ramaprasan, Arvind; Wagner, Edward H.; Weeks, Jane C.; Ritzwoller, Debra P.

    2014-01-01

    Purpose: Fee-for-service (FFS) Medicare expenditures for advanced imaging studies (defined as computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET] scans, and nuclear medicine studies [NM]) rapidly increased in the past two decades for patients with cancer. Imaging rates are unknown for patients with cancer, whether under or over age 65 years, in health maintenance organizations (HMOs), where incentives may differ. Materials and Methods: Incident cases of breast, colorectal, lung, prostate, leukemia, and non-Hodgkin lymphoma (NHL) cancers diagnosed in 2003 and 2006 from four HMOs in the Cancer Research Network were used to determine 2-year overall mean imaging counts and average total imaging costs per HMO enrollee by cancer type for those under and over age 65. Results: There were 44,446 incident cancer patient cases, with a median age of 75 (interquartile range, 71-81), and 454,029 imaging procedures were performed. The mean number of images per patient increased from 7.4 in 2003 to 12.9 in 2006. Rates of imaging were similar across age groups, with the exception of greater use of echocardiograms and NM studies in younger patients with breast cancer and greater use of PET among younger patients with lung cancer. Advanced imaging accounted for approximately 41% of all imaging, or approximately 85% of the $8.7 million in imaging expenditures. Costs were nearly $2,000 per HMO enrollee; costs for younger patients with NHL, leukemia, and lung cancer were nearly $1,000 more in 2003. Conclusion: Rates of advanced imaging appear comparable among FFS and HMO participants of any age with these six cancers. PMID:24844241

  18. 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

  19. Anti-angiogenic agents in ovarian cancer: past, present, and future.

    PubMed

    Monk, B J; Minion, L E; Coleman, R L

    2016-04-01

    Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the progression of ovarian cancer through ascites formation and metastatic spread. Bevacizumab (Avastin(®), Genentech; South San Francisco, CA, USA), a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, is the most widely studied anti-angiogenesis agent both across tumor types and specifically in epithelial ovarian cancer. In 2005, single-agent bevacizumab at 15 mg/kg (IV) every 3 weeks was first reported to be active in a case of recurrent high-grade serous ovarian cancer after failing 11th line cytotoxic treatment. Since then, many case series, phase II and phase III trials have confirmed these results leading to regulatory approval in most countries including the US Food and Drug Administration in 2014. Guidelines now give clear recommendations as to when and how bevacizumab should be integrated into the ovarian cancer treatment paradigm. Other anti-VEGF agents such as the VEGF receptor (VEGFR) tyrosine kinase inhibitors have not shown increased activity or reduced toxicity relative to bevacizumab. However, anti-angiogenics other than anti-VEGF/VEGFR agents such as those targeting Angiopoietin-1 and -2 are in development as well as novel combinations with vascular disrupting agents (VDAs), PARP inhibitors and immune checkpoint inhibitors. Clearly, the benefits of anti-angiogenic agents such as bevacizumab must be carefully weighed against the cost and associated toxicities. Although almost all patients with ovarian cancer will receive an anti-angiogenic compound, cures are not increased. Predictive biomarkers are an urgent unmet need. PMID:27141068

  20. 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.

  1. 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

  2. Rapid assessment of drug resistance of cancer cells to gefitinib and carboplatin using optical imaging.

    PubMed

    Luo, Zhen; Samadzadeh, Kiana Michelle; Nitin, Nitin

    2016-07-01

    The overall goal of this study was to evaluate optical molecular imaging approaches to determine the drug response of chemotherapy and molecular targeted agents in drug sensitive and drug resistant cell lines. The optical molecular imaging approaches selected in this study were based on changes in intracellular uptake and retention of choline and glucose molecules. The breast cancer cell lines were treated with a molecular targeted anti-EGFR therapy. The bladder cancer cell lines were treated with a conventional chemotherapy approach. Sensitivity of optical molecular imaging approach was also compared with conventional cell viability and cell growth inhibition assays. Results demonstrate that optical molecular imaging of changes in intracellular uptake of metabolites was effective in detecting drug susceptibility for both molecular targeted therapy in breast cancer cells and chemotherapy in bladder cancer cells. Between the selected metabolites for optical molecular imaging, changes in glucose metabolic activity showed higher sensitivity in discrimination between the drug sensitive and drug resistant cell lines. The results demonstrated that optical molecular imaging approaches more significantly sensitive as compared to the conventional cell viability and growth assays. Overall, the results demonstrate potential of optical molecular imaging of metabolic activity to improve sensitivity of in-vitro drug response assays. PMID:27059751

  3. 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.

  4. 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

  5. Continuous-wave terahertz imaging of nonmelanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Joseph, Cecil Sudhir

    Continuous wave terahertz imaging has the potential to offer a safe, non-invasive medical imaging modality for detecting different types of human skin cancers. Terahertz pulse imaging (TPI) has already shown that there is contrast between basal cell carcinoma and normal skin. Continuous-wave imaging offers a simpler, lower cost alternative to terahertz pulse imaging. This project aims to isolate the optimal contrast frequency for a continuous wave terahertz imaging system and demonstrate transmission based, in-vitro , imaging of thin sections of non-melanoma skin cancers and correlate the images to sample histology. The aim of this project is to conduct a proof-of-principle experiment that establishes whether continuous-wave terahertz imaging can detect differences between cancerous and normal tissue while outlining the basic requirements for building a system capable of performing in vivo tests.

  6. 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.

  7. Self-assembled levan nanoparticles for targeted breast cancer imaging.

    PubMed

    Kim, Sun-Jung; Bae, Pan Kee; Chung, Bong Hyun

    2015-01-01

    We report on the targeted imaging of breast cancer using self-assembled levan nanoparticles. Indocyanine green (ICG) was encapsulated in levan nanoparticles via self-assembly. Levan-ICG nanoparticles were found to be successfully accumulated in breast cancer via specific interaction between fructose moieties in levan and overexpressed glucose transporter 5 in breast cancer cells. PMID:25383444

  8. 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.

  9. 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