WorldWideScience

Sample records for cancer molecular imaging

  1. Molecular imaging in ovarian cancer.

    Science.gov (United States)

    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

  2. Molecular imaging in cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Michalski, Mark H. [Stanford University School of Medicine, Stanford, CA (United States); Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States)

    2011-02-15

    The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. (orig.)

  3. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing radiatio

  4. Molecular imaging of prostate cancer with PET.

    Science.gov (United States)

    Jadvar, Hossein

    2013-10-01

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

  5. Molecular Imaging of Pulmonary Cancer and Inflammation

    OpenAIRE

    Divgi, Chaitanya R.

    2009-01-01

    Molecular imaging (MI) may be defined as imaging in vivo using molecules that report on biologic function. This review will focus on the clinical use of radioactive tracers (nonpharmacologic amounts of compounds labeled with a radioactive substance) that permit external imaging using single photon emission computed tomography (planar, SPECT) or positron emission tomography (PET) imaging. Imaging of lung cancer has been revolutionized with the use of fluorine-18–labeled fluorodeoxyglucose (18F...

  6. Molecular Imaging of Biomarkers in Breast Cancer

    Science.gov (United States)

    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

  7. Molecular imaging of apoptosis in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hakumaeki, Juhana M. [Cellular and Molecular Imaging Group, Department of Biomedical NMR, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland) and Department of Clinical Radiology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)]. E-mail: juhana.hakumaki@uku.fi; Liimatainen, Timo [Cellular and Molecular Imaging Group, Department of Biomedical NMR, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland)

    2005-11-01

    Apoptosis plays an important role in cancer. Mechanisms hindering its action are implicated in a number of malignancies. Also, the induction of apoptosis plays a pivotal role in non-surgical cancer treatment regimes such as irradiation, chemotherapy, or hormones. Recent advanced in imaging science have made it now possible for us to detect and visualize previously inaccessible and even unrecognized biological phenomena in cells and tissue undergoing apoptosis in vivo. Not only are these imaging techniques painting an intriguing picture of the spatiotemporal characteristics and metabolic and biophysical of apoptosis in situ, but they are expected to have an ever increasing impact in preclinical testing and design of new anticancer agents as well. Rapid and accurate visualization of apoptotic response in the clinical settings can also be of significant diagnostic and prognostic worth. With the advent of molecular medicine and patient-tailored treatment options and therapeutic agents, such monitoring techniques are becoming paramount.

  8. Applications of molecular MRI and optical imaging in cancer

    OpenAIRE

    Penet, Marie-France; Mikhaylova, Maria; Li, Cong; Krishnamachary, Balaji; Glunde, Kristine; Pathak, Arvind P.; Bhujwalla, Zaver M.

    2010-01-01

    Some of the most exciting advances in molecular-functional imaging of cancer are occurring at the interface between chemistry and imaging. Several of these advances have occurred through the development of novel imaging probes that report on molecular pathways, the tumor micro-environment and the response of tumors to treatment; as well as through novel image-guided platforms such as nanoparticles and nanovesicles that deliver therapeutic agents against specific targets and pathways. Cancer c...

  9. The Utility of Molecular Imaging in Prostate Cancer.

    Science.gov (United States)

    Leiblich, Aaron; Stevens, Daniel; Sooriakumaran, Prasanna

    2016-03-01

    Prostate cancer is the commonest solid-organ cancer diagnosed in males and represents an important source of morbidity and mortality worldwide. Imaging plays a crucial role in diagnosing prostate cancer and informs the ongoing management of the disease at all stages. Several novel molecular imaging technologies have been developed recently that have the potential to revolutionise disease diagnosis and the surveillance of patients living with prostate cancer. These innovations include hyperpolarised MRI, choline PET/CT and PSMA PET/CT. The major utility of choline and PSMA PET/CT currently lies in their sensitivity for detecting early recurrence after radical treatment for prostate cancer and identifying discrete lesions that may be amenable to salvage therapy. Molecular imaging is likely to play a future role in characterising genetic and biochemical signatures in individual tumours, which may be of particular significance as cancer therapies move into an era of precision medicine. PMID:26894753

  10. Molecular imaging of HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Capala, Jacek; Bouchelouche, Kirsten

    2010-01-01

    HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcome. Therefore, HER2 has become an important prognostic and predictive factor, as well as a target for molecular therapies. The article reviews recent advances in molecular imaging of HER2 that could facilitate...... individual approaches to targeted therapy of HER2-positive breast cancers....

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

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

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

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

    Science.gov (United States)

    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.

  13. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    ABSTRACT: BACKGROUND: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers m

  14. Non-invasive Optical Molecular Imaging for Cancer Detection

    Science.gov (United States)

    Luo, Zhen

    Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide

  15. Status and Advances of RGD Molecular Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning YUE

    2014-12-01

    Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  16. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Science.gov (United States)

    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.

  17. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    Science.gov (United States)

    Subramaniam, Prasad

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

  18. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  19. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    International Nuclear Information System (INIS)

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Bishnu P. [Division of Gastroenterology, Department of Medicine, University of Michigan, School of Medicine, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109 (United States); Wang, Thomas D., E-mail: thomaswa@umich.edu [Division of Gastroenterology, Department of Medicine, University of Michigan, School of Medicine, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109 (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2010-06-11

    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.

  3. Molecular markers in breast cancer: new tools in imaging and prognosis

    OpenAIRE

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared fluorescent labeled (NIRF) tracers for detection of breast cancer. Thus far, only a few molecular imaging tracers have been taken to the clinic of which most are suitable for PET. My thesis describes the e...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

  5. Molecular imaging of cancer: MR spectroscopy and beyond

    International Nuclear Information System (INIS)

    Proton magnetic resonance spectroscopic imaging is a non-invasive diagnostic tool for the investigation of cancer metabolism. As an adjunct to morphologic and dynamic magnetic resonance imaging, it is routinely used for the staging, assessment of treatment response, and therapy monitoring in brain, breast, and prostate cancer. Recently, its application was extended to other cancerous diseases, such as malignant soft-tissue tumours, gastrointestinal and gynecological cancers, as well as nodal metastasis. In this review, we discuss the current and evolving clinical applications of proton magnetic resonance spectroscopic imaging. In addition, we will briefly discuss other evolving techniques, such as phosphorus magnetic resonance spectroscopic imaging, sodium imaging and diffusion-weighted imaging in cancer assessment.

  6. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas

    2006-01-01

    Molecular imaging allows for the study of molecular and cellular events in the living intact organism. The nuclear medicine methodologies of positron emission tomography (PET) and single photon emission computer tomography (SPECT) posses several advantages, which make them particularly suited...

  7. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    International Nuclear Information System (INIS)

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging

  8. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H

    2014-06-01

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

  9. Molecular markers in breast cancer: new tools in imaging and prognosis

    NARCIS (Netherlands)

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared fluoresc

  10. Breast imaging technology: Probing physiology and molecular function using optical imaging - applications to breast cancer

    International Nuclear Information System (INIS)

    The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring

  11. Basic research and clinical application of optical molecular imaging in breast cancer

    International Nuclear Information System (INIS)

    As a rapidly developing biomedical imaging technology,in vivo optical molecular imaging has been widely applied in various research fields owing to its unique real-time, quantitative and noninvasive characteristics. The applications of in vivo optical imaging technology in the basic and clinical research of breast cancer were reviewed, including detection of distant metastasis,tumor apoptosis, cell cycle, hypoxia and angiogenesis, ER-mediated molecular pathway, breast cancer stem cells, early diagnosis, sentinel node biopsy, evaluation of drug efficacy and detection of human epidermal growth factor receptor-2 (HER-2) expression. They all seem to have a promising potential in in vivo optical molecular imaging. (authors)

  12. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qingqing Meng

    2013-01-01

    Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

  13. From molecular imaging to personalized radionuclide therapy of cancer

    International Nuclear Information System (INIS)

    Full text of publication follows. 68Gallium is a positron emitter (t1/2 68 min) which can be produced from a generator in a convenient, 'in-house' preparation and used for labeling of peptides, e.g. somatostatin analogues (SA) like DOTATOC or DOTATATE for molecular imaging of SSTR expressing tumors. Since 2004, we have performed over 7700 68Ga PET/CT studies in patients with neuroendocrine tumors (NET) and have established SSTR PET/CT as the new gold standard for imaging G1 and G2 NET (staging, re-staging, therapy response evaluation and detection of unknown primary NET). The same peptides can be labeled with 177Lutetium or 90Yttrium for radionuclide therapy, a form of personalized treatment (THERANOSTICS approach). PRRNT is based on the receptor-mediated internalization of SA. Several clinical trials indicate that PRRNT can deliver effective radiation doses to tumors. A German multi-institutional registry study with prospective follow up in 450 patients indicates that PRRT is an effective therapy for patients with G1-2 neuroendocrine tumors, irrespective of previous therapies, with a survival advantage of several years compared to other therapies and only minor side effects. Median overall survival (OS) of all patients from the start of treatment was 59 months. Median progression-free survival (PFS) measured from last cycle of therapy accounted to 41 mo. Median PFS of pancreatic NET was 39 mo. Similar results were obtained for NET of unknown primary (median PFS: 38 mo) whereas NET of small bowel had a median PFS of 51 months. Side effects like 3-4 NEThro- or hemato-toxicity were observed in only 0.2% and 2% of patients respectively. PRRNT is highly effective in the management of NET, even in advanced cases. In patients with progressive neuroendocrine tumors, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period of time (Bad Berka Concept using sequential (DUO) PRRNT) results in excellent therapeutic responses. By

  14. Molecular imaging of cancer with radiolabeled peptides and PET.

    Science.gov (United States)

    Vāvere, Amy L; Rossin, Raffaella

    2012-06-01

    Radiolabeled peptides hold promise for diagnosis and therapy of cancer as well as for early monitoring of therapy outcomes, patient stratification, etc. This manuscript focuses on the development of peptides labeled with 18F, 64Cu, 68Ga and other positron-emitting radionuclides for PET imaging. The major techniques for radionuclide incorporation are briefly discussed. Then, examples of positron-emitting peptides targeting somatostatin receptors, integrins, gastrin-releasing peptide receptors, vasointestinal peptide receptors, melanocortin 1 receptors and others are reviewed. PMID:22292762

  15. Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

    Science.gov (United States)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

    2014-11-01

    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

  16. Peptide-Targeted Nanoglobular Gd-DOTA Monoamide Conjugates for Magnetic Resonance Cancer Molecular Imaging

    OpenAIRE

    Tan, Mingqian; Wu, Xueming; Jeong, Eun-Kee; Chen, Qianjin; Lu, Zheng-Rong

    2010-01-01

    Effective imaging of cancer molecular biomarker is critical for accurate cancer diagnosis and prognosis. CLT1 peptide was observed to specifically bind to the fibrin-fibronectin complexes presented in tumor extracellular matrix. In this study, we synthesized and evaluated CLT1 peptide-targeted nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance (MR) imaging of the fibrin-fibronectin complexes in tumor. The targeted nanoglobular contrast agents were prepared by conjugating peptide...

  17. Early Cancer Detection and Targeted Therapy by Magnetic Resonance Molecular Imaging and Nano Medicine

    OpenAIRE

    Li, Zhao

    2015-01-01

    The common theme of my 5-year PhD research is to channel progress in spin physics and nano-bio-materials into meaningful improvements in the theoretical studies, methodological developments, and advanced applications of magnetic resonance (MR) to: 1) MR Molecular Imaging: to detect lesions (especially cancers) at early stages through imaging the existence and locations of physiologically important biomarkers; and2) MR Nano Medicine: to cure diseases (especially cancers) by targeted therapy th...

  18. Molecular imaging of HER2-positive breast cancer: a step toward an individualized 'image and treat' strategy

    DEFF Research Database (Denmark)

    Capala, Jacek; Bouchelouche, Kirsten

    2010-01-01

    HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcome. Therefore, HER2 has become an important prognostic and predictive factor, as well as a target for molecular therapies. The article reviews recent advances in molecular imaging of HER2 that could facilitate...... individual approaches to targeted therapy of HER2-positive breast cancers....

  19. Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer

    OpenAIRE

    Wu, Xueming; Burden-Gulley, Susan M.; Yu, Guan-Ping; Tan, Mingqian; Lindner, Daniel; Brady-Kalnay, Susann M.; Lu, Zheng-Rong

    2012-01-01

    Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)4 specific to clotted plasma proteins in tumor stroma for cancer MR molecula...

  20. Molecular and Functional Imaging for Detection of Lymph Node Metastases in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ansje Fortuin

    2013-07-01

    Full Text Available Knowledge on lymph node metastases is crucial for the prognosis and treatment of prostate cancer patients. Conventional anatomic imaging often fails to differentiate benign from metastatic lymph nodes. Pelvic lymph node dissection is an invasive technique and underestimates the extent of lymph node metastases. Therefore, there is a need for more accurate non-invasive diagnostic techniques. Molecular and functional imaging has been subject of research for the last decades, in this respect. Therefore, in this article the value of imaging techniques to detect lymph node metastases is reviewed. These techniques include scintigraphy, sentinel node imaging, positron emission tomography/computed tomography (PET/CT, diffusion weighted magnetic resonance imaging (DWI MRI and magnetic resonance lymphography (MRL. Knowledge on pathway and size of lymph node metastases has increased with molecular and functional imaging. Furthermore, improved detection and localization of lymph node metastases will enable (focal treatment of the positive nodes only.

  1. Molecular and functional imaging for detection of lymph node metastases in prostate cancer.

    Science.gov (United States)

    Fortuin, Ansje; Rooij, Maarten de; Zamecnik, Patrik; Haberkorn, Uwe; Barentsz, Jelle

    2013-07-03

    Knowledge on lymph node metastases is crucial for the prognosis and treatment of prostate cancer patients. Conventional anatomic imaging often fails to differentiate benign from metastatic lymph nodes. Pelvic lymph node dissection is an invasive technique and underestimates the extent of lymph node metastases. Therefore, there is a need for more accurate non-invasive diagnostic techniques. Molecular and functional imaging has been subject of research for the last decades, in this respect. Therefore, in this article the value of imaging techniques to detect lymph node metastases is reviewed. These techniques include scintigraphy, sentinel node imaging, positron emission tomography/computed tomography (PET/CT), diffusion weighted magnetic resonance imaging (DWI MRI) and magnetic resonance lymphography (MRL). Knowledge on pathway and size of lymph node metastases has increased with molecular and functional imaging. Furthermore, improved detection and localization of lymph node metastases will enable (focal) treatment of the positive nodes only.

  2. Molecular imaging of hypoxia in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  3. Preanalytical considerations in detection of colorectal cancer in blood serum using Raman molecular imaging (Conference Presentation)

    Science.gov (United States)

    Treado, Patrick J.; Stewart, Shona D.; Smith, Aaron; Kirschner, Heather; Post, Christopher; Overholt, Bergein F.

    2016-03-01

    Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. Raman Molecular Imaging (RMI) is an effective technique to evaluate human tissue, cells and bodily fluids, including blood serum for disease diagnosis. ChemImage Corporation, in collaboration with clinicians, has been engaged in development of an in vitro diagnostic Raman assay focused on CRC detection. The Raman Assay for Colorectal Cancer (RACC) exploits the high specificity of Raman imaging to distinguish diseased from normal dried blood serum droplets without additional reagents. Pilot Study results from testing of hundreds of biobank patient samples have demonstrated that RACC detects CRC with high sensitivity and specificity. However, expanded clinical trials, which are ongoing, are revealing a host of important preanalytical considerations associated with sample collection, sample storage and stability, sample shipping, sample preparation and sample interferents, which impact detection performance. Results from recent clinical studies will be presented.

  4. Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

    Science.gov (United States)

    Luker, Gary D

    2002-04-01

    The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

  5. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

    International Nuclear Information System (INIS)

    Introduction: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Methods: Dynamic α-[11C]methyl-L-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Results: Tumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Conclusions: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.

  6. Hyperpolarized 13C MR for Molecular Imaging of Prostate Cancer

    OpenAIRE

    Wilson, David M.; Kurhanewicz, John

    2014-01-01

    Hyperpolarization using dissolution dynamic nuclear polarization has emerged as a versatile method to dramatically improve the MR signal of low-sensitivity nuclei. This technique facilitates the study of real-time metabolism in vitro and in vivo using 13C-enriched substrates and has been applied to numerous models of human disease. In particular, several mechanisms underlying prostate cancer have been interrogated using hyperpolarized 13C MR spectroscopy. This review highlights key metabolic ...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Adi ePais

    2016-04-01

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

  9. Early detection of breast cancer: a molecular optical imaging approach using novel estrogen conjugate fluorescent dye

    Science.gov (United States)

    Bhattacharjee, Shubhadeep; Jose, Iven

    2011-02-01

    Estrogen induced proliferation of mutant cells is widely understood to be the one of major risk determining factor in the development of breast cancer. Hence determination of the Estrogen Receptor[ER] status is of paramount importance if cancer pathogenesis is to be detected and rectified at an early stage. Near Infrared Fluorescence [NIRf] Molecular Optical Imaging is emerging as a powerful tool to monitor bio-molecular changes in living subjects. We discuss pre-clinical results in our efforts to develop an optical imaging diagnostic modality for the early detection of breast cancer. We have successfully carried out the synthesis and characterization of a novel target-specific NIRf dye conjugate aimed at measuring Estrogen Receptor[ER] status. The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of Indocyanine Green (ICG) cyanine dye, bis-1,1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. In-vitro studies regarding specific binding and endocytocis of the dye performed on ER+ve [MCF-7] and control [MDA-MB-231] adenocarcinoma breast cancer cell lines clearly indicated nuclear localization of the dye for MCF-7 as compared to plasma level staining for MDA-MB-231. Furthermore, MCF-7 cells showed ~4.5-fold increase in fluorescence signal intensity compared to MDA-MB-231. A 3-D mesh model mimicking the human breast placed in a parallel-plate DOT Scanner is created to examine the in-vivo efficacy of the dye before proceeding with clinical trials. Photon migration and florescence flux intensity is modeled using the finite-element method with the coefficients (quantum yield, molar extinction co-efficient etc.) pertaining to the dye as obtained from photo-physical and in-vitro studies. We conclude by stating that this lipophilic dye can be potentially used as a target specific exogenous contrast agent in molecular optical imaging for early detection of breast cancer.

  10. Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

    Directory of Open Access Journals (Sweden)

    Balasundaram G

    2015-01-01

    Full Text Available Ghayathri Balasundaram,1,* Chris Jun Hui Ho,1,* Kai Li,2 Wouter Driessen,3 US Dinish,1 Chi Lok Wong,1 Vasilis Ntziachristos,3 Bin Liu,2 Malini Olivo1,41Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC, 2Institute of Materials Research and Engineering (IMRE, Agency for Science, Technology and Research (A*STAR, Singapore; 3Institute of Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany; 4School of Physics, National University of Ireland, Galway, Ireland *These authors contributed equally to this work Abstract: Conjugated polymers (CPs are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used

  11. Radiogenomic analysis of breast cancer: dynamic contrast enhanced - magnetic resonance imaging based features are associated with molecular subtypes

    Science.gov (United States)

    Wang, Shijian; Fan, Ming; Zhang, Juan; Zheng, Bin; Wang, Xiaojia; Li, Lihua

    2016-03-01

    Breast cancer is one of the most common malignant tumor with upgrading incidence in females. The key to decrease the mortality is early diagnosis and reasonable treatment. Molecular classification could provide better insights into patient-directed therapy and prognosis prediction of breast cancer. It is known that different molecular subtypes have different characteristics in magnetic resonance imaging (MRI) examination. Therefore, we assumed that imaging features can reflect molecular information in breast cancer. In this study, we investigated associations between dynamic contrasts enhanced MRI (DCE-MRI) features and molecular subtypes in breast cancer. Sixty patients with breast cancer were enrolled and the MR images were pre-processed for noise reduction, registration and segmentation. Sixty-five dimensional imaging features including statistical characteristics, morphology, texture and dynamic enhancement in breast lesion and background regions were semiautomatically extracted. The associations between imaging features and molecular subtypes were assessed by using statistical analyses, including univariate logistic regression and multivariate logistic regression. The results of multivariate regression showed that imaging features are significantly associated with molecular subtypes of Luminal A (p=0.00473), HER2-enriched (p=0.00277) and Basal like (p=0.0117), respectively. The results indicated that three molecular subtypes are correlated with DCE-MRI features in breast cancer. Specifically, patients with a higher level of compactness or lower level of skewness in breast lesion are more likely to be Luminal A subtype. Besides, the higher value of the dynamic enhancement at T1 time in normal side reflect higher possibility of HER2-enriched subtype in breast cancer.

  12. Radiofrequency Heat-Enhanced Chemotherapy for Breast Cancer: Towards Interventional Molecular Image-Guided Chemotherapy

    OpenAIRE

    Zhou, Yurong; Han, Guocan; Wang, Yue; Hu, Xi; Li, Zhiming; Chen, Lumin; Bai, Weixian; Luo, Jingfeng; Zhang, Yajing; Sun, Jihong; Yang, Xiaoming

    2014-01-01

    Breast cancer is the most common malignancy in women worldwide. Recent developments in minimally invasive interventional radiology techniques have significantly improved breast cancer treatment. This study aimed to develop a novel technique for the local management of breast cancers using radiofrequency heat (RFH). We performed both in vitro experiments using human breast cancer cells and in vivo validation in xenograft animal models with magnetic resonance imaging (MRI) and pathological corr...

  13. REAL-TIME DETECTION OF SURVIVIN mRNA EXPRESSION IN CERVICAL CANCER CELL LINES USING MOLECULAR BEACON IMAGING

    Institute of Scientific and Technical Information of China (English)

    An Ruifang; He Dalin; Xue Yan; Wang Shu; Xie Li; Zhao Jun; Wang Xinyang; Yang Lili

    2006-01-01

    Objective To detect the expression of survivin mRNA in cervical cancer cell lines using molecular beacon imaging technology. Methods Human cervical cancer cells (HeLa and SiHa) and human fetal lung fibroblast HFL-I were cultured in vitro. After adding 100 nmol/L survivin mRNA molecular beacon, the fluorescent signals were observed under fluorescent microscope. The expressions of survivin in cervical cancer cells and HFL-I cell were examined by immunocytochemical streptravidin-biothin peroxidase (SP) assay at the same time. Results Two kinds of survivin mRNA molecular beacon, with different color fluorescence, had strong fluorescent signal in cervical cancer cell lines, and the signal in SiHa cell line was stronger, but these signals were not found in HFL-I ; Immunocytochemical staining of positive survivin was located in the cytoplasm of cervical cancer cell lines HeLa and SiHa, whereas, no expression of survivin was detected in HFL-I cell line. Conclusion The technology of molecular beacon imaging can be used to detect the expression of survivin mRNA in viable cells successfully, and may provide a new approach to the diagnosis of early stage cervical cancer and the following-up in the clinic.

  14. Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging.

    Science.gov (United States)

    Yang, Yaliang; Li, Fuhai; Gao, Liang; Wang, Zhiyong; Thrall, Michael J; Shen, Steven S; Wong, Kelvin K; Wong, Stephen T C

    2011-08-01

    We present a label-free, chemically-selective, quantitative imaging strategy to identify breast cancer and differentiate its subtypes using coherent anti-Stokes Raman scattering (CARS) microscopy. Human normal breast tissue, benign proliferative, as well as in situ and invasive carcinomas, were imaged ex vivo. Simply by visualizing cellular and tissue features appearing on CARS images, cancerous lesions can be readily separated from normal tissue and benign proliferative lesion. To further distinguish cancer subtypes, quantitative disease-related features, describing the geometry and distribution of cancer cell nuclei, were extracted and applied to a computerized classification system. The results show that in situ carcinoma was successfully distinguished from invasive carcinoma, while invasive ductal carcinoma (IDC) and invasive lobular carcinoma were also distinguished from each other. Furthermore, 80% of intermediate-grade IDC and 85% of high-grade IDC were correctly distinguished from each other. The proposed quantitative CARS imaging method has the potential to enable rapid diagnosis of breast cancer.

  15. NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring

    OpenAIRE

    Komljenovic, Dorde; Wiessler, Manfred; Waldeck, Waldemar; Ehemann, Volker; Pipkorn, Ruediger; Schrenk, Hans-Hermann; Debus, Jürgen; Braun, Klaus

    2016-01-01

    Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the ...

  16. Radiolabelled nanoparticles: novel classification of radiopharmaceuticals for molecular imaging of cancer.

    Science.gov (United States)

    Mirshojaei, Seyedeh Fatemeh; Ahmadi, Amirhossein; Morales-Avila, Enrique; Ortiz-Reynoso, Mariana; Reyes-Perez, Horacio

    2016-01-01

    Nanotechnology has been used for every single modality in the molecular imaging arena for imaging purposes. Synergic advantages can be explored when multiple molecular imaging modalities are combined with respect to single imaging modalities. Multifunctional nanoparticles have large surface areas, where multiple functional moieties can be incorporated, including ligands for site-specific targeting and radionuclides, which can be detected to create 3D images. Recently, radiolabeled nanoparticles with individual properties have attracted great interest regarding their use in multimodality tumor imaging. Multifunctional nanoparticles can combine diagnostic and therapeutic capabilities for both target-specific diagnosis and the treatment of a given disease. The future of nanomedicine lies in multifunctional nanoplatforms that combine the diagnostic ability and therapeutic effects using appropriate ligands, drugs, responses and technological devices, which together are collectively called theranostic drugs. Co-delivery of radiolabeled nanoparticles is useful in multifunctional molecular imaging areas because it comprises several advantages based on nanoparticles architecture, pharmacokinetics and pharmacodynamic properties.

  17. Cardiovascular molecular MR imaging

    OpenAIRE

    Lamb, H J; van der Meer, R. W.; Roos, A. (Anna); Bax, J J

    2007-01-01

    Introduction Cardiovascular molecular imaging is a rapidly evolving field of research, aiming to image and quantify molecular and cellular targets in vivo. MR imaging has some inherent properties that make it very suitable for cardiovascular molecular imaging. Until now, only a limited number of studies have been published on cardiovascular molecular imaging using MR imaging. Review In the current review, MR techniques that have already shown potential are discussed. Metabolic MR imaging can ...

  18. Progresses in molecular imaging of prostate cancer%前列腺癌的分子影像学进展

    Institute of Scientific and Technical Information of China (English)

    范校周; 郭燕丽

    2013-01-01

    前列腺癌是严重威胁男性健康的疾病.分子影像学的出现,从一个全新角度为前列腺癌的早期诊断与治疗提供了可能,新的前列腺癌标志物也不断出现.本文对当前分子影像学技术,包括核素显像、MRI、超声和光学技术在前列腺癌诊治中的应用进展进行回顾.%Prostate cancer is a serious threat to male health, and the development of molecular imaging provides the possibility for early diagnosis and treatment of prostate cancer from a new perspective. With the emerging markers of prostate cancer, the current modalities of molecular imaging, including radionuclide imaging, MRI, ultrasound and optical imaging in diagnosis and treatment of prostate cancer were reviewed in this article.

  19. Molecular breast imaging. An update

    International Nuclear Information System (INIS)

    The aim of molecular imaging is to visualize and quantify biological, physiological and pathological processes at cellular and molecular levels. Molecular imaging using various techniques has recently become established in breast imaging. Currently molecular imaging techniques comprise multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), proton MR spectroscopy (1H-MRSI), nuclear imaging by breast-specific gamma imaging (BSGI), positron emission tomography (PET) and positron emission mammography (PEM) and combinations of techniques (e.g. PET-CT and multiparametric PET-MRI). Recently, novel techniques for molecular imaging of breast tumors, such as sodium imaging (23Na-MRI), phosphorus spectroscopy (31P-MRSI) and hyperpolarized MRI as well as specific radiotracers have been developed and are currently under investigation. It can be expected that molecular imaging of breast tumors will enable a simultaneous assessment of the multiple metabolic and molecular processes involved in cancer development and thus an improved detection, characterization, staging and monitoring of response to treatment will become possible. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Larson, Timothy A [Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 (United States); Bankson, James [Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Aaron, Jesse [Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 (United States); Sokolov, Konstantin [Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 (United States)

    2007-08-15

    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 T{sub 2} (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.

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

    International Nuclear Information System (INIS)

    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

  2. Molecular and functional imaging for detection of lymph node metastases in prostate cancer

    NARCIS (Netherlands)

    Fortuin, A.S.; Rooij, M. de; Zamecnik, P.; Haberkorn, U.; Barentsz, J.

    2013-01-01

    Knowledge on lymph node metastases is crucial for the prognosis and treatment of prostate cancer patients. Conventional anatomic imaging often fails to differentiate benign from metastatic lymph nodes. Pelvic lymph node dissection is an invasive technique and underestimates the extent of lymph node

  3. Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast

    International Nuclear Information System (INIS)

    Purpose: Recent studies have raised concerns about exposure to low-dose ionizing radiation from medical imaging procedures. Little has been published regarding the relative exposure and risks associated with breast imaging techniques such as breast specific gamma imaging (BSGI), molecular breast imaging (MBI), or positron emission mammography (PEM). The purpose of this article was to estimate and compare the risks of radiation-induced cancer from mammography and techniques such as PEM, BSGI, and MBI in a screening environment. Methods: The authors used a common scheme for all estimates of cancer incidence and mortality based on the excess absolute risk model from the BEIR VII report. The lifetime attributable risk model was used to estimate the lifetime risk of radiation-induced breast cancer incidence and mortality. All estimates of cancer incidence and mortality were based on a population of 100 000 females followed from birth to age 80 and adjusted for the fraction that survives to various ages between 0 and 80. Assuming annual screening from ages 40 to 80 and from ages 50 to 80, the cumulative cancer incidence and mortality attributed to digital mammography, screen-film mammography, MBI, BSGI, and PEM was calculated. The corresponding cancer incidence and mortality from natural background radiation was calculated as a useful reference. Assuming a 15%-32% reduction in mortality from screening, the benefit/risk ratio for the different imaging modalities was evaluated. Results: Using conventional doses of 925 MBq Tc-99m sestamibi for MBI and BSGI and 370 MBq F-18 FDG for PEM, the cumulative cancer incidence and mortality were found to be 15-30 times higher than digital mammography. The benefit/risk ratio for annual digital mammography was >50:1 for both the 40-80 and 50-80 screening groups, but dropped to 3:1 for the 40-49 age group. If the primary use of MBI, BSGI, and PEM is in women with dense breast tissue, then the administered doses need to be in the range

  4. The application of surgical navigation system using optical molecular imaging technology in orthotopic breast cancer and metastasis studies

    Science.gov (United States)

    Chi, Chongwei; Zhang, Qian; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Du, Yang; Tian, Jie

    2014-02-01

    Currently, it has been an international focus on intraoperative precise positioning and accurate resection of tumor and metastases. The methods such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role in preoperative accurate diagnosis. However, most of them are inapplicable for intraoperative surgery. We have proposed a surgical navigation system based on optical molecular imaging technology for intraoperative detection of tumors and metastasis. This system collects images from two CCD cameras for real-time fluorescent and color imaging. For image processing, the template matching algorithm is used for multispectral image fusion. For the application of tumor detection, the mouse breast cancer cell line 4T1-luc, which shows highly metastasis, was used for tumor model establishment and a model of matrix metalloproteinase (MMP) expressing breast cancer. The tumor-bearing nude mice were given tail vein injection of MMP 750FAST (PerkinElmer, Inc. USA) probe and imaged with both bioluminescence and fluorescence to assess in vivo binding of the probe to the tumor and metastases sites. Hematoxylin and eosin (H&E) staining was performed to confirm the presence of tumor and metastasis. As a result, one tumor can be observed visually in vivo. However liver metastasis has been detected under surgical navigation system and all were confirmed by histology. This approach helps surgeons to find orthotopic tumors and metastasis during intraoperative resection and visualize tumor borders for precise positioning. Further investigation is needed for future application in clinics.

  5. Quantitative imaging of atomic and molecular species in cancer cell cultures with TOF-SIMS and Laser-SNMS

    International Nuclear Information System (INIS)

    For boron neutron capture therapy, a promising cancer therapy under development, knowledge about the subcellular boron distribution is important. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and nonresonant laser secondary neutral mass spectrometry (NR-Laser-SNMS) have been used for examining freeze-fractured, freeze-dried human melanoma cells incubated with sodium mercaptoundecahydro-closo-dodecaborate (Na210B12H11SH,BSH), a 10B containing drug. With both techniques, elemental and molecular images were obtained from the cancer cells with very high sensitivity and subcellular resolution. The measurement of the K/Na ratio demonstrated that the preparation technique used was appropriate for preserving the chemical and structural integrity of living cells. The boron images showed that the intensity of intracellular and extracellular boron signals was clearly different after incubation of cells in different boron concentrations

  6. Quantitative imaging of atomic and molecular species in cancer cell cultures with TOF-SIMS and Laser-SNMS

    Science.gov (United States)

    Fartmann, M.; Kriegeskotte, C.; Dambach, S.; Wittig, A.; Sauerwein, W.; Arlinghaus, H. F.

    2004-06-01

    For boron neutron capture therapy, a promising cancer therapy under development, knowledge about the subcellular boron distribution is important. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and nonresonant laser secondary neutral mass spectrometry (NR-Laser-SNMS) have been used for examining freeze-fractured, freeze-dried human melanoma cells incubated with sodium mercaptoundecahydro-closo-dodecaborate ( Na210B12H11SH, BSH), a 10B containing drug. With both techniques, elemental and molecular images were obtained from the cancer cells with very high sensitivity and subcellular resolution. The measurement of the K/Na ratio demonstrated that the preparation technique used was appropriate for preserving the chemical and structural integrity of living cells. The boron images showed that the intensity of intracellular and extracellular boron signals was clearly different after incubation of cells in different boron concentrations.

  7. NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring

    Science.gov (United States)

    Komljenovic, Dorde; Wiessler, Manfred; Waldeck, Waldemar; Ehemann, Volker; Pipkorn, Ruediger; Schrenk, Hans-Hermann; Debus, Jürgen; Braun, Klaus

    2016-01-01

    Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the Cy7 molecule whose indolenine-N residues were substituted with a propylene linker are described. Methylating agent temozolomide is functionalized with a tetrazine as a diene component whereas Cy7-cell penetrating peptide conjugate acts as a dienophilic reaction partner for the inverse Diels-Alder click chemistry-mediated ligation route yielding a theranostic conjugate, 3-mercapto-propionic-cyclohexenyl-Cy7-bis-temozolomide-bromide-cell penetrating peptide. Synthesis route described here may facilitate targeted delivery of the therapeutic compound to achieve sufficient local concentrations at the target site or tissue. Its versatility allows a choice of adequate imaging tags applicable in e.g. PET, SPECT, CT, near-infrared imaging, and therapeutic substances including cytotoxic agents. Imaging tags and therapeutics may be simultaneously bound to the conjugate applying click chemistry. Theranostic compound presented here offers a solid basis for a further improvement of cancer management in a precise, patient-specific manner. PMID:26722379

  8. NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring.

    Science.gov (United States)

    Komljenovic, Dorde; Wiessler, Manfred; Waldeck, Waldemar; Ehemann, Volker; Pipkorn, Ruediger; Schrenk, Hans-Hermann; Debus, Jürgen; Braun, Klaus

    2016-01-01

    Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the Cy7 molecule whose indolenine-N residues were substituted with a propylene linker are described. Methylating agent temozolomide is functionalized with a tetrazine as a diene component whereas Cy7-cell penetrating peptide conjugate acts as a dienophilic reaction partner for the inverse Diels-Alder click chemistry-mediated ligation route yielding a theranostic conjugate, 3-mercapto-propionic-cyclohexenyl-Cy7-bis-temozolomide-bromide-cell penetrating peptide. Synthesis route described here may facilitate targeted delivery of the therapeutic compound to achieve sufficient local concentrations at the target site or tissue. Its versatility allows a choice of adequate imaging tags applicable in e.g. PET, SPECT, CT, near-infrared imaging, and therapeutic substances including cytotoxic agents. Imaging tags and therapeutics may be simultaneously bound to the conjugate applying click chemistry. Theranostic compound presented here offers a solid basis for a further improvement of cancer management in a precise, patient-specific manner. PMID:26722379

  9. Molecular imaging with terahertz waves.

    Science.gov (United States)

    Oh, Seung Jae; Choi, Jihye; Maeng, Inhee; Park, Jae Yeon; Lee, Kwangyeol; Huh, Yong-Min; Suh, Jin-Suck; Haam, Seungjoo; Son, Joo-Hiuk

    2011-02-28

    We demonstrate a highly sensitive THz molecular imaging (TMI) technique involving differential modulation of surface plasmons induced on nanoparticles and obtain target specific in vivo images of cancers. This technique can detect quantities of gold nanoparticles as small as 15 µM in vivo. A comparison of TMI images with near infrared absorption images shows the superior sensitivity of TMI. Furthermore, the quantification property of TMI is excellent, being linearly proportional to the concentration of nanoparticles. The target specificity issue is also addressed at the ex vivo and cell levels. The high thermal sensitivity of TMI can help extend photonic-based photothermal molecular imaging researches from the in vitro level to the in vivo level. The TMI technique can be used for monitoring drug delivery processes and for early cancer diagnosis.

  10. Sentinel lymph node detection in breast cancer patients using surgical navigation system based on fluorescence molecular imaging technology

    Science.gov (United States)

    Chi, Chongwei; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Tian, Jie

    2015-03-01

    Introduction: Precision and personalization treatments are expected to be effective methods for early stage cancer studies. Breast cancer is a major threat to women's health and sentinel lymph node biopsy (SLNB) is an effective method to realize precision and personalized treatment for axillary lymph node (ALN) negative patients. In this study, we developed a surgical navigation system (SNS) based on optical molecular imaging technology for the precise detection of the sentinel lymph node (SLN) in breast cancer patients. This approach helps surgeons in precise positioning during surgery. Methods: The SNS was mainly based on the technology of optical molecular imaging. A novel optical path has been designed in our hardware system and a feature-matching algorithm has been devised to achieve rapid fluorescence and color image registration fusion. Ten in vivo studies of SLN detection in rabbits using indocyanine green (ICG) and blue dye were executed for system evaluation and 8 breast cancer patients accepted the combination method for therapy. Results: The detection rate of the combination method was 100% and an average of 2.6 SLNs was found in all patients. Our results showed that the method of using SNS to detect SLN has the potential to promote its application. Conclusion: The advantage of this system is the real-time tracing of lymph flow in a one-step procedure. The results demonstrated the feasibility of the system for providing accurate location and reliable treatment for surgeons. Our approach delivers valuable information and facilitates more detailed exploration for image-guided surgery research.

  11. PET for molecular imaging of cancer: a tool for tailored therapy

    International Nuclear Information System (INIS)

    The concept of personalised medicine has led to a need for improved phenotyping as well as prediction of treatment response early after therapy initiation. Most of the molecular biology methods used today need tissue sampling for in vitro analysis. In contrast, molecular imaging allows for non-invasive studies at the molecular level in living, intact organisms. Accordingly, molecular imaging with PET has been one of the most successful techniques in such phenotyping and response prediction using FDG. In addition, recent development of new PET tracers has further improved the value of PET in tumor characterization. Such new PET tracers allow for visualization of tumor specific receptors and tissue characteristics such as ability to metastasize. Furthermore, PET has a high sensitivity and allows for quantification and is not prone to sampling error as seen with biopsies. We will present examples of development of probes targeting the somatostatin receptor type 2, over-expressed in neuroendocrine tumors, including our first-in-man studies of 64Cu-DOTATATE. Also development in probes for visualization of the invasive phenotype will be presented. Finally, with the most recent development of true integrated PET/MRI scanners it has now become possible to add information from MRI. The value of such hybrid imaging will also be briefly discussed. (author)

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

    Science.gov (United States)

    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

  13. The development of EGFR molecular imaging and gene mutation in non-small cell lung cancer

    International Nuclear Information System (INIS)

    In vivo epidermal growth factor receptor (EGFR) imaging has great potential to affect patient-specific treatment for NSCLC, applying a targeted therapy, and measuring molecular-specific effects of treatment. New PET/CT radiotracers,such as N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl) methoxy]quinazolin-4-amine (ZD6476), five 4-(anilino) quinazoline derivatives (ML01) and 4-[(3-iodophenyl) amino]-7-(2-[2-{2-(2-[2-{2-([18F]fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)- ethoxy }-ethoxy]-quinazoline-6-yl-acrylamide) ([18F]F-PEG6-IPQA) are now available. But, 11C labeled-4-N-(3-bromoanilino)-6, 7-dimethoxyquinazoline (PD153035) is the only PET/CT radiotracer used for human clinical evaluation,primarily for EGFR imaging. Finally, the most important aspect of successful imaging is the identification and characterization of EGFR at the cellular or sub-cellular level with high specificity for the target. Considering the need for further development of such PET/CT tracers, EGFR molecular imaging will be presented along with an important examination of the progression that has been made thus far in the field. (authors)

  14. Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hoeben, Bianca A. W.; Bussink, Johan; Kaanders, Johannes H. A. M. [Dept. of Radiation Oncology, Radboud Univ. Nijmegen Medical Centre, Nijmegen (Netherlands)], e-mail: b.hoeben@rther.umcn.nl; Oyen, Wim J. G. [Dept. of Nuclear Medicine, Radboud Univ. Nijmegen Medical Centre, Nijmegen (Netherlands); Troost, Esther G. C. [Maastro Clinic, GROW School for Oncology and Developmental Biology, Maastricht Univ. Medical Centre, Maastricht (Netherlands)

    2013-10-15

    Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer 18F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

  15. In vitro prediction of the efficacy of molecularly targeted cancer therapy by Raman spectral imaging.

    Science.gov (United States)

    Yosef, Hesham K; Mavarani, Laven; Maghnouj, Abdelouahid; Hahn, Stephan; El-Mashtoly, Samir F; Gerwert, Klaus

    2015-11-01

    Mutational acquired resistance is a major challenge in cancer therapy. Somatic tumours harbouring some oncogenic mutations are characterised by a high mortality rate. Surprisingly, preclinical evaluation methods do not show clearly resistance of mutated cancers to some drugs. Here, we implemented Raman spectral imaging to investigate the oncogenic mutation resistance to epidermal growth factor receptor targeting therapy. Colon cancer cells with and without oncogenic mutations such as KRAS and BRAF mutations were treated with erlotinib, an inhibitor of epidermal growth factor receptor, in order to detect the impact of these mutations on Raman spectra of the cells. Clinical studies suggested that oncogenic KRAS and BRAF mutations inhibit the response to erlotinib therapy in patients, but this effect is not observed in vitro. The Raman results indicate that erlotinib induces large spectral changes in SW-48 cells that harbour wild-type KRAS and BRAF. These spectral changes can be used as a marker of response to therapy. HT-29 cells (BRAF mutated) and SW-480 cells (KRAS mutated) display a smaller and no significant response, respectively. However, the erlotinib effect on these cells is not observed when phosphorylation of extracellular-signal-regulated kinase and AKT is monitored by Western blot, where this phosphorylation is the conventional in vitro test. Lipid droplets show a large response to erlotinib only in the case of cells harbouring wild-type KRAS and BRAF, as indicated by Raman difference spectra. This study shows the great potential of Raman spectral imaging as an in vitro tool for detecting mutational drug resistance.

  16. Molecular imaging in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Schober, Otmar; Riemann, Burkhard (eds.) [Universitaetsklinikum Muenster (Germany). Klinik fuer Nuklearmedizin

    2013-02-01

    Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

  17. Molecular imaging in oncology

    OpenAIRE

    Dzik-Jurasz, A S K

    2004-01-01

    Cancer is a genetic disease that manifests in loss of normal cellular homeostatic mechanisms. The biology and therapeutic modulation of neoplasia occurs at the molecular level. An understanding of these molecular processes is therefore required to develop novel prognostic and early biomarkers of response. In addition to clinical applications, increased impetus for the development of such technologies has been catalysed by pharmaceutical companies investing in the development of molecular ther...

  18. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, S., E-mail: sdoyle2@nhs.net [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom); Steel, J.; Porter, G. [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom)

    2011-11-15

    Male breast cancer is rare, with some pathological and radiological differences from female breast cancer. There is less familiarity with the imaging appearances of male breast cancer, due to its rarity and the more variable use of preoperative imaging. This review will illustrate the commonest imaging appearances of male breast cancer, with emphasis on differences from female breast cancer and potential pitfalls in diagnosis, based on a 10 year experience in our institution.

  19. Molecular Imaging in the Management of Adrenocortical Cancer: A Systematic Review.

    Science.gov (United States)

    Wong, Ka Kit; Miller, Barbra S; Viglianti, Benjamin L; Dwamena, Ben A; Gauger, Paul G; Cook, Gary J; Colletti, Patrick M; Rubello, Domenico; Gross, Milton D

    2016-08-01

    Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical hormone hypersecretion and abdominal mass effect or is incidentally detected as an adrenal mass on imaging performed for other indications. Endocrine evaluation, comprehensive staging, and meticulous resection are crucial to ensure the best possible outcome. Despite extensive initial surgical resection, local and distant metastases are not uncommon with disappointing 5-year survival, although progress is being made at high-volume centers. Accurate restaging of recurrent disease is important to guide further management. Mitotane, external beam radiation and chemotherapy, and newer anticancer systemic treatments are used as adjunctives for inoperable disease and distant metastases. Contrast-enhanced CT and MRI are first-line imaging modalities for evaluation of ACC to characterize adrenal masses and to determine tumor resectability. Emerging literature supports F-FDG PET/CT use to determine the malignant potential of adrenal masses. In patients with a diagnosis of ACC, FDG PET/CT is sensitive for detecting metastatic disease, and its tumor accumulation has been correlated to pathology, Weiss scores, and prognosis. Metomidate, labeled with C for PET or with I for SPECT/CT, allows characterization of an adrenal mass as being of adrenocortical origin with high specificity. Taking advantage of its adrenocortical avidity, metomidate has been labeled with I for radionuclide therapy in a subset of ACC. In this review, we describe how nuclear medicine imaging, and specifically PET, can assist surgical management of ACC. PMID:26825212

  20. Molecular Imaging of the Kidneys

    Science.gov (United States)

    Szabo, Zsolt; Alachkar, Nada; Xia, Jinsong; Mathews, William B.; Rabb, Hamid

    2010-01-01

    Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms in order to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive and accurate diagnosis. The most recent imaging technology, PET, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H215O, 82RbCl, and [64Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype AT1R using in vivo PET imaging. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc-99m MAG3 as well as some novel radiopharmaceuticals such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands have been utilized for molecular renal imaging. Additionally, other radioligands that interact with the organic cation transporters or peptide transporters have developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule- 1 (KIM-1) that is highly expressed in kidney injury and renal cancer but not in normal kidneys. While pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on upregulated molecules in response to tissue stress resulted from obstruction will be of great implication. Monocyte chemoattractant protein -1 (MCP-1) is a well-suited molecule in this case. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [18F]FDG, other radioligands such as [11C]acetate and anti-[18F]FACBC have emerged. Radioimmuno-imaging with [124I]G250 could lead to radioimmunotherapy for renal cancer

  1. Molecular photonic imaging of cancer using light-emitting e. coli

    International Nuclear Information System (INIS)

    Cancer research has long sought a magic bullet that would selectively target and destroy malignant cells. In this study, we exploited that E. coli injected into tumor-bearing mice selectively target and proliferate in solid tumors by employing optical imaging technique. Lux operon or GFP has been cloned into pUC19 plasmid to engineer pUC19Lux or pUC19gfp which was transformed into varying kinds of wild type (MG1655) or mutant E.coli strains. For stable expression, lux operon was cloned with asd (aspartate β-semialdehyde dehydrogenase) gene and transformed into asd defective E. coli (MG1655asd-/asd+lux). These bacteria were i.v. injected into tumor mice or directly into central necrosis of tumor. The imaging signal from wild type E.coli was detected initially at liver (20min), then migrated to and shine in the tumor mass until 2 weeks of injection which was consistently observed in immuno-defective (nude) and -competent (Balb/c) mice. Imaging signal of stbaly transformed strain (MG1655asd-/asd+lux) was stronger and longer-lasting than that of transiently transformed strain (MG1655lux). Flagella defective E. coli strain failed to reach tumor loci. Only a few amounts of stress regulatory defective E. coli strain arrived at but couldn't survive at the tumor loci. E. coli colonies expressing GFP was mostly observed at the border of central necrosis and peripheral proliferative areas in immunofluorescence studies. Directly injected MG1655ad-/asd+lux was transiently observed at central necrosis followed by spreading to the peripheral tumor mass which was consistent with the finding by tail vein injection. We successfully engineered E. coli strain stably expressing lux reporter gene. E. coli strongly targeted solid tumor regardless of host immune status. Our results support that the targeting of tumor by E.coli is an active process and would be applied as a delivery vehicle of varying imaging markers or therapeutic molecules

  2. Cardiovascular Molecular Imaging

    OpenAIRE

    Khanicheh, Elham

    2009-01-01

    Although there have been significant improvements in the treatment of cardiovascular diseases they still remain the main cause of morbidity and mortality globally. Currently available diagnostic approaches may not be adequate to detect pathologic changes during the early disease stages, which may be valuable for risk stratification and also to assess a response to a therapy. Therefore molecular imaging techniques such as Contrast Enhanced Ultrasound (CEU) molecular imaging to noninvasively i...

  3. Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging

    International Nuclear Information System (INIS)

    Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters (Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ∼5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f7/2∼83.97 eV and Au 4f5/2∼87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ∼1 nm and protein cluster aggregates of size ∼8 nm. Photoluminescence studies show bright fluorescence with peak maximum at ∼674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 μg ml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the

  4. Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Retnakumari, Archana; Setua, Sonali; Menon, Deepthy; Ravindran, Prasanth; Nair, Shantikumar; Koyakutty, Manzoor [Amrita Centre for Nanoscience and Molecular Medicine, Amrita Institute of Medical Science, Cochin, 682 041 (India); Muhammed, Habeeb; Pradeep, Thalappil, E-mail: manzoor_nanomed@yahoo.com [Indian Institute of Technology, DST unit on Nanoscience, Chennai, 600 036 (India)

    2010-02-05

    Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au{sub 25} nanoclusters (Au NCs) is reported. Highly fluorescent Au{sub 25} clusters were synthesized by controlled reduction of Au{sup +} ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of {approx}5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f{sub 7/2{approx}}83.97 eV and Au 4f{sub 5/2{approx}}87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size {approx}1 nm and protein cluster aggregates of size {approx}8 nm. Photoluminescence studies show bright fluorescence with peak maximum at {approx}674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 {mu}g ml{sup -1}. Receptor-targeted cancer detection using Au clusters is demonstrated on FR{sup +ve} oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au{sub 25} clusters were found internalized in significantly higher concentrations

  5. Molecular image in biomedical research. Molecular imaging unit of the National Cancer Research Center; Imagen molecular an investigation biomedica. La Unidad de Imagen Molecular del Centro Nacional de Investigaciones Oncologicas

    Energy Technology Data Exchange (ETDEWEB)

    Perez Bruzon, J.; Mulero Anhiorte, F.

    2010-07-01

    This article has two basic objectives. firstly, it will review briefly the most important imaging techniques used in biomedical research indicting the most significant aspects related to their application in the preclinical stage. Secondly, it will present a practical application of these techniques in a pure biomedical research centre (not associated to a clinical facility). Practical aspects such as organisation, equipment, work norms, shielding of the Spanish National Cancer Research Centre (CNIO) Imaging Unit will be shown. This is a pioneering facility in the application of these techniques in research centres without any dependence or any direct relationship with other hospital Nuclear Medicine services. (Author) 7 refs.

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

    Science.gov (United States)

    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

  7. Ultrasound molecular imaging: Moving toward clinical translation

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K., E-mail: willmann@stanford.edu

    2015-09-15

    Highlights: • Ultrasound molecular imaging is a highly sensitive modality. • A clinical grade ultrasound contrast agent has entered first in human clinical trials. • Several new potential future clinical applications of ultrasound molecular imaging are being explored. - Abstract: Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.

  8. ICMIC Institutions - Cancer Imaging Program

    Science.gov (United States)

    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.

  9. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik

    2011-01-01

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  10. Principle and applications of terahertz molecular imaging.

    Science.gov (United States)

    Son, Joo-Hiuk

    2013-05-31

    The principle, characteristics and applications of molecular imaging with terahertz electromagnetic waves are reviewed herein. The terahertz molecular imaging (TMI) technique uses nanoparticle probes to achieve dramatically enhanced sensitivity compared with that of conventional terahertz imaging. Surface plasmons, induced around the nanoparticles, raise the temperature of water in biological cells, and the temperature-dependent changes in the optical properties of water, which are large in the terahertz range, are measured differentially by terahertz waves. TMI has been applied to cancer diagnosis and nanoparticle drug delivery imaging. The technique is also compared with magnetic resonance imaging by using a dual-modality nanoparticle probe.

  11. Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET

    Directory of Open Access Journals (Sweden)

    B. B. Koolen

    2012-01-01

    Full Text Available Positron emission tomography (PET, with or without integrated computed tomography (CT, using 18F-fluorodeoxyglucose (FDG is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

  12. Molecular constituents of colorectal cancer metastatic to the liver by imaging infrared spectroscopy

    Science.gov (United States)

    Coe, James V.; Chen, Zhaomin; Li, Ran; Nystrom, Steven V.; Butke, Ryan; Miller, Barrie; Hitchcock, Charles L.; Allen, Heather C.; Povoski, Stephen P.; Martin, Edward W.

    2015-03-01

    Infrared (IR) imaging spectroscopy of human liver tissue slices has been used to identify and characterize liver metastasis of colorectal origin which was surgically removed from a consenting patient and frozen without formalin fixation or dehydration procedures, so that lipids and water remain in the tissues. First, a k-means clustering analysis, using metrics from the IR spectra, identified groups within the image. The groups were identified as tumor or nontumor regions by comparing to an H and E stain of the same sample after IR imaging. Then, calibrant IR spectra of protein, several fats, glycogen, and polyvinyl alcohol were isolated by differencing spectra from different regions or groups in the image space. Finally, inner products (or scores) of the IR spectra at each pixel in the image with each of the various calibrants were calculated showing how the calibrant molecules vary in tumor and nontumor regions. In this particular case, glycogen and protein changes enable separation of tumor and nontumor regions as shown with a contour plot of the glycogen scores versus the protein scores.

  13. Computational methods for molecular imaging

    CERN Document Server

    Shi, Kuangyu; Li, Shuo

    2015-01-01

    This volume contains original submissions on the development and application of molecular imaging computing. The editors invited authors to submit high-quality contributions on a wide range of topics including, but not limited to: • Image Synthesis & Reconstruction of Emission Tomography (PET, SPECT) and other Molecular Imaging Modalities • Molecular Imaging Enhancement • Data Analysis of Clinical & Pre-clinical Molecular Imaging • Multi-Modal Image Processing (PET/CT, PET/MR, SPECT/CT, etc.) • Machine Learning and Data Mining in Molecular Imaging. Molecular imaging is an evolving clinical and research discipline enabling the visualization, characterization and quantification of biological processes taking place at the cellular and subcellular levels within intact living subjects. Computational methods play an important role in the development of molecular imaging, from image synthesis to data analysis and from clinical diagnosis to therapy individualization. This work will bring readers fro...

  14. REAL-TIME DETECTION OF SURVIVIN mRNA EXPRESSION IN CERVICAL CANCER CELL LINES USING MOLECULAR BEACON IMAGING

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The initiated growth of human cancer cells of-ten mostly come fromthe abnor mal expression ofgenes.Survivinis anapotosis inhibitor of IAPfami-ly,cloned by Ambrosini in1997usingthe cDNAofeffector cell protease receptor-1(EPR-1),and is thekey gene for the development and advancement oftumor.Inthe present study,the feasibility of detec-ting the expression of survivin mRNA was exam-inedincervical cancer cell lines using molecular bea-coni maging technology.MATERIALS AND METHODS1Cervical cancer cell lines and ce...

  15. Lymphatic drainage, CTV and molecular imaging in non-small cell lung cancer.

    Science.gov (United States)

    Trodella, Lucio; Ciresa, Marzia; D'Angelillo, Rolando; Ramella, Sara

    2003-01-01

    Prognosis for non-small cell lung cancer (NSCLC) patients who have locally advanced unresectable disease is poor for persistent thoracic disease and development of distant metastasis. In view of the poor rate of local control following conventional radiation therapy, there is a great need for methods to improve its efficacy. Three-dimensional conformal radiation therapy (3DCRT) is a high precision radiotherapy able to deliver higher doses with smaller doses to the surrounding normal tissues. However, the real problem is: "what do I want to treat?" This question is addressed based on the clinical and biological target volume definition. Selection of the CTV is therefore basically the clinical compromise between the most radical possible CTV and the critical normal tissue tolerance. The clinical target volume includes the GTV plus a margin to encompass subclinical or microscopic malignant disease immediately adjacent to it. Standard radiation therapy consists of a dose of 40 Gy to the entire mediastinum, supraclavicular fossa, and ipsilateral hilum, even if there is no evidence of disease in these areas. Despite the high risk of nodal spread in lung cancer, the benefit of additional elective nodal irradiation (ENI) is not proven while it seems to significantly increase the rate of radiation morbidity. Several studies have been published where ENI was systematically omitted. The main arguments for omitting ENI and the principal clinical experiences, are discussed. PMID:15018317

  16. Generation and characterization of nanobodies targeting PSMA for molecular imaging of prostate cancer.

    Science.gov (United States)

    Evazalipour, Mehdi; D'Huyvetter, Matthias; Tehrani, Bahram Soltani; Abolhassani, Mohsen; Omidfar, Kobra; Abdoli, Shahriyar; Arezumand, Roghaye; Morovvati, Hamid; Lahoutte, Tony; Muyldermans, Serge; Devoogdt, Nick

    2014-01-01

    Nanobodies show attractive characteristics for tumor targeting in cancer diagnosis and therapy. A radiolabeled nanobody binding the prostate-specific membrane antigen (PSMA) could offer a noninvasive strategy to select prostate cancer patients eligible for PSMA-targeted therapies. We here describe the generation, production and in vivo evaluation of anti-PSMA nanobodies. Nanobodies were derived from heavy-chain-only antibodies, raised in immunized dromedaries. Binding characteristics were evaluated through ELISA and flow cytometry. Selected nanobodies were radiolabeled with (99m) Tc at their hexahistidine tail, after which cell binding capacity and internalization were evaluated on PSMA(pos) LNCaP and PSMA(neg) PC3 cell lines. In vivo tumor targeting was analyzed in both LNCaP and PC3 xenografted mice through SPECT/microCT and tissue sampling. A panel of 72 generated clones scored positive on ELISA, all contributing to three nanobody groups, of which group 3 dominated with 70 clones. ELISA and FACS analysis led to the selection of two dominant nanobodies. (99m) Tc-labeled PSMA6 and PSMA30 both showed specific binding on LNCAP cells, but not on PC3 cells. (99m) Tc-PSMA30 internalized significantly more in LNCaP cells compared to (99m) Tc-PSMA6. Higher absolute tumor uptake and tumor-to-normal organ ratios were observed for (99m) Tc-PSMA30 compared with (99m) Tc-PSMA6 and a (99m) Tc-control nanobody in LNCaP but not in PC3 tumor-bearing mice. PSMA30 nanobody has improved targeting characteristics both in vitro as well as in vivo compared with PSMA6 and the control nanobody, and was therefore selected as our in-house-developed lead compound for PSMA targeting.

  17. Preparation of MR molecular probes targeting CD40 mutant and the preliminary study of imaging ovarian cancer in vitro

    International Nuclear Information System (INIS)

    Objective: To develop an ultrasmall superparamagnetic iron oxide (USPIO) based MR probe targeting CD40 mutant and investigate its biological and chemical properties and its targeting effect on ovarian cancer cells in vitro. Methods: To prepare immunologically competent probe, the monoclonal antibody was conjugated with USPIO particles modified by DMSA based on chemical crosslinking method. The USPIO labeled anti-human CD40 mutant monoclonal antibody 5H6 (5H6-USPIO) was the experimental probe, and the USPIO labeled anti-human CD40 monoclonal antibody 5C11 (5C11-USPIO) and USPIO served as control agents. The flow cytometry, confocal microscopy and Prussian blue staining were employed to assess the magnetic performance and analyze its bioactivity of the probe. The probe's cell MR imaging in vitro was carried out using ovarian caner cells (HO8910) with high CD40 mutant expression. The analysis of signal data of different groups was conducted by using one-way ANOVA and LSD test. The probe's effect on ovarian caner cells' growth was measured by CCK-8 kit. Results: The stable molecular probe carrying nanoparticles and CD40 mutant antibody was built and purified successfully. The probe had similar magnetic property compared with original USPIO. Immunofluorescence and Prussian blue staining confirmed that the molecular probe could recognize CD40 mutant on ovarian cancer cells (HO8910) with high specificity. The probe had no effect on the growth of HO8910 cells. MR cell imaging in vitro showed that the value of T2 and T2* decreased significantly after the probe binding with HO8910 cells and T2WI became darker than control groups. The T2 and T2* relaxation time of 5H6-USPIO group was (40.05 ± 1.62) ms and (3.08 ± 0.11) ms, respectively. The T2 and T2* relaxation time of 5H6-USPIO group was shorter than 5C11-USPIO [(85.38 ± 4.74) and (11.82 ± 1.00) ms, respectively] and USPIO [(91.62 ± 3.35) and (13.60 ± 1.92) ms, respectively] groups with statistical

  18. Epidermal growth factor receptor-targeted ultra-small superparamagnetic iron oxide particles for magnetic resonance molecular imaging of lung cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    CHEN Chun-li; HU Guang-yuan; MEI Qi; QIU Hong; LONG Guo-xian; HU Guo-qing

    2012-01-01

    Background Magnetic resonance (MR) molecular imaging can detect abnormalities associated with disease at the level of cell and molecule.The epidermal growth factor receptor (EGFR) plays an important role in the development of lung cancer.This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells.Methods We attached ultra-small superparamagnetic iron oxide (USPIO) particles to cetuximab (C225) anti-human IgG using the carbodiimide method.We made the molecular MR contrast agents C225-USPIO and IgG-USPIO,the latter as a control reagent,and determined concentrations according to the Fe content.Lung cancer A549 cells were cultured and immunocytochemistry (SP) was used to detect the expression of EGFR on cells.We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry.We cultured A549 cells with C225-USPIO at a Fe concentration of 50 μg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy (TEM).We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRi.We did scanning on the cells labeled with C225-USPIO,IgG-USPIO,and distilled water,respectively.The scanning sequences included axial T1W1,T2W1.Results Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression.Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control.Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group.The 4.7T MR imaging (MRI) scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells,but there was no significant difference between the time gradients

  19. Molecular Biomedical Imaging Laboratory (MBIL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Molecular Biomedical Imaging Laboratory (MBIL) is adjacent-a nd has access-to the Department of Radiology and Imaging Sciences clinical imaging facilities. MBIL...

  20. Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

    Directory of Open Access Journals (Sweden)

    Li K

    2013-07-01

    Full Text Available Kangan Li,1,4,5,* Shihui Wen,2,* Andrew C Larson,4,5 Mingwu Shen,2 Zhuoli Zhang,4,5 Qian Chen,3 Xiangyang Shi,2,3 Guixiang Zhang1 1Department of Radiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People’s Republic of China; 4Departments of Radiology and Biomedical Engineering, Northwestern University, Chicago, IL, USA; 5Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA *These authors contributed equally to this work Abstract: Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP as a dual-modality contrast agent for magnetic resonance (MR/computed tomography (CT imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine dendrimers modified with gadolinium chelate (DOTA-NHS and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results

  1. A targeted approach to cancer imaging and therapy

    Science.gov (United States)

    Li, Chun

    2014-02-01

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

  2. Molecular imaging in quality health care

    International Nuclear Information System (INIS)

    Full text: Quality health care results from translating fundamental bench discoveries and making them available to patients. During the past decade, 'molecular imaging' has emerged both as a new tool/technology and as a research and clinical discipline. Molecular imaging is an interdisciplinary approach involving biologists, physicists, physicians, mathematicians, conventional chemists, radiochemists and other specialists who have joined forces for better understanding and visualizing of both normal physiological processes and the molecular processes preceding the morphological manifestations of disease in vivo. Molecular imaging has been defined as 'non-invasive, quantitative, and repetitive imaging of targeted macromolecules and biological processes in living organisms' or as 'the visual representation, characterization, and quantification of biological processes at the cellular and sub-cellular levels within intact living organisms'. Weissleder defined molecular imaging in the most simple terms as 'studying diseases non-invasively at the molecular level'. Regardless of these semantic differences molecular imaging can contribute significantly to the preclinical and clinical drug and disease evaluation process. It is interesting to note, that despite major advances in imaging technology, cancer mortality has remained largely unchanged over the last three decades. Imaging has thus far enabled us to look through a magnifying glass at disease processes but has failed to dramatically influence disease outcomes. Emerging data suggest that molecular PET imaging is about to change this situation. High resolution molecular imaging devices designed for small animal research have developed into valuable tools for drug evaluation and imaging probe design. These include microPET, microCT, microMRI and optical imaging devices. These have enabled us to study drug effects in vivo by monitoring longitudinally their effects on tumour cell metabolism or proliferation. The only

  3. Radiogenomic imaging-linking diagnostic imaging and molecular diagnostics

    Institute of Scientific and Technical Information of China (English)

    Mathias; Goyen

    2014-01-01

    Radiogenomic imaging refers to the correlation between cancer imaging features and gene expression and is one of the most promising areas within science and medicine. High-throughput biological techniques have reshaped the perspective of biomedical research allowing for fast and efficient assessment of the entire molecular topography of a cell’s physiology providing new insights into human cancers. The use of non-invasive imaging tools for gene expression profiling of solid tumors could serve as a means for linking specific imaging features with specific gene expression patterns thereby allowing for more accurate diagnosis and prognosis and obviating the need for high-risk invasive biopsy procedures. This review focuses on the medical imaging part as one of the main drivers for the development of radiogenomic imaging.

  4. A Preclinical Evaluation of Antrodia camphorata Alcohol Extracts in the Treatment of Non-Small Cell Lung Cancer Using Non-Invasive Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Jeng-Feng Chiou

    2011-01-01

    Full Text Available This study was carried out to provide a platform for the pre-clinical evaluation of anti-cancer properties of a unique CAM (complementary and alternative medicine agent, Antrodia camphorata alcohol extract (ACAE, in a mouse model with the advantageous non-invasive in vivo bioluminescence molecular imaging technology. In vitro analyses on the proliferation, migration/invasion, cell cycle and apoptosis were performed on ACAE-treated non-small cell lung cancer cells, H441GL and control CGL1 cells. In vivo, immune-deficient mice were inoculated subcutaneously with H441GL followed by oral gavages of ACAE. The effect of ACAE on tumor progression was monitored by non-invasive bioluminescence imaging. The proliferation and migration/invasion of H441GL cells were inhibited by ACAE in a dose-dependent manner. In addition, ACAE induced cell cycle arrest at G0/G1 phase and apoptosis in H441GL cells as shown by flow cytometric analysis, Annexin-V immunoflourescence and DNA fragmentation. In vivo bioluminescence imaging revealed that tumorigenesis was significantly retarded by oral treatment of ACAE in a dose-dependent fashion. Based on our experimental data, ACAE contains anti-cancer properties and could be considered as a potential CAM agent in future clinical evaluation.

  5. Evolution of Imaging in Breast Cancer.

    Science.gov (United States)

    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

  6. Time-resolved molecular imaging

    Science.gov (United States)

    Xu, Junliang; Blaga, Cosmin I.; Agostini, Pierre; DiMauro, Louis F.

    2016-06-01

    Time-resolved molecular imaging is a frontier of ultrafast optical science and physical chemistry. In this article, we review present and future key spectroscopic and microscopic techniques for ultrafast imaging of molecular dynamics and show their differences and connections. The advent of femtosecond lasers and free electron x-ray lasers bring us closer to this goal, which eventually will extend our knowledge about molecular dynamics to the attosecond time domain.

  7. Dose reduction in molecular breast imaging

    Science.gov (United States)

    Wagenaar, Douglas J.; Chowdhury, Samir; Hugg, James W.; Moats, Rex A.; Patt, Bradley E.

    2011-10-01

    Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of 99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

  8. Molecular imaging in quality health care

    International Nuclear Information System (INIS)

    Full text: Quality Health Care results from applying fundamental basic science and preclinical concepts as well as novel technologies to patient care within specific socio-economic frameworks. Cancer mortality has improved recently but outcomes of cancer patients are still unacceptably poor. Molecular Imaging has the potential to improve the outcome of cancer patients in several ways. In the preclinical setting, high resolution molecular imaging devices designed for small animal research have developed into valuable tools for drug evaluation and imaging probe design. These have enabled us to study drug effects in vivo by monitoring longitudinally their effects on tumor cell metabolism or proliferation. The success of Imatinib in treating chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST) has demonstrated that targeted drugs can induce remarkable tumor responses and may even cure cancer patients. Targeted drugs have been used for treating various common solid human tumors, including breast cancer, colorectal cancer, and non-small cell lung cancer. However, diverse signaling pathways are involved in the development and progression of these genetically heterogeneous diseases. Consequently, inhibition of one specific pathway is likely to be efficacious in only in small subsets of patients with specific histological tumor types. It is unlikely that a single 'blockbuster' drug can be effective for all patients with a 'common' tumor. Rather, it will be necessary to develop multiple targeted drugs even for patients that share a single histologically defined tumor type. The inevitable consequence is a decreased revenue/cost ratio for the industry and increasing costs for patients and health care systems. It is therefore of paramount importance to identify drug failure as early as possible in preclinical and clinical trials. Human studies with positron emission tomography (PET) with molecular imaging probes targeting physiological processes such as

  9. Molecular Imaging of Urogenital Diseases

    Science.gov (United States)

    Cho, Steve Y.; Szabo, Zsolt; Morgan, Russell H.

    2013-01-01

    There is an expanding and exciting repertoire of PET imaging radiotracers for urogenital diseases, particularly in prostate cancer, renal cell cancer, and renal function. Prostate cancer is the most commonly diagnosed cancer in men. With growing therapeutics options for the treatment of metastatic and advanced prostate cancer, improved functional imaging of prostate cancer beyond the limitations of conventional computed tomography (CT) and bone scan (BS) is becoming increasingly important for both clinical management and drug development. PET radiotracers beyond 18F-Fluorodeoxyglucose (FDG) for prostate cancer include 18F-Sodium Fluoride, 11C-Choline and 18F-Fluorocholine and 11C-Acetate. Other emerging and promising PET radiotracers include a synthetic L-leucine amino acid analog (anti-18F-FACBC), dihydrotestosterone analog (18F-FDHT) and prostate specific membrane antigen (PSMA) based PET radiotracers (ex. 18F-DCFBC, 89Zr-DFO-J591, 68Ga(HBED-CC)). Larger prospective and comparison trials of these PET radiotracers are needed to establish the role of PET/CT in prostate cancer. Renal cell cancer imaging with FDG PET/CT although available can be limited, especially for detection of the primary tumor. Improved renal cell cancer detection with carbonic anhydrase IX (CAIX) based antibody (124I-girentuximab) and radioimmunotherapy targeting with 177Lu-cG250 appear promising. Evaluation of renal injury by imaging renal perfusion and function with novel PET radiotracers include p-18F-fluorohippurate (18F-PFH) and hippurate m-cyano-p-18F-fluorohippurate (18F-CNPFH) and Rubidium-82 chloride (typically used for myocardial perfusion imaging). Renal receptor imaging of the renal renin angiotensin system with a variety of selective PET radioligands are also becoming available for clinical translation. PMID:24484747

  10. Cardiovascular molecular imaging of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

    2007-06-15

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  11. The research progress of radionuclide molecular imaging for breast cancer%乳腺癌放射性核素分子成像研究进展

    Institute of Scientific and Technical Information of China (English)

    王健; 宋秀宇; 徐文贵; 周雯

    2015-01-01

    随着新型特异性显像剂和成像设备的出现,乳腺癌分子成像技术得以快速发展。乳腺癌放射性核素分子成像技术主要包括单光子发射体层成像(SPECT)、正电子发射体层成像(PET)、PET/CT以及正电子发射乳腺成像(PEM)。显像剂包括临床应用最广泛的正电子示踪剂18F-氟代脱氧葡萄糖(18F-FDG )、用于研究肿瘤细胞增殖显像的5-18F-氟尿嘧啶(5-FU)及3-脱氧-3-氟胸腺嘧啶(FLT)、通过肿瘤氨基酸代谢显像的精氨酸-甘氨酸-天冬氨酸(RGD)类,还包括受体类的靶向显像剂如雌激素受体相关的16α-[18F]-17β-雌二醇(FES)、放射性标记的人表皮生长因子受体2(HER2)及表皮生长因子受体(EGFR)等。目前用于乳腺显像的PEM技术对乳腺癌的早期诊断及疗效预测效果显著,就乳腺癌放射性核素分子成像技术的研究进展予以综述。%With the developments of new type specific imaging agent and imaging device, the molecular imaging technology of breast cancer is being developed rapidly. Radionuclide molecular imaging techniques for breast cancer include single photon emission tomography (SPECT) and positron emission body tomography (PET), PET/CT and positron emission (PEM) imaging. In addition to the most widely used radiotracer 18F -FDG, for study of tumor cell proliferation imaging 5-18F-FU and FLT can be used. For imaging tumor amino acid metabolism, RGD-based tracers are available. The receptor-targeted agents include estrogen receptor related FES, radiolabeled human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR). At present, the PEM technique had an important clinical value in the early diagnosis and prognosis prediction of breast cancer. We reviewed the research progress of the radionuclide molecular imaging for breast cancer.

  12. Virtual cancer image data warehouse.

    Science.gov (United States)

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

    1997-01-01

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

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

    OpenAIRE

    Hardiani Rahmania; Abdul Mutalib; Martalena Ramli; Jutti Levita

    2015-01-01

    Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obtain better sensitivity, specificity and depiction localization of the disease. In this study, we developed a new molecular imaging agent, radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab in the form of 147Gd-DOTA-PAMAM G3.0-trastuzumab, that can be both target-specific radiopharmaceutical in SPECT as well as targeted contrast agent in MRI for the purpose of diagnosis of HER-2 positive breast cancer...

  14. Molecular genetics of colorectal cancer.

    Science.gov (United States)

    Bogaert, Julie; Prenen, Hans

    2014-01-01

    Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764

  15. Image Similarity to Improve the Classification of Breast Cancer Images

    OpenAIRE

    Dave Tahmoush

    2009-01-01

    Techniques in image similarity can be used to improve the classification of breast cancer images. Breast cancer images in the mammogram modality have an abundance of non-cancerous structures that are similar to cancer, which make classification of images as containing cancer especially difficult to work with. Only the cancerous part of the image is relevant, so the techniques must learn to recognize cancer in noisy mammograms and extract features from that cancer to appropriately classify ima...

  16. Molecular oncology of lung cancer.

    Science.gov (United States)

    Toyooka, Shinichi; Mitsudomi, Tetsuya; Soh, Junichi; Aokage, Keiju; Yamane, Masaomi; Oto, Takahiro; Kiura, Katsuyuki; Miyoshi, Shinichiro

    2011-08-01

    Progress in genetic engineering has made it possible to elucidate the molecular biological abnormalities in lung cancer. Mutations in KRAS and P53 genes, loss of specific alleles, and DNA methylation of the tumor suppressor genes were the major abnormalities investigated between 1980 and the 2000s. In 2004, mutations in the epidermal growth factor receptor (EGFR) gene that cause oncogene addiction were discovered in non-small-cell lung cancers (NSCLCs), especially in adenocarcinomas. Because they are strongly associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), a great deal of knowledge has been acquired in regard to both EGFR and other genes in the EGFR family and their downstream genes. Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was discovered in NSCLC; and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers that have this translocation. These discoveries graphically illustrate that molecular biological findings are directly linked to the development of clinical oncology and to improving the survival rates of lung cancer patients. Here, we review the remarkable progress in molecular biological knowledge acquired thus far in regard to lung cancer, especially NSCLC, and the future possibilities. PMID:21850578

  17. Two wavelength-shifting molecular beacons for simultaneous and selective imaging of vesicular miRNA-21 and miRNA-31 in living cancer cells.

    Science.gov (United States)

    Bohländer, Peggy R; Abba, Mohammed L; Bestvater, Felix; Allgayer, Heike; Wagenknecht, Hans-Achim

    2016-06-14

    Two molecular beacons were designed as complementary fluorescent imaging probes for miRNA-21 and miRNA-31. Both beacons were prepared by a combination of solid-phase protocol and Cu(i)-catalyzed cycloaddition chemistry. The four photostable and bright fluorophores were attached to 2'-positions in the stem part of the two beacons. One beacon was labeled by a green-to-red emitting and the other by a blue-to-yellow emitting energy transfer pair. This two by two combination yields the four color emission readout. In vitro experiments demonstrate rapid and highly selective opening of both molecular beacons upon addition of the complementary target RNA and excellent green : red and blue : yellow emission color contrasts. Confocal microscopy of selected cancer cell lines provides evidence that a four color imaging of versicular miRNA-21 and miRNA-31 can be achieved both selectively and simultaneously upon transfection by the beacons, and that the fluorescent readouts track well with miRNA levels determined by PCR. PMID:27114268

  18. Imaging of multidrug resistance in cancer

    OpenAIRE

    Dizdarevic, S.; Peters, A M

    2011-01-01

    Abstract Primary intrinsic and/or acquired multidrug resistance (MDR) is the main obstacle to successful cancer treatment. Functional molecular imaging of MDR in cancer using single photon or positron emitters may be helpful to identify multidrug-resistant tumours and predict not only those patients who are resistant to treatment, with a clinically unfavourable prognosis, but also those who are susceptible to the development of drug toxicity or even certain tumours . Variations in the mdr1 ge...

  19. Advances in Multimodality Molecular Imaging

    International Nuclear Information System (INIS)

    Multimodality molecular imaging is now playing a pivotal role in clinical setting and biomedical research. Modern molecular imaging technologies are deemed to potentially lead to a revolutionary paradigm shift in healthcare and revolutionize clinical practice. Within the spectrum of macroscopic medical imaging, sensitivity ranges from the detection of millimolar to submillimolar concentrations of contrast media with computed tomography (CT) and magnetic resonance imaging (MRI), respectively, to picomolar concentrations in single-photon emission computed tomography (SPECT) and positron emission 8 9 tomography (PET): a 108-109 difference. Even though the introduction of dedicated dual-modality imaging systems designed specifically and available commercially for clinical practice is relatively recent, the concept of combining anatomical and functional imaging has been recognized for several decades. Software- and hardware-based correlation between anatomical (x-ray CT, MRI) and physiological (PET) information is a promising research field and now offers unique capabilities for the medical imaging community and biomedical researchers. The introduction of dual-modality PET/CT imaging systems in clinical environments has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT) and functional or metabolic (PET) information provided in a 'one-stop shop' and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI) in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging where the first patient images have been shown late in 2006. This paper discusses the

  20. Radiolabeling and evaluation of 64Cu-DOTA-F56 peptide targeting vascular endothelial growth factor receptor 1 in the molecular imaging of gastric cancer

    OpenAIRE

    Zhu, Hua; Zhao, Chuanke; Liu, Fei; Wang, Lixin; Feng, Junnan; Zhou, Zheng; Qu, Like; Shou, Chengchao; Yang, Zhi

    2015-01-01

    Noninvasive imaging of vascular endothelial growth factor receptor 1 (VEGFR1) remains a great challenge in early diagnosis of gastric cancer. Here we reported the synthesis, radiolabeling, and evaluation of a novel 64Cu-radiolabeled peptide for noninvasive positron emission tomography (PET) imaging of VEGFR1 positive gastric cancer. The binding of modified peptide WHSDMEWWYLLG (termed as F56) to VEGER-1 expressed in gastric cancer cell BCG823 has been confirmed by immune-fluorescence overlap....

  1. Molecular classification of gastric cancer.

    Science.gov (United States)

    Chia, N-Y; Tan, P

    2016-05-01

    Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future. PMID:26861606

  2. Molecular imaging with little anatomic information: combined scintigraphic-radiologic imaging of thyroid cancer and sentinel-lymph-node; Molekulare Bildgebung bei geringer anatomischer Bildinformation: Kombinierte szintigraphisch-radiologische Darstellung beim Schilddruesenkarzinom und Sentinel-Lymph-Node

    Energy Technology Data Exchange (ETDEWEB)

    Schlemmer, H.; Jigalin, A.; Freter, B.T.; Gasthaus, K.; Langer, H.; Lerch, H. [Klinik fuer Nuklearmedizin, HELIOS Klinikum Wuppertal, Univ. Witten-Herdecke (Germany)

    2006-09-15

    The combined SPECT-CT examination is a procedure applied for acquisition, overlaying, and analysis of the scintigraphic functional data with the anatomic information in one single examination. This is considered especially for the molecular imaging with only little anatomic information. By giving examples, this elaboration demonstrates the advantages of the method of combining SPECT and radiologic presentation at the iodine-131-radio-nuclide imaging of differentiated thyroid cancer and the sentinel-lymph-node-scanning of different tumor entities. The possibility of combined imaging permits the examiner more diagnostic accuracy by better recognizing of pathologic processes with exact anatomic localisation. It is a simple examination which can be done in one process and hardly stresses the patient. (orig.)

  3. Status and Advances of RGD Molecular Imaging in Lung Cancer%RGD分子影像在肺癌的研究现状与进展

    Institute of Scientific and Technical Information of China (English)

    岳宁; 袁双虎; 杨国仁

    2014-01-01

    肺癌是国内外最常见、死亡率最高的恶性肿瘤之一。持续的新生血管生成是恶性肿瘤的特征,是肿瘤增殖、浸润、复发和转移的基础,也是目前肺癌生物学治疗热点之一。肿瘤血管生成过程中,整合素的作用至关重要。精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp, RGD)肽能特异地与整合素结合,应用放射性核素标记的RGD分子探针,可使肿瘤血管显像,能反映肿瘤血管的变化。本文对近年来国内外RGD肽的肺癌显像研究进展进行综述。%Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD) peptides could combine with integrins speciif-cally, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to relfect its changes. hTe lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  4. Molecular imaging. Fundamentals and applications

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Jie (ed.) [Chinese Academy of Sciences, Beijing (China). Intelligent Medical Research Center

    2013-07-01

    Covers a wide range of new theory, new techniques and new applications. Contributed by many experts in China. The editor has obtained the National Science and Technology Progress Award twice. ''Molecular Imaging: Fundamentals and Applications'' is a comprehensive monograph which describes not only the theory of the underlying algorithms and key technologies but also introduces a prototype system and its applications, bringing together theory, technology and applications. By explaining the basic concepts and principles of molecular imaging, imaging techniques, as well as research and applications in detail, the book provides both detailed theoretical background information and technical methods for researchers working in medical imaging and the life sciences. Clinical doctors and graduate students will also benefit from this book.

  5. Information Systems - Cancer Imaging Program

    Science.gov (United States)

    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.

  6. [Molecular diagnostics of lung cancer].

    Science.gov (United States)

    Ryska, A; Dziadziuszko, R; Olszewski, W; Berzinec, P; Öz, B; Gottfried, M; Cufer, T; Samarzija, M; Plank, L; Ostoros, Gy; Tímár, J

    2015-09-01

    Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field.

  7. Molecular Imaging Challenges With PET

    CERN Document Server

    Lecoq, P

    2010-01-01

    The future trends in molecular imaging and associated challenges for in-vivo functional imaging are illustrated on the basis of a few examples, such as atherosclerosis vulnerable plaques imaging or stem cells tracking. A set of parameters are derived to define the specifications of a new generation of in-vivo imaging devices in terms of sensitivity, spatial resolution and signal-to-noise ratio. The limitations of strategies used in present PET scanners are discussed and new approaches are proposed taking advantage of recent progress on materials, photodetectors and readout electronics. A special focus is put on metamaterials, as a new approach to bring more functionality to detection devices. It is shown that the route is now open towards a fully digital detector head with very high photon counting capability over a large energy range, excellent timing precision and possibility of imaging the energy deposition process.

  8. 3D molecular imaging SIMS

    Energy Technology Data Exchange (ETDEWEB)

    Gillen, Greg [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)]. E-mail: Greg.gillen@nist.gov; Fahey, Albert [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Wagner, Matt [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Mahoney, Christine [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)

    2006-07-30

    Thin monolayer and bilayer films of spin cast poly(methyl methacrylate) (PMMA), poly(2-hydroxyethyl methacrylate) (PHEMA), poly(lactic) acid (PLA) and PLA doped with several pharmaceuticals have been analyzed by dynamic SIMS using SF{sub 5} {sup +} polyatomic primary ion bombardment. Each of these systems exhibited minimal primary beam-induced degradation under cluster ion bombardment allowing molecular depth profiles to be obtained through the film. By combing secondary ion imaging with depth profiling, three-dimensional molecular image depth profiles have been obtained from these systems. In another approach, bevel cross-sections are cut in the samples with the SF{sub 5} {sup +} primary ion beam to produce a laterally magnified cross-section of the sample that does not contain the beam-induced damage that would be induced by conventional focussed ion beam (FIB) cross-sectioning. The bevel surface can then be examined using cluster SIMS imaging or other appropriate microanalysis technique.

  9. Advances in multimodality molecular imaging

    Directory of Open Access Journals (Sweden)

    Zaidi Habib

    2009-01-01

    Full Text Available Multimodality molecular imaging using high resolution positron emission tomography (PET combined with other modalities is now playing a pivotal role in basic and clinical research. The introduction of combined PET/CT systems in clinical setting has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT and functional or metabolic (PET information provided in a "one-stop shop" and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging. This paper discusses recent advances in PET instrumentation and the advantages and challenges of multimodality imaging systems. Future opportunities and the challenges facing the adoption of multimodality imaging instrumentation will also be addressed.

  10. Molecular Epidemiology of Female Lung Cancer

    OpenAIRE

    Seon-Hee Yim; Yeun-Jun Chung

    2011-01-01

    Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differenc...

  11. The molecular biology of cancer.

    Science.gov (United States)

    Bertram, J S

    2000-12-01

    identifies key genes directly involved in carcinogenesis and demonstrates how mutations in these genes allow cells to circumvent cellular controls. This detailed understanding of the process of carcinogenesis at the molecular level has only been possible because of the advent of modern molecular biology. This new discipline, by precisely identifying the molecular basis of the differences between normal and malignant cells, has created novel opportunities and provided the means to specifically target these modified genes. Whenever possible this review highlights these opportunities and the attempts being made to generate novel, molecular based therapies against cancer. Successful use of these new therapies will rely upon a detailed knowledge of the genetic defects in individual tumors. The review concludes with a discussion of how the use of high throughput molecular arrays will allow the molecular pathologist/therapist to identify these defects and direct specific therapies to specific mutations.

  12. Sparse image reconstruction for molecular imaging

    CERN Document Server

    Ting, Michael; Hero, Alfred O

    2008-01-01

    The application that motivates this paper is molecular imaging at the atomic level. When discretized at sub-atomic distances, the volume is inherently sparse. Noiseless measurements from an imaging technology can be modeled by convolution of the image with the system point spread function (psf). Such is the case with magnetic resonance force microscopy (MRFM), an emerging technology where imaging of an individual tobacco mosaic virus was recently demonstrated with nanometer resolution. We also consider additive white Gaussian noise (AWGN) in the measurements. Many prior works of sparse estimators have focused on the case when H has low coherence; however, the system matrix H in our application is the convolution matrix for the system psf. A typical convolution matrix has high coherence. The paper therefore does not assume a low coherence H. A discrete-continuous form of the Laplacian and atom at zero (LAZE) p.d.f. used by Johnstone and Silverman is formulated, and two sparse estimators derived by maximizing t...

  13. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  14. Tobacco and cancer (image)

    Science.gov (United States)

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

  15. Correlation of morphological and molecular parameters for colon cancer

    Science.gov (United States)

    Yuan, Shuai; Roney, Celeste A.; Li, Qian; Jiang, James; Cable, Alex; Summers, Ronald M.; Chen, Yu

    2010-02-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. There is great interest in studying the relationship among microstructures and molecular processes of colorectal cancer during its progression at early stages. In this study, we use our multi-modality optical system that could obtain co-registered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) images simultaneously to study CRC. The overexpressed carbohydrate α-L-fucose on the surfaces of polyps facilitates the bond of adenomatous polyps with UEA-1 and is used as biomarker. Tissue scattering coefficient derived from OCT axial scan is used as quantitative value of structural information. Both structural images from OCT and molecular images show spatial heterogeneity of tumors. Correlations between those values are analyzed and demonstrate that scattering coefficients are positively correlated with FMI signals in conjugated. In UEA-1 conjugated samples (8 polyps and 8 control regions), the correlation coefficient is ranged from 0.45 to 0.99. These findings indicate that the microstructure of polyps is changed gradually during cancer progression and the change is well correlated with certain molecular process. Our study demonstrated that multi-parametric imaging is able to simultaneously detect morphology and molecular information and it can enable spatially and temporally correlated studies of structure-function relationships during tumor progression.

  16. Molecular imaging of cholinergic processes in prostate cancer using 11C-donepezil and 18F-FEOBV

    International Nuclear Information System (INIS)

    High-grade prostate cancer (PC) displays parasympathetic neoneurogenesis. We investigated the binding of two PET tracers that visualize cholinergic nerves in PC tissue using autoradiography. Prostatectomy tissue was subjected to autoradiography with 11C-donepezil and 18F-FEOBV and correlated with Gleason scores (GS). Regions of interest on the autoradiograms were defined and quantified. Tracer binding in cancer tissue regions was compared with that in normal tissue. We included 13 patients with biopsy-verified PC. In particular, 11C-donepezil uptake was higher in ''high-grade'' PC (GS ≥4 + 3) than in ''low-grade'' PC and benign hyperplasia. 11C-donepezil uptake ranged from a mean of 56 % higher (GS 3 + 3) to 409 % higher (GS 4 + 4), and 18F-FEOBV uptake ranged from 67 % higher (GS 3 + 3) to 194 % higher (GS 4 + 5). The uptake of both tracers was higher in PC with a high GS than in PC with a low GS, but the difference was significant only for 11C-donepezil (p = 0.003). Uptake of PET tracers binding to cholinergic nerves was markedly higher in PC with a high GS than in PC with a low GS. This finding implies that 11C-donepezil PET/CT may be able to differentiate between low-grade and high-grade PC. (orig.)

  17. Molecular imaging of cholinergic processes in prostate cancer using {sup 11}C-donepezil and {sup 18}F-FEOBV

    Energy Technology Data Exchange (ETDEWEB)

    Stokholm, Morten Gersel; Bender, Dirk; Jakobsen, Steen; Froekiaer, Joergen; Borghammer, Per [Aarhus University Hospital, Department of Nuclear Medicine and PET Centre, Aarhus C (Denmark); Hoeyer, Soeren [Aarhus University Hospital, Department of Histopathology, Aarhus C (Denmark); Borre, Michael [Aarhus University Hospital, Department of Urology, Aarhus C (Denmark)

    2016-05-15

    High-grade prostate cancer (PC) displays parasympathetic neoneurogenesis. We investigated the binding of two PET tracers that visualize cholinergic nerves in PC tissue using autoradiography. Prostatectomy tissue was subjected to autoradiography with {sup 11}C-donepezil and {sup 18}F-FEOBV and correlated with Gleason scores (GS). Regions of interest on the autoradiograms were defined and quantified. Tracer binding in cancer tissue regions was compared with that in normal tissue. We included 13 patients with biopsy-verified PC. In particular, {sup 11}C-donepezil uptake was higher in ''high-grade'' PC (GS ≥4 + 3) than in ''low-grade'' PC and benign hyperplasia. {sup 11}C-donepezil uptake ranged from a mean of 56 % higher (GS 3 + 3) to 409 % higher (GS 4 + 4), and {sup 18}F-FEOBV uptake ranged from 67 % higher (GS 3 + 3) to 194 % higher (GS 4 + 5). The uptake of both tracers was higher in PC with a high GS than in PC with a low GS, but the difference was significant only for {sup 11}C-donepezil (p = 0.003). Uptake of PET tracers binding to cholinergic nerves was markedly higher in PC with a high GS than in PC with a low GS. This finding implies that {sup 11}C-donepezil PET/CT may be able to differentiate between low-grade and high-grade PC. (orig.)

  18. PET Imaging - from Physics to Clinical Molecular Imaging

    Science.gov (United States)

    Majewski, Stan

    2008-03-01

    From the beginnings many years ago in a few physics laboratories and first applications as a research brain function imager, PET became lately a leading molecular imaging modality used in diagnosis, staging and therapy monitoring of cancer, as well as has increased use in assessment of brain function (early diagnosis of Alzheimer's, etc) and in cardiac function. To assist with anatomic structure map and with absorption correction CT is often used with PET in a duo system. Growing interest in the last 5-10 years in dedicated organ specific PET imagers (breast, prostate, brain, etc) presents again an opportunity to the particle physics instrumentation community to contribute to the important field of medical imaging. In addition to the bulky standard ring structures, compact, economical and high performance mobile imagers are being proposed and build. The latest development in standard PET imaging is introduction of the well known TOF concept enabling clearer tomographic pictures of the patient organs. Development and availability of novel photodetectors such as Silicon PMT immune to magnetic fields offers an exciting opportunity to use PET in conjunction with MRI and fMRI. As before with avalanche photodiodes, particle physics community plays a leading role in developing these devices. The presentation will mostly focus on present and future opportunities for better PET designs based on new technologies and methods: new scintillators, photodetectors, readout, software.

  19. Circadian molecular clocks and cancer.

    Science.gov (United States)

    Kelleher, Fergal C; Rao, Aparna; Maguire, Anne

    2014-01-01

    Physiological processes such as the sleep-wake cycle, metabolism and hormone secretion are controlled by a circadian rhythm adapted to 24h day-night periodicity. This circadian synchronisation is in part controlled by ambient light decreasing melatonin secretion by the pineal gland and co-ordinated by the suprachiasmatic nucleus of the hypothalamus. Peripheral cell autonomous circadian clocks controlled by the suprachiasmatic nucleus, the master regulator, exist within every cell of the body and are comprised of at least twelve genes. These include the basic helix-loop-helix/PAS domain containing transcription factors; Clock, BMal1 and Npas2 which activate transcription of the periodic genes (Per1 and Per2) and cryptochrome genes (Cry1 and Cry2). Points of coupling exist between the cellular clock and the cell cycle. Cell cycle genes which are affected by the molecular circadian clock include c-Myc, Wee1, cyclin D and p21. Therefore the rhythm of the circadian clock and cancer are interlinked. Molecular examples exist including activation of Per2 leads to c-myc overexpression and an increased tumor incidence. Mice with mutations in Cryptochrome 1 and 2 are arrhythmic (lack a circadian rhythm) and arrhythmic mice have a faster rate of growth of implanted tumors. Epidemiological finding of relevance include 'The Nurses' Health Study' where it was established that women working rotational night shifts have an increased incidence of breast cancer. Compounds that affect circadian rhythm exist with attendant future therapeutic possibilities. These include casein kinase I inhibitors and a candidate small molecule KL001 that affects the degradation of cryptochrome. Theoretically the cell cycle and malignant disease may be targeted vicariously by selective alteration of the cellular molecular clock. PMID:24099911

  20. MR imaging of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu E-mail: yosirad@med.kokbe-u.ac.jpyosirad@kobe-u.ac.jpyoshiharuohno@aol.com; Sugimura, Kazuro; Hatabu, Hiroto

    2002-12-01

    Since publication of the Radiologic Diagnostic Oncology Group Report in 1991, the clinical application of pulmonary magnetic resonance (MR) imaging to patients with lung cancer has been limited. Computed tomography has been much more widely available for staging of lung cancer in clinical situations. Currently, ventilation and perfusion scintigraphy is the only modality that demonstrates pulmonary function while 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography is the only modality that reveals biological glucose metabolism of lung cancer. However, recent advancements in MR imaging have made it possible to evaluate morphological and functional information in lung cancer patients more accurately and quantitatively. Pulmonary MR imaging may hold significant potential to substitute for nuclear medicine examinations. In this review, we describe recent advances in MR imaging of lung cancer, focusing on (1) characterization of solitary pulmonary nodules; (2) differentiation from secondary change; evaluation of (3) medastinal invasion, (4) chest wall invasion, (5) lymph node metastasis, and (6) distant metastasis; and (7) pulmonary functional imaging. We believe that further basic studies, as well as clinical applications of newer MR techniques, will play an important role in the management of patients with lung cancer.

  1. Radiological imaging of rectal cancer

    Directory of Open Access Journals (Sweden)

    Lidija Lincender-Cvijetić

    2012-11-01

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

  2. Prostate Cancer Imaging with Novel PET Tracers.

    Science.gov (United States)

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

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

  3. Imaging of liver cancer

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identi-fication 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.

  4. Molecular Diagnostic Applications in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Laura Huth

    2014-06-01

    Full Text Available Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer patients.  Distinction of these applications is based on the different molecular principles found in colorectal cancer (CRC. Strategies for molecular analysis of single genes (as KRAS or TP53 as well as microarray based techniques are discussed. Moreover, in addition to the fecal occult blood testing (FOBT and colonoscopy some novel assays offer approaches for early detection of colorectal cancer like the multitarget stool DNA test or the blood-based Septin 9 DNA methylation test. Liquid biopsy analysis may also exhibit great diagnostic potential in CRC for monitoring developing resistance to treatment. These new diagnostic tools and the definition of molecular biomarkers in CRC will improve early detection and targeted therapy of colorectal cancer.

  5. Quantitative Imaging in Cancer Clinical Trials.

    Science.gov (United States)

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

    2016-01-15

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

  6. Molecular therapeutics in pancreas cancer.

    Science.gov (United States)

    Narayanan, Vignesh; Weekes, Colin D

    2016-04-15

    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease. PMID:27096032

  7. Fecal Molecular Markers for Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    Rani Kanthan

    2012-01-01

    Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

  8. Magnetic resonance imaging for prostate cancer clinical application

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Yong Du; Hanfeng Yang; Yayong Huang; Jun Meng; Dongmei Xiao

    2013-01-01

    As prostate cancer is a biologically heterogeneous disease for which a variety of treatment options are available,the major objective of prostate cancer imaging is to achieve more precise disease characterization.In clinical practice,magnetic resonance imaging (MRI) is one of the imaging tools for the evaluation of prostate cancer,the fusion of MRI or dynamic contrast-enhanced MRI (DCE-MRI) with magnetic resonance spectroscopic imaging (MRSI) is improving the evaluation of cancer location,size,and extent,while providing an indication of tumor aggressiveness.This review summarizes the role of MRI in the application of prostate cancer and describes molecular MRI techniques (including MRSI and DCE-MRI)for aiding prostate cancer management.

  9. Continuous-terahertz-wave molecular imaging system for biomedical applications

    Science.gov (United States)

    Zhang, Rui; Zhang, Liangliang; Wu, Tong; Wang, Ruixue; Zuo, Shasha; Wu, Dong; Zhang, Cunlin; Zhang, Jue; Fang, Jing

    2016-07-01

    Molecular imaging techniques are becoming increasingly important in biomedical research and potentially in clinical practice. We present a continuous-terahertz (THz)-wave molecular imaging system for biomedical applications, in which an infrared (IR) laser is integrated into a 0.2-THz reflection-mode continuous-THz-wave imaging system to induce surface plasmon polaritons on the nanoparticles and further improve the intensity of the reflected signal from the water around the nanoparticles. A strong and rapid increment of the reflected THz signal in the nanoparticle solution upon the IR laser irradiation is demonstrated, using either gold or silver nanoparticles. This low-cost, simple, and stable continuous-THz-wave molecular imaging system is suitable for miniaturization and practical imaging applications; in particular, it shows great promise for cancer diagnosis and nanoparticle drug-delivery monitoring.

  10. Imaging in early phase childhood cancer trials

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-02-15

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

  11. Molecular and Functional Imaging of Internet Addiction

    OpenAIRE

    Yunqi Zhu; Hong Zhang; Mei Tian

    2015-01-01

    Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) an...

  12. Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

    OpenAIRE

    Lee, Soo Jin; Paeng, Jin Chul

    2015-01-01

    Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell...

  13. Radiology Network (ACRIN) - Cancer Imaging Program

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter;

    2010-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an essential role in the clinical management of patients. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and...... molecular imaging information. Developments in imaging technologies, specifically magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), have improved the detection rate of prostate cancer. MRI has improved lesion detection and local staging. Furthermore, MRI....../CT imaging of prostate cancer. Among these, choline (labeled with (18)F or (11)C), (11)C-acetate, and (18)F-fluoride have demonstrated promising results, and other new radiopharmaceuticals are currently under evaluation in preclinical and clinical studies....

  15. Molecular Biology of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    HuanXi; JanBrabender; RalfMetzger; PaulM.Schneider

    2004-01-01

    There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett's esophagus. Interesting and promising findings have included overexpression of proto-oncogenes,loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silencing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the field of molecular carcinogenesis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

  16. Clinical photoacoustic imaging of cancer

    Science.gov (United States)

    2016-01-01

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented. PMID:27669961

  17. Integrated Molecular Profiling in Advanced Cancers Trial

    Science.gov (United States)

    2016-06-21

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  18. Genetic and molecular changes in ovarian cancer

    Science.gov (United States)

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  19. Nanodiamond Imaging: a New Molecular Imaging Approach

    OpenAIRE

    Hegyi, Alex Nathan

    2013-01-01

    Nanodiamond imaging is a novel biomedical imaging technique that non-invasively records the distribution of biologically-tagged nanodiamonds in vivo, in two or three dimensions. A nanodiamond imaging system optically detects electron spin resonance of nitrogen-vacancy centers in nanodiamonds, a non-toxic nanomaterial that is easily biologically functionalized. Two systems were built to demonstrate the feasibility of the technique. Using the first system, we imaged 2D projections of multipl...

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

    Science.gov (United States)

    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

  1. Molecular Profiling of Prostate Cancer Patients

    OpenAIRE

    Nna, Emmanuel Okechukwu

    2009-01-01

    In the UK, more than 30 000 men are diagnosed annually with prostate cancer (PCa) and about 10 000 men die from it each year. Although several molecular markers have been associated with prostate cancer development and/ or progression, only few of them are used in diagnostic pathology. The current standard tests include serum PSA test, digital rectal examination and histology of prostate biopsy. Recently the PCA-3 molecular test was approved in the European Union, and it is now...

  2. Molecular imaging of mental disorders

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) techniques have made it possible to measure changes in neurochemical components in living human brain. PET can be used to investigate various brain functions such as receptors, transporters, enzymes and various biochemical pathways; therefore, it could be a powerful tool for molecular imaging of mental disorders. Since the pathophysiology of schizophrenia has been discussed with a functional alteration of dopaminergic transmission in the brain, we have focused the dopaminergic components for the research target of schizophrenia using PET. Using high affinity ligand [11C]FLB 457, we found reduced D2 receptor binding in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation was observed between D2 receptor binding and the positive symptom score. Subregions of interest were defined on the thalamus using individual magnetic resonance images. D2 receptor binding was also lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. Alterations in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia. On the other hand D1 receptor binding was found to be lower in the prefrontal cortex and a significant negative correlation was observed between D1 receptor binding and the negative symptom score. Abnormality of D1 receptor function would be at the bottom of the negative symptoms and cognitive impairment of schizophrenia. Regarding the effect of antipsychotics on dopamine D2 receptor, occupancy and it's time-course have been measured in a living body using PET. This approach can provide in vivo pharmacological evidences of antipsychotics and establish the rational therapeutic strategy. PET is a powerful tool not only in the field of brain research but also drug discovery. (author)

  3. Spectroscopic Imaging of Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Frequency Domain Fluorescent Molecular Tomography and Molecular Probes for Small Animal Imaging

    Science.gov (United States)

    Kujala, Naresh Gandhi

    Fluorescent molecular tomography (FMT) is a noninvasive biomedical optical imaging that enables 3-dimensional quantitative determination of fluorochromes distributed in biological tissues. There are three methods for imaging large volume tissues based on different light sources: (a) using a light source of constant intensity, through a continuous or constant wave, (b) using a light source that is intensity modulated with a radio frequency (RF), and (c) using ultrafast pulses in the femtosecond range. In this study, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique, using a single source and detector pair that can be used for small animal imaging. In our system, the intensity of the laser source is modulated with a RF frequency to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from the tissue using a phasemeter. The data acquisition was performed by using a Labview program. The results suggest that we can measure the phase change from the heterogeneous inside tissue. Combined with fiber optics and filter sets, the system can be used to sensitively image the targeted fluorescent molecular probes, allowing the detection of cancer at an early stage. We used the system to detect the tumor-targeting molecular probe Alexa Fluor 680 and Alexa Fluor 750 bombesin peptide conjugates in phantoms as well as mouse tissues. We also developed and evaluated fluorescent Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors for optical molecular imaging. GRP receptors are over-expressed in several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. BBN is a 14 amino acid peptide that is an analogue to human gastrin-releasing peptide that binds specifically to GRPr receptors. BBN conjugates are significant in cancer detection and therapy. The

  5. Molecular breast imaging with gamma emitters.

    Science.gov (United States)

    Schillaci, O; Spanu, A; Danieli, R; Madeddu, G

    2013-12-01

    Following a diagnosis of breast cancer (BC), the early detection of local recurrence is important to define appropriate therapeutic strategies and increase the chances of a cure. In fact, despite major progress in surgical treatment, radiotherapy, and chemotherapy protocols, tumor recurrence is still a major problem. Moreover, the diagnosis of recurrence with conventional imaging methods can be difficult as a result of the presence of scar tissue. Molecular breast imaging (MBI) with gamma-ray emitting radiotracers may be very useful in this clinical setting, because it is not affected by the post-therapy morphologic changes. This review summarises the applications of 99mTc-sestamibi and 99mTc-tetrofosmin, the two most employed gamma emitter radiopharmaceuticals for MBI, in the diagnosis of local disease recurrence in patients with BC. The main limitation of MBI using conventional gamma-cameras is the low sensitivity for small BCs. The recent development of hybrid single photon emission computed tomography/computed tomography devices and especially of high-resolution specific breast cameras can improve the detection rate of sub-centimetric malignant lesions. Nevertheless, probably only the large availability of dedicated cameras will allow the clinical acceptance of MBI as useful complementary diagnostic technique in BC recurrence. The possible role of MBI with specific cameras in monitoring the local response of BC to neoadjuvant chemotherapy is also briefly discussed. PMID:24322791

  6. New horizons in prostate cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ravizzini, Gregory; Turkbey, Baris; Kurdziel, Karen [Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Choyke, Peter L. [Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)], E-mail: pchoyke@nih.gov

    2009-05-15

    Prostate cancer is the most common non-cutaneous malignancy among American men. Imaging has recently become more important in detection of prostate cancer since screening techniques such as digital rectal examination (DRE), prostate specific and transrectal ultrasound guided biopsy have considerable limitations in diagnosis and localization of prostate cancer. In this manuscript, we reviewed conventional, functional and targeted imaging modalities used in diagnosis and local staging of prostate cancer with exquisite images.

  7. Multidisciplinary Functional MR Imaging for Prostate Cancer

    OpenAIRE

    Kim, Jeong Kon; Jang, Yun-Jin; Cho, Gyunggoo

    2009-01-01

    Various functional magnetic resonance (MR) imaging techniques are used for evaluating prostate cancer including diffusion-weighted imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy. These techniques provide unique information that is helpful to differentiate prostate cancer from non-cancerous tissue and have been proven to improve the diagnostic performance of MRI not only for cancer detection, but also for staging, post-treatment monitoring, and guiding prostate biopsies. Ho...

  8. Molecular and genetic bases of pancreatic cancer.

    Science.gov (United States)

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

    2012-06-01

    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  9. Molecular biology of the lung cancer

    International Nuclear Information System (INIS)

    Background. Lung cancer is one of the most common malignant diseases and leading cause of cancer death worldwide. The advances in molecular biology and genetics, including the modern microarray technology and rapid sequencing techniques, have enabled a remarkable progress into elucidating the lung cancer ethiopathogenesis. Numerous studies suggest that more than 20 different genetic and epigenetic alterations are accumulating during the pathogenesis of clinically evident pulmonary cancers as a clonal, multistep process. Thus far, the most investigated alterations are the inactivational mutations and losses of tumour suppressor genes and the overexpression of growth-promoting oncogenes. More recently, the acquired epigenetic inactivation of tumour suppressor genes by promoter hypermethylation has been recognized. The early clonal genetic abnormalities that occur in preneoplastic bronchial epithelium damaged by smoking or other carcinogenes are being identified. The molecular distinctions between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as between tumors with different clinical outcomes have been described. These investigations lead to the hallmarks of lung cancer. Conclusions. It is realistic to expect that the molecular and cell culture-based investigations will lead to discoveries of new clinical applications with the potential to provide new avenues for early diagnosis, risk assessment, prevention, and most important, new more effective treatment approaches for the lung cancer patients. (author)

  10. Radionuclide molecular target therapy for lung cancer

    International Nuclear Information System (INIS)

    Lung cancer harms people's health or even lives severely. Currently, the morbidity and mortality of lung cancer are ascending all over the world. Accounting for 38.08% of malignant tumor caused death in male and 16% in female in cities,ranking top in both sex. Especially, the therapy of non-small cell lung cancer has not been obviously improved for many years. Recently, sodium/iodide transporter gene transfection and the therapy of molecular target drugs mediated radionuclide are being taken into account and become the new research directions in treatment of advanced lung cancer patients with the development of technology and theory for medical molecular biology and the new knowledge of lung cancer's pathogenesis. (authors)

  11. Exploiting novel molecular targets in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.

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

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter;

    2010-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an essential role in the clinical management of patients. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and ....../CT imaging of prostate cancer. Among these, choline (labeled with (18)F or (11)C), (11)C-acetate, and (18)F-fluoride have demonstrated promising results, and other new radiopharmaceuticals are currently under evaluation in preclinical and clinical studies.......Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an essential role in the clinical management of patients. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional......, and molecular imaging information. Developments in imaging technologies, specifically magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), have improved the detection rate of prostate cancer. MRI has improved lesion detection and local staging. Furthermore, MRI...

  13. Clinical PET-MR Imaging in Breast Cancer and Lung Cancer.

    Science.gov (United States)

    Rice, Samuel L; Friedman, Kent P

    2016-10-01

    Hybrid imaging systems have dramatically improved thoracic oncology patient care over the past 2 decades. PET-MR imaging systems have the potential to further improve imaging of thoracic neoplasms, resulting in diagnostic and therapeutic advantages compared with current MR imaging and PET-computed tomography systems. Increasing soft tissue contrast and lesion sensitivity, improved image registration, reduced radiation exposure, and improved patient convenience are immediate clinical advantages. Multiparametric quantitative imaging capabilities of PET-MR imaging have the potential to improve understanding of the molecular mechanisms of cancer and treatment effects, potentially guiding improvements in diagnosis and therapy. PMID:27593245

  14. Image guided prostate cancer treatments

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

  15. Quantification of mouse pulmonary cancer models by microcomputed tomography imaging

    International Nuclear Information System (INIS)

    The advances in preclinical cancer models, including orthotopic implantation models or genetically engineered mouse models of cancer, enable pursuing the molecular mechanism of cancer disease that might mimic genetic and biological processes in humans. Lung cancer is the major cause of cancer deaths; therefore, the treatment and prevention of lung cancer are expected to be improved by a better understanding of the complex mechanism of disease. In this study, we have examined the quantification of two distinct mouse lung cancer models by utilizing imaging modalities for monitoring tumor progression and drug efficacy evaluation. The utility of microcomputed tomography (micro-CT) for real-time/non-invasive monitoring of lung cancer progression has been confirmed by combining bioluminescent imaging and histopathological analyses. Further, we have developed a more clinically relevant lung cancer model by utilizing K-rasLSL-G12D/p53LSL-R270H mutant mice. Using micro-CT imaging, we monitored the development and progression of solitary lung tumor in K-rasLSL-G12D/p53LSL-R270H mutant mouse, and further demonstrated tumor growth inhibition by anticancer drug treatment. These results clearly indicate that imaging-guided evaluation of more clinically relevant tumor models would improve the process of new drug discovery and increase the probability of success in subsequent clinical studies. (author)

  16. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

  17. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Progress of molecular biology, genetic engineering, and polymer chemistry provide various tools to target molecules and cells in vivo. In this paper, recent achievements in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune, and stem cells using molecular nuclear imaging techniques are introduced

  18. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  19. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  20. Molecular markers for prostate cancer.

    NARCIS (Netherlands)

    Reynolds, M.A.; Kastury, K.; Groskopf, J.; Schalken, J.A.; Rittenhouse, H.G.

    2007-01-01

    Serum PSA testing has been used for over 20 years as an aid in the diagnosis and management of prostate cancer. Although highly sensitive, it suffers from a lack of specificity, showing elevated serum levels in a variety of other conditions including prostatitis, benign prostate hyperplasia, and non

  1. Molecular Mechanisms Underlying Psychological Stress and Cancer.

    Science.gov (United States)

    Shin, Kyeong Jin; Lee, Yu Jin; Yang, Yong Ryoul; Park, Seorim; Suh, Pann-Ghill; Follo, Matilde Yung; Cocco, Lucio; Ryu, Sung Ho

    2016-01-01

    Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients. Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS). These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.

  2. Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.

    Science.gov (United States)

    Manning, H Charles; Buck, Jason R; Cook, Rebecca S

    2016-02-01

    Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed.

  3. Molecular imaging of apoptosis: from micro to macro.

    Science.gov (United States)

    Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei; Liu, Gang; Eden, Henry S; Chen, Xiaoyuan

    2015-01-01

    Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus.

  4. MR imaging of prostate cancer

    International Nuclear Information System (INIS)

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

  5. In vivo imaging of cancer cells with electroporation of quantum dots and multispectral imaging

    Science.gov (United States)

    Yoo, Jung Sun; Won, Nayoun; Kim, Hong Bae; Bang, Jiwon; Kim, Sungjee; Ahn, Saeyoung; Soh, Kwang-Sup

    2010-06-01

    Our understanding of dissemination and growth of cancer cells is limited by our inability for long-term followup of this process in vivo. Fluorescence molecular imaging has the potential to track cancer cells with high contrast and sensitivity in living animals. For this purpose, intracellular delivery of near-infrared fluorescence quantum dots (QDs) by electroporation offers considerable advantages over organic fluorophores and other cell tagging methods. In this research we developed a multispectral imaging system that could eliminate two major parameters compromising in vivo fluorescence imaging performance, i.e., variations in the tissue optical properties and tissue autofluorescence. We demonstrated that electroporation of QDs and multispectral imaging allowed in vivo assessment of cancer development and progression in the xenograft mouse tumor model for more than 1 month, providing a powerful means to learn more about the biology of cancer and metastasis.

  6. New molecular targets against cervical cancer

    Directory of Open Access Journals (Sweden)

    Duenas-Gonzalez A

    2014-12-01

    Full Text Available Alfonso Duenas-Gonzalez,1,2 Alberto Serrano-Olvera,3 Lucely Cetina,4 Jaime Coronel4 1Unit of Biomedical Research in Cancer, Instituto de Investigaciones Biomedicas UNAM/Instituto Nacional de Cancerologia, Mexico City, 2ISSEMyM Cancer Center, Toluca, 3Medical Oncology Service, ABC Medical Center, Mexico City, 4Division of Clinical Research, Instituto Nacional de Cancerologia, Mexico City, Mexico On behalf of the Tumor Study Group Abstract: Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer death in women. Major advances but still insufficient achievements in the treatment of locally advanced and high-risk early stage patients have occurred in the last decade with the incorporation of concurrent cisplatin with radiation and, lately, gemcitabine added to cisplatin chemoradiation. Despite a number of clinical studies incorporating molecular-targeted therapy as radiosensitizers being in progress, so far, only antiangiogenic therapy with bevacizumab added to cisplatin chemoradiation has demonstrated safety and shown encouraging results in a Phase II study. In advanced disease, cisplatin doublets do not have a great impact on the natural history of the disease with median survival rates not exceeding 13 months. The first Phase III study of bevacizumab, added to cisplatin or a non-cisplatin-containing doublet, showed significant increase in both overall survival and progression-free survival. Further studies are needed before bevacizumab plus chemotherapy can be considered the standard of care for advanced disease. Characterization of the mutational landscape of cervical cancer has already been initiated, indicating that, for now, few of these targetable alterations match with available agents. Progress in both the mutational landscape knowledge and developments of novel targeted therapies may result in more effective and individualized treatments for cervical cancer. The potential efficacy of

  7. Molecular and functional imaging of internet addiction.

    Science.gov (United States)

    Zhu, Yunqi; Zhang, Hong; Tian, Mei

    2015-01-01

    Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) and single photon emission computed tomography (SPECT). MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC) could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects. Further investigations are needed to determine specific changes in the Internet addictive brain, as well as their implications for behavior and cognition.

  8. Molecular and Functional Imaging of Internet Addiction

    Directory of Open Access Journals (Sweden)

    Yunqi Zhu

    2015-01-01

    Full Text Available Maladaptive use of the Internet results in Internet addiction (IA, which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI and nuclear imaging modalities including positron emission tomography (PET and single photon emission computed tomography (SPECT. MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects. Further investigations are needed to determine specific changes in the Internet addictive brain, as well as their implications for behavior and cognition.

  9. Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

    Science.gov (United States)

    Qin, Zhengtao

    Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

  10. Molecular markers for thyroid cancer

    International Nuclear Information System (INIS)

    The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more accessible and potentially usable from a methodological viewpoint for diagnosis of the thyroid nodule before surgery. The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more

  11. Multimodality Magnetic Resonance Imaging of Prostate Cancer

    NARCIS (Netherlands)

    M.R. Engelbrecht; P. Puech; P. Colin; O. Akin; L. Lemaître; A. Villers

    2010-01-01

    The purpose of this article is to review both routine T2-weighted and new MRI techniques in the imaging of prostate cancer (PCa) for focal therapy. T2-weighted imaging, knowledge of MRI prostate zonal anatomy, cancer morphology, and intraprostatic tumor spread remain essential for clinical PCa imagi

  12. Molecular pathogenesis ofsporadic colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    HidetsuguYamagishi; HajimeKuroda; YasuoImai; HideyukiHiraishi

    2016-01-01

    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classiifed into three major groups according to frequently altered/mutated genes. These genes have been identiifed by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the ifrst half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a lim-ited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research ifeld and discuss its prospects.

  13. A refined molecular taxonomy of breast cancer. : molecular classification of breast cancer

    OpenAIRE

    Guedj, Michael; Marisa, Laëtitia; De Reynies, Aurélien; Orsetti, Béatrice; Schiappa, Renaud; Bibeau, Frédéric; MacGrogan, Gaëtan; Lerebours, Florence; Finetti, Pascal; Longy, Michel; Bertheau, Philippe; Bertrand, Françoise; Bonnet, Françoise; Martin, Anne-Laure; Feugeas, Jean-Paul

    2012-01-01

    International audience; The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. ...

  14. Molecular imaging of atherosclerosis in translational medicine

    Energy Technology Data Exchange (ETDEWEB)

    Perrone-Filardi, Pasquale; Costanzo, Pierluigi; Marciano, Caterina; Vassallo, Enrico; Marsico, Fabio; Ruggiero, Donatella; Petretta, Maria Piera; Chiariello, Massimo [University Federico II, Department of Internal Medicine, Cardiovascular and Immunological Sciences, Naples (Italy); Dellegrottaglie, Santo [University Federico II, Department of Internal Medicine, Cardiovascular and Immunological Sciences, Naples (Italy); Mount Sinai Medical Center, Z. and M.A. Wiener Cardiovascular Institute and M.-J. and H.R. Kravis Center for Cardiovascular Health, New York, NY (United States); Rudd, James H.F. [University of Cambridge, School of Clinical Medicine, Cambridge (United Kingdom); Cuocolo, Alberto [University Federico II, Department of Biomorphological and Functional Sciences, Naples (Italy); SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples (Italy)

    2011-05-15

    Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events. (orig.)

  15. [Molecular bases of cancer immunology].

    Science.gov (United States)

    Barrera-Rodríguez, R; Peralta-Zaragoza, O; Madrid-Marina, V

    1995-01-01

    The immune system is a tight network of different types of cells and molecules. The coordinated action of these elements mounts a precise immune response against tumor cells. However, these cells present several escape mechanisms, leading to tumor progression. This paper shows several cellular and molecular events involved in the regulation of the immune response against tumor cells. The interaction of several molecules such as MHC, TcR, adhesins, tumor antigens and cytokines are discussed, as well as the most recent knowledge about escape mechanisms and immunotherapy. PMID:7502157

  16. The developme nt of epidermal growth factor receptor molecular imaging in cancer%表皮生长因子受体-酪氨酸激酶肿瘤分子显像剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    周晓靓; 王浩; 施培基; 刘鉴峰; 孟爱民

    2013-01-01

    In vivo epidermal growth factor receptor(EGFR)targeted therapy has great potential for cancer diagnosis and the evaluation of curative effects.Enhancement of EGFR-targeted therapy needs a reliable quantitative molecular imaging method which eould enable monitoring of receptor drug binding and receptor occupancy in vivo,and identification of the mutation in EGFR.PET or SPECT is the most advanced molecular imaging technology of non-invasively selecting responders,predicting therapeutic outeome and monitoring EGFR-targeted treatment.This review analyzed the present situation and research progress of molecular imaging agents.%目前治疗肿瘤最重要的分子靶向药物是以表皮生长因子受体(EGFR)为靶点的一类化合物,为了更好地实现靶向治疗效果,需要借助分子显像技术实现快速、定量地检测体内EGFR的分布及突变等情况.利用不同核素标记的分子探针实施PET或SPECT显像能够实现快速、无创地对患者进行遴选、疗效评价和监测EGFR靶向治疗,从而提高肿瘤治疗效果 该文介绍了 EGFR-酪氨酸激酶小分子显像剂及其最新的研究进展.

  17. Molecular Imaging with Small Animal PET/CT

    DEFF Research Database (Denmark)

    Binderup, T.; El-Ali, H.H.; Skovgaard, D.;

    2011-01-01

    Small animal positron emission tomography (PET) and computer tomography (CT) is an emerging field in pre-clinical imaging. High quality, state-of-the-art instruments are required for full optimization of the translational value of the small animal studies with PET and CT. However, with this achie...... small animal PET/CT for studies of muscle and tendon in exercise models. © 2011 Bentham Science Publishers Ltd.......Small animal positron emission tomography (PET) and computer tomography (CT) is an emerging field in pre-clinical imaging. High quality, state-of-the-art instruments are required for full optimization of the translational value of the small animal studies with PET and CT. However, with this...... this field of small animal molecular imaging with special emphasis on the targets for tissue characterization in tumor biology such as hypoxia, proliferation and cancer specific over-expression of receptors. The added value of applying CT imaging for anatomical localization and tumor volume...

  18. Urinary bladder cancer: role of MR imaging.

    Science.gov (United States)

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

    2012-01-01

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

  19. Gastric cancer-molecular and clinical dimensions.

    Science.gov (United States)

    Wadhwa, Roopma; Song, Shumei; Lee, Ju-Seog; Yao, Yixin; Wei, Qingyi; Ajani, Jaffer A

    2013-11-01

    Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets). A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1 and MET) alterations are emerging and some are being pursued clinically. Novel somatic gene targets (ARID1A, FAT4, MLL and KMT2C) have also been identified and are of interest. Variations in the therapeutic approaches dependent on geographical region are evident for localized gastric cancer-differences that are driven by preferences for the adjuvant strategies and the extent of surgery coupled with philosophical divides. However, greater uniformity in approach has been noted in the metastatic cancer setting, an incurable condition. Having realized only modest successes, momentum is building for carrying out more phase III comparative trials, with some using biomarker-based patient selection strategies. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here, we review representative molecular and clinical dimensions of gastric cancer.

  20. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and 99mTc as a radionuclide. We developed 99mTc-galactosylated chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed 99mTc-HYNIC-chitosan-transferrin to target inflammatory cells, which was more effective than 67Ga-citrate for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of 99mTc-HMPAO-labeled liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that 99mTc-labeled biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques

  1. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Shorte, S.L. [Institut Pasteur, 75 - Paris (France). Plateforme d' Imagerie Dynamique PFID-Imagopole; Frischknecht, F. (eds.) [Heidelberg Univ. Medical School (Germany). Dept. of Parasitology

    2007-07-01

    'Imaging cellular and molecular biological function' provides a unique selection of essays by leading experts, aiming at scientist and student alike who are interested in all aspects of modern imaging, from its application and up-scaling to its development. Indeed the philosophy of this volume is to provide student, researcher, PI, professional or provost the means to enter this applications field with confidence, and to construct the means to answer their own specific questions. (orig.)

  2. Quantitative cardiovascular magnetic resonance for molecular imaging

    OpenAIRE

    Lanza Gregory M; Caruthers Shelton D; Winter Patrick M; Wickline Samuel A

    2010-01-01

    Abstract Cardiovascular magnetic resonance (CMR) molecular imaging aims to identify and map the expression of important biomarkers on a cellular scale utilizing contrast agents that are specifically targeted to the biochemical signatures of disease and are capable of generating sufficient image contrast. In some cases, the contrast agents may be designed to carry a drug payload or to be sensitive to important physiological factors, such as pH, temperature or oxygenation. In this review, examp...

  3. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev

    2014-01-01

    Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

  4. Molecular diagnosis of prostate cancer: Topical issues

    OpenAIRE

    E. N. Knyazev; K. A. Fomicheva; K. M. Nyushko; Kaprin, A. D.; B. Ya. Alekseev; M. Yu. Shkurnikov

    2014-01-01

    Prostate cancer (PC) is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androge...

  5. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev

    2014-12-01

    Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

  6. Cellular and molecular aspects of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Malcolm G Smith; Georgina L Hold; Eiichi Tahara; Emad M El-Omar

    2006-01-01

    Gastric cancer remains a global killer with a shifting burden from the developed to the developing world.The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori (H pylori) as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie H pyloriinduced gastric cancer.

  7. NAOMI: nanoparticle assisted optical molecular imaging

    Science.gov (United States)

    Faber, Dirk J.; van Velthoven, Mirjam E. J.; de Bruin, Martijn; Aalders, Maurice C. G.; Verbraak, Frank D.; Graf, Christina; van Leeuwen, Ton G.

    2006-02-01

    Our first steps towards nanoparticle assisted, optical molecular imaging (NAOMI) using OCT as the imaging modality are presented. We derive an expression to estimate the sensitivity of this technique. We propose to use nanoparticles based on biodegradable polymers, loaded with suitable dyes as contrast agent, and outline a method for establishing their desired optical properties prior to synthesis. This report presents preliminary results of our investigation on the use of nanoshells to serve as contrast agents We injected nanoshells with specific contrast features in the 800 nm wavelength region in excised porcine eyes. The nanoshells showed up as bright reflecting structures in the OCT images, which confirm their potential as contrast agents.

  8. Molecular mechanisms of metastasis in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Noel W.Clarke; Claire A.Hart; Mick D.Brown

    2009-01-01

    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  9. Molecular photoacoustic imaging of follicular thyroid carcinoma

    DEFF Research Database (Denmark)

    Levi, Jelena; Kothapalli, Sri-Rajashekar; Bohndiek, Sarah;

    2013-01-01

    Purpose To evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma. Experimental Design We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers...... for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP activatable agent was imaged after intratumoral and intravenous injections...... in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual wavelength imaging method. Results Active forms of both MMP2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent...

  10. CPFP Summer Curriculum: Molecular Prevention Course | Division of Cancer Prevention

    Science.gov (United States)

    This Cancer Prevention Fellowship Program (CPFP) one-week course on molecular aspects of cancer prevention follows the Principles and Practice of Cancer Prevention and Control course. It provides a strong background about molecular biology and genetics of cancer, and an overview of cutting-edge research and techniques in the fields of molecular epidemiology, biomarkers, multi-omic, and translational research. The following topics will be typically presented: |

  11. Molecular basis of the triple negative breast cancer

    OpenAIRE

    Ayse Feyda Nursal

    2015-01-01

    Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-...

  12. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy

    Directory of Open Access Journals (Sweden)

    Gann Ting

    2010-01-01

    Full Text Available Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, α-, β-, and γ-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients.

  13. Lung Cancer Detection Using Image Processing Techniques

    Directory of Open Access Journals (Sweden)

    Mokhled S. AL-TARAWNEH

    2012-08-01

    Full Text Available Recently, image processing techniques are widely used in several medical areas for image improvement in earlier detection and treatment stages, where the time factor is very important to discover the abnormality issues in target images, especially in various cancer tumours such as lung cancer, breast cancer, etc. Image quality and accuracy is the core factors of this research, image quality assessment as well as improvement are depending on the enhancement stage where low pre-processing techniques is used based on Gabor filter within Gaussian rules. Following the segmentation principles, an enhanced region of the object of interest that is used as a basic foundation of feature extraction is obtained. Relying on general features, a normality comparison is made. In this research, the main detected features for accurate images comparison are pixels percentage and mask-labelling.

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

    Directory of Open Access Journals (Sweden)

    Zhi-Yi Chen

    2014-01-01

    Full Text Available 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.

  15. Single Institution Feasibility Trials - Cancer Imaging Program

    Science.gov (United States)

    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.

  16. Imaging strategy in differentiated thyroid cancer

    NARCIS (Netherlands)

    Phan, Thi Thanh Ha

    2007-01-01

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

  17. Three Dimensional Molecular Imaging for Lignocellulosic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Bohn, Paul W.; Sweedler, Jonathan V.

    2011-06-09

    The development of high efficiency, inexpensive processing protocols to render biomass components into fermentable substrates for the sequential processing of cell wall components into fuels and important feedstocks for the biorefinery of the future is a key goal of the national roadmap for renewable energy. Furthermore, the development of such protocols depends critically on detailed knowledge of the spatial and temporal infiltration of reagents designed to remove and separate the phenylpropenoid heteropolymer (lignin) from the processable sugar components sequestered in the rigid cell walls of plants. A detailed chemical and structural understanding of this pre-enzymatic processing in space and time was the focus of this program. We worked to develop new imaging strategies that produce real-time molecular speciation information in situ; extract sub-surface information about the effects of processing; and follow the spatial and temporal characteristics of the molecular species in the matrix and correlate this complex profile with saccharification. Spatially correlated SIMS and Raman imaging were used to provide high quality, high resolution subcellular images of Miscanthus cross sections. Furthermore, the combination of information from the mass spectrometry and Raman scattering allows specific chemical assignments of observed structures, difficult to assign from either imaging approach alone and lays the foundation for subsequent heterocorrelated imaging experiments targeted at more challenging biological systems, such as the interacting plant-microbe systems relevant to the rhizosphere.

  18. NAOMI: nanoparticle-assisted optical molecular imaging

    Science.gov (United States)

    Faber, Dirk J.; de Bruin, Martijn; Aalders, Maurice C. G.; Verbraak, Frank D.; van Leeuwen, Ton G.

    2007-02-01

    We present our first steps towards nanoparticle assisted, optical molecular imaging (NAOMI) using biodegradable nanoparticles. Our focus is on using optical coherence tomography(OCT) as the imaging modality. We propose to use nanoparticles based on biodegradable polymers, loaded with carefully selected dyes as contrast agent, and outline a method for establishing their desired optical properties prior to synthesis. Moreover, we perform a qualitative pilot study using these biodegradable nanoparticles, measuring their optical properties which are found to be in line with theoretical predictions.

  19. Diagnostic Imaging of Lung Cancer

    OpenAIRE

    Kemal Kara; Ersin Ozturk

    2012-01-01

    Lung cancer is the most common cause of cancer related death in men and women. It is frequently seen among men than in women and male-female ratio is 1.5:1. Common epidemiological factors that increase risk of lung cancer is smoking. Early age to start smoking, high number of smoking cigarettes per a day and depth of inhalation increase risk of lung cancer. 25% of patients with lung cancer are nonsmokers that passively exposed to cigarette smoke. Occupational exposure to substances such as as...

  20. Diagnostic Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kemal Kara

    2012-12-01

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

  1. Molecular imaging for the diagnosis of dementia

    International Nuclear Information System (INIS)

    Many radiotracers have been developed to visualize pathological protein accumulation and neurotransmitter deficits in the brains of patients with dementia using positron emission tomography (PET). Recent advances in the development of β-sheet binding agents enabled in vivo detection of senile plaques in Alzheimer's disease. Molecular imaging using these agents would contribute to the early and accurate diagnosis of dementia and monitoring therapeutic effect of anti-dementia drugs. (author)

  2. Multimodal optical imaging for detecting breast cancer

    Science.gov (United States)

    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.

  3. Molecular Taxonomy and Tumourigenesis of Colorectal Cancer.

    Science.gov (United States)

    Biswas, S; Holyoake, D; Maughan, T S

    2016-02-01

    Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy.

  4. Oral cancer: molecular technologies for risk assessment and diagnosis

    Institute of Scientific and Technical Information of China (English)

    Wan Tao Chen

    2008-01-01

    @@ Purpose: The effective biomarkers related to diagnosis, metastasis, drug resistance and irradiation sensitivity of oral cancers will help the pathologist and oncologist to determine the molecular taxonomy diagnosis and design the individualization treatment for the patients with oral cancers.

  5. Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

    Science.gov (United States)

    Coughlin, Andrew James

    Cancer accounts for nearly 1 out of every 4 deaths in the United States, and because conventional treatments are limited by morbidity and off-target toxicities, improvements in cancer management are needed. This thesis further develops nanoparticle-assisted photothermal therapy (NAPT) as a viable treatment option for cancer patients. NAPT enables localized ablation of disease because heat generation only occurs where tissue permissive near-infrared (NIR) light and absorbing nanoparticles are combined, leaving surrounding normal tissue unharmed. Two principle approaches were investigated to improve the specificity of this technique: multimodal imaging and molecular targeting. Multimodal imaging affords the ability to guide NIR laser application for site-specific NAPT and more holistic characterization of disease by combining the advantages of several diagnostic technologies. Towards the goal of image-guided NAPT, gadolinium-conjugated gold-silica nanoshells were engineered and demonstrated to enhance imaging contrast across a range of diagnostic modes, including T1-weighted magnetic resonance imaging, X-Ray, optical coherence tomography, reflective confocal microscopy, and two-photon luminescence in vitro as well as within an animal tumor model. Additionally, the nanoparticle conjugates were shown to effectively convert NIR light to heat for applications in photothermal therapy. Therefore, the broad utility of gadolinium-nanoshells for anatomic localization of tissue lesions, molecular characterization of malignancy, and mediators of ablation was established. Molecular targeting strategies may also improve NAPT by promoting nanoparticle uptake and retention within tumors and enhancing specificity when malignant and normal tissue interdigitate. Here, ephrinA1 protein ligands were conjugated to nanoshell surfaces for particle homing to overexpressed EphA2 receptors on prostate cancer cells. In vitro, successful targeting and subsequent photothermal ablation of

  6. A Review of Tumor Specific Imaging Methods: A Glance at the Use of Molecular Imaging

    Directory of Open Access Journals (Sweden)

    M.A. Oghabian

    2005-08-01

    Full Text Available Introduction & Background: Conventional imaging modalities of CT, MRI, ultrasound, radionuclide, and even metabolic PET are insensitive to reveal tumor and metastasis of less than few millimeters containing not much fewer than 500,000 cells. At this size, a tu-mor has effectively undergone about 20 cell dou-blings, and is sufficiently stuffed with gene defects and likely to metastasize. New techniques generally known as molecular imaging lead to a patient-specific approach based on physiologic, antigenic, molecular, and genetic disease markers. In this article, Current and the near term trends and techniques in early de-tection of cancer using gene specific, cell specific, or even patient specific approaches are summarized. A number of markers are used for cancer imaging. Anatomic markers show cell morphology defects at the sub-10-µm level on CT, MRI, and OCT (Optical Coherence Tomography. These techniques often fail to provide accurate and basic information necessary to manage the patient’s disease such as true metastatic extent. Functional markers use dynamic features, such as capillary leak (using ICG, IndoCyanine Green, lymphatic transport (by colloid, or Tc-Sestamibi, blood oxygenation, and blood flow. The features provide signal by a bulk phenomenon, and hence are still insensitive. More specifically, anti-genic probes, such as targeted antibodies have been demonstrated effectively in vivo for both diagnostic and therapeutic purposes, such as PSMA in the pros-tate cancer, CEA in colorectal cancer, and HER-2/neu in breast cancer. Metabolic probes accumulate at the site of a specific metabolic activity, and rely on imag-ing agents involving certain enzymatic pathways or transport functions of the cell. Examples are 18FDG (18F-fluoroDeoxyGlucose in PET and 11C-thymidine. Recent spectroscopy techniques do not need such labeled probes. The common method for in-vivo spectroscopy is MRSI (Proton Magnetic Resonance Spectroscopy that can

  7. Molecular Breast Imaging Using Emission Tomosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Gopan, O. [University of Florida; Gilland, D. [University of Florida; Weisenberger, Andrew G. [JLAB; Kross, Brian J. [JLAB; Welch, Benjamin L. [Dilon Technologies

    2013-06-01

    Purpose: Tour objective is to design a novel SPECT system for molecular breast imaging (MBI) and evaluate its performance. The limited angle SPECT system, or emission tomosynthesis, is designed to achieve 3D images of the breast with high spatial resolution/sensitivity. The system uses a simplified detector motion and is conducive to on-board biopsy and mult-modal imaging with mammography. Methods: The novel feature of the proposed gamma camera is a variable-angle, slant-hole (VASH) collimator, which is well suited for limited angle SPECT of a mildly compressed breast. The collimator holes change slant angle while the camera surface remains flush against the compression paddle. This allows the camera to vary the angular view ({+-}30{degrees}, {+-}45{degrees}) for tomographic imaging while keeping the camera close to the object for high spatial resolution and/or sensitivity. Theoretical analysis and Monte Carlo simulations were performed assuming a point source and isolated breast phantom. Spatial resolution, sensitivity, contrast and SNR were measured. Results were compared to single-view, planar images and conventional SPECT. For both conventional SPECT and VASH, data were reconstructed using iterative algorithms. Finally, a proof-of-concept VASH collimator was constructed for experimental evaluation. Results: Measured spatial resolution/sensitivity with VASH showed good agreement with theory including depth-of-interaction (DOI) effects. The DOI effect diminished the depth resolution by approximately 2 mm. Increasing the slant angle range from {+-}30{degrees} to {+-}45{degrees} resulted in an approximately 1 mm improvement in the depth resolution. In the breast phantom images, VASH showed improved contrast and SNR over conventional SPECT and improved contrast over planar scintimmammography. Reconstructed images from the proof-of-concept VASH collimator demonstrated reasonable depth resolution capabilities using limited angle projection data. Conclusion: We

  8. Molecular markers′ progress of breast cancer treatment efficacy

    OpenAIRE

    Dan Wang; Jingwei Xu; Guang Shi; Guanghao Yin

    2015-01-01

    Breast cancer is a famous malignant tumor which is caused by varieties of mutation in multiple genes. In order to detect breast cancer in an earlier time and take appropriate treatment which includes  predicting treatment efficacy, we need a more accurate method of discovering the occurrence of breast cancer. With the development of molecular biology and biological detection technologies continue to emerge, molecular markers of breast cancer have gaining more and more widespread attention, an...

  9. Imaging and Endoscopic Approaches to Pancreatic Cancer.

    Science.gov (United States)

    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.

  10. Molecular profiling of childhood cancer: Biomarkers and novel therapies

    Directory of Open Access Journals (Sweden)

    Federica Saletta

    2014-06-01

    General significance: The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

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

    Directory of Open Access Journals (Sweden)

    Hardiani Rahmania

    2015-01-01

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

  12. First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer : a phase II study including molecular imaging

    NARCIS (Netherlands)

    Dingemans, A. -M. C.; de Langen, A. J.; van den Boogaart, V.; Marcus, J. T.; Backes, W. H.; Scholtens, H. T. G. M.; van Tinteren, H.; Hoekstra, O. S.; Pruim, J.; Brans, B.; Thunnissen, F. B.; Smit, E. F.; Groen, H. J. M.

    2011-01-01

    Background: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. Patients and methods: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotini

  13. Neutron imaging for inertial confinement fusion and molecular optic imaging

    International Nuclear Information System (INIS)

    Scientific domains that require imaging of micrometric/nano-metric objects are dramatically increasing (Plasma Physics, Astrophysics, Biotechnology, Earth Sciences...). Difficulties encountered in imaging smaller and smaller objects make this research area more and more challenging and in constant evolution. The two scientific domains, through which this study has been led, are the neutron imaging in the context of the inertial confinement fusion and the fluorescence molecular imaging. Work presented in this thesis has two main objectives. The first one is to describe the instrumentation characteristics that require such imagery and, relatively to the scientific domains considered, identify parameters likely to optimize the imaging system accuracy. The second one is to present the developed data analysis and reconstruction methods able to provide spatial resolution adapted to the size of the observed object. Similarities of numerical algorithms used in these two scientific domains, which goals are quiet different, show how micrometric/nano-metric object imaging is a research area at the border of a large number of scientific disciplines. (author)

  14. Molecular Imaging with Activatable Reporter Systems

    Directory of Open Access Journals (Sweden)

    Gang Niu, Xiaoyuan Chen

    2012-01-01

    Full Text Available Molecular imaging is a newly emerged multiple disciplinary field that aims to visualize, characterize and quantitatively measure biological processes at cellular and molecular levels in humans and other living systems. A reporter gene is a piece of DNA encoding reporter protein, which presents as a readily measurable phenotype that can be distinguished easily from the background of endogenous protein. After being transferred into cells of organ systems (transgenes, the reporter gene can be utilized to visualize transcriptional and posttranscriptional regulation of gene expression, protein-protein interactions, or trafficking of proteins or cells in living subjects. Herein, we review previous classification of reporter genes and regroup the reporter gene based imaging as basic, inducible and activatable, based on the regulation of reporter gene transcription and post-translational modification of reporter proteins. We then focus on activatable reporters, in which the signal can be activated at the posttranslational level for visualizing protein-protein interactions, protein phosphorylation or tertiary structure changes. The applications of several types of activatable reporters will also be summarized. We conclude that activatable reporter imaging can benefit both basic biomedical research and drug development.

  15. Molecular diagnosis for personalized target therapy in gastric cancer.

    Science.gov (United States)

    Cho, Jae Yong

    2013-09-01

    Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy. PMID:24156032

  16. Molecular probes for malignant melanoma imaging.

    Science.gov (United States)

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  17. The identification value of diffusion weighted imaging in different molecular subtypes for breast cancer classification%磁共振 DWI 对乳腺癌分子亚型的鉴别诊断应用价值

    Institute of Scientific and Technical Information of China (English)

    金观桥; 苏丹柯; 罗殿中; 赖少侣; 罗宁斌; 康巍; 黄向阳; 方献柳

    2015-01-01

    目的:探讨 MR 扩散加权成像(DWI)对乳腺癌不同分子亚型的鉴别诊断价值。方法乳腺癌患者依据 ER、Ki-67、PR、HER2的组化结果分成4种分子亚型,即 Luminal A、Luminal B、人类表皮生长因子受体2(HER2-OE)阳性和三阴型(triple nega-tive breast cancer,TNBC)。所有患者于乳腺癌手术/活检至少前2周进行 MR 检查,测定肿瘤最大横断面的 ADC 值(包括最大ADC 值、最小 ADC 值、平均 ADC 值)。采用单因素方差分析、LSD-t 进行统计学分析。结果72例乳腺癌中,Luninal A 亚型21例,Luminal B 亚型22例,HER2-OE 亚型17例,TNBC 亚型12例。4种亚型中,年龄、瘤灶大小均数的差异无统计学意义(P >0.05)。经 AVONA 统计,Luminal A,Luminal B,HER2-OE 和 TNBC 亚型的最大 ADC 值、平均 ADC 值以及最小 ADC 值的均数之间差异有统计学意义(P =0.025,0.039,0.041)。Luminal A,Luminal B,HER2-OE 和 TNBC 亚型的最大 ADC 值、平均 ADC 值以及最小 ADC 值的均数多重比较中,每一个均数两两比较差异不能同时均有统计学意义。结论手术或活检前,MR DWI 对乳腺癌不同分子亚型的鉴别诊断价值具有一定局限性。%Objective To investigate the value of diffusion weighted imaging (DWI)in identification of different molecular sub-types for breast cancer classifications.Methods All patients with breast cancer were divided into four subtypes groups by immuno-histochemistry results including Luminal A subtype,Luminal B subtype,HER2-over expressing (HER2-OE)subtype,and triple negative breast cancer (TNBC),respectively.The means of maximum,average,and minimum ADC of the lesions in all patients were recorded.The analysis of ANOVA and least significant difference test (LSD-t )were used for the statistical evaluation.Results There were significant differences in maximum ADC,average ADC,and minimum ADC among Luminal A subtype (n=21),Lu-minal B subtype (n=22),HER2-OE subtype (n=1 7)and TNBC subtype (n=12)groups (P

  18. Narrow band imaging for bladder cancer

    OpenAIRE

    Thomas Y. Hsueh; Allen W. Chiu

    2016-01-01

    Narrow band imaging (NBI) is a newly developed technology aiming to provide additional endoscopic information for patients with bladder cancer. This review focuses on the diagnostic accuracy and treatment outcome using NBI cystoscopy for the treatment of non-muscle invasive bladder cancer. Current results showed improved sensitivity of NBI cystoscopy compared to conventional white light cystoscopy, although lower specificity and increased false-positive results were reported using NBI cystosc...

  19. Breast cancer. From molecular biology to personified therapy

    Directory of Open Access Journals (Sweden)

    Bondarenko I.N.

    2016-03-01

    Full Text Available Advances in molecular biology had changed approaches to systemic treatment of breast cancer. Clinical decisions on the choice of optimal treatment regimens are performing on the basis of immunohistochemical and molecular genetic classifications. Their increasing uses have contributed changes of paradigm for cancer treatment - from the empirical to the individualized and personalized. The basis for such approaches is knowledge of molecular epidemiology, heterogeneity of expression of molecular subtypes, prognostic and predictive biomarkers of breast cancer. Breast cancer is a widely heterogeneous disease with 20 histological types, 8, molecular-genetic, 6 genomic subtypes, which are characterized by specific molecular and biochemical properties, different clinical course and different outcomes. Molecular genetic classification, created not on the basis of clinical, anatomical and morphological heterogeneity of tumor cells, and on the basis of their molecular-genetic heterogeneity is widely used in clinical practice. This allowed to separate the patients with breast cancer to molecular 4 subtypes - luminal A, luminal B, HER / 2 positive and triple-negative. The significant role of immunohistochemical tissue tumor markers, estrogen and progesterone receptors, HER / 2-neu, Ki-67, p53 for selection the optimal treatment strategy is analyzing in this review. To increase the effectiveness of breast cancer treatment is possible, using a differentiated and personalized approach based on new molecular genetic classification of breast cancer (gene profiling or to its analogue - expression classification of breast cancer, based on the principle of diversity of immunohistochemical tumor tissue. Personification of cancer treatment involves a therapy based on the study of individual characteristics of tissue is not only the primary tumor but also its metastases. Citation: Bondarenko IN, Elhajj Mohammad H, Prokhach AV, Zavizion VF, Chebanov KO. [Breast cancer

  20. Optical Coherence Tomography in Cancer Imaging

    Science.gov (United States)

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

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

  1. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

    NARCIS (Netherlands)

    A.N.A. Milne; R. Carvalho; F.M. Morsink; A.R. Musler; W.W.J. de Leng; A. Ristimaki; G.J.A. Offerhaus

    2006-01-01

    Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (<= 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in g

  2. The consensus molecular subtypes of colorectal cancer.

    Science.gov (United States)

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-11-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.

  3. Hormonal and molecular aspects of endometrioid endometrial cancer

    NARCIS (Netherlands)

    Jongen, Vincentius Hubertus Willibrordus Maria

    2008-01-01

    This thesis concerns the expression and prognostic value of various hormones and molecular markers playing a role n endometrioid endometrial cancer. Especially we were interested in the enzyme aromatase, its expression and (prognostic) role in endometrioid endometrial cancer. Endometrial cancer is t

  4. Bioresponsive probes for molecular imaging: concepts and in vivo applications

    NARCIS (Netherlands)

    Duijnhoven, S.M. van; Robillard, M.S.; Langereis, S.; Grull, H.

    2015-01-01

    Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecu

  5. Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Alphy Rose-James

    2012-01-01

    Full Text Available Lung cancer accounts for the majority of cancer-related deaths worldwide of which non-small-cell lung carcinoma alone takes a toll of around 85%. Platinum-based therapy is the stronghold for lung cancer at present. The discovery of various molecular alterations that underlie lung cancer has contributed to the development of specifically targeted therapies employing specific mutation inhibitors. Targeted chemotherapy based on molecular profiling has shown great promise in lung cancer treatment. Various molecular markers with predictive and prognostic significance in lung cancer have evolved as a result of advanced research. Testing of EGFR and Kras mutations is now a common practice among community oncologists, and more recently, ALK rearrangements have been added to this group. This paper discusses various predictive and prognostic markers that are being investigated and have shown significant relevance which can be exploited for targeted treatment in lung cancer.

  6. Molecular Pathways: Estrogen Pathway in Colorectal Cancer

    Science.gov (United States)

    Barzi, Afsaneh; Lenz, Annika Medea; Labonte, Melissa J.; Lenz, Heinz-Josef

    2013-01-01

    Worldwide colorectal cancer (CRC) has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data supports a role for estrogen and its receptors in the initiation and progression of CRC and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of CRC. In the Women’s Health Initiative (WHI) trial use of HRT in postmenopausal women reduced the risk of colon cancer by 56% (95% CI, 0.38 to 0.81; P=0.003). A recent meta-analysis showed that in females, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03 to 0.35; P=0.026). In this review, utilizing the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of CRC. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT or soy products, exerts its effects through preventing this loss. Thus in the adenoma to carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of CRC depends on identification of susceptible CRC population(s). Thus research to better understand the estrogen pathway is fundamental for clinical delivery of these agents. PMID:23965904

  7. IND Regulatory & Manufacturing Resources - Cancer Imaging Program

    Science.gov (United States)

    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).

  8. On Sensitivity of Molecular Specific Photoacoustic Imaging Using Plasmonic Gold Nanoparticles

    OpenAIRE

    Mallidi, Srivalleesha; Joshi, Pratixa P.; Sokolov, Konstantin; Emelianov, Stanislav

    2009-01-01

    Functionalized gold nanospheres undergo receptor mediated aggregation on cancer cells that overexpress the epidermal growth factor receptor (EGFR). This phenomenon leads to a red shift in the plasmon resonance frequency of the EGFR-targeted gold nanoparticles. Previously we demonstrated that highly selective detection of cancer cells can be achieved using the combination of multi-wavelength photoacoustic imaging and molecular specific gold nanoparticles. In this study, we use tissue models to...

  9. Fluorescent nanoparticle probes for imaging of cancer.

    Science.gov (United States)

    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

  10. Cancer detection by quantitative fluorescence image analysis.

    Science.gov (United States)

    Parry, W L; Hemstreet, G P

    1988-02-01

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

  11. Molecular aspects of carcinogenesis in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexandros Koliopanos; Constantinos Avgerinos; Constantina Paraskeva; Zisis Touloumis; Dionisisa Kelgiorgi; Christos Dervenis

    2008-01-01

    BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, signiifcant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation. DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology. RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local inifltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor. CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

  12. Pancreatic Cancer Imaging: Which Method?

    Directory of Open Access Journals (Sweden)

    Santo E

    2004-07-01

    Full Text Available Pancreatic cancer is the 10th most common malignancy and the 4th largest cancer killer in adults. Surgery offers the only chance of curing these patients. Complete surgical resection is associated with a 5-year survival rate of between 20 and 30%. The challenge is how to best select those patients for curative surgery. Early studies demonstrated excellent sensitivity of EUS in detecting pancreatic tumors in comparison to CT. Similarly, EUS showed an 85-94% accuracy rate for T staging and 70-80% accuracy rate for N staging. Later studies report on substantially less TN staging accuracy for EUS. Possible explanations and the problem of vascular involvement assessment by EUS will be provided. Considering the role of EUS in M staging and a comparison between EUS, MRI, and positron emission tomography, scanning will be presented. A diagnostic algorithm for the evaluation of patients with a suspected pancreatic mass will be offered, stressing the pivotal role of EUS.

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

    Science.gov (United States)

    Kircher, Moritz F.

    2016-05-01

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

  14. Antibody-based imaging strategies for cancer

    NARCIS (Netherlands)

    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

  15. Optical imaging of cancer and cell death

    NARCIS (Netherlands)

    Xie, Bangwen

    2013-01-01

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

  16. Fluorescence lifetime imaging of skin cancer

    Science.gov (United States)

    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.

  17. Current Progress of Aptamer-Based Molecular Imaging

    OpenAIRE

    Wang, Andrew Z.; Farokhzad, Omid C.

    2014-01-01

    Aptamers, single-stranded oligonucleotides, are an important class of molecular targeting ligand. Since their discovery, aptamers have been rapidly translated into clinical practice. They have been approved as therapeutics and molecular diagnostics. Aptamers also possess several properties that make them uniquely suited to molecular imaging. This review aims to provide an overview of aptamers’ advantages as targeting ligands and their application in molecular imaging.

  18. Molecular imaging probes derived from natural peptides.

    Science.gov (United States)

    Charron, C L; Hickey, J L; Nsiama, T K; Cruickshank, D R; Turnbull, W L; Luyt, L G

    2016-06-01

    Covering: up to the end of 2015.Peptides are naturally occurring compounds that play an important role in all living systems and are responsible for a range of essential functions. Peptide receptors have been implicated in disease states such as oncology, metabolic disorders and cardiovascular disease. Therefore, natural peptides have been exploited as diagnostic and therapeutic agents due to the unique target specificity for their endogenous receptors. This review discusses a variety of natural peptides highlighting their discovery, endogenous receptors, as well as their derivatization to create molecular imaging agents, with an emphasis on the design of radiolabelled peptides. This review also highlights methods for discovering new and novel peptides when knowledge of specific targets and endogenous ligands are not available. PMID:26911790

  19. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

    Science.gov (United States)

    Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

    2016-01-01

    Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine. PMID:26498010

  20. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    OpenAIRE

    Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.; Nimmagadda, Sridhar; Jung, Hyeyun; Goddard, James S.; Lee, Seungjoon; McKisson, John; Smith, Mark F.; Stolin, Alexander V.; Weisenberger, Andrew G.; Pomper, Martin G.

    2013-01-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques.

  1. Ultrasound Biomicroscopy in Small Animal Research: Applications in Molecular and Preclinical Imaging

    Directory of Open Access Journals (Sweden)

    A. Greco

    2012-01-01

    Full Text Available Ultrasound biomicroscopy (UBM is a noninvasive multimodality technique that allows high-resolution imaging in mice. It is affordable, widely available, and portable. When it is coupled to Doppler ultrasound with color and power Doppler, it can be used to quantify blood flow and to image microcirculation as well as the response of tumor blood supply to cancer therapy. Target contrast ultrasound combines ultrasound with novel molecular targeted contrast agent to assess biological processes at molecular level. UBM is useful to investigate the growth and differentiation of tumors as well as to detect early molecular expression of cancer-related biomarkers in vivo and to monitor the effects of cancer therapies. It can be also used to visualize the embryological development of mice in uterus or to examine their cardiovascular development. The availability of real-time imaging of mice anatomy allows performing aspiration procedures under ultrasound guidance as well as the microinjection of cells, viruses, or other agents into precise locations. This paper will describe some basic principles of high-resolution imaging equipment, and the most important applications in molecular and preclinical imaging in small animal research.

  2. Imaging beyond the diagnosis: image-guided enzyme/prodrug cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Xinyi Tong; Xishan Chen; Cong Li

    2011-01-01

    The ideal therapy would target cancer cells while sparing normal tissue. However, in most conventional chemothera-pies normal cells are damaged together with cancer cells resulting in the unfortunate side effects. The principle underlying enzyme/prodrug therapy is that a prodrug-activating enzyme is delivered or expressed in tumor tissue following which a non-toxic prodrug is administered sys-temically. Non-invasive imaging modalities can fill an important niche in guiding prodrug administration when the enzyme concentration is detected to be high in the tumor tissue but low in the normal tissue. Therefore, high therapeutic efficacy with minimized toxic effect can be anticipated. This review introduces the latest developments of molecular imaging in enzyme/prodrug cancer therapies, We focus on the application of imaging modalities includ-ing magnetic resonance imaging, position emission tom-ography and optical imaging in monitoring the enzyme delivery/expression, guiding the prodrug administration and evaluating the real-time therapeutic response in vivo.

  3. Diagnosis of Rectal Cancer through Images

    Directory of Open Access Journals (Sweden)

    Dr.K.Sivakami Sundari

    2014-11-01

    Full Text Available Human health is the real wealth for a society. Consequently prevention of health from complex diseases like cancer needs the diagnosis of these entire viruses at an early stage. Colon cancer, the most common one, reached the highest rate among all the other types recently. Colorectal cancer gets developed either in colon or in the rectum inside the large intestine, due to the abnormal growth of the cells. Computer-aided decision support system has become one of the major research topics in medical imaging field during the past two decades to detect cancers. Detecting and screening of colorectal cancers are done by a Computed Tomography. The implemented algorithm determines the locations and features of glands which are affected by cancer tissues and save this information for the subsequent diagnosis. The proposed algorithm carries out the diagnosis with two modules: One known as the gland detection and the other one referred as the nuclei detection. Gland detection is performed in the proposed algorithm using color segmentation either through HSV or LAB transformation. Noise removal and erosion of the input image is performed for enhancing the selection of the affected tissues. The boundary detection and connection is established through Markov Chain model to identify the affected tissues with proper threshold. The first module detects the glands where the possibly of miss detection is more. Hence to remove the miss detected glands the algorithm proceed for the second module referred as nuclei detection. The most well known region growing methodology is slightly modified to increase the speed and reduce the memory size To provide the execution in low-end clients, the whole image is cracked into smaller tiles and after the processing of each individual tiles , the results are to be merged to get back the original size. After nuclei detection if the number of nucleus is more that glands are miss detected glands and they are removed.

  4. MR imaging of small liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sekoguchi, Bon; Horiguchi, Yuji; Takagawa, Hiroko (Fujita-Gakuen Health Univ., Toyoake, Aichi (Japan)) (and others)

    1992-03-01

    With recent development of diagnostic modalities, many hepatic nodules smaller than 2 cm in diameter have been able to be detected in patients with chronic liver diseases. Magnetic resonance imaging (MRI) is one of the most efficacious modalities for detecting small nodules and differentiating carcinoma from other benign lesions. In this paper, we present specific findings on MRI to small liver cancer. Signal intensity of the tumor on T1-weighted images was high in 12 (63%) out of 19 cases, T2-weighted images showed hyperintensity of the tumor in 14 cases (74%), and isointensity in 5 cases. To compare the signal intensity on MRI with the echo level on ultrasound, hypoechoic lesions represented hyperintensity on T1-weighted images in 6 of 11 cases, and isointensity 5 cases. The latter pattern was considered to be consistent with compact type hepatocellular carcinomas, but the pathogenesis of the former pattern remained uncertain. With respect to hyperechoic nodules, MRI showed hyperintensity on T1-weighted images in 6 of 8 cases; these findings were common in fatty change of tumor cells. In conclusion, characteristic findings on MRI in small liver cancer are hyperintensity on T1-weighted images; its pathogenesis is in part fatty change in the tumor, but unknown in the remaining cases. (author).

  5. [Molecular biological predictors for kidney cancer].

    Science.gov (United States)

    Vtorushin, S V; Tarakanova, V O; Zavyalova, M V

    2016-01-01

    The paper considers the data available in the modern literature on studies of potential molecular predictors for renal cell carcinoma (RCC). Investigations of cell death markers, namely; Bcl-2 as an inhibitor of apoptosis, are of interest. Its high expression correlates with a more favorable prognosis. Inactivation of Berclin 1 that is an authophagy indicator in intact tissues gives rise to t high risk for tumorigenesis. At the same time, high Beclin 1 expression in the tissue of the tumor itself results in the lower efficiency of performed chemotherapy. Excess annexin A2 in the tumor promotes the growth and invasion of cancer cells. Patients with tumor over-expression of SAM68 protein involved in cell proliferation have a lower overall survival rate. The lifespan of patients without distinct metastases survive significantly longer in the overexpression of epithelial cell adhesion molecule (EpCAM). High PD-L1 protein expression on the cell membrane is considered to be a potential marker of effective immunotherapy for RCC. PMID:27077146

  6. Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

    International Nuclear Information System (INIS)

    During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

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

    Science.gov (United States)

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

    2016-02-01

    Treatment planning, outcome and prognosis are strongly related to the adequate tumor staging for bladder cancer (BC). Unfortunately, a large discrepancy exists between the preoperative clinical and final pathologic staging. Therefore, an advanced imaging-based technique is crucial for adequate staging. Although Magnetic Resonance Imaging (MRI) is currently the best in vivo imaging technique for BC staging because of its excellent soft-tissue contrast and absence of ionizing radiation it lacks cancer-specificity. Tumor-specific positron emission tomography (PET), which is based on the Warburg effect (preferential uptake of glucose by cancer cells), exploits the radioactively-labeled glucose analogs, i.e., FDG. Although FDG-PET is highly cancer specific, it lacks resolution and contrast quality comparable with MRI. Chemical Exchange Saturation Transfer (CEST) MRI enables the detection of low concentrations of metabolites containing protons. BC is an attractive target for glucose CEST MRI because, in addition to the typical systemic administration, glucose might also be directly applied into the bladder to reduce toxicity-related complications. As a first stage of the development of a contrast-specific BC imaging technique we have studied glucose uptake by bladder epithelial cells and have observed that glucose is, indeed, consumed by BC cells with higher intensity than by non-transformed urothelial cells. This effect might be partly explained by increased expression of glucose transporters GLUT1 and GLUT3 in transformed cells as compared to normal urothelium. We also detected higher lactate production by BC cells which is another cancer-specific manifestation of the Warburg effect. In addition, we have observed other metabolic alterations in BC cells as compared to non-transformed cells: in particular, increased pyruvate synthesis. When glucose was substituted by glutamine in culture media, preferential uptake of glutamine by BC cells was observed. The preferential

  8. Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

    Science.gov (United States)

    Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

    2016-06-01

    Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual

  9. Molecular imaging of stem cell transplantation for neurodegenerative diseases.

    Science.gov (United States)

    Wang, Ping; Moore, Anna

    2012-01-01

    Cell replacement therapy with stem cells holds tremendous therapeutic potential for treating neurodegenerative diseases. Over the last decade, molecular imaging techniques have proven to be of great value in tracking transplanted cells and assessing the therapeutic efficacy. This current review summarizes the role and capabilities of different molecular imaging modalities including optical imaging, nuclear imaging and magnetic resonance imaging in the field of stem cell therapy for neurodegenerative disorders. We discuss current challenges and perspectives of these techniques and encompass updated information such as theranostic imaging and optogenetics in stem cell-based treatment of neurodegenerative diseases.

  10. Photoacoustic Image Analysis for Cancer Detection and Building a Novel Ultrasound Imaging System

    Science.gov (United States)

    Sinha, Saugata

    Photoacoustic (PA) imaging is a rapidly emerging non-invasive soft tissue imaging modality which has the potential to detect tissue abnormality at early stage. Photoacoustic images map the spatially varying optical absorption property of tissue. In multiwavelength photoacoustic imaging, the soft tissue is imaged with different wavelengths, tuned to the absorption peaks of the specific light absorbing tissue constituents or chromophores to obtain images with different contrasts of the same tissue sample. From those images, spatially varying concentration of the chromophores can be recovered. As multiwavelength PA images can provide important physiological information related to function and molecular composition of the tissue, so they can be used for diagnosis of cancer lesions and differentiation of malignant tumors from benign tumors. In this research, a number of parameters have been extracted from multiwavelength 3D PA images of freshly excised human prostate and thyroid specimens, imaged at five different wavelengths. Using marked histology slides as ground truths, region of interests (ROI) corresponding to cancer, benign and normal regions have been identified in the PA images. The extracted parameters belong to different categories namely chromophore concentration, frequency parameters and PA image pixels and they represent different physiological and optical properties of the tissue specimens. Statistical analysis has been performed to test whether the extracted parameters are significantly different between cancer, benign and normal regions. A multidimensional [29 dimensional] feature set, built with the extracted parameters from the 3D PA images, has been divided randomly into training and testing sets. The training set has been used to train support vector machine (SVM) and neural network (NN) classifiers while the performance of the classifiers in differentiating different tissue pathologies have been determined by the testing dataset. Using the NN

  11. Pitfalls of Imaging in Breast Cancer Diagnosis:

    Directory of Open Access Journals (Sweden)

    M. Kalantari

    2009-01-01

    Full Text Available "nWith the introduction of mammography for early diagnosis of breast cancer a new horizon is created in breast cancer diagnosis. Instead of palpated easy-to-manage lesions, now the surgeon is confronted with non palpable findings on the mammogram, sometimes very difficult for decision, that highlight the importance of the role of the interventional breast radiologist in the team and surgeon-radiologist collaboration. "nThis close collaboration would eliminate many difficulties in correct cancer diagnosis, both for the radiologist and the surgeon. "nIn this study, reviewing interesting difficult cases during the last 8 years, we present all pitfalls in imaging that can be avoided in majority by team work collaboration.  

  12. Hyperspectral imaging of skin and lung cancers

    Science.gov (United States)

    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.

  13. Molecular mechanisms of tamoxifen-associated endometrial cancer (Review)

    OpenAIRE

    Hu, Rong; Hilakivi-Clarke, Leena; Clarke, Robert

    2015-01-01

    Tamoxifen has been prescribed to millions of females for breast cancer prevention or treatment. However, tamoxifen is known to significantly enhance the risk of developing endometrial lesions, including hyperplasia, polyps, carcinomas, and sarcoma. Notably, tamoxifen-associated endometrial cancer often has a poor clinical outcome. Understanding the molecular mechanism of tamoxifen-induced endometrial cancer is essential for developing strategies that minimize tamoxifen’s effects on the endome...

  14. Molecular imaging in Libman-Sacks endocarditis.

    Science.gov (United States)

    Dahl, Anders; Schaadt, Bente K; Santoni-Rugiu, Eric; Bruun, Niels E

    2015-04-01

    We present a 54-year-old woman with systemic lupus erythematosus (SLE), fever, pericardial effusion and a mitral valve vegetation. (18)F-Fluorodesoxyglucose positron emission tomography CT ((18)F-FDG-PET-CT) showed very high accumulation of the isotope at the mitral valve. The patient underwent cardiothoracic surgery and pathologic examinations showed characteristic morphology of Libman-Sacks vegetations. All microbiological examinations including blood cultures, microscopy, culture and 16s PCR of the valve were negative and the diagnosis of Libman-Sacks endocarditis was convincing. It is difficult to distinguish Libman-Sacks endocarditis from culture-negative infective endocarditis (IE). Molecular imaging techniques are being used increasingly in cases of suspected IE but no studies have previously reported the use in patients with Libman-Sacks endocarditis. In the present case, (18)F-FDG-PET-CT clearly demonstrated the increased glucose uptake caused by infiltrating white blood cells in the ongoing inflammatory process at the mitral valve. In conclusion, (18)F-FDG-PET-CT cannot be used to distinguish between IE and non-infective Libman-Sacks vegetations.

  15. Investigations on the usefulness of CEACAMs as potential imaging targets for molecular imaging purposes.

    Directory of Open Access Journals (Sweden)

    Markus Heine

    Full Text Available Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well.In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.

  16. Molecular imaging of macrophage enzyme activity in cardiac inflammation

    OpenAIRE

    Ali, Muhammad; Pulli, Benjamin; Chen, John W.

    2014-01-01

    Molecular imaging is highly advantageous as various insidious inflammatory events can be imaged in a serial and quantitative fashion. Combined with the conventional imaging modalities like computed tomography (CT), magnetic resonance (MR) and nuclear imaging, it helps us resolve the extent of ongoing pathology, quantify inflammation and predict outcome. Macrophages are increasingly gaining importance as an imaging biomarker in inflammatory cardiovascular diseases. Macrophages, recruited to th...

  17. Three-photon imaging of ovarian cancer

    Science.gov (United States)

    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.

  18. Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hiroaki; Itamochi

    2010-01-01

    Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.

  19. New generation of breast cancer clinical trials implementing molecular profiling

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Zardavas; Martine Piccart-Gebhart

    2016-01-01

    The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

  20. Molecular markers for detection, surveillance and prognostication of bladder cancer.

    NARCIS (Netherlands)

    Vrooman, O.P.; Witjes, J.A.

    2009-01-01

    Many markers for the detection of bladder cancers have been tested and almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. Currently molecular and genetic changes play an important role in the discovery of new molecular marker

  1. Novel approaches for the molecular classification of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Robert H. Getzenberg

    2010-01-01

    @@ Among the urologic cancers, prostate cancer is by far the most common, and it appears to have the potential to affect almost all men throughout the world as they age. A number of studies have shown that many men with prostate cancer will not die from their disease, but rather with the disease but from other causes. These men have a form of prostate cancer that is de-scribed as "very low risk" and has often been called indolent. There are however a group of men that have a form of prostate cancer that is much more aggressive and life threatening. Unlike other cancer types, we have few tools to provide for the molecular classification of prostate cancer.

  2. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads;

    2016-01-01

    . The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

  3. Functional and molecular image guidance in radiotherapy treatment planning optimization.

    Science.gov (United States)

    Das, Shiva K; Ten Haken, Randall K

    2011-04-01

    Functional and molecular imaging techniques are increasingly being developed and used to quantitatively map the spatial distribution of parameters, such as metabolism, proliferation, hypoxia, perfusion, and ventilation, onto anatomically imaged normal organs and tumor. In radiotherapy optimization, these imaging modalities offer the promise of increased dose sparing to high-functioning subregions of normal organs or dose escalation to selected subregions of the tumor as well as the potential to adapt radiotherapy to functional changes that occur during the course of treatment. The practical use of functional/molecular imaging in radiotherapy optimization must take into cautious consideration several factors whose influences are still not clearly quantified or well understood including patient positioning differences between the planning computed tomography and functional/molecular imaging sessions, image reconstruction parameters and techniques, image registration, target/normal organ functional segmentation, the relationship governing the dose escalation/sparing warranted by the functional/molecular image intensity map, and radiotherapy-induced changes in the image intensity map over the course of treatment. The clinical benefit of functional/molecular image guidance in the form of improved local control or decreased normal organ toxicity has yet to be shown and awaits prospective clinical trials addressing this issue. PMID:21356479

  4. Disease-specific target gene expression profiling of molecular imaging probes: database development and clinical validation.

    Science.gov (United States)

    Chan, Lawrence Wing-Chi; Ngo, Connie Hiu-Ching; Wang, Fengfeng; Zhao, Moss Y; Zhao, Mengying; Law, Helen Ka-Wai; Wong, Sze Chuen Cesar; Yung, Benjamin Yat-Ming

    2014-01-01

    Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2-deoxy-2-d-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/. PMID:25022454

  5. Differential diagnosis of lung carcinoma with three-dimensional quantitative molecular vibrational imaging

    Science.gov (United States)

    Gao, Liang; Hammoudi, Ahmad A.; Li, Fuhai; Thrall, Michael J.; Cagle, Philip T.; Chen, Yuanxin; Yang, Jian; Xia, Xiaofeng; Fan, Yubo; Massoud, Yehia; Wang, Zhiyong; Wong, Stephen T. C.

    2012-06-01

    The advent of molecularly targeted therapies requires effective identification of the various cell types of non-small cell lung carcinomas (NSCLC). Currently, cell type diagnosis is performed using small biopsies or cytology specimens that are often insufficient for molecular testing after morphologic analysis. Thus, the ability to rapidly recognize different cancer cell types, with minimal tissue consumption, would accelerate diagnosis and preserve tissue samples for subsequent molecular testing in targeted therapy. We report a label-free molecular vibrational imaging framework enabling three-dimensional (3-D) image acquisition and quantitative analysis of cellular structures for identification of NSCLC cell types. This diagnostic imaging system employs superpixel-based 3-D nuclear segmentation for extracting such disease-related features as nuclear shape, volume, and cell-cell distance. These features are used to characterize cancer cell types using machine learning. Using fresh unstained tissue samples derived from cell lines grown in a mouse model, the platform showed greater than 97% accuracy for diagnosis of NSCLC cell types within a few minutes. As an adjunct to subsequent histology tests, our novel system would allow fast delineation of cancer cell types with minimum tissue consumption, potentially facilitating on-the-spot diagnosis, while preserving specimens for additional tests. Furthermore, 3-D measurements of cellular structure permit evaluation closer to the native state of cells, creating an alternative to traditional 2-D histology specimen evaluation, potentially increasing accuracy in diagnosing cell type of lung carcinomas.

  6. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs.

  7. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs. PMID:26454049

  8. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    Science.gov (United States)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  9. Inversion of Strong Field Photoelectron Spectra for Molecular Orbital Imaging

    CERN Document Server

    Puthumpally-Joseph, R; Peters, M; Nguyen-Dang, T T; Atabek, O; Charron, E

    2016-01-01

    Imaging structures at the molecular level is a fast developing interdisciplinary research field that spans across the boundaries of physics and chemistry. High spatial resolution images of molecules can be obtained with photons or ultrafast electrons. In addition, images of valence molecular orbitals can be extracted via tomographic techniques based on the coherent XUV radiation emitted by a molecular gas exposed to an intense ultra-short infrared laser pulse. In this paper, we demonstrate that similar information can be obtained by inverting energy resolved photoelectron spectra using a simplified analytical model.

  10. 靶向超声微泡对结肠癌新生血管分子成像的实验研究%Molecular imaging of tumor angiogenesis with VEGFR2 targeting microbubbles in colon cancer bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    位红芹; 何洁; 杨莉; 纪丽景; 张霞; 王冬晓; 文戈; 谷英士; 李颖嘉

    2013-01-01

    Objective To evaluate the effect of tumor neovascularization imaging in a nude mouse model of colon cancer by contrast ultrasound molecular imaging (UMI) of VEGF receptor 2 (kinase insert domain receptor,KDR).Methods Targeted microbubbles (MBt) were built by conjugating K237,a small peptide with high affinity for KDR,to liposome microbubbles through a biotin-avidin bridge.Control microbubbles (MBc) with control peptide were prepared by the same method.Nude mice models of LS174T human colon cancer were established.MBt and MBc were injected intravenously in twelve mice in random order with an interval of 30 min.MBt were injected in another six mice after K237-peptide blocking.UMI was performed in all mice at 5 min postinjection to observe the imaging difference and measure the video intensity (Ⅵ) of tumor tissues in different groups.One-way analysis of variance and the least significant difference t test were performed to analyze the difference of tumor VI in the groups with MBt,MBc and K237 blocking.Immunohistochemistry was applied to detect the expression and distribution of KDR in tumor tissue and adjacent tumor tissues.Results K237 peptide was successfully conjugated to the surface of microbubbles through biotin-avidin mediation.Ultrasound imaging signal of the tumor was high in the MBt group,while there were no significant enhancement in the groups of K237 blocking and MBc.The VI in MBt,MBc and K237 blocking groups was significantly different (F =39.130,P < 0.01).There was a significant difference of VI in the MBt group compared to the MBc group (30.18 ± 9.56 vs 8.28 ± 4.74,t =6.91,P <0.01).In the K237 blocking group Ⅵ was significantly lower than that in the MBt group (9.23 ± 3.44 vs 30.18 ± 9.56,t =4.91,P < 0.01).Immunohistochemistry results showed that KDR was highy expressed in tumor tissue.Conclusions KDR-targeting liposome contrast microbubbles may specifically and efficiently link to tumor vascular endothelial cells in vivo.Thus it may be

  11. Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Suneet Gupta

    2016-01-01

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

  13. Diffusion tensor imaging of the prostate cancer

    International Nuclear Information System (INIS)

    Objective: To explore the diagnostic value of DTI for prostate cancer. Methods: From October 2009 to December 2010,44 patients suspected of prostate cancer received MRI and DTI. The data of MRI and DTI were analyzed retrospectively. By histopathology, prostate cancer was proved in 16 patients,and benign prostatic hyperplasia (BPH) was proved in 28 patients. Differences in ADC and FA values between prostate cancer and BPH were compared by independent samples t test. Diagnostic accuracy of FA value and ADC value for prostate cancer was analyzed by using ROC curve, and the diagnostic threshold of FA value and ADC value for prostate cancer was determined. Results: The mean FA value of the tumor regions and BPH were 0.308±0.084 and 0.203 ±0.029, respectively. The mean ADC value of the tumor regions and BPH were (0.883±0.192) × 10-3 mm2/s and ( 1.408 ±0.130) × 10-3 mm2/s, respectively. There were statistically significant differences in ADC and FA values between tumor regions and BPH (t values were 4.833 and 10.779 respectively, P<0.01). The ADC value area under curve of ROC was 0.996 (95% CI was 0.984 to 1.007); the FA value area under curve of ROC was 0.904 (95% CI was 0.812 to 0.996); Combined the FA and ADC value area under curve of ROC is 0.996 (95% CI was 0.984 to 1.007); Using the ADC value of 0.725 × 10-3 mm2/s as the ROC cut off point, the diagnostic sensitivity and specificity were 100.0% and 96.0%, respectively; Using the FA value of 0.311 as the ROC cut off point,the diagnostic sensitivity and specificity was 100.0% and 68.7%, respectively. Conclusion: DTI imaging can provide valuable information for prostate cancer diagnosis and differential diagnosis, and improve the diagnosis ability of prostate cancer. (authors)

  14. Novel imaging strategies for upper gastrointestinal tract cancers

    DEFF Research Database (Denmark)

    Mortensen, Michael Bau

    2015-01-01

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

  15. [Matrix metalloproteases as molecular markers in gastric cancer].

    Science.gov (United States)

    de la Peña, Sol; Sampieri, Clara L; León-Córdoba, Kenneth

    2010-02-01

    Gastric cancer is the second leading cause of cancer-associated mortality in the world. Prognosis in patients with gastric cancer is difficult to establish because it is commonly diagnosed when gastric wall invasion and metastasis have occurred. Currently, some members of the extracellular matrix metalloproteinases have been identified, whose expression in gastric tumor tissue is significantly elevated compared to healthy gastric tissue. Matrix metalloproteinases are 24 zinc-dependent endopeptidases that catalyze the proteolysis of the extracellular matrix. This degradation allows the cancer cells invade the surrounding stroma and trigger metastasis. Upregulation of certain matrix metalloproteinases in gastric cancer has been associated with a poor prognosis and elevated invasive capacity. This review compiles evidence about the genetic expression of matrix metalloproteinases in gastric cancer and their role in tumour invasion and metastasis, emphasizing their potential as molecular markers of prognosis.

  16. 2. Molecular Biology as a Tool in Cancer Epidemiology

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@There can be little doubt that we are entering a new era in our understanding of the origins of human cancer. Unfortunately from the point of view of the cancer epidemiology community, some of the more recent advances in the molecular biology of cancer (once fully assimilated) will tend to make the talk of the up-to-date cancer epidemiologist a great deal less straightforward than many of us had previously envisaged it to be, There may still be a few cancers that will prove to result from only a few distinctive types of mutation in a relatively small number of genes, but I strongly suspect that the great majority of human cancers that we wish to study will prove to have their origins in a complex set of DNA changes whose precise

  17. [Comparative imaging of cancers of the tongue].

    Science.gov (United States)

    Maradji-Melia, P; Bruneton, J N; Balu-Maestro, C; Marcy, P Y; Dubruque, F; Dassonville, O

    1993-05-01

    In a comparative study of 18 cases of tongue cancer examined with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI), the authors assess the advantages and disadvantages of each technique. MRI seems to be more effective for the detection of small lesions, the examination of the mobile part of the tongue, in case of dental artifacts, for the study of regional extension and to screen recurrence. CT retains its indications for large tumors in patients who are in a poor general condition, tired, and cannot stand lengthy examinations. Ultrasonography remains the first-intention examination in all cases because of its indisputable superiority for lymph node examination.

  18. Potential of biological images for radiation therapy of cancer

    International Nuclear Information System (INIS)

    Full text: Recent technical advances in 3D conformal and intensity modulated radiotherapy (3DCRT and IMRT) based, on patient-specific CT and MRI images, have the potential of delivering exquisitely conformal dose distributions to the target volume while avoiding critical structures. Emerging clinical results in terms of reducing treatment-related morbidity and increasing local control appear promising. Recent developments in imaging have suggested that biological images may further positively impact cancer diagnosis, characterization and therapy. While in the past radiological images are largely anatomical, the new types of images can provide metabolic, biochemical, physiological, functional and molecular (genotypic and phenotypic) information. For radiation therapy, images that give information about factors (e.g. tumor hypoxia, Tpot) that influence radiosensitivity and treatment outcome can be regarded as radiobiological images. The ability of IMRT to 'paint' (in 2D) or 'sculpt' (in 3D) the dose, and produce exquisitely conformal dose distributions begs the '64 million dollar question' as to how to paint or sculpt, and whether biological imaging may provide the pertinent information. Can this new approach provide 'radiobiological phenotypes' non-invasively, and incrementally improve upon the predictive assays of radiobiological characteristics such as proliferative activity (Tpot - the potential doubling time), radiosensitivity (SF2 - the surviving fraction at a dose of 2 Gy), energy status (relative to sublethal damage repair), pH (a possible surrogate of hypoxia), tumor hypoxia, etc. as prognosticator(s) of radiation treatment outcome. Important for IMRT, the spatial (geometrical) distribution of the radiobiological phenotypes provide the basis for dose distribution design to conform to both the physical (geometrical) and the biological attributes. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  19. Molecular genetics of breast cancer progression

    OpenAIRE

    Sigurður Ingvarsson 1956

    1999-01-01

    Somatic changes in the genome of breast cancer cells include amplifications, deletions and gene mutations. Several chromosome regions harboring known oncogenes are found amplified in breast tumors. Despite the high number of chromosome regions deleted in breast tumors the functional relationship to known genes at these locations and cancer growth is mainly undiscovered. Mutations in two tumor suppressor genes (TSG) have been described in a subset of breast carcinomas. These TSG are the TP53, ...

  20. Catalytic Molecular Imaging of MicroRNA in Living Cells by DNA-Programmed Nanoparticle Disassembly.

    Science.gov (United States)

    He, Xuewen; Zeng, Tao; Li, Zhi; Wang, Ganglin; Ma, Nan

    2016-02-24

    Molecular imaging is an essential tool for disease diagnostics and treatment. Direct imaging of low-abundance nucleic acids in living cells remains challenging because of the relatively low sensitivity and insufficient signal-to-background ratio of conventional molecular imaging probes. Herein, we report a class of DNA-templated gold nanoparticle (GNP)-quantum dot (QD) assembly-based probes for catalytic imaging of cancer-related microRNAs (miRNA) in living cells with signal amplification capacity. We show that a single miRNA molecule could catalyze the disassembly of multiple QDs with the GNP through a DNA-programmed thermodynamically driven entropy gain process, yielding significantly amplified QD photoluminescence (PL) for miRNA imaging. By combining the robust PL of QDs with the catalytic amplification strategy, three orders of magnitude improvement in detection sensitivity is achieved in comparison with non-catalytic imaging probe, which enables facile and accurate differentiation between cancer cells and normal cells by miRNA imaging in living cells. PMID:26694689

  1. Designing an university-level module on molecular imaging chemistry

    International Nuclear Information System (INIS)

    Full text: Why do we need radiopharmacy, radiopharmacy, radiopharmacy training? In this post-genomic era, molecular imaging has gain tremendous interest not only amongst physicians but also from biologists, chemists, physicists, engineers, statisticians, pharmaceutical companies and even from governments. There is no doubt that nuclear medicine has been engaged in molecular medicine more than one decade ago. Positron emission tomography (PET) has reawaken interest in long forgotten radiopharmacy. Only major hospitals in the developed countries have invested in the development of dedicated radiopharmacy laboratory and training or recruitment of radiopharmacist. But PET has forced nuclear medicine to create a radiopharmacy unit and adopt radiopharmacy guidelines such as good radiopharmaceutical practice (GRPP) and good manufacturing practice (GMP). It is compounded by the fact that SPECT radiopharmaceutical chemistry has advanced significantly for both diagnostics and therapeutics, which calls for a high level of understanding on radiopharmaceutical chemistry and technical know-how. These factors eventually lead to introduction of tran ing program, courses and degree program. The most striking examples will be European Association of Nuclear Medicine (EANM) radiopharmacy courses and a series of IAEA activities on GRPP, GMP and technologist training programs. Various forms of training or education program can be formulated for various levels, starting from basic radiopharmacy course to PhD program, depending on the following factors; (1) National interest and policies on bio/medical sector; (2) Size of the nuclear medicine community in the respective country; (3) Institution interest and policies; and (4) Existing infrastructure and programs. Current Radiopharmacy Education in Singapore: In Singapore, all of the major nuclear medicine centers are supervised by radiopharmacists with PhD degree. All of the nuclear medicine technologists in the major centers have got

  2. The Center for Integrated Molecular Brain Imaging (Cimbi) database

    DEFF Research Database (Denmark)

    Knudsen, Gitte M.; Jensen, Peter S.; Erritzoe, David;

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions...

  3. Imaging the Breakdown of Molecular Frame Dynamics through Rotational Uncoupling

    CERN Document Server

    Zipp, Lucas J; Bucksbaum, Philip H

    2016-01-01

    We have observed directly in the time domain the uncoupling of electron motion from the molecular frame due to rotational-electronic coupling in a molecular Rydberg system. In contrast to Born- Oppenheimer dynamics, in which the electron is firmly fixed to the molecular frame, there exists a regime of molecular dynamics known as $l$-uncoupling where the motion of a non-penetrating Rydberg electron decouples from the instantaneous alignment of the molecular frame. We have imaged this unusual regime in time-dependent photoelectron angular distributions of a coherently prepared electron wave packet in the 4$f$ manifold of $N_2$.

  4. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

    Science.gov (United States)

    Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

    2015-01-01

    In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

  5. Prostate cancer: multiparametric MR imaging for detection, localization, and staging

    NARCIS (Netherlands)

    Hoeks, C.M.A.; Barentsz, J.O.; Hambrock, T.; Yakar, D.; Somford, D.M.; Heijmink, S.W.T.P.J.; Scheenen, T.W.J.; Vos, P.C.; Huisman, H.J.; Oort, I.M. van; Witjes, J.A.; Heerschap, A.; Futterer, J.J.

    2011-01-01

    This review presents the current state of the art regarding multiparametric magnetic resonance (MR) imaging of prostate cancer. Technical requirements and clinical indications for the use of multiparametric MR imaging in detection, localization, characterization, staging, biopsy guidance, and active

  6. Molecular Imaging Approaches to Understanding the Roles of Hydrogen Peroxide Biology in Stress and Development

    OpenAIRE

    Dickinson, Bryan Craig

    2010-01-01

    The production of hydrogen peroxide (H2O2) in biological systems is associated with a variety of pathologies including neurodegenerative diseases, cancer, and the general process of aging. However, a growing body of evidence suggests that the reactivity of this particular reactive oxygen species (ROS) is also harnessed for physiological processes. Molecular imaging using fluorescence microscopy offers a valuable approach for deciphering the multifaceted roles of H2O2 in biological processes. ...

  7. Molecular Sensing and Imaging of Human Disease Cells and Their Responses to Biochemical Stimuli

    OpenAIRE

    Xiao, Lifu

    2015-01-01

    The overall goal of this dissertation is to develop noninvasive imaging techniques that allow us not only to detect diseased cells but also to study the molecular mechanisms underlying these diseases. Atomic force microscopy and Raman spectroscopy are applied to measure cellular mechanical properties (e.g. Young’s Modulus, adhesion force) and biochemical composition of living cancerous vs. healthy (A549 vs. SAEC) human lung epithelial cells. These biomechanical and biochemical properties c...

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

    Science.gov (United States)

    Oshima, Takashi; Masuda, Munetaka

    2012-04-01

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

  9. Weakly supervised histopathology cancer image segmentation and classification.

    Science.gov (United States)

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

    2014-04-01

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

  10. Choline metabolism-based molecular diagnosis of cancer: an update

    OpenAIRE

    Glunde, Kristine; Penet, Marie-France; Jiang, Lu; Jacobs, Michael A.; Zaver M Bhujwalla

    2015-01-01

    Abnormal choline metabolism continues to be identified in multiple cancers. Molecular causes of abnormal choline metabolism are changes in choline kinase-α, ethanolamine kinase-α, phosphatidylcholine-specific phospholipase C and -D and glycerophosphocholine phosphodiesterases, as well as several choline transporters. The net outcome of these enzymatic changes is an increase in phosphocholine and total choline (tCho) and, in some cancers, a relative decrease of glycerophosphocholine. The incre...

  11. Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

    OpenAIRE

    Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

    2013-01-01

    There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol...

  12. Integrated molecular portrait of non-small cell lung cancers

    OpenAIRE

    Lazar, Vladimir; Suo, Chen; Orear, Cedric; van den Oord, Joost; Balogh, Zsofia; Guegan, Justine; Job, Bastien; Meurice, Guillaume; Ripoche, Hugues; Calza, Stefano; Hasmats, Johanna; Lundeberg, Joakim; Lacroix, Ludovic; Vielh, Philippe; Dufour, Fabienne

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridiz...

  13. Molecular mechanisms of TRAIL-induced apoptosis of cancer cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a recently identified member of the tumor necrosis factor (TNF) family[1]. Numerous studies indicate that TRAIL can induce apoptosis of cancer cells but not of normal cells, pointing to the possibility of de-veloping TRAIL into a cancer drug[2-4]. This review will summary the molecular mechanisms of TRAIL-induced apoptosis and discuss the questions to be resolved in this field.

  14. Tight binding description of the STM image of molecular chains

    OpenAIRE

    Calev, Yoel; Cohen, Hezy; Cuniberti, Gianaurelio; Nitzan, Abraham; Porath, Danny

    2004-01-01

    A tight binding model for scanning tunneling microscopy images of a molecule adsorbed on a metal surface is described. The model is similar in spirit to that used to analyze conduction along molecular wires connecting two metal leads and makes it possible to relate these two measurements and the information that may be gleaned from the corresponding results. In particular, the dependence of molecular conduction properties along and across a molecular chain on the chain length, intersite elect...

  15. MRI Reporter Genes for Noninvasive Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Caixia Yang

    2016-05-01

    Full Text Available Magnetic resonance imaging (MRI is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase, the receptor on the cells (e.g., transferrin receptor, and endogenous reporter genes (e.g., ferritin reporter gene. However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies.

  16. DNA aptamers as molecular probes for colorectal cancer study.

    Directory of Open Access Journals (Sweden)

    Kwame Sefah

    Full Text Available BACKGROUND: Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development. METHODOLOGY AND RESULTS: Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh, nor do they recognize most other cancer cell lines tested. CONCLUSION/SIGNIFICANCE: The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers.

  17. [Molecular classification of bladder cancer. Possible similarities to breast cancer].

    Science.gov (United States)

    Wirtz, R M; Fritz, V; Stöhr, R; Hartmann, A

    2016-02-01

    Therapeutic decisions for breast cancer are increasingly becoming based on subtype-specific gene expression tests. For bladder cancer very similar subtypes have been identified by genome-wide mRNA analysis, which as for breast cancer differ with respect to the prognosis and response to therapy on the basis of their hormone dependency. At the DNA level, however, the type of mutations and their frequencies within the subtypes are strikingly different between bladder and breast cancers. It will be interesting to see whether possible driver mutations can serve as therapeutic targets in both indications. In contrast, the apparent hormone dependency of a substantial number of bladder carcinomas suggests that hormonal and anti-hormonal treatment can be valid therapy options similar to breast cancer. Moreover, gender-specific differences with respect to the incidence and aggressiveness of male compared to female bladder cancers can be explained by hormonal effects. Together with forthcoming immunomodulatory therapies these multiple therapy options raise and give new hope to efficiently combat this aggressive disease. PMID:26780243

  18. Colorectal Cancer & Molecular Mutations and Polymorphism

    Directory of Open Access Journals (Sweden)

    Aga Syed Sameer

    2013-05-01

    Full Text Available Colorectal cancer (CRC is one of the major causes of mortality and morbidity, and is the third most common cancer in men and the second most common cancer in women worldwide. The incidence of CRC shows considerable variation among racially or ethnically defined populations in multiracial/ethnic countries. The tumorigenesis of CRC is either because of the chromosomal instability (CIN or microsatellite instability (MIN or involving various proto-oncogenes, tumor suppressor genes and also epigenetic changes in the DNA. In this review I have focused on the mutations and polymorphisms of various important genes of the CIN and MIN pathways which have been implicated in the development of CRC.

  19. Gastrointestinal cancers in inflammatory bowel disease: An update with emphasis on imaging findings.

    Science.gov (United States)

    Barral, Matthias; Dohan, Anthony; Allez, Matthieu; Boudiaf, Mourad; Camus, Marine; Laurent, Valérie; Hoeffel, Christine; Soyer, Philippe

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers depending on the specific type of IBD, the extent of the disease and its location. Patients with IBD and extensive colonic involvement are at increased risk of colorectal cancer whereas patients with Crohn disease have an increased risk for small-bowel and anal carcinoma. These cancers preferentially develop on sites of longstanding inflammation. In regards to colon cancer, several key pathogenic events are involved, including chromosomal instability, microsatellite instability and hypermethylation. The risk for colon cancer in IBD patients correlates with longer disease duration, presence of sclerosing cholangitis, pancolitis, family history of colorectal cancer, early onset of the disease and severity of bowel inflammation. Identification of increased colorectal cancer risk in individual IBD patients has led to formal surveillance guidelines. Conversely, although an increased risk for other types of cancer has been well identified, no specific formal screening recommendations exist. Consequently, the role of the radiologist is crucial to alert the referring gastroenterologist when a patient with IBD presents with unusual imaging findings at either computed tomography (CT) or magnetic resonance (MR) imaging. This review provides an update on demographics, molecular, clinical and histopathological features of gastrointestinal cancers in IBD patients including colorectal carcinoma, small bowel adenocarcinoma, neuroendocrine tumors and anal carcinoma, along with a special emphasis on the current role of CT and MR imaging. PMID:26315381

  20. Optical and Functional Imaging in Lung Cancer

    NARCIS (Netherlands)

    K.H. van der Leest (Cor)

    2010-01-01

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

  1. Molecular Concordance Between Primary Breast Cancer and Matched Metastases.

    Science.gov (United States)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads; Kruse, Torben A

    2016-07-01

    Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both with respect to traditional clinical treatment targets and on the genomic and transcriptomic level. With the increasing use of molecularly targeted therapy, discordance of actionable molecular targets between primary tumors and recurrences can result in nonoptimal treatment or unnecessary side effects. The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight into the biology underlying metastatic progression and has the potential to identify novel, potentially druggable, drivers of progression. PMID:27089067

  2. The motivations and methodology for high-throughput PET imaging of small animals in cancer research

    OpenAIRE

    Aide, Nicolas; Visser, Eric P.; Lheureux, Stéphanie; Heutte, Natacha; Szanda, Istvan; Hicks, Rodney J.

    2012-01-01

    Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the num...

  3. In vivo medical imaging technologies: new possibility in diagnosis of gastric cancer.

    Science.gov (United States)

    Cesaretti, Manuela; Zarzavadjian LE Bian, Alban

    2016-08-01

    Gastric cancer is one of the most common cancers with an important related-mortality worldwide. It is preceded by a multistage pathological state arising from environmental and dietary factors. These factors influence intracellular molecular changes associated with the gastric carcinogenesis. Gastroenterology imaging, such as endoscopy, is essential for an early diagnosis as patients are typically asymptomatic at the onset of gastric cancer. Recent technological advances have allowed the development of novel imaging devices such as narrow-band imaging or high-definition endoscopy. Their accuracy in determining early gastric lesions makes biopsy of tissue unnecessary. They may largely simplify early diagnosis and improved prognosis. We performed a qualitative review about endoscopic application of advanced imaging technologies. PMID:26837334

  4. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  5. Enhancing contrast and quantitation by spatial frequency domain fluorescence molecular imaging

    Science.gov (United States)

    Sun, Jessica; Hathi, Deep; Zhou, Haiying; Shokeen, Monica; Akers, Walter J.

    2016-03-01

    Optical imaging with fluorescent contrast agents is highly sensitive for molecular imaging but is limited in depth to a few centimeters below the skin. Planar fluorescence imaging with full-field, uniform illumination and scientific camera image capture provides a portable and robust configuration for real-time, sensitive fluorescence detection with scalable resolution, but is inherently surface weighted and therefore limited in depth to a few millimeters. At the NIR region (700-1000 nm), tissue absorption and autofluorescence are relatively reduced, increasing depth penetration and reducing background signal, respectively. Optical imaging resolution scales with depth, limiting microscopic resolution with multiphoton microscopy and optical coherence tomography to skin and peri-tumoral tissues are not uniform, varying in thickness and color, complicating subsurface fluorescence measurements. Diffuse optical imaging methods have been developed that better quantify optical signals relative to faster full-field planar reflectance imaging, but require long scan times, complex instrumentation, and reconstruction algorithms. Here we report a novel strategy for rapid measurement of subsurface fluorescence using structured light illumination to improve quantitation of deep-seated fluorescence molecular probe accumulation. This technique, in combination with highly specific, tumor-avid fluorescent molecular probes, will easily integrate noninvasive diagnostics for superficial cancers and fluorescence guided surgery.

  6. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes.

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  7. Endometrial cancer : from a molecular genetic perspective

    NARCIS (Netherlands)

    E. Smid-Koopman (Ellen)

    2002-01-01

    textabstractThe first observations indicative of a role of genetic factors in carcinogenesis were made as early as 1912, when Rous demonstrated that a filterable agent (i.e. virus) could induce cancer in chicken (Rous 1965). In 1914, Boveri postulated a "genetic" theory on carcinogenesis by hypothes

  8. Molecular pathology of colorectal cancer predisposing syndromes

    NARCIS (Netherlands)

    Puijenbroek, Marjo van

    2008-01-01

    Each year, approximately eleven thousand new colorectal cancer (CRC) patients are registered in the Netherlands. Half of these patients will eventually die of this disease. Consequently, it is of great importance to identify individuals with an increased risk for CRC. In this thesis, we evaluate the

  9. The consensus molecular subtypes of colorectal cancer

    NARCIS (Netherlands)

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-01-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data shar

  10. Molecular-Genetic Aspects of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Krasteva M.

    2014-12-01

    Full Text Available Breast cancer is the most frequent malignancy among women. Advances in breast cancer knowledge have deciphered the involvement of a number of tumor suppressor genes and proto-oncogenes in disease pathogenesis. These genes are part of the complex biochemical pathways, which enable cell cycle control and maintenance of genome integrity. Their function may be disrupted as a result of alterations in gene sequence or misregulation of gene expression including alterations in DNA methylation pattern. The present review summarizes the main findings on major breast cancer related genes BRCA1/2, p53, ATM, CHEK2, HER2, PIK3CA and their tumorigenic inactivation/activation. The potential clinical importance of these genes with respect to patients’ prognosis and therapy are also discussed. The possible implication of other putative breast cancer related genes is also outlined. The first elaborate data on the genetic and epigenetic status of the above mentioned genes concerning Bulgarian patients with the sporadic form of the disease are presented. The studies indicate for a characteristic mutational spectrum in some of the genes for the Bulgarian patients and specific correlation between the status of different genes and clinicopathological characteristics.

  11. The epidemiology and molecular mechanisms linking obesity, diabetes, and cancer.

    Science.gov (United States)

    Ferguson, Rosalyn D; Gallagher, Emily J; Scheinman, Eyal J; Damouni, Rawan; LeRoith, Derek

    2013-01-01

    The worldwide epidemic of obesity is associated with increasing rates of the metabolic syndrome and type 2 diabetes. Epidemiological studies have reported that these conditions are linked to increased rates of cancer incidence and mortality. Obesity, particularly abdominal obesity, is associated with insulin resistance and the development of dyslipidemia, hyperglycemia, and ultimately type 2 diabetes. Although many metabolic abnormalities occur with obesity and type 2 diabetes, insulin resistance and hyperinsulinemia appear to be central to these conditions and may contribute to dyslipidemia and altered levels of circulating estrogens and androgens. In this review, we will discuss the epidemiological and molecular links between obesity, type 2 diabetes, and cancer, and how hyperinsulinemia and dyslipidemia may contribute to cancer development. We will discuss how these metabolic abnormalities may interact with estrogen signaling in breast cancer growth. Finally, we will discuss the effects of type 2 diabetes medications on cancer risk. PMID:23810003

  12. Molecular markers as therapeutic targets in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hsin-Hui Tseng; Biao He

    2013-01-01

    Lung cancer is responsible for 29% of cancer deaths in the United States and has very low 5-year survival rates of approximately 11% in men and 15% in women.Although the early diagnosis of lung cancer may increase the survival rate with adequate treatment,advanced lung cancers are often metastasized and receive limited benefit from therapeutic regimens.As conventional treatments for lung cancer reach their limitations,researchers have attempted to discover novel drug therapies aimed at specific targets contributing to the progression of tumorigenesis.Recent advances in systems biology have enabled the molecular biology of lung carcinogenesis to be elucidated.Our understanding of the physiologic processes of tumor development provide a means to design more effective and specific drugs with less toxicity,thereby accelerating the delivery of new drug therapies to the patient's bedside.

  13. Functional and Molecular Image Guidance in Radiotherapy Treatment Planning Optimization

    OpenAIRE

    Das, Shiva K.; Ten Haken, Randall K.

    2011-01-01

    Functional and molecular imaging techniques are increasingly being developed and used to quantitatively map the spatial distribution of parameters such as metabolism, proliferation, hypoxia, perfusion and ventilation, among others, onto anatomically-imaged normal organs and tumor. In radiotherapy optimization, these imaging modalities offer the promise of increased dose sparing to high functioning subregions of normal organs or dose escalation to selected subregions of tumor, as well as the p...

  14. Molecular Imaging of Healing After Myocardial Infarction

    OpenAIRE

    Naresh, Nivedita K; Ben-Mordechai, Tamar; Leor, Jonathan; Epstein, Frederick H

    2011-01-01

    The progression from acute myocardial infarction (MI) to heart failure continues to be a major cause of morbidity and mortality. Potential new therapies for improved infarct healing such as stem cells, gene therapy, and tissue engineering are being investigated. Noninvasive imaging plays a central role in the evaluation of MI and infarct healing, both clinically and in preclinical research. Traditionally, imaging has been used to assess cardiac structure, function, perfusion, and viability. H...

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

    Science.gov (United States)

    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

  16. Novel approach to improve molecular imaging research: Correlation between macroscopic and molecular pathological findings in patients

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, Ingrid, E-mail: i.boehm@uni-bonn.de [Department of Diagnostic Radiology, ZARF Project, Center for Molecular Imaging Research MBMB, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany)

    2011-09-15

    Purpose: Currently, clinical research approaches are sparse in molecular imaging studies. Moreover, possible links between imaging features and pathological laboratory parameters are unknown, so far. Therefore, the goal was to find a possible relationship between imaging features and peripheral blood cell apoptosis, and thereby to present a novel way to complement molecular imaging research. Materials and methods: The investigation has been done in systemic lupus erythematosus (SLE), a prototype of an autoimmune disease characterized by multiorgan involvement, autoantibody production, and disturbed apoptosis. Retrospectively, radiological findings have been compared to both autoantibody findings and percentage apoptotic blood cells. Results: Two SLE groups could be identified: patients with normal (annexin V binding < 20%), and with increased apoptosis (annexin V binding > 20%) of peripheral blood cells. The frequency of radiological examinations in SLE patients significantly correlated with an increased percentage of apoptotic cells (p < 0.005). In patients with characteristic imaging findings (e.g. lymph node swelling, pleural effusion) an elevated percentage of apoptotic cells was present. In contrast SLE-patients with normal imaging findings or uncharacteristic results of minimal severity had normal percentages of apoptotic blood cells. Conclusion: This correlation between radiographic findings and percentage of apoptotic blood cells provides (1) further insight into pathological mechanisms of SLE, (2) will offer the possibility to introduce apoptotic biomarkers as molecular probes for clinical molecular imaging approaches in future to early diagnose organ complaints in patients with SLE, and (3) is a plea to complement molecular imaging research by this clinical approach.

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

    Science.gov (United States)

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

    2016-03-01

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

  18. Integrating tumor microenvironment with cancer molecular classifications

    OpenAIRE

    Becht, Etienne; De Reyniès, Aurélien; Fridman, Wolf H.

    2015-01-01

    Editorial summary The composition of the tumor microenvironment is associated with a patient's prognosis and can be therapeutically targeted. A link between the cellular composition and genomic features of the tumor and its response to immunotherapy is beginning to emerge. Analyzing the microenvironment of tumor molecular subgroups can be a useful approach to tailor immunotherapies.

  19. TCGA divides gastric cancer into four molecular subtypes:implications for individualized therapeutics

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is chalenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especialy the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

  20. Rapid Cancer Fluorescence Imaging Using A γ-Glutamyltranspeptidase-Specific Probe For Primary Lung Cancer

    OpenAIRE

    Hino, Haruaki; Kamiya, Mako; Kitano, Kentaro; Mizuno, Kazue; Tanaka, Sayaka; Nishiyama, Nobuhiro; Kataoka, Kazunori; Urano, Yasuteru; Nakajima, Jun

    2016-01-01

    BACKGROUND: We set out to examine the activity of γ-glutamyltranspeptidase (GGT) in lung cancer and the validity of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) for intraoperative imaging of primary lung cancer. METHODS: GGT activities and mRNA expression levels of GGT1 (one of the GGT subtypes) in five human lung cancer cell lines were examined by fluorescence imaging and quantitative reverse transcription polymerase chain reaction. In vivo imaging of an orthotopic A549 xenograft mod...

  1. Molecular imaging in neuroendocrine tumors : Molecular uptake mechanisms and clinical results

    NARCIS (Netherlands)

    Koopmans, Klaas P.; Neels, Oliver N.; Kema, Ido P.; Elsinga, Philip H.; Links, Thera P.; de Vries, Elisabeth G. E.; Jager, Pieter L.

    2009-01-01

    Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-

  2. Diffusion-weighted imaging of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Riccardo; De; Robertis; Paolo; Tinazzi; Martini; Emanuele; Demozzi; Flavia; Dal; Corso; Claudio; Bassi; Paolo; Pederzoli; Mirko; D’Onofrio

    2015-01-01

    Magnetic resonance imaging(MRI) is a reliable and accurate imaging method for the evaluation of patients with pancreatic ductal adenocarcinoma(PDAC). Diffusion-weighted imaging(DWI) is a relatively recent technological improvement that expanded MRI capabilities, having brought functional aspects into conventional morphologic MRI evaluation. DWI can depict the random diffusion of water molecules within tissues(the so-called Brownian motions). Modifications of water diffusion induced by different factors acting on the extracellular and intracellular spaces, as increased cell density, edema, fibrosis, or altered functionality of cell membranes, can be detected using this MR sequence. The intravoxel incoherent motion(IVIM) model is an advanced DWI technique that consent a separate quantitative evaluation of all the microscopic random motions that contribute to DWI, which are essentially represented by molecular diffusion and blood microcirculation(perfusion). Technological improvements have made possible the routine use of DWI during abdominal MRI study. Several authors have reported that the addition of DWI sequence can be of value for the evaluation of patients with PDAC, especially improving the staging; nevertheless, it is still unclear whether and how DWI could be helpful for identification, characterization, prognostic stratification and follow-up during treatment. The aim of this paper is to review up-to-date literature data regarding the applications of DWI and IVIM to PDACs.

  3. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  4. Dynamic infrared imaging for skin cancer screening

    Science.gov (United States)

    Godoy, Sebastián E.; Ramirez, David A.; Myers, Stephen A.; von Winckel, Greg; Krishna, Sanchita; Berwick, Marianne; Padilla, R. Steven; Sen, Pradeep; Krishna, Sanjay

    2015-05-01

    Dynamic thermal imaging (DTI) with infrared cameras is a non-invasive technique with the ability to detect the most common types of skin cancer. We discuss and propose a standardized analysis method for DTI of actual patient data, which achieves high levels of sensitivity and specificity by judiciously selecting pixels with the same initial temperature. This process compensates the intrinsic limitations of the cooling unit and is the key enabling tool in the DTI data analysis. We have extensively tested the methodology on human subjects using thermal infrared image sequences from a pilot study conducted jointly with the University of New Mexico Dermatology Clinic in Albuquerque, New Mexico (ClinicalTrials ID number NCT02154451). All individuals were adult subjects who were scheduled for biopsy or adult volunteers with clinically diagnosed benign condition. The sample size was 102 subjects for the present study. Statistically significant results were obtained that allowed us to distinguish between benign and malignant skin conditions. The sensitivity and specificity was 95% (with a 95% confidence interval of [87.8% 100.0%]) and 83% (with a 95% confidence interval of [73.4% 92.5%]), respectively, and with an area under the curve of 95%. Our results lead us to conclude that the DTI approach in conjunction with the judicious selection of pixels has the potential to provide a fast, accurate, non-contact, and non-invasive way to screen for common types of skin cancer. As such, it has the potential to significantly reduce the number of biopsies performed on suspicious lesions.

  5. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    Science.gov (United States)

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  6. Identification of a novel luminal molecular subtype of breast cancer.

    Directory of Open Access Journals (Sweden)

    Anna Dvorkin-Gheva

    Full Text Available The molecular classification of human breast tumors has afforded insights into subtype specific biological processes, patient prognosis and response to therapies. However, using current methods roughly one quarter of breast tumors cannot be classified into one or another molecular subtype. To explore the possibility that the unclassifiable samples might comprise one or more novel subtypes we employed a collection of publically available breast tumor datasets with accompanying clinical information to assemble 1,593 transcript profiles: 25% of these samples could not be assigned to one of the current molecular subtypes of breast cancer. All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed "luminal-like". We also identified the luminal-like subtype in an independent collection of tumor samples (NKI295. We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors. Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.

  7. Multifunctional hydroxyapatite nanoparticles for drug delivery and multimodal molecular imaging

    International Nuclear Information System (INIS)

    Hydroxyapatite (HAp) is the most important constituent of biological tissues such as bone and teeth and exhibits several characteristic features. HAp nanoparticles (NPs) are good host materials and can be functionalized with various kinds of dopants and substrates. By endowing HAp NPs with desired properties in order to render them suitable for biomedical applications including cellular imaging, non-invasive and quantitative visualisation of molecular process occurring at cellular and subcellular levels becomes possible. Depending on their functional properties, HAp based nanoprobes can be divided into three classes, i.e., luminescent HAp NPs (for both down conversion and up conversion luminescence), magnetic HAp NPs, and luminomagnetic HAp NPs. Luminomagnetic HAp NPs are particularly attractive in terms of bimodal imaging and even multimodal imaging by virtue of their luminescence and magnetism. Functionalized HAp NPs are potential candidates for targeted drug delivery applications. This review (with 166 references) spotlights the cellular imaging applications of three types of HAp NPs. Specific sections cover aspects of molecular imaging and the various imaging modes, a comparison of the common types of nanoprobes for bioimaging, synthetic methods for making the various kinds of HAp NPs, followed by overviews on fluorescent NPs for bioimaging (such as quantum dots, gold nanoclusters, lanthanide-doped or fluorophore-doped NPs), magnetic HAp NPs for use in magnetic resonance imaging (MRI), luminomagnetic HAp NPs for bimodal imaging, and sections on drug delivery as well as cellular imaging applications of HAp based nanoprobes (including targeted imaging). (author)

  8. Application of Proteomics to Cancer Molecular Diagnostics

    Institute of Scientific and Technical Information of China (English)

    Sam HANASH

    2009-01-01

    @@ Strategies to achieve personalized medicine and improve public health encompass assessment of an individual's risk for disease, early detection and molecular classification of disease resulting in an informed choice of the most appropriate treatment instituted at an early stage of disease develop- ment. A major contribution of proteomics in this field is the development of blood based tests to achieve the goals of personalized medicine.

  9. Emerging applications of conjugated polymers in molecular imaging.

    Science.gov (United States)

    Li, Junwei; Liu, Jie; Wei, Chen-Wei; Liu, Bin; O'Donnell, Matthew; Gao, Xiaohu

    2013-10-28

    In recent years, conjugated polymers have attracted considerable attention from the imaging community as a new class of contrast agent due to their intriguing structural, chemical, and optical properties. Their size and emission wavelength tunability, brightness, photostability, and low toxicity have been demonstrated in a wide range of in vitro sensing and cellular imaging applications, and have just begun to show impact in in vivo settings. In this Perspective, we summarize recent advances in engineering conjugated polymers as imaging contrast agents, their emerging applications in molecular imaging (referred to as in vivo uses in this paper), as well as our perspectives on future research.

  10. Prostate cancer: multiparametric MR imaging for detection, localization, and staging.

    Science.gov (United States)

    Hoeks, Caroline M A; Barentsz, Jelle O; Hambrock, Thomas; Yakar, Derya; Somford, Diederik M; Heijmink, Stijn W T P J; Scheenen, Tom W J; Vos, Pieter C; Huisman, Henkjan; van Oort, Inge M; Witjes, J Alfred; Heerschap, Arend; Fütterer, Jurgen J

    2011-10-01

    This review presents the current state of the art regarding multiparametric magnetic resonance (MR) imaging of prostate cancer. Technical requirements and clinical indications for the use of multiparametric MR imaging in detection, localization, characterization, staging, biopsy guidance, and active surveillance of prostate cancer are discussed. Although reported accuracies of the separate and combined multiparametric MR imaging techniques vary for diverse clinical prostate cancer indications, multiparametric MR imaging of the prostate has shown promising results and may be of additional value in prostate cancer localization and local staging. Consensus on which technical approaches (field strengths, sequences, use of an endorectal coil) and combination of multiparametric MR imaging techniques should be used for specific clinical indications remains a challenge. Because guidelines are currently lacking, suggestions for a general minimal protocol for multiparametric MR imaging of the prostate based on the literature and the authors' experience are presented. Computer programs that allow evaluation of the various components of a multiparametric MR imaging examination in one view should be developed. In this way, an integrated interpretation of anatomic and functional MR imaging techniques in a multiparametric MR imaging examination is possible. Education and experience of specialist radiologists are essential for correct interpretation of multiparametric prostate MR imaging findings. Supportive techniques, such as computer-aided diagnosis are needed to obtain a fast, cost-effective, easy, and more reproducible prostate cancer diagnosis out of more and more complex multiparametric MR imaging data. PMID:21931141

  11. Molecular imaging in myeloma precursor disease

    OpenAIRE

    Mena, E.; Choyke, P; Tan, E; Landgren, O; Kurdziel, K

    2011-01-01

    Multiple myeloma (MM) is consistently preceded by its pre-malignant states, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). By definition, precursor conditions do not exhibit end-organ disease (anemia, hypercalcemia, renal failure, skeletal lytic lesions, or a combination of these). However, new imaging methods are demonstrating that some patients in the MGUS or SNM category are exhibiting early signs of MM.

  12. Clinical imaging of multidrug resistance in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Del Vecchi, S.; Ciarmiello, A.; Salvatore, M. [Naples Univ. Federico 2. (Italy). Medicina Nucleare. Dipt. di Scienze Biomorfologiche e Funzionali

    1999-06-01

    The most well-characterized mechanism of multidrug resistance (MDR) involves P-glycoprotein (Pgp), a transmembrane protein acting as an ATP-dependent drug efflux pump. The recognition of {sup 9}9mTc-Sestamibi and other lipophilic cations as transport substrates for Pgp provided the necessary tool for the clinical assessment of Pgp function in patients with cancer. Many clinical studies from different institutions and trials including variety of malignancies indicate that both tumor uptake and clearance of {sup 9}9mTc-Sestamibi are correlate with Pgp expression and may be used for the phenotypic assessment of multidrug resistance. Although both parameters may predict tumor responsible to chemotherapy, the extraction of efflux rate constants appeared o provide a more direct index of Pgp function as compared tp tracer uptake ratio allowing to trace a continuous spectrum of drug transport activity. Preliminary studies the use of MDR imaging agents to monitor the modulating ability of revertant compounds. Although the results support the feasibility of this approach, the alteration of tracer pharmacokinetics induced by the modulators certainly constitute a challenge in the development of a simple functional test suitable in clinical practice. The extension of the acquired imaging methodology to tumors with redundant intrinsic resistant mechanism. Due to multifactorial nature of phenomenon, the development of new tracers with substrate specificity for other known the complex array of cellular mechanisms contributing to treatment failure.

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

    DEFF Research Database (Denmark)

    Korreman, Stine

    2015-01-01

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

  14. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

    of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies) and small volume...... antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate cancer.......Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...

  15. Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Advanced prostate cancer commonly metastasizes to bone leading to osteoblastic and osteolytic lesions. Although an osteolytic component governed by activation of bone resorbing osteoclasts is prominent in prostate cancer metastasis, the molecular mechanisms of prostate cancer-induced osteoclastogenesis are not well-understood. We studied the effect of soluble mediators released from human prostate carcinoma cells on osteoclast formation from mouse bone marrow and RAW 264.7 monocytes. Soluble factors released from human prostate carcinoma cells significantly increased viability of naïve bone marrow monocytes, as well as osteoclastogenesis from precursors primed with receptor activator of nuclear factor κ-B ligand (RANKL). The prostate cancer-induced osteoclastogenesis was not mediated by RANKL as it was not inhibited by osteoprotegerin (OPG). However inhibition of TGFβ receptor I (TβRI), or macrophage-colony stimulating factor (MCSF) resulted in attenuation of prostate cancer-induced osteoclastogenesis. We characterized the signaling pathways induced in osteoclast precursors by soluble mediators released from human prostate carcinoma cells. Prostate cancer factors increased basal calcium levels and calcium fluctuations, induced nuclear localization of nuclear factor of activated t-cells (NFAT)c1, and activated prolonged phosphorylation of ERK1/2 in RANKL-primed osteoclast precursors. Inhibition of calcium signaling, NFATc1 activation, and ERK1/2 phosphorylation significantly reduced the ability of prostate cancer mediators to stimulate osteoclastogenesis. This study reveals the molecular mechanisms underlying the direct osteoclastogenic effect of prostate cancer derived factors, which may be beneficial in developing novel osteoclast-targeting therapeutic approaches

  16. Nanosized multifunctional liposomes for tumor diagnosis and molecular imaging by SPECT/CT.

    Science.gov (United States)

    Silindir, Mine; Erdoğan, Suna; Özer, A Yekta; Doğan, A Lale; Tuncel, Murat; Uğur, Ömer; Torchilin, Vladimir P

    2013-03-01

    Among currently used cancer imaging methods, nuclear medicine modalities provide metabolic information, whereas modalities in radiology provide anatomical information. However, different modalities, having different acquisition times in separate machines, decrease the specificity and accuracy of images. To solve this problem, hybrid imaging modalities were developed as a new era, especially in the cancer imaging field. With widespread usage of hybrid imaging modalities, specific contrast agents are essentially needed to use in both modalities, such as single-photon emission computed tomography/computed tomography (SPECT/CT). Liposomes are one of the most desirable drug delivery systems, depending on their suitable properties. The aim of this study was to develop a liposomal contrast agent for the diagnosis and molecular imaging of tumor by SPECT/CT. Liposomes were prepared nanosized, coated with polyethylene glycol to obtain long blood circulation, and modified with monoclonal antibody 2C5 for specific tumor targeting. Although DTPA-PE and DTPA-PLL-NGPE (polychelating amphilic polymers; PAPs) were loaded onto liposomes for stable radiolabeling for SPECT imaging, iopromide was encapsulated into liposomes for CT imaging. Liposomes [(DPPC:PEG(2000)-PE:Chol:DTPA-PE), (PL 90G:PEG(2000)-PE:Chol:DTPA-PE), (DPPC:PEG(2000)-PE:Chol:PAPs), (PL 90G:PEG(2000)-PE:Chol:PAPs), (60:0.9:39:0.1% mol ratio)] were characterized in terms of entrapment efficiency, particle size, physical stability, and release kinetics. Additionally, in vitro cell-binding studies were carried out on two tumor cell lines (MCF-7 and EL 4) by counting radioactivity. Tumor-specific antibody-modified liposomes were found to be effective multimodal contrast agents by designating almost 3-8 fold more uptake than nonmodified ones in different tumor cell lines. These results could be considered as an important step in the development of tumor-targeted SPECT/CT contrast agents for cancer imaging. PMID:23078019

  17. ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome.

    Science.gov (United States)

    Riesco-Eizaguirre, Garcilaso; Santisteban, Pilar

    2016-11-01

    Thyroid cancer is the most common endocrine malignancy giving rise to one of the most indolent solid cancers, but also one of the most lethal. In recent years, systematic studies of the cancer genome, most importantly those derived from The Cancer Genome Altas (TCGA), have catalogued aberrations in the DNA, chromatin, and RNA of the genomes of thousands of tumors relative to matched normal cellular genomes and have analyzed their epigenetic and protein consequences. Cancer genomics is therefore providing new information on cancer development and behavior, as well as new insights into genetic alterations and molecular pathways. From this genomic perspective, we will review the main advances concerning some essential aspects of the molecular pathogenesis of thyroid cancer such as mutational mechanisms, new cancer genes implicated in tumor initiation and progression, the role of non-coding RNA, and the advent of new susceptibility genes in thyroid cancer predisposition. This look across these genomic and cellular alterations results in the reshaping of the multistep development of thyroid tumors and offers new tools and opportunities for further research and clinical development of novel treatment strategies. PMID:27666535

  18. Environmental effects on molecular biomarkers expression in pancreatic and brain cancer

    Science.gov (United States)

    Mensah, Lawrence; Mallidi, Srivalleesha; Massodi, Iqbal; Anbil, Sriram; Mai, Zhiming; Hasan, Tayyaba

    2013-03-01

    A complete understanding of the biological mechanisms regulating devastating disease such as cancer remains elusive. Pancreatic and brain cancers are primary among the cancer types with poor prognosis. Molecular biomarkers have emerged as group of proteins that are preferentially overexpressed in cancers and with a key role in driving disease progression and resistance to chemotherapy. The epidermal growth factor receptor (EGFR), a cell proliferative biomarker is particularly highly expressed in most cancers including brain and pancreatic cancers. The ability of EGFR to sustain prolong cell proliferation is augmented by biomarkers such as Bax, Bcl-XL and Bcl-2, proteins regulating the apoptotic process. To better understand the role and effect of the microenvironment on these biomarkers in pancreatic cancer (PaCa); we analysed two pancreatic tumor lines (AsPc-1 and MiaPaCa-2) in 2D, 3D in-vitro cultures and in orthotopic tumors at different growth stages. We also investigated in patient derived glioblastoma (GBM) tumor cultures, the ability to utilize the EGFR expression to specifically deliver photosensitizer to the cells for photodynamic therapy. Overall, our results suggest that (1) microenvironment changes affect biomarker expression; thereby it is critical to understand these effects prior to designing combination therapies and (2) EGFR expression in tumor cells indeed could serve as a reliable and a robust biomarker that could be used to design targeted and image-guided photodynamic therapy.

  19. Retinoic acid receptors: from molecular mechanisms to cancer therapy.

    Science.gov (United States)

    di Masi, Alessandra; Leboffe, Loris; De Marinis, Elisabetta; Pagano, Francesca; Cicconi, Laura; Rochette-Egly, Cécile; Lo-Coco, Francesco; Ascenzi, Paolo; Nervi, Clara

    2015-02-01

    Retinoic acid (RA), the major bioactive metabolite of retinol or vitamin A, induces a spectrum of pleiotropic effects in cell growth and differentiation that are relevant for embryonic development and adult physiology. The RA activity is mediated primarily by members of the retinoic acid receptor (RAR) subfamily, namely RARα, RARβ and RARγ, which belong to the nuclear receptor (NR) superfamily of transcription factors. RARs form heterodimers with members of the retinoid X receptor (RXR) subfamily and act as ligand-regulated transcription factors through binding specific RA response elements (RAREs) located in target genes promoters. RARs also have non-genomic effects and activate kinase signaling pathways, which fine-tune the transcription of the RA target genes. The disruption of RA signaling pathways is thought to underlie the etiology of a number of hematological and non-hematological malignancies, including leukemias, skin cancer, head/neck cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, renal cell carcinoma, pancreatic cancer, liver cancer, glioblastoma and neuroblastoma. Of note, RA and its derivatives (retinoids) are employed as potential chemotherapeutic or chemopreventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. In humans, retinoids reverse premalignant epithelial lesions, induce the differentiation of myeloid normal and leukemic cells, and prevent lung, liver, and breast cancer. Here, we provide an overview of the biochemical and molecular mechanisms that regulate the RA and retinoid signaling pathways. Moreover, mechanisms through which deregulation of RA signaling pathways ultimately impact on cancer are examined. Finally, the therapeutic effects of retinoids are reported. PMID:25543955

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

    Science.gov (United States)

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

    2016-03-01

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

  1. [Development of molecular targeted therapies in lung cancers].

    Science.gov (United States)

    Suda, Kenichi; Mitsudomi, Tetsuya

    2014-05-01

    Human cancers usually possess cumulative genetic aberrations. However, recent studies have revealed that the proliferation and survival of specific subsets of lung cancer depend on a few somatic mutation(s), so-called driver mutations. Representative driver mutations include the EGFR mutation and ALK translocation identified in about 40% and 3% of lung adenocarcinomas in Japan, respectively. These tumors are extremely sensitive to the respective tyrosine kinase inhibitors. This sensitivity has encouraged researchers and clinicians to explore novel driver mutations in lung cancers as future molecular targets. Driver mutations reported so far include the HER2 mutation, BRAF mutation, ROS1 translocation, RET translocation, and NTRK translocation in lung adenocarcinomas, and FGFR1 amplification, DDR2 mutation, and FGFR3 translocation in lung squamous cell carcinomas. However, despite initial dramatic responses, the acquisition of resistance to molecular targeted drugs is almost inevitable. Overcoming resistance to molecular targeted drugs, the key drugs at this time, is an urgent issue to improve the outcomes of lung cancer patients. PMID:24946519

  2. Molecular imaging with dynamic contrast-enhanced computed tomography

    International Nuclear Information System (INIS)

    Dynamic contrast-enhanced computed tomography (DCE-CT) is a quantitative technique that employs rapid sequences of CT images after bolus administration of intravenous contrast material to measure a range of physiological processes related to the microvasculature of tissues. By combining knowledge of the molecular processes underlying changes in vascular physiology with an understanding of the relationship between vascular physiology and CT contrast enhancement, DCE-CT can be redefined as a molecular imaging technique. Some DCE-CT derived parameters reflect tissue hypoxia and can, therefore, provide information about the cellular microenvironment. DCE-CT can also depict physiological processes, such as vasodilatation, that represent the physiological consequences of molecular responses to tissue hypoxia. To date the main applications have been in stroke and oncology. Unlike some other molecular imaging approaches, DCE-CT benefits from wide availability and ease of application along with the use of contrast materials and software packages that have achieved full regulatory approval. Hence, DCE-CT represents a molecular imaging technique that is applicable in clinical practice today.

  3. Assessment and Development of Microwave Imaging for Breast Cancer Detection

    DEFF Research Database (Denmark)

    Jensen, Peter Damsgaard

    At the Technical University of Denmark (DTU), a 3D tomographic microwave imaging system is currently being developed with the aim of using nonlinear microwave imaging for breast-cancer detection. The imaging algorithm used in the system is based on an iterative Newton-type scheme. In this algorithm...

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

    Directory of Open Access Journals (Sweden)

    Lee H

    2015-08-01

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

  5. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

    Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2016-03-15

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  6. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  7. Molecular imaging in cardiovascular diseases; Molekulare kardiovaskulaere MRT-Bildgebung

    Energy Technology Data Exchange (ETDEWEB)

    Botnar, R.M. [King' s College London (United Kingdom). Imaging Sciences; St. Thomas' NHS Foundation Trust, London (United Kingdom); Ebersberger, H. [Heart Center Munich-Bogenhausen, Munich (Germany). Dept. of Cardiology and Intensive Care Medicine; Noerenberg, D. [Charite, Berlin (Germany). Inst. for Radiology; and others

    2015-02-15

    Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced.

  8. Molecular Imaging: A Promising Tool to Monitor Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Ping Wang

    2011-01-01

    Full Text Available Replacement of insulin production by pancreatic islet transplantation has great potential as a therapy for type 1 diabetes mellitus. At present, the lack of an effective approach to islet grafts assessment limits the success of this treatment. The development of molecular imaging techniques has the potential to fulfill the goal of real-time noninvasive monitoring of the functional status and viability of the islet grafts. We review the application of a variety of imaging modalities for detecting endogenous and transplanted beta-cell mass. The review also explores the various molecular imaging strategies for assessing islet delivery, the metabolic effects on the islet grafts as well as detection of immunorejection. Here, we highlight the use of combined imaging and therapeutic interventions in islet transplantation and the in vivo monitoring of stem cells differentiation into insulin-producing cells.

  9. Development of molecular imaging in the European radiological community

    International Nuclear Information System (INIS)

    The recent and concomitant advances in molecular biology and imaging for diagnosis and therapy will place in vivo imaging techniques at the centre of their clinical transfer. Before that, a wide range of multidisciplinary preclinical research is already taking place. The involvement of radiologists in this new field of imaging sciences is therefore absolutely mandatory during these two phases of development. Achievement of such objectives requires the refinement of strategy within the European radiological community and the European Society of Radiology (ESR) will have to drive a number of actions to stimulate the younger generation of radiologists and to facilitate their access to knowledge. For that purpose, a molecular imaging (MI) subcommittee of the ESR Research Committee based on a group of involved radiologists will be constituted to develop contacts with other constitutive committees and associated societies to provide proposals to our community. (orig.)

  10. Molecular subtyping of breast cancer: opportunities for new therapeutic approaches.

    Science.gov (United States)

    Mullan, P B; Millikan, R C

    2007-12-01

    Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from unnecessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basal-like breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives. (Part of a Multi-author Review). PMID:17957336

  11. Molecular markers and targets for colorectal cancer prevention

    Institute of Scientific and Technical Information of China (English)

    Naveena B JANAKIRAM; Chinthalapally V RAO

    2008-01-01

    Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from pro-moting/developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the bio-logical and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarkerin biomolecular pathwayare elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.

  12. Simultaneous molecular imaging of EGFR and HER2 using hyperspectral darkfield microscopy and immunotargeted nanoparticles

    Science.gov (United States)

    Crow, Matthew J.; Marinakos, Stella; Chilkoti, Ashutosh; Wax, Adam P.

    2009-02-01

    Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER2) contribute to the regulation of cell proliferation, and when jointly over-expressed are associated with several types of cancer. The ability to monitor both receptors simultaneously results in a more accurate indicator of degree of cancerous activity than either receptor alone. Plasmonic nanoparticles (NPs) show promise as a potential EGFR and HER2 biomarker over alternatives such as fluorophores and quantum dots, which are limited by their cytotoxicity and photobleaching. To observe immunolabeled NPs bound to receptor-expressing cells, our past experiments were conducted using a novel optical darkfield microspectroscopy system. We implemented an epi-illumination darkfield broadband light train, which allows for darkfield analysis of live cells in culture with enhanced NP contrast. Under this setup, molecularly specific binding of NPs immunolabeled with anti-EGFR was confirmed. We have since adapted our darkfield setup, which previously only obtained spectral information from a line imaging spectrometer, to incorporate hyperspectral imaging capabilities, allowing widefield data acquisition within seconds. The new system has been validated through observation of shifts in the peak wavelength of scattering by gold NPs on silanated cover glasses using several immersion media. Peak resonant scattering wavelengths match well with that predicted by Mie theory. We will further demonstrate the potential of the system with simultaneous molecular imaging of multiple receptors in vitro using labeled EGFR+/HER2+ SK-BR-3 human breast cancer cells with anti-EGFR immunolabeled gold nanospheres and anti-HER2 immunolabeled gold nanorods, with each scattering in different spectral windows. Additional trials will be performed to demonstrate molecularly specific binding using EGFR+/HER2- MDA-MB-468 and HER2+/EGFR- MDA-MB-453 breast cancer cells.

  13. Terahertz imaging diagnostics of cancer tissues with a chemometrics technique

    Science.gov (United States)

    Nakajima, Sachiko; Hoshina, Hiromichi; Yamashita, Masatsugu; Otani, Chiko; Miyoshi, Norio

    2007-01-01

    Terahertz spectroscopic images of paraffin-embedded cancer tissues have been measured by a terahertz time domain spectrometer. For the systematic identification of cancer tumors, the principal component analysis and the clustering analysis were applied. In three of the four samples, the cancer tissue was recognized as an aggregate of the data points in the principal component plots. By the agglomerative hierarchical clustering, the data points were well categorized into cancer and the other tissues. This method can be also applied to various kinds of automatic discrimination of plural components by terahertz spectroscopic imaging.

  14. Molecular imaging of vessels in mouse models of disease

    International Nuclear Information System (INIS)

    Vascular imaging of angiogenesis in mouse models of disease requires multi modal imaging hardware capable of targeting both structure and function at different physical scales. The three dimensional (3D) structure and function vascular information allows for accurate differentiation between biological processes. For example, image analysis of vessel development in angiogenesis vs. arteriogenesis enables more accurate detection of biological variation between subjects and more robust and reliable diagnosis of disease. In the recent years a number of micro imaging modalities have emerged in the field as preferred means for this purpose. They provide 3D volumetric data suitable for analysis, quantification, validation, and visualization of results in animal models. This review highlights the capabilities of microCT, ultrasound and microPET for multimodal imaging of angiogenesis and molecular vascular targets in a mouse model of tumor angiogenesis. The basic principles of the imaging modalities are described and experimental results are presented.

  15. Cancer Imaging at the Crossroads of Precision Medicine: Perspective From an Academic Imaging Department in a Comprehensive Cancer Center.

    Science.gov (United States)

    Van den Abbeele, Annick D; Krajewski, Katherine M; Tirumani, Sree Harsha; Fennessy, Fiona M; DiPiro, Pamela J; Nguyen, Quang-Dé; Harris, Gordon J; Jacene, Heather A; Lefever, Greg; Ramaiya, Nikhil H

    2016-04-01

    The authors propose one possible vision for the transformative role that cancer imaging in an academic setting can play in the current era of personalized and precision medicine by sharing a conceptual model that is based on experience and lessons learned designing a multidisciplinary, integrated clinical and research practice at their institution. The authors' practice and focus are disease-centric rather than imaging-centric. A "wall-less" infrastructure has been developed, with bidirectional integration of preclinical and clinical cancer imaging research platforms, enabling rapid translation of novel cancer drugs from discovery to clinical trial evaluation. The talents and expertise of medical professionals, scientists, and staff members have been coordinated in a horizontal and vertical fashion through the creation of Cancer Imaging Consultation Services and the "Adopt-a-Radiologist" campaign. Subspecialized imaging consultation services at the hub of an outpatient cancer center facilitate patient decision support and management at the point of care. The Adopt-a-Radiologist campaign has led to the creation of a novel generation of imaging clinician-scientists, fostered new collaborations, increased clinical and academic productivity, and improved employee satisfaction. Translational cancer research is supported, with a focus on early in vivo testing of novel cancer drugs, co-clinical trials, and longitudinal tumor imaging metrics through the imaging research core laboratory. Finally, a dedicated cancer imaging fellowship has been developed, promoting the future generation of cancer imaging specialists as multidisciplinary, multitalented professionals who are trained to effectively communicate with clinical colleagues and positively influence patient care. PMID:26774886

  16. Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis

    OpenAIRE

    Maiseyeu, Andrei; Mihai, Georgeta; Kampfrath, Thomas; Simonetti, Orlando P.; Sen, Chandan K.; Roy, Sashwati; Rajagopalan, Sanjay; Parthasarathy, Sampath

    2009-01-01

    Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellula...

  17. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Justin S. [Oak Ridge National Laboratory; Endres, Christopher J. [Johns Hopkins, Baltimore; Foss, Catherine A. [Johns Hopkins, Baltimore; Nimmagadda, Sridhar [Johns Hopkins, Baltimore; Jung, Hyeyun [Johns Hopkins, Baltimore; Goddard, James S. [Oak Ridge National Laboratory; Lee, Seung Joon [JLAB; McKisson, John [JLAB; Smith, Mark F. [University of Maryland; Stolin, Alexander V. [West Virginia University; Weisenberger, Andrew G. [JLAB; Pomper, Martin G. [Johns Hopkins, Baltimore

    2013-06-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a ^99mTc-pertechnetate phantom, ^99mTc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand ^123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of ^123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.

  18. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Justin S [ORNL; Endres, Christopher [Johns Hopkins University; Foss, Catherine [Johns Hopkins University; Nimmagadda, Sridhar [Johns Hopkins University; Jung, Hyeyun [Johns Hopkins University; Goddard Jr, James Samuel [ORNL; Lee, Seung Joon [Jefferson Lab; McKisson, John [Jefferson Lab; Smith, Mark F. [University of Maryland School of Medicine, The, Baltimore, MD; Stolin, Alexander [West Virginia University, Morgantown; Weisenberger, Andrew G. [Jefferson Lab; Pomper, Martin [Johns Hopkins University

    2013-01-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.

  19. Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

    Science.gov (United States)

    Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.; Nimmagadda, Sridhar; Jung, Hyeyun; Goddard, James S.; Lee, Seungjoon; McKisson, John; Smith, Mark F.; Stolin, Alexander V.; Weisenberger, Andrew G.; Pomper, Martin G.

    2014-01-01

    We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake. PMID:23536223

  20. MicroRNAs as molecular markers in lung cancer

    Directory of Open Access Journals (Sweden)

    Javier Silva

    2013-10-01

    Full Text Available Lung cancer is the most common cause of cancer death in the western world for both men and women. Lung cancer appears to be a perfect candidate for a screening program, since it is the number one cancer killer, it has a long preclinical phase, curative treatment for the minority of patients who are diagnosed early and a target population at risk (smokers and it is also a major economic burden. The earliest approaches to identifying cancer markers were based on preliminary clinical or pathological observations, although molecular biology is a strong candidate for occupying a place among the set of methods. In search of markers, several alterations, such as mutations, loss of heterozygosity, microsatellite instability, DNA methylation, mitochondrial DNA mutations, viral DNA, modified expression of mRNA, miRNA and proteins, and structurally altered proteins have all been analysed. MicroRNAs (miRNA are small RNA molecules, about 19-25 nucleotides long and encoded in genomes of plants, animals, fungi and viruses. It has been reported that miRNAs may have multiple functions in lung development and that aberrant expression of miRNAs could induce lung tumorigenesis. We review here the role of miRNAs in lung tumorigenesis and also as a novel type of biomarker.-----------------------------------Cite this article as:Silva J, Garcia V, Lopez-Gonzalez A, Provencio M. MicroRNAs as molecular markers in lung cancer. Int J Cancer Ther Oncol 2013;1(1:010111. DOI: http://dx.doi.org/10.14319/ijcto.0101.11

  1. Image-derived biomarkers and multimodal imaging strategies for lung cancer management

    Energy Technology Data Exchange (ETDEWEB)

    Sauter, Alexander W. [Eberhard Karls University Tuebingen, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Eberhard Karls University Tuebingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany); Schwenzer, Nina; Pfannenberg, Christina [Eberhard Karls University Tuebingen, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Divine, Mathew R.; Pichler, Bernd J. [Eberhard Karls University Tuebingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany)

    2015-04-01

    Non-small-cell lung cancer is the most common type of lung cancer and one of the leading causes of cancer-related death worldwide. For this reason, advances in diagnosis and treatment are urgently needed. With the introduction of new, highly innovative hybrid imaging technologies such as PET/CT, staging and therapy response monitoring in lung cancer patients have substantially evolved. In this review, we discuss the role of FDG PET/CT in the management of lung cancer patients and the importance of new emerging imaging technologies and radiotracer developments on the path to personalized medicine. (orig.)

  2. Molecular aspects of prostate cancer: implications for future directions

    Directory of Open Access Journals (Sweden)

    Etel R. P. Gimba

    2003-10-01

    Full Text Available Many studies have been developed trying to understand the complex molecular mechanisms involved in oncogenesis and progression of prostate cancer (PCa. Current biotechnological methodologies, especially genomic studies, are adding important aspects to this area. The construction of extensive DNA sequence data and gene expression profiles have been intensively explored to search for candidate biomarkers to evaluate PCa. The use of DNA micro-array robotic systems constitutes a powerful approach to simultaneously monitor the expression of a great number of genes. The resulting gene expressing profiles can be used to specifically describe tumor staging and response to cancer therapies. Also, it is possible to follow PCa pathological properties and to identify genes that anticipate the behavior of clinical disease. The molecular pathogenesis of PCa involves many contributing factors, such as alterations in signal transduction pathways, angiogenesis, adhesion molecules expression and cell cycle control. Also, molecular studies are making clear that many genes, scattered through several different chromosomal regions probably cause predisposition to PCa. The discovery of new molecular markers for PCa is another relevant advance resulting from molecular biology studies of prostate tumors. Interesting tissue and serum markers have been reported, resulting in many cases in useful novelties to diagnostic and prognostic approaches to follow-up PCa. Finally, gene therapy comes as an important approach for therapeutic intervention in PCa. Clinical trials for PCa have been demonstrating that gene therapy is relatively safe and well tolerated, although some improvements are yet to be developed.

  3. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    Energy Technology Data Exchange (ETDEWEB)

    Malviya, G.; Dierckx, R.A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Conti, F. [Rheumatology Unit, I Faculty of Medicine and Surgery, Sapienza University of Rome (Italy); Chianelli, M. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Unit of Nuclear Medicine, Regina apostolorum Hospital, Albano, Rome (Italy); Scopinaro, F. [Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy); Signore, A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy)

    2010-02-15

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-{alpha}, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with {sup 99m}Tc or {sup 111}In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for

  4. Lung cancer and angiogenesis imaging using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu Xiaoxia; Zhao Jun; Xu, Lisa X [Biomedical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai (China); Sun Jianqi; Gu Xiang; Liu Ping [Med-X Research Institute, Shanghai Jiao Tong University, Shanghai (China); Xiao Tiqiao [Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai (China)], E-mail: pingliu@sjtu.edu.cn, E-mail: lisaxu@sjtu.edu.cn

    2010-04-21

    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.

  5. The current status of imaging diagnosis of breast cancer

    International Nuclear Information System (INIS)

    In recent years, the incidence and the mortality rate of female breast cancer in our country is increasing, Early diagnosis of breast cancer is particularly important. Precious preoperative staging in the breast cancer is advantageous for the treatment planning. Evaluating the efficacy of chemotherapy is beneficial for adjusting the follow-up plan. Imaging examination has become an important role in breast cancer management. At present, commonly used equipment include mammography, ultrasound, CT, and MRI, etc. This article reviews the present study status of these tools in diagnosis of breast cancer. A reasonable and effective choice of those tools can facilitate clinic diagnosis and treatment. (authors)

  6. Sodium Iodide Symporter for Nuclear Molecular Imaging and Gene Therapy: From Bedside to Bench and Back

    Directory of Open Access Journals (Sweden)

    Byeong-Cheol Ahn

    2012-01-01

    Full Text Available Molecular imaging, defined as the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms, can be obtained by various imaging technologies, including nuclear imaging methods. Imaging of normal thyroid tissue and differentiated thyroid cancer, and treatment of thyroid cancer with radioiodine rely on the expression of the sodium iodide symporter (NIS in these cells. NIS is an intrinsic membrane protein with 13 transmembrane domains and it takes up iodide into the cytosol from the extracellular fluid. By transferring NIS function to various cells via gene transfer, the cells can be visualized with gamma or positron emitting radioisotopes such as Tc-99m, I-123, I-131, I-124 and F-18 tetrafluoroborate, which are accumulated by NIS. They can also be treated with beta- or alpha-emitting radionuclides, such as I-131, Re-186, Re-188 and At-211, which are also accumulated by NIS. This article demonstrates the diagnostic and therapeutic applications of NIS as a radionuclide-based reporter gene for trafficking cells and a therapeutic gene for treating cancers.

  7. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel art and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significartly, OR is 3.905 ( 95 % CI = 1.079 ~ 14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  8. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Obieaites. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-besed case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymemse chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3.905(95% CI = 1.079—14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blnod relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LDH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome abermtions were observed.Condusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  9. Clinical implications of the intrinsic molecular subtypes of breast cancer.

    Science.gov (United States)

    Prat, Aleix; Pineda, Estela; Adamo, Barbara; Galván, Patricia; Fernández, Aranzazu; Gaba, Lydia; Díez, Marc; Viladot, Margarita; Arance, Ana; Muñoz, Montserrat

    2015-11-01

    Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

  10. Molecular Targeted Therapies Using Botanicals for Prostate Cancer Chemoprevention

    OpenAIRE

    Kumar, Nagi; Chornokur, Ganna

    2012-01-01

    In spite of the large number of botanicals demonstrating promise as potential cancer chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving botanical agents to recommendation for clinical use include adopting a systematic, molecular-target based approach and utilizing the same ethical and rigorous methods that are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity...

  11. Multi-modality systems for molecular tomographic imaging

    Science.gov (United States)

    Li, Mingze; Bai, Jing

    2009-11-01

    In vivo small animal imaging is a cornerstone in the study of human diseases by providing important clues on the pathogenesis, progression and treatment of many disorders. Molecular tomographic imaging can probe complex biologic interactions dynamically and to study diseases and treatment responses over time in the same animal. Current imaging technique including microCT, microMRI, microPET, microSPECT, microUS, BLT and FMT has its own advantages and applications, however, none of them can provide structural, functional and molecular information in one context. Multi-modality imaging, which utilizes the strengths of different modalities to provide a complete understanding of the object under investigation, emerges as an important alternative in small animal imaging. This article is to introduce the latest development of multimodality systems for small animal tomographic imaging. After a systematic review of imaging principles, systems and commerical products for each stand-alone method, we introduce some multimodality strategies in the latest years. In particular, two dual-modality systems, i.e. FMT-CT and FMT-PET are presented in detail. The end of this article concludes that though most multimodality systems are still in a laboratory research stage, they will surely undergo deep development and wide application in the near future.

  12. Clinical study of imaging skin cancer margins using polarized light imaging

    Science.gov (United States)

    Samatham, Ravikant; Lee, Ken; Jacques, Steven L.

    2012-02-01

    Skin cancer is most commons type of cancer in United States that occur on sun-exposed cosmetically sensitive areas like face, neck, and forearms. Surgical excision of skin cancer is challenging as more than one-third the actual margins extend beyond the clinically determined margins. Polarized light camera (polCAM) provides images of the superficial layers of the tissue with enhanced contrast which was used to image skin cancer margins. In a NIH-funded pilot study polCAM was used to image skin cancer in patients undergoing Mohs micrographic surgery for skin cancer. Polarized light imaging utilizes the polarization properties of light to create an image of a lesion comprised only of light scattering from the superficial layers of the skin which yields a characteristic "fabric pattern" of the putative lesion and the surrounding normal tissue. In several case studies conducted with a system developed for the clinic, we have found that skin cancer disrupts this fabric pattern, allowing the doctor a new means of identifying the margins of the lesion. Data is acquired before the patient underwent surgery. The clinically determined skin cancer margins were compared with margins determined by examination of the polCAM images. The true margins were provided by the dermatophathologist on examination of the frozen sections. Our initial data suggests that the contrast due to polarization changes associated with cancerous lesions can elucidate margins that were not recognized by the surgeon under normal conditions but were later confirmed by the pathologist.

  13. Imaging Pancreatic Cancer with Folic Acid Terminated Luminescent Silicon Nanocrystals

    Science.gov (United States)

    Erogbogbo, Folarin; Swihart, Mark T.

    2010-10-01

    Quantum dots have great potential for visualization of medically relevant targets such as cancer. However, potential toxicity, stemming from the use of heavy metal based semidonductor materials, has been a major impediment to use of quantum dots in vivo. Silicon is an inherently non-toxic element. By combining the unique optical properties of silicon quantum dots with fundamentals of cancer biology, we can develop probes that safely target and enable the visualization of cancer cells. Many cancer cells overexpress folate receptors, making the folate receptors a suitable target for cancer imaging evaluations. Here, we report the synthesis of folic acid coated silicon quantum dots for targeting pancreatic cancer cells. Folic acid on the silicon quantum dots improves selectivity and may decrease possible negative side effects. This demonstration adds to the evidence that silicon can be sucessfully used for biological imaging.

  14. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  15. IMAGE-GUIDED RADIOTHERAPY AND -BRACHYTHERAPY FOR CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Suresh eDutta

    2015-03-01

    Full Text Available Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT, and 2-dimensional intracavitary brachytherapy.Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron emission tomography (PET and magnetic resonance imaging (MRI has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT, allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer.

  16. Laser Illumination Modality of Photoacoustic Imaging Technique for Prostate Cancer

    Science.gov (United States)

    Peng, Dong-qing; Peng, Yuan-yuan; Guo, Jian; Li, Hui

    2016-02-01

    Photoacoustic imaging (PAI) has recently emerged as a promising imaging technique for prostate cancer. But there was still a lot of challenge in the PAI for prostate cancer detection, such as laser illumination modality. Knowledge of absorbed light distribution in prostate tissue was essential since the distribution characteristic of absorbed light energy would influence the imaging depth and range of PAI. In order to make a comparison of different laser illumination modality of photoacoustic imaging technique for prostate cancer, optical model of human prostate was established and combined with Monte Carlo simulation method to calculate the light absorption distribution in the prostate tissue. Characteristic of light absorption distribution of transurethral and trans-rectal illumination case, and of tumor at different location was compared with each other.The relevant conclusions would be significant for optimizing the light illumination in a PAI system for prostate cancer detection.

  17. Image-guided radiotherapy and -brachytherapy for cervical cancer.

    Science.gov (United States)

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  18. Molecular Classification of Gastric Cancer: A new paradigm

    Science.gov (United States)

    Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.

    2011-01-01

    Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

  19. Low-Noise CMOS Image Sensors for Radio-Molecular Imaging

    NARCIS (Netherlands)

    Chen, Y.

    2012-01-01

    This thesis presents the development of low-noise CMOS image sensors for radio-molecular imaging. The development is described in two directions: firstly, from the technology point of view to reduce the pixel noise level, and secondly from the design point of view to reduce the pixel readout circuit

  20. Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX.

    Directory of Open Access Journals (Sweden)

    Jiehua Xu

    Full Text Available Most clinical cases of liver cancer cannot be diagnosed until they have evolved to an advanced stage, thus resulting in high mortality. It is well recognized that the implementation of early detection methods and the development of targeted therapies for liver cancer are essential to reducing the high mortality rates associated with this disease. To achieve these goals, molecular probes capable of recognizing liver cancer cell-specific targets are needed. Here we describe a panel of aptamers able to distinguish hepatocarcinoma from normal liver cells. The aptamers, which were selected by cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment, have Kd values in the range of 64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian cancer cells and lung adenocarcinoma. The proteinase treatment experiment indicated that all aptamers could recognize target HepG2 cells through surface proteins. This outcome suggested that these aptamers could be used as potential probes for further research in cancer studies, such as developing early detection assays, targeted therapies, and imaging agents, as well as for the investigation of common membrane proteins in these distinguishable cancers.

  1. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration.

    Science.gov (United States)

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

  2. PET molecular imaging in stem cell therapy for neurological diseases

    International Nuclear Information System (INIS)

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  3. PET molecular imaging in stem cell therapy for neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiachuan; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [University of Texas, M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-10-15

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  4. Imaging of Isotopically Enhanced Molecular Targeting Agents Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Quong, J N

    2004-02-19

    The goal of this project is to develop experimental and computational protocols to use SIMS to image the chemical composition of biological samples, focusing on optimizing sample preparation protocols and developing multivariate data analysis methods. Our results on sample preparation, molecular imaging, and multivariate analysis have been presented at several meeting abstracts (UCRL151797ABS, UCRL151797ABSREV1, UCRL151426ABS, UCRL201277, UCRL154757). A refereed paper describing our results for sample preparation and molecular imaging of various endogenous biomolecules as well as the mutagen PhIP has been accepted for publication (UCRL-JC-151797). We are also preparing two additional papers describing our multivariate analysis methods to analyze spectral data. As these papers have not been submitted, their content is included in this final report.

  5. Image-guided focal therapy for prostate cancer

    OpenAIRE

    Sankineni, Sandeep; Wood, Bradford J.; Rais-Bahrami, Soroush; Diaz, Annerleim Walton; Hoang, Anthony N.; Pinto, Peter A.; Peter L. Choyke; Türkbey, Barış

    2014-01-01

    The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now ...

  6. Molecular Imaging of Transporters with Positron Emission Tomography

    Science.gov (United States)

    Antoni, Gunnar; Sörensen, Jens; Hall, Håkan

    Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a really useful PET ligand for NET still remains to be identified. The most promising tracer to date is (S,S)-[18F]FMeNER-D2. The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditions related to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands based on cocaine were not selective, but more recently several selective tracers such as [11C]PE2I have been characterized and shown to be suitable as PET radioligands. Although there are a large number of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when [11C]McN5652 was synthesized, that this transporter was studied using PET. New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASB and [11C]MADAM and their analogues are today the most promising ligands. The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheral and central drug

  7. Differential expression of growth factor receptors and membrane-bound tumor markers for imaging in male and female breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available INTRODUCTION: Male breast cancer accounts for 0.5-1% of all breast cancers and is generally diagnosed at higher stage than female breast cancers and therefore might benefit from earlier detection and targeted therapy. Except for HER2 and EGFR, little is known about expression of growth factor receptors in male breast cancer. We therefore investigated expression profiles of growth factor receptors and membrane-bound tumor markers in male breast cancer and gynecomastia, in comparison with female breast cancer. METHODS: Tissue microarrays containing 133 male breast cancer and 32 gynecomastia cases were stained by immunohistochemistry for a panel of membrane-bound targets and compared with data on 266 female breast cancers. RESULTS: Growth factor receptors were variably expressed in 4.5% (MET up to 38.5% (IGF1-R of male breast cancers. Compared to female breast cancer, IGF1-R and carbonic anhydrase 12 (CAXII were more frequently and CD44v6, MET and FGFR2 less frequently expressed in male breast cancer. Expression of EGFR, HER2, CAIX, and GLUT1 was not significantly different between male and female breast cancer. Further, 48.1% of male breast cancers expressed at least one and 18.0% expressed multiple growth factor receptors. Since individual membrane receptors are expressed in only half of male breast cancers, a panel of membrane markers will be required for molecular imaging strategies to reach sensitivity. A potential panel of markers for molecular imaging, consisting of EGFR, IGF1-R, FGFR2, CD44v6, CAXII, GLUT1, and CD44v6 was positive in 77% of male breast cancers, comparable to female breast cancers. CONCLUSIONS: Expression patterns of growth factor receptors and hypoxia membrane proteins in male breast cancer are different from female breast cancer. For molecular imaging strategies, a putative panel consisting of markers for EGFR, IGF1-R, FGFR2, GLUT1, CAXII, CD44v6 was positive in 77% of cases and might be considered for development of

  8. Image-guided Coring for Large-scale Studies in Molecular Pathology.

    Science.gov (United States)

    Montaser-Kouhsari, Laleh; Knoblauch, Nicholas W; Oh, Eun-Yeong; Baker, Gabrielle; Christensen, Stephen; Hazra, Aditi; Tamimi, Rulla M; Beck, Andrew H

    2016-07-01

    Sampling of formalin-fixed paraffin-embedded (FFPE) tissue blocks is a critical initial step in molecular pathology. Image-guided coring (IGC) is a new method for using digital pathology images to guide tissue block coring for molecular analyses. The goal of our study is to evaluate the use of IGC for both tissue-based and nucleic acid-based projects in molecular pathology. First, we used IGC to construct a tissue microarray (TMA); second, we used IGC for FFPE block sampling followed by RNA extraction; and third, we assessed the correlation between nuclear counts quantitated from the IGC images and RNA yields. We used IGC to construct a TMA containing 198 normal and breast cancer cores. Histopathologic analysis showed high accuracy for obtaining tumor and normal breast tissue. Next, we used IGC to obtain normal and tumor breast samples before RNA extraction. We selected a random subset of tumor and normal samples to perform computational image analysis to quantify nuclear density, and we built regression models to estimate RNA yields from nuclear count, age of the block, and core diameter. Number of nuclei and core diameter were the strongest predictors of RNA yields in both normal and tumor tissue. IGC is an effective method for sampling FFPE tissue blocks for TMA construction and nucleic acid extraction. We identify significant associations between quantitative nuclear counts obtained from IGC images and RNA yields, suggesting that the integration of computational image analysis with IGC may be an effective approach for tumor sampling in large-scale molecular studies. PMID:26186251

  9. Magnetic resonance imaging for lung cancer screen

    OpenAIRE

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

    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 relationshi...

  10. Development of New Molecular EZH2 on Lung Cancer Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Hui XIA

    2016-02-01

    Full Text Available Lung cancer is a serious threat to human health malignancies upward trend in morbidity and mortality. It is hot topic to investigate the molecular mechanisms of lung cancer development and explore the new therapeutic targets. The underlying mechanism of EZH2 on lung cancer development will demonstrate the new pathway of lung cancer development, invasion and metastasis. The exploration and application of new targeted molecular will improve the survival rate and living quality of lung cancer patients in future.

  11. Appraisal of progenitor markers in the context of molecular classification of breast cancers

    OpenAIRE

    Haviv, Izhak

    2011-01-01

    Clinical management of breast cancer relies on case stratification, which increasingly employs molecular markers. The motivation behind delineating breast epithelial differentiation is to better target cancer cases through innate sensitivities bequeathed to the cancer from its normal progenitor state. A combination of histopathological and molecular classification of breast cancer cases suggests a role for progenitors in particular breast cancer cases. Although a remarkable fraction of the re...

  12. Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies

    OpenAIRE

    Matsuoka, Tasuku; Yashiro, Masakazu

    2016-01-01

    Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the...

  13. Dynamic infrared imaging in identification of breast cancer tissue with combined image processing and frequency analysis.

    Science.gov (United States)

    Joro, R; Lääperi, A-L; Soimakallio, S; Järvenpää, R; Kuukasjärvi, T; Toivonen, T; Saaristo, R; Dastidar, P

    2008-01-01

    Five combinations of image-processing algorithms were applied to dynamic infrared (IR) images of six breast cancer patients preoperatively to establish optimal enhancement of cancer tissue before frequency analysis. mid-wave photovoltaic (PV) IR cameras with 320x254 and 640x512 pixels were used. The signal-to-noise ratio and the specificity for breast cancer were evaluated with the image-processing combinations from the image series of each patient. Before image processing and frequency analysis the effect of patient movement was minimized with a stabilization program developed and tested in the study by stabilizing image slices using surface markers set as measurement points on the skin of the imaged breast. A mathematical equation for superiority value was developed for comparison of the key ratios of the image-processing combinations. The ability of each combination to locate the mammography finding of breast cancer in each patient was compared. Our results show that data collected with a 640x512-pixel mid-wave PV camera applying image-processing methods optimizing signal-to-noise ratio, morphological image processing and linear image restoration before frequency analysis possess the greatest superiority value, showing the cancer area most clearly also in the match centre of the mammography estimation. PMID:18666012

  14. A novel spectral imaging system for use during pancreatic cancer surgery

    Science.gov (United States)

    Peller, Joseph; Shipley, A. E.; Trammell, Susan R.; Abolbashari, Mehrdad; Farahi, Faramarz

    2015-03-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Most pancreatic cancer patients will die within the first year of diagnosis, and just 6% will survive five years. Currently, surgery is the only treatment that offers a chance of cure for pancreatic cancer patients. Accurately identifying the tumors margins in real time is a significant difficulty during pancreatic cancer surgery and contributes to the low 5-year survival rate. We are developing a hyperspectral imaging system based on compressive sampling for real-time tumor margin detection to facilitate more effective removal of diseased tissue and result in better patient outcomes. Recent research has shown that optical spectroscopy can be used to distinguish between healthy and diseased tissue and will likely become an important minimally invasive diagnostic tool for a range of diseases. Reflectance spectroscopy provides information about tissue morphology, while laser-induced autofluorescence spectra give accurate information about the content and molecular structure of the emitting tissue. We are developing a spectral imaging system that targets emission from collagen and NAD(P)H as diagnostics for differentiating healthy and diseased pancreatic tissue. In this study, we demonstrate the ability of our camera system to acquire hyperspectral images and its potential application for imaging autofluorescent emission from pancreatic tissue.

  15. Molecular imaging of brown adipose tissue in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Bauwens, Matthias [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Maastricht University, Research School NUTRIM, Maastricht (Netherlands); Wierts, Roel; Brans, Boudewijn [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Royen, Bart van; Backes, Walter [MUMC, Department of Medical Imaging, Division of Radiology, Maastricht (Netherlands); Bucerius, Jan [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany); Maastricht University, Research School CARIM, Maastricht (Netherlands); Mottaghy, Felix [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany)

    2014-04-15

    Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, {sup 18}F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to {sup 18}F-FDG, other radiopharmaceuticals such as {sup 99m}Tc-sestamibi, {sup 123}I-metaiodobenzylguanidine (MIBG), {sup 18}F-fluorodopa and {sup 18}F-14(R,S)-[{sup 18}F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

  16. Nanoradiopharmaceuticals for breast cancer imaging: development, characterization, and imaging in inducted animals

    Directory of Open Access Journals (Sweden)

    Sarcinelli MA

    2016-09-01

    potential of -14,6 mV. The cytotoxicity results demonstrated that the nanoparticles were capable of reaching breast cancer cells. The biodistribution data demonstrated that the PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal clearance and also a high uptake by the lesion, as ~45% of the PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as nanoradiopharmaceuticals for breast cancer imaging. Keywords: radiopharmaceuticals, nanotechnology, oncology, breast cancer, molecular imaging, nanomedicine, nuclear pharmacy

  17. Xenogeneic homologous genes, molecular evolution and cancer therapy

    Institute of Scientific and Technical Information of China (English)

    田聆; 魏于全

    2001-01-01

    Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.

  18. Epigenetic: a molecular link between testicular cancer and environmental exposures?

    Directory of Open Access Journals (Sweden)

    Aurelie eVega

    2012-11-01

    Full Text Available In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters (EDs exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the Testicular Dysgenesis Syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Futhermore, infertility has been stated as a risk factor for testicular cancer. The incidence of testicular cancer has been increasing over the past decades. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS from fetal germ cells (primordial germ cell or gonocyte. During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications plays an important role in normal development as well as in various diseases, including testicular cancer.Here we will review chromatin modifications which can affect testicular physiology leading to the development of testicular cancer; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

  19. Molecular targets of cancer chemoprevention by garlic-derived organosulfides

    Institute of Scientific and Technical Information of China (English)

    Anna HERMAN-ANTOSIEWICZ; Anna A POWOLNY; Shivendra V SINGH

    2007-01-01

    The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables in-eluding garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer Cellsare frequently associated with perturbations in cell cycle progression and induc-tion of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bc1-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC.

  20. Imprints of Molecular Clouds in Radio Continuum Images

    CERN Document Server

    Yusef-Zadeh, F

    2012-01-01

    We show radio continuum images of several molecular complexes in the inner Galaxy and report the presence of dark features that coincide with dense molecular clouds. Unlike infrared dark clouds, these features which we call "radio dark clouds" are produced by a deficiency in radio continuum emission from molecular clouds that are embedded in a bath of UV radiation field or synchrotron emitting cosmic ray particles. The contribution of the continuum emission along different pathlengths results in dark features that trace embedded molecular clouds. The new technique of identifying cold clouds can place constraints on the depth and the magnetic field of molecular clouds when compared to those of the surrounding hot plasma radiating at radio wavelengths. The study of five molecular complexes in the inner Galaxy, Sgr A, Sgr B2, radio Arc, the snake filament and G359.75-0.13 demonstrate an anti--correlation between the distributions of radio continuum and molecular line and dust emission. Radio dark clouds are iden...

  1. Engineering imaging probes and molecular machines for nanomedicine.

    Science.gov (United States)

    Tong, Sheng; Cradick, Thomas J; Ma, Yan; Dai, Zhifei; Bao, Gang

    2012-10-01

    Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarriers and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of functional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carriers for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imaging probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nanomedicine approaches to clinical applications are discussed.

  2. Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for cancer discrimination.

    Science.gov (United States)

    Roebuck, Joseph R; Haker, Steven J; Mitsouras, Dimitris; Rybicki, Frank J; Tempany, Clare M; Mulkern, Robert V

    2009-05-01

    Quantitative, apparent T(2) values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T(2) values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in 10.7 min, resulting in data sets suitable for generating high-quality images with variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T(1)- and T(2)-weighted signal intensities and available histopathology reports, yielded significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging alone, including quantitative T(2) values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time FSE sequences. PMID:18823731

  3. Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response

    Science.gov (United States)

    Giedt, Randy J.; Fumene Feruglio, Paolo; Pathania, Divya; Yang, Katherine S.; Kilcoyne, Aoife; Vinegoni, Claudio; Mitchison, Timothy J.; Weissleder, Ralph

    2016-09-01

    Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is known about longer-term mitochondrial behavior such as the overall makeup of cell populations’ morphological patterns and whether these patterns can be used as biomarkers of drug response in human cells. We developed an image-based analytical technique to phenotype mitochondrial morphology in different cancers, including cancer cell lines and patient-derived cancer cells. We demonstrate that (i) cancer cells of different origins, including patient-derived xenografts, express highly diverse mitochondrial phenotypes; (ii) a given phenotype is characteristic of a cell population and fairly constant over time; (iii) mitochondrial patterns correlate with cell metabolic measurements and (iv) therapeutic interventions can alter mitochondrial phenotypes in drug-sensitive cancers as measured in pre- versus post-treatment fine needle aspirates in mice. These observations shed light on the role of mitochondrial dynamics in the biology and drug response of cancer cells. On the basis of these findings, we propose that image-based mitochondrial phenotyping can provide biomarkers for assessing cancer phenotype and drug response.

  4. Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response

    Science.gov (United States)

    Giedt, Randy J.; Fumene Feruglio, Paolo; Pathania, Divya; Yang, Katherine S.; Kilcoyne, Aoife; Vinegoni, Claudio; Mitchison, Timothy J.; Weissleder, Ralph

    2016-01-01

    Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is known about longer-term mitochondrial behavior such as the overall makeup of cell populations’ morphological patterns and whether these patterns can be used as biomarkers of drug response in human cells. We developed an image-based analytical technique to phenotype mitochondrial morphology in different cancers, including cancer cell lines and patient-derived cancer cells. We demonstrate that (i) cancer cells of different origins, including patient-derived xenografts, express highly diverse mitochondrial phenotypes; (ii) a given phenotype is characteristic of a cell population and fairly constant over time; (iii) mitochondrial patterns correlate with cell metabolic measurements and (iv) therapeutic interventions can alter mitochondrial phenotypes in drug-sensitive cancers as measured in pre- versus post-treatment fine needle aspirates in mice. These observations shed light on the role of mitochondrial dynamics in the biology and drug response of cancer cells. On the basis of these findings, we propose that image-based mitochondrial phenotyping can provide biomarkers for assessing cancer phenotype and drug response. PMID:27609668

  5. Targeting and Imaging of Cancer Cells via Monosaccharide-Imprinted Fluorescent Nanoparticles

    Science.gov (United States)

    Wang, Shuangshou; Yin, Danyang; Wang, Wenjing; Shen, Xiaojing; Zhu, Jun-Jie; Chen, Hong-Yuan; Liu, Zhen

    2016-03-01

    The recognition of cancer cells is a key for cancer diagnosis and therapy, but the specificity highly relies on the use of biorecognition molecules particularly antibodies. Because biorecognition molecules suffer from some apparent disadvantages, such as hard to prepare and poor storage stability, novel alternatives that can overcome these disadvantages are highly important. Here we present monosaccharide-imprinted fluorescent nanoparticles (NPs) for targeting and imaging of cancer cells. The molecularly imprinted polymer (MIP) probe was fluorescein isothiocyanate (FITC) doped silica NPs with a shell imprinted with sialic acid, fucose or mannose as the template. The monosaccharide-imprinted NPs exhibited high specificity toward the target monosaccharides. As the template monosaccharides used are over-expressed on cancer cells, these monosaccharide-imprinted NPs allowed for specific targeting cancer cells over normal cells. Fluorescence imaging of human hepatoma carcinoma cells (HepG-2) over normal hepatic cells (L-02) and mammary cancer cells (MCF-7) over normal mammary epithelial cells (MCF-10A) by these NPs was demonstrated. As the imprinting approach employed herein is generally applicable and highly efficient, monosaccharide-imprinted NPs can be promising probes for targeting cancer cells.

  6. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  7. Fluorescence polarization imaging for delineating nonmelanoma skin cancers

    Science.gov (United States)

    Yaroslavsky, A. N.; Neel, V.; Anderson, R. R.

    2004-09-01

    We present a method for detecting nonmelanoma skin cancers using exogenous fluorescence polarization. We built an automated system that permits exogenous fluorescence polarization imaging. It includes a tunable linearly polarized monochromatic light source and a CCD camera equipped with a rotating linear polarizer and a filter to reject excitation light. Two fluorophores that are retained in tumors, toluidine blue and methylene blue, are employed. We demonstrate that fluorescence polarization imaging can be used for accurate delineation of nonmelanoma cancers. The results suggest that this optical technique may be suitable for real-time noninvasive demarcation of epithelial cancers.

  8. Molecular Imaging of Tumor Hypoxia: Existing Problems and Their Potential Model-Based Solutions.

    Science.gov (United States)

    Shi, Kuangyu; Ziegler, Sibylle I; Vaupel, Peter

    2016-01-01

    Molecular imaging of tissue hypoxia generates contrast in hypoxic areas by applying hypoxia-specific tracers in organisms. In cancer tissue, the injected tracer needs to be transported over relatively long distances and accumulates slowly in hypoxic regions. Thus, the signal-to-background ratio of hypoxia imaging is very small and a non-specific accumulation may suppress the real hypoxia-specific signals. In addition, the heterogeneous tumor microenvironment makes the assessment of the tissue oxygenation status more challenging. In this study, the diffusion potential of oxygen and of a hypoxia tracer for 4 different hypoxia subtypes: ischemic acute hypoxia, hypoxemic acute hypoxia, diffusion-limited chronic hypoxia and anemic chronic hypoxia are theoretically assessed. In particular, a reaction-diffusion equation is introduced to quantitatively analyze the interstitial diffusion of the hypoxia tracer [(18)F]FMISO. Imaging analysis strategies are explored based on reaction-diffusion simulations. For hypoxia imaging of low signal-to-background ratio, pharmacokinetic modelling has advantages to extract underlying specific binding signals from non-specific background signals and to improve the assessment of tumor oxygenation. Different pharmacokinetic models are evaluated for the analysis of the hypoxia tracer [(18)F]FMISO and optimal analysis model were identified accordingly. The improvements by model-based methods for the estimation of tumor oxygenation are in agreement with experimental data. The computational modelling offers a tool to explore molecular imaging of hypoxia and pharmacokinetic modelling is encouraged to be employed in the corresponding data analysis. PMID:27526129

  9. Microwave Imaging for Breast Cancer Detection

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Fhager, Andreas; Jensen, Peter Damsgaard;

    2011-01-01

    Still more research groups are promoting microwave imaging as a viable supplement or substitution to more conventional imaging modalities. A widespread approach for microwave imaging of the breast is tomographic imaging in which one seeks to reconstruct the distributions of permittivity...

  10. Ultrafast Molecular Imaging by Laser Induced Electron Diffraction

    CERN Document Server

    Peters, Michel; Cornaggia, Christian; Saugout, Sébastien; Charron, Eric; Keller, Arne; Atabek, Osman

    2010-01-01

    We address the feasibility of imaging geometric and orbital structure of a polyatomic molecule on an attosecond time-scale using the Laser Induced Electron Diffraction, LIED, technique [T. Zuo \\textit{et al.}, Chem. Phys. Lett. \\textbf{259}, 313 (1996)]. We present numerical results obtained for the CO$_2$ molecule using a single active electron model. The molecular geometry (bond-lengths) is determined within 3% of accuracy from a diffraction pattern which also reflects the nodal properties of the initial molecular orbital. Robustness of the structure determination is discussed with respect to vibrational and rotational motions with a complete interpretation of the laser-induced mechanisms.

  11. Targeted imaging of EGFR overexpressed cancer cells by brightly fluorescent nanoparticles conjugated with cetuximab.

    Science.gov (United States)

    Gao, Meng; Su, Huifang; Lin, Gengwei; Li, Shiwu; Yu, Xingsu; Qin, Anjun; Zhao, Zujin; Zhang, Zhenfeng; Tang, Ben Zhong

    2016-08-11

    To improve the treatment efficiency and reduce side effects in cancer therapy, accurate diagnosis of cancer cell types at a molecular level is highly desirable. Fluorescent nanoparticles (NPs) are especially suitable for detecting molecular biomarkers of cancer with advantages of superior brightness, easy decoration and high resolution. However, the conventional organic fluorophores, conjugated polymers, and inorganic quantum dots suffer from the drawbacks of aggregation-caused quenching (ACQ), low photostability, and heavy metal toxicity, respectively, which severely restrict their applications in NPs-based fluorescence imaging. To overcome these limitations, herein, we have developed fluorescent nanoparticles based on a t-BuPITBT-TPE fluorophore derived from aggregation-induced emission (AIE)-active tetraphenylethene. Through encapsulating t-BuPITBT-TPE within biocompatible DSPE-PEG and further decorating with a monoclonal antibody cetuximab (C225), the obtained t-BuPITBT-TPE-C225 NPs can be used for targeted imaging of non-small cell lung cancer cells with an overexpressed epidermal growth factor receptor (EGFR). The specific targeting ability of t-BuPITBT-TPE-C225 NPs has been well verified by confocal microscopy and flow cytometry experiments. The t-BuPITBT-TPE-C225 NPs have shown significant advantages in terms of highly efficient red emission, good bio-compatibility, and excellent photostability. This work provides a promising method for precise diagnosis of cancer cells by antibody-functionalized fluorescent NPs with high brightness. PMID:27468980

  12. Prototype of Microwave Imaging System for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Zhurbenko, Vitaliy

    2009-01-01

    Microwave imaging for breast-cancer detection has received the attention of a large number of research groups in the last decade. In this paper, the imaging system currently being developed at the Technical university of Denmark is presented. This includes a description of the antenna system...

  13. Ultrasound molecular imaging of secreted frizzled related protein-2 expression in murine angiosarcoma.

    Directory of Open Access Journals (Sweden)

    James K Tsuruta

    Full Text Available Angiosarcoma is a biologically aggressive vascular malignancy with a high metastatic potential. In the era of targeted medicine, knowledge of specific molecular tumor characteristics has become more important. Molecular imaging using targeted ultrasound contrast agents can monitor tumor progression non-invasively. Secreted frizzled related protein 2 (SFRP2 is a tumor endothelial marker expressed in angiosarcoma. We hypothesize that SFRP2-directed imaging could be a novel approach to imaging the tumor vasculature. To develop an SFRP2 contrast agent, SFRP2 polyclonal antibody was biotinylated and incubated with streptavidin-coated microbubbles. SVR angiosarcoma cells were injected into nude mice, and when tumors were established the mice were injected intravenously with the SFRP2 -targeted contrast agent, or a control streptavidin-coated contrast agent. SFRP2 -targeted contrast agent detected tumor vasculature with significantly more signal intensity than control contrast agent: the normalized fold-change was 1.6 ± 0.27 (n = 13, p = 0.0032. The kidney was largely devoid of echogenicity with no significant difference between the control contrast agent and the SFRP2-targeted contrast agent demonstrating that the SFRP2-targeted contrast agent was specific to tumor vessels. Plotting average pixel intensity obtained from SFRP2-targeted contrast agent against tumor volume showed that the average pixel intensity increased as tumor volume increased. In conclusion, molecularly-targeted imaging of SFRP2 visualizes angiosarcoma vessels, but not normal vessels, and intensity increases with tumor size. Molecular imaging of SFRP2 expression may provide a rapid, non-invasive method to monitor tumor regression during therapy for angiosarcoma and other SFRP2 expressing cancers, and contribute to our understanding of the biology of SFRP2 during tumor development and progression.

  14. Molecular imaging and the neuropathologies of Parkinson's disease

    DEFF Research Database (Denmark)

    Cumming, Paul; Borghammer, Per

    2012-01-01

    The main motor symptoms of Parkinson's disease (PD) are linked to degeneration of the nigrostriatal dopamine (DA) fibers, especially those innervating the putamen. This degeneration can be assessed in molecular imaging studies with presynaptic tracers such as [(18)F]-fluoro-L-DOPA (FDOPA...... with denervation upregulation, but there is an accelerated rate of DA receptor loss as the disease advances. Animal studies and post mortem investigations reveal changes in brain opioid peptide systems, but these are poorly documented in imaging studies of PD. Relatively minor changes in the binding sites for GABA...

  15. Advances in radionuclide molecular imaging of pancreatic β-cells

    International Nuclear Information System (INIS)

    In both type 1 and type 2 diabetes mellitus, β-cell mass (BCM) is lost.Various treatments are developed to restore or reconstruct BCM. The development of non-invasive methods to quantify BCM in vivo offers the potential for early detection of β-cell dysfunction prior to the clinical onset of diabetes. PET imaging with radioligands that directly target the pancreatic β-cells appears promising. The ability to determine the BCM has been investigated in several targets and their corresponding radiotracers, including radiolabeled receptor ligands, antibodies, metabolites and reporter genes. Therefore, we summarize the recent progress in radionuclide molecular imaging of pancreatic β-cells. (authors)

  16. A feasibility assessment of automated FISH image and signal analysis to assist cervical cancer detection

    Science.gov (United States)

    Wang, Xingwei; Li, Yuhua; Liu, Hong; Li, Shibo; Zhang, Roy R.; Zheng, Bin

    2012-02-01

    Fluorescence in situ hybridization (FISH) technology provides a promising molecular imaging tool to detect cervical cancer. Since manual FISH analysis is difficult, time-consuming, and inconsistent, the automated FISH image scanning systems have been developed. Due to limited focal depth of scanned microscopic image, a FISH-probed specimen needs to be scanned in multiple layers that generate huge image data. To improve diagnostic efficiency of using automated FISH image analysis, we developed a computer-aided detection (CAD) scheme. In this experiment, four pap-smear specimen slides were scanned by a dual-detector fluorescence image scanning system that acquired two spectrum images simultaneously, which represent images of interphase cells and FISH-probed chromosome X. During image scanning, once detecting a cell signal, system captured nine image slides by automatically adjusting optical focus. Based on the sharpness index and maximum intensity measurement, cells and FISH signals distributed in 3-D space were projected into a 2-D con-focal image. CAD scheme was applied to each con-focal image to detect analyzable interphase cells using an adaptive multiple-threshold algorithm and detect FISH-probed signals using a top-hat transform. The ratio of abnormal cells was calculated to detect positive cases. In four scanned specimen slides, CAD generated 1676 con-focal images that depicted analyzable cells. FISH-probed signals were independently detected by our CAD algorithm and an observer. The Kappa coefficients for agreement between CAD and observer ranged from 0.69 to 1.0 in detecting/counting FISH signal spots. The study demonstrated the feasibility of applying automated FISH image and signal analysis to assist cyto-geneticists in detecting cervical cancers.

  17. CT/FMT dual-model imaging of breast cancer based on peptide-lipid nanoparticles

    Science.gov (United States)

    Xu, Guoqiang; Lin, Qiaoya; Lian, Lichao; Qian, Yuan; Lu, Lisen; Zhang, Zhihong

    2016-03-01

    Breast cancer is one of the most harmful cancers in human. Its early diagnosis is expected to improve the patients' survival rate. X-ray computed tomography (CT) has been widely used in tumor detection for obtaining three-dimentional information. Fluorescence Molecular Tomography (FMT) imaging combined with near-infrared fluorescent dyes provides a powerful tool for the acquisition of molecular biodistribution information in deep tissues. Thus, the combination of CT and FMT imaging modalities allows us to better differentiate diseased tissues from normal tissues. Here we developed a tumor-targeting nanoparticle for dual-modality imaging based on a biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier. By incorporation of CT contrast agents (iodinated oil) and far-infrared fluorescent dyes (DiR-BOA) into the hydrophobic core of HPPS, we obtained the FMT and CT signals simultaneously. Increased accumulation of the nanoparticles in the tumor lesions was achieved through the effect of the tumor-targeting peptide on the surface of nanoparticle. It resulted in excellent contrast between lesions and normal tissues. Together, the abilities to sensitively separate the lesions from adjacent normal tissues with the aid of a FMT/CT dual-model imaging approach make the targeting nanoparticles a useful tool for the diagnostics of breast cancer.

  18. Statistical approach for detecting cancer lesions from prostate ultrasound images

    Science.gov (United States)

    Houston, A. G.; Premkumar, Saganti B.; Babaian, Richard J.; Pitts, David E.

    1993-07-01

    Sequential digitized cross-sectional ultrasound image planes of several prostates have been studied at the pixel level during the past year. The statistical distribution of gray scale values in terms of simple statistics, sample means and sample standard deviations, have been considered for estimating the differences between cross-sectional image planes of the gland due to the presence of cancer lesions. Based on a variability measure, the results for identifying the presence of cancer lesions in the peripheral zone of the gland for 25 blind test cases were found to be 64% accurate. This accuracy is higher than that obtained by visual photo interpretation of the image data, though not as high as our earlier results were indicating. Axial-view ultrasound image planes of prostate glands were obtained from the apex to the base of the gland at 2 mm intervals. Results for the 25 different prostate glands, which include pathologically confirmed benign and cancer cases, are presented.

  19. Imaging hallmarks of cancer in living mice

    NARCIS (Netherlands)

    Ellenbroek, Saskia I J; van Rheenen, Jacco

    2014-01-01

    To comprehend the complexity of cancer, the biological characteristics acquired during the initiation and progression of tumours were classified as the 'hallmarks of cancer'. Intravital microscopy techniques have been developed to study individual cells that acquire these crucial traits, by visualiz

  20. Intelligent Design of Nano-Scale Molecular Imaging Agents

    Directory of Open Access Journals (Sweden)

    Takeaki Ozawa

    2012-12-01

    Full Text Available 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.

  1. Tau PET: the next frontier in molecular imaging of dementia.

    Science.gov (United States)

    Xia, Chenjie; Dickerson, Bradford C

    2016-09-01

    We have arrived at an exciting juncture in dementia research: the second major pathological hallmark of Alzheimer's disease (AD)-tau-can now be seen for the first time in the living human brain. The major proteinopathies in AD include amyloid-β plaques and neurofibrillary tangles (NFTs) made of hyperphosphorylated paired helical filament (PHF) tau. Since its advent more than a decade ago, amyloid PET imaging has revolutionized the field of dementia research, enabling more confident diagnosis of the likely pathology in patients with a variety of clinical dementia syndromes, paving the way for the identification of people with preclinical or prodromal AD pathology, and serving as a minimally invasive molecular readout in clinical trials of putative disease-modifying interventions. Now that we are on the brink of a second revolution in molecular imaging in dementia, it is worth considering the likely potential impact of this development on the field. PMID:27334648

  2. Monitoring molecular, functional and morphologic aspects of bone metastases using non-invasive imaging.

    Science.gov (United States)

    Bauerle, Tobias; Komljenovic, Dorde; Semmler, Wolfhard

    2012-03-01

    Bone is among the most common locations of metastasis and therefore represents an important clinical target for diagnostic follow-up in cancer patients. In the pathogenesis of bone metastases, disseminated tumor cells proliferating in bone interact with the local microenvironment stimulating or inhibiting osteoclast and osteoblast activity. Non-invasive imaging methods monitor molecular, functional and morphologic changes in both compartments of these skeletal lesions - the bone and the soft tissue tumor compartment. In the bone compartment, morphologic information on skeletal destruction is assessed by computed tomography (CT) and radiography. Pathogenic processes of osteoclast and osteoblast activity, however, can be imaged using optical imaging, positron emission tomography (PET), single photon emission CT (SPECT) and skeletal scintigraphy. Accordingly, conventional magnetic resonance imaging (MRI) and CT as well as diffusion- weighted MRI and optical imaging are used to assess morphologic aspects on the macroscopic and cellular level of the soft tissue tumor compartment. Imaging methods such as PET, MR spectroscopy, dynamic contrast-enhanced techniques and vessel size imaging further elucidate on pathogenic processes in this compartment including information on metabolism and vascularization. By monitoring these aspects in bone lesions, new insights in the pathogenesis of skeletal metastases can be gained. In translation to the clinical situation, these novel methods for the monitoring of bone metastases might be applied in patients to improve follow-up of these lesions, in particular after therapeutic intervention. This review summarizes established and experimental imaging techniques for the monitoring of tumor and bone cell activity including molecular, functional and morphological aspects in bone metastases. PMID:22214500

  3. Molecular mechanisms of pharmacological doses of ascorbate on cancer cells.

    Science.gov (United States)

    Venturelli, Sascha; Sinnberg, Tobias W; Niessner, Heike; Busch, Christian

    2015-06-01

    Intravenous application of high-dose ascorbate (vitamin C) has been used in complementary medicine since the 1970s to treat cancer patients. In recent years it became evident that high-dose ascorbate in the millimolar range bears selective cytotoxic effects on cancer cells in vitro and in vivo. This anticancer effect is dose dependent, catalyzed by serum components and mediated by reactive oxygen species and ascorbyl radicals, making ascorbate a pro-oxidative pro-drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. It further depends on HIF-1 signaling and oxygen pressure, and shows a strong epigenetic signature (alteration of DNA-methylation and induction of tumor-suppressing microRNAs in cancer cells). The detailed understanding of ascorbate-induced antiproliferative molecular mechanisms warrants in-depth preclinical evaluation in cancer-bearing animal models for the optimization of an efficacious therapy regimen (e.g., combination with hyperbaric oxygen or O2-sensitizers) that subsequently need to be evaluated in clinical trials. PMID:26065536

  4. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

    2011-02-24

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  5. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Pierre Cordelier

    2011-02-01

    Full Text Available Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  6. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer

  7. Multimodal and three-dimensional imaging of prostate cancer.

    Science.gov (United States)

    Lee, Zhenghong; Sodee, D Bruce; Resnick, Martin; Maclennan, Gregory T

    2005-09-01

    Accurate characterization of prostate cancer is crucial for treatment planning and patient management. Non-invasive SPECT imaging using a radiolabeled monoclonal antibody, 111In-labeled capromab pendetide, offers advantage over existing means for prostate cancer diagnosis and staging. However, there are difficulties associated with the interpretation of these SPECT images. In this study, we developed a 3D surface-volume hybrid rendering method that utilizes multi-modality image data to facilitate diagnosis of prostate cancer. SPECT and CT or MRI (or both) images were aligned either manually or automatically. 3D hybrid rendering was implemented to blend prostate tumor distribution from SPECT in pelvis with anatomic structures from CT/MRI. Feature extraction technique was also implemented within the hybrid rendering for tumor uptake enhancement. Autoradiographic imaging and histological evaluation were performed to correlate with the in-vivo SPECT images. Warping registration of histological sections was carried out to compensate the deformation of histology slices during fixation to help the alignment between histology and in-vivo images. Overall, the rendered volumetric evaluation of prostate cancer has the potential to greatly increase the confidence in the reading of radiolabeled monoclonal antibody scans, especially in patients where there is a high suspicion of prostate tumor metastasis. PMID:15893911

  8. M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

    Science.gov (United States)

    Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G.; Yun, Dong Soo; Belcher, Angela M.; Kelly, Kimberly A.

    2012-10-01

    Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

  9. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  10. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    International Nuclear Information System (INIS)

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed

  11. Genomics Study of Gastric Cancer and Its Molecular Subtypes.

    Science.gov (United States)

    Yuen, Siu Tsan; Leung, Suet Yi

    2016-01-01

    Gastric cancer is a heterogeneous disease encompassing diverse morphological (intestinal versus diffuse) and molecular subtypes (MSI, EBV, TP53 mutation). Recent advances in genomic technology have led to an improved understanding of the driver gene mutational profile, gene expression, and epigenetic alterations that underlie each of the subgroups, with therapeutic implications in some of these alterations. There have been attempts to classify gastric cancers based on these genomic features, with an aim to improve prognostication and predict responsiveness to specific drug therapy. The eventual aims of these genomic studies are to develop deep biological insights into the carcinogenic pathway in each of these subtypes. Future large-scale drug screening strategies may then be able to link these genomic features to drug responsiveness, eventually leading to genome-guided personalized medicine with improved cure rates. PMID:27573784

  12. Molecular Characterization of ERα-positive and Triple Negative Breast Cancer

    NARCIS (Netherlands)

    Severson, T.M.

    2016-01-01

    Breast cancer, one of the most common of all cancers, is diagnosed in over 1.5 million people world-wide each year. Overall, treatments for breast cancer are considered relatively successful, however recurrence is a clinical problem of paramount importance. Molecular subtypes of breast cancer, defin

  13. Molecular imaging using Cu-ATSM and FDG in solid canine tumors

    DEFF Research Database (Denmark)

    Hansen, Anders Elias

    Tumor hypoxia is one of the key factors in the development of aggressive and treatment resistant tumors. The negative effects of tumor hypoxia are mediated both by the direct lack of molecular oxygen for therapeutic efficacy and by pro- teomic and genomic changes induced in hypoxic tumor cells....... Identification of hypoxic tumor and intratumoral hypoxic regions therefore hold the potential to serve as a basis for individualized treatment protocols, including image guided radiation therapy. The current PhD project was undertaken to study tumor hypoxia in cancer bearing dogs, with the aims of 1) identifying...... the potential of implementing canine cancer patients in translational research on tumor hypoxia. 2) Non- invasively evaluate the hypoxia positron emission tomography (PET) tracer 64 Copper(II)diacetyl-bis(N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), including the comparison to non-invasive measures of tumor...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Lobular breast cancer: Clinical, molecular and morphological characteristics.

    Science.gov (United States)

    Christgen, Matthias; Steinemann, Doris; Kühnle, Elna; Länger, Florian; Gluz, Oleg; Harbeck, Nadia; Kreipe, Hans

    2016-07-01

    Infiltrating lobular breast cancer (ILBC) is the most common special breast cancer subtype. This review provides a comprehensive description of ILBC characteristics, including epidemiology, clinical features, molecular genetics and histomorphology. Twenty detailed supplemental data tables guide through primary data of more than 200 original studies. Meta-analyses indicate that ILBC is at least twice as common in the Western world as it is in other geographic regions. ILBC is over-represented in so-called interval carcinomas and in primary metastatic breast cancer. ILBC is also associated higher age, higher pT stage and hormone receptor (ER/PR) positivity. Pathological complete response rates after neoadjuvant chemotherapy are low, ranging between 0% and 11%. Positive resection margins after breast-conserving surgery are comparatively frequent and 17% to 65% of patients undergo a second surgical intervention. Depending on the morphological stringency in the diagnosis of ILBC, lack of E-cadherin expression is observed in 55% to 100% of cases. CDH1/E-cadherin mutation detection rates vary between 12% and 83%. Various additional molecular factors, including PIK3CA, TP53, FOXA1, FGFR1, ZNF703 and BCAR4, have been implicated in ILBC or progression of lobular carcinoma in situ (LCIS) to invasive cancer and are discussed in detail. Eight instructive figure plates recapitulate the histomorphology of ILBC and its variants. Furthermore, we draw attention to rarely addressed histological details, such as two-sided nuclear compression and fat-avoiding growth at the invasion front. Last but not least, we discuss future translational research directions and emphasize the concept of synthetic lethality, which promises new options for targeted ILBC therapy.

  17. Novel tracers and their development for the imaging of metastatic prostate cancer.

    Science.gov (United States)

    Apolo, Andrea B; Pandit-Taskar, Neeta; Morris, Michael J

    2008-12-01

    There are presently no accurate methods of imaging prostate cancer metastases to bone. An unprecedented number of novel imaging agents, based on the biology of the disease, are now available for testing. We reviewed contemporary molecular imaging modalities that have been tested in humans with metastatic prostate cancer, with consideration of the studies' adherence to current prostate cancer clinical trial designs. Articles from the years 2002 to 2008 on PET using (18)F-FDG, (11)C-choline, (18)F-choline, (18)F-flouride, (11)C-acetate, (11)C-methionine, and (18)F-fluoro-5alpha-dihydrotestosterone in patients with metastatic prostate cancer were reviewed. Although these studies are encouraging, most focus on the rising population with prostate-specific antigen, and many involve small numbers of patients and do not adhere to consensus criteria for clinical trial designs in prostate cancer. Hence, although many promising agents are available for testing, such studies would benefit from closer collaboration between those in the fields of medical oncology and nuclear medicine.

  18. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev;

    2014-01-01

    with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published...... to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer...... to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline...

  19. PET and PET/CT for imaging of prostate cancer

    International Nuclear Information System (INIS)

    This review article provides an overview of the current literature data regarding the value of PET and PET/CT for imaging of prostate cancer. Most widely used PET tracers for prostate cancer imaging are 11C-acetate and 11C- or 18F-labeled choline. Available literature data on the performance of PET and PET/CT in the detection of the primary malignancy as well as local or distant metastases are presented and discussed. In addition, our own preliminary results regarding the diagnostic efficacy of 11C-choline PET and PET/CT in 43 patients with suspected prostate cancer are provided. The prevalence of prostate cancer in this patient sample was 55.8%. PET and PET/CT showed a sensitivity of 88% with a specificity of 63% in the detection of the primary prostate cancer. The sensitivity in the detection of metastatic spread was 77% and no false-positives were found. The possible value and limitations of combined PET/CT systems when compared to stand alone PET scanners are discussed. PET and PET/CT is at present the single imaging modality providing functional information not only regarding the primary malignancy but also its metastases. This unique feature distinguishes PET from MRI complemented with magnetic resonance spectroscopy - a competing procedure. Our own results as well as the still limited literature data suggest, that PET and PET/CT may prove to be useful methods for imaging of prostate cancer. (orig.)

  20. MR images of oral cancer treated with preoperative radiotherapy

    International Nuclear Information System (INIS)

    This study was carried out to evaluate the relationship between the effect of preoperative radiotherapy for oral cancer and the changes of signal intensity with MR images. T2-weighted images were compared before and after radiotherapy in 18 patients with primary oral cancer, and the effect on the lesions was histologically evaluated in surgically resected specimens obtained four weeks after the therapy. The MR images showed significantly decreased signal intensity of the lesions. The decrease of signal intensity was remarkable starting at two weeks after completion of the radiotherapy, compared with the decrease at less than two weeks after the therapy. The change of signal intensity was more obvious in tongue cancer than in other oral cancers. There was no significant difference in the change of the signal intensity between cancers with histologically poor response to the therapy and those with good response. These results suggested that signal intensity of oral cancer on T2-weighted images showed a significant decrease after preoperative radiotherapy, and that the intensity could be affected by duration after radiotherapy and primary sites. (author)

  1. SU-E-J-10: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, L [Yale University, New Haven, CT (United States); Bai, S [Sichuan University, Chengdu, Sichuan (China); Zhang, Y [Key laboratory of Carcinogenesis and Translational Research, Ministry of Ed, Beijing, Beijing (China); Deng, J [Yale University, New Haven, CT (United States)

    2015-06-15

    Purpose: To systematically evaluate imaging doses and cancer risks to organs-at-risk as a Result of cumulative doses from various radiological imaging procedures in image-guided radiotherapy (IGRT) in a large cohort of cancer patients. Methods: With IRB approval, imaging procedures (computed tomography, kilo-voltage portal imaging, megavoltage portal imaging and kilo-voltage cone-beam computed tomography) of 4832 cancer patients treated during 4.5 years were collected with their gender, age and circumference. Correlations between patient’s circumference and Monte Carlo simulated-organ dose were applied to estimate organ doses while the cancer risks were reported as 1+ERR using BEIR VII models. Results: 80 cGy or more doses were deposited to brain, lungs and RBM in 273 patients (maximum 136, 278 and 267 cGy, respectively), due largely to repetitive imaging procedures and non-personalized imaging settings. Regardless of gender, relative cancer risk estimates for brain, lungs, and RBM were 3.4 (n = 55), 2.6 (n = 49), 1.8 (n = 25) for age group of 0–19; 1.2 (n = 87), 1.4 (n = 98), 1.3 (n = 51) for age group of 20–39; 1.0 (n = 457), 1.1 (n = 880), 1.8 (n=360) for age group of 40–59; 1.0 (n = 646), 1.1 (n = 1400), 2.3 (n = 716) for age group of 60–79 and 1.0 (n = 108),1.1 (n = 305),1.6 (n = 147) for age group of 80–99. Conclusion: The cumulative imaging doses and associated cancer risks from multi-imaging procedures were patient-specific and site-dependent, with up to 2.7 Gy imaging dose deposited to critical structures in some pediatric patients. The associated cancer risks in brain and lungs for children of age 0 to 19 were 2–3 times larger than those for adults. This study indicated a pressing need for personalized imaging protocol to maximize its clinical benefits while reducing associated cancer risks. Sichuan University Scholarship.

  2. Magnetic resonance imaging in the staging of cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Camisao, Claudia C. [Hospital Sao Lucas, Rio de Janeiro, RJ (Brazil)]. E-mail: ccamisao@inca.gov.br; Brenna, Sylvia M.F. [Hospital Maternidade Leonor Mendes de Barros, Sao Paulo, SP (Brazil); Lombardelli, Karen V.P. [Hospital do Cancer (HCII), Rio de Janeiro, RJ (Brazil); Djahjah, Maria Celia R. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia; Zeferino, Luiz Carlos [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Ginecologia

    2007-05-15

    Cervical cancer is the worldwide leading cause of cancer-related death of women, especially in developing countries. The International Federation of Gynecology and Obstetrics recommends staging during surgery, however, surgical-pathologic staging would not be feasible in cases of more advanced cancers. Generally, in these cases, the staging is performed by means of clinical and gynecological examination and basic imaging studies. However, such an approach fails to demonstrate the actual extent of the disease, and does not include significant prognostic factors such as tumor volume, stromal invasion and lymph node involvement. Magnetic resonance imaging has increasingly been utilized in cervical cancer staging, since at early stages of the disease its performance may be compared to intraoperative findings and, at advanced stages, it shows to be superior to the clinical evaluation. Additionally, magnetic resonance imaging presents an excellent imaging resolution for the different densities of pelvic structures, does not require ionizing radiation, is comfortable for the patient, improves de staging, allowing the early detection of recurrence and the identification of reliable prognostic factors which contribute to the therapeutic decision making process and results prediction with an excellent cost-effectiveness. The present article is aimed at reviewing the most significant aspects of magnetic resonance imaging in the cervical cancer staging. (author)

  3. Advances in Bio-Optical Imaging for the Diagnosis of Early Oral Cancer

    Directory of Open Access Journals (Sweden)

    Ivan Keogh

    2011-07-01

    Full Text Available Oral cancer is among the most common malignancies worldwide, therefore early detection and treatment is imperative. The 5-year survival rate has remained at a dismal 50% for the past several decades. The main reason for the poor survival rate is the fact that most of the oral cancers, despite the general accessibility of the oral cavity, are not diagnosed until the advanced stage. Early detection of the oral tumors and its precursor lesions may be the most effective means to improve clinical outcome and cure most patients. One of the emerging technologies is the use of non-invasive in vivo tissue imaging to capture the molecular changes at high-resolution to improve the detection capability of early stage disease. This review will discuss the use of optical probes and highlight the role of optical imaging such as autofluorescence, fluorescence diagnosis (FD, laser confocal endomicroscopy (LCE, surface enhanced Raman spectroscopy (SERS, optical coherence tomography (OCT and confocal reflectance microscopy (CRM in early oral cancer detection. FD is a promising method to differentiate cancerous lesions from benign, thus helping in the determination of adequate resolution of surgical resection margin. LCE offers in vivo cellular imaging of tissue structures from surface to subsurface layers and has demonstrated the potential to be used as a minimally invasive optical biopsy technique for early diagnosis of oral cancer lesions. SERS was able to differentiate between normal and oral cancer patients based on the spectra acquired from saliva of patients. OCT has been used to visualize the detailed histological features of the oral lesions with an imaging depth down to 2–3 mm. CRM is an optical tool to noninvasively image tissue with near histological resolution. These comprehensive diagnostic modalities can also be used to define surgical margin and to provide a direct assessment of the therapeutic effectiveness.

  4. Advances in bio-optical imaging for the diagnosis of early oral cancer.

    Science.gov (United States)

    Olivo, Malini; Bhuvaneswari, Ramaswamy; Keogh, Ivan

    2011-01-01

    Oral cancer is among the most common malignancies worldwide, therefore early detection and treatment is imperative. The 5-year survival rate has remained at a dismal 50% for the past several decades. The main reason for the poor survival rate is the fact that most of the oral cancers, despite the general accessibility of the oral cavity, are not diagnosed until the advanced stage. Early detection of the oral tumors and its precursor lesions may be the most effective means to improve clinical outcome and cure most patients. One of the emerging technologies is the use of non-invasive in vivo tissue imaging to capture the molecular changes at high-resolution to improve the detection capability of early stage disease. This review will discuss the use of optical probes and highlight the role of optical imaging such as autofluorescence, fluorescence diagnosis (FD), laser confocal endomicroscopy (LCE), surface enhanced Raman spectroscopy (SERS), optical coherence tomography (OCT) and confocal reflectance microscopy (CRM) in early oral cancer detection. FD is a promising method to differentiate cancerous lesions from benign, thus helping in the determination of adequate resolution of surgical resection margin. LCE offers in vivo cellular imaging of tissue structures from surface to subsurface layers and has demonstrated the potential to be used as a minimally invasive optical biopsy technique for early diagnosis of oral cancer lesions. SERS was able to differentiate between normal and oral cancer patients based on the spectra acquired from saliva of patients. OCT has been used to visualize the detailed histological features of the oral lesions with an imaging depth down to 2-3 mm. CRM is an optical tool to noninvasively image tissue with near histological resolution. These comprehensive diagnostic modalities can also be used to define surgical margin and to provide a direct assessment of the therapeutic effectiveness. PMID:24310585

  5. PET-based molecular nuclear neuro-imaging

    International Nuclear Information System (INIS)

    Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy

  6. Photoacoustic molecular imaging for in vivo liver iron quantitation

    Science.gov (United States)

    Maccarinelli, Federica; Carmona, Fernando; Regoni, Maria; Arosio, Paolo

    2016-05-01

    A recent study showed that ferritin is a suitable endogenous contrast agent for photoacoustic molecular imaging in cultured mammalian cells. We have therefore tested whether this imaging technique can be used for in vivo quantification of iron in mouse livers. To verify this hypothesis, we used multispectral optoacoustic tomography (MSOT) to image albino CD1 mice before and after experimental iron loading. Postmortem assays showed that the iron treatment caused a 15-fold increase in liver iron and a 40-fold increase in liver ferritin levels, while in vivo longitudinal analysis using MSOT revealed just a 1.6-fold increase in the ferritin/iron photoacoustic signal in the same animals. We conclude that MSOT can monitor changes in ferritin/iron levels in vivo, but its sensitivity is much lower than that of ex vivo iron assays.

  7. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Hao Hong

    2008-01-01

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

  8. Image-Based Brachytherapy for the Treatment of Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harkenrider, Matthew M., E-mail: mharkenrider@lumc.edu; Alite, Fiori; Silva, Scott R.; Small, William

    2015-07-15

    Cervical cancer is a disease that requires considerable multidisciplinary coordination of care and labor in order to maximize tumor control and survival while minimizing treatment-related toxicity. As with external beam radiation therapy, the use of advanced imaging and 3-dimensional treatment planning has generated a paradigm shift in the delivery of brachytherapy for the treatment of cervical cancer. The use of image-based brachytherapy, most commonly with magnetic resonance imaging (MRI), requires additional attention and effort by the treating physician to prescribe dose to the proper volume and account for adjacent organs at risk. This represents a dramatic change from the classic Manchester approach of orthogonal radiographic images and prescribing dose to point A. We reviewed the history and currently evolving data and recommendations for the clinical use of image-based brachytherapy with an emphasis on MRI-based brachytherapy.

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

    Directory of Open Access Journals (Sweden)

    Sinem Ozyurt

    2015-07-01

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

  10. Breast cancer molecular subtypes: from TNBC to QNBC

    Science.gov (United States)

    Hon, Jane Date C; Singh, Baljit; Sahin, Aysegul; Du, Gang; Wang, Jinhua; Wang, Vincent Y; Deng, Fang-Ming; Zhang, David Y; Monaco, Marie E; Lee, Peng

    2016-01-01

    Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.

  11. Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

    Science.gov (United States)

    Willis, Rudolph E.

    2016-01-01

    It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

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

    Science.gov (United States)

    Tichauer, Kenneth M.

    2016-03-01

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

  13. The Analysis of High-Risk Molecular Markers for Cervical Cancer Patients under Thirty-Five

    Institute of Scientific and Technical Information of China (English)

    Yi Luo; Jian Wang; Changyin Zhao

    2006-01-01

    OBJECTIVE To explore molecular markers for cervical cancer in female patients below thirty-five years of age, so that the markers may be used to formulate a prognosis and to provide some useful targets for improving therapy.METHODS Pathological data were collected from 64 cervical cancer patients under the age of 35 from June, 1995 to June, 2000 in our institution.The data were retrospectively analyzed as a study group, and compared to data obtained from 90 cervical cancer cases over the age of 35 as controls who underwent treatment during the same time period. Immunohistochemical and quantified image analyses were conducted to look for differences between the two groups in expression of survivin, p27,CD44v6, MMP-2 and TIMP-2.RESULTS The overall 5-year survival rate (65.6%) of the study group was significantly lower (P<0.05) compared to the control group (84.4%). The expression of survivin, MMP-2 and CD44v6 was much higher in the younger study group compared to the older control group, but TIMP-2 displayed higher expression in the control group (P<0.05). There was no significant difference in p27 expression between the two groups (P>0.05).CONCLUSION Young women patients with cervical cancer have a poorer prognosis compared to old women. Our study reveals that survivin,MMP-2, TIMP-2 and CD44v6 expression have a correlation with shorter 5-year survival. Improvement in the prognosis for young cervical cancer patients can be expected using biomedical therapy which targets these molecular markers.

  14. Photoacoustic imaging and temperature measurement for photothermal cancer therapy

    OpenAIRE

    Shah, Jignesh; Park, Suhyun; Aglyamov, Salavat; Larson, Timothy; Ma, Li; Sokolov, Konstantin; Johnston, Keith; Milner, Thomas; Emelianov, Stanislav Y.

    2008-01-01

    Photothermal therapy is a noninvasive, targeted, laser-based technique for cancer treatment. During photothermal therapy, light energy is converted to heat by tumor-specific photoabsorbers. The corresponding temperature rise causes localized cancer destruction. For effective treatment, however, the presence of photoabsorbers in the tumor must be ascertained before therapy and thermal imaging must be performed during therapy. This study investigates the feasibility of guiding photothermal ther...

  15. Research progress of molecular diagnostics of lung cancer%肺癌分子诊断学研究进展

    Institute of Scientific and Technical Information of China (English)

    薛剑; 娄加陶

    2011-01-01

    As a complement to imaging and c tology-based screening strategies, molecular diagnostics of lung cancer include not only the early detection but also the prognosis index and prediction of target therapy. In this paper, gene mutation, prediction of target therapy, miRNA, cancer stem cells and methylation in molecular diagnostics of lung cancer are reviewed.%肺癌的分子诊断作为影像学和细胞学筛查策略的重要补充,其内容不仅包括早期诊断,还包括预后指标及靶向治疗的预测等.该文拟对当前肺癌分子诊断的研究热点基因突变与靶向治疗预测、miRNA、肿瘤干细胞、甲基化及相关检测方法进行综述.

  16. Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker.

    Directory of Open Access Journals (Sweden)

    Saleh M Rachidi

    Full Text Available BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An "Inflammatory Gene Integrated Score" was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2 is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only

  17. Contributions on biomedical imaging, with a side-look at molecular imaging

    International Nuclear Information System (INIS)

    This report is intended as a brief introduction to the emerging scientific field of biomedical imaging. The breadth of the subject is shown and future fields of research are indicated, which hopefully will serve as a guide to the identification of starting points for the research in 'Biomedical and/or Molecular Imaging' at the GSF-National Research Center for Environment and Health. The report starts with a brief sketch of the history. Then a - necessarily incomplete - list of research topics is presented. It is organized in two parts: the first one addresses medical imaging, and the second one is concerned with biological point aspects of the matter. (orig.)

  18. Medical image diagnosis of liver cancer using artificial intelligence

    International Nuclear Information System (INIS)

    A revised Group Method of Data Handling (GMDH)-type neural network algorithm using artificial intelligence technology for medical image diagnosis is proposed and is applied to medical image diagnosis of liver cancer. In this algorithm, the knowledge base for medical image diagnosis are used for organizing the neural network architecture for medical image diagnosis. Furthermore, the revised GMDH-type neural network algorithm has a feedback loop and can identify the characteristics of the medical images accurately using feedback loop calculations. The optimum neural network architecture fitting the complexity of the medical images is automatically organized so as to minimize the prediction error criterion defined as Prediction Sum of Squares (PSS). It is shown that the revised GMDH-type neural network can be easily applied to the medical image diagnosis. (author)

  19. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models.

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE(-/-) and ApoE(-/-)Fbn1C1039G(+/-) mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  20. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  1. Fluorescence imaging to study cancer burden on lymph nodes

    Science.gov (United States)

    D'Souza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2015-03-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue along with a cancer targeting tracer, Affibody labeled with IRDYE800CW and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

  2. Dye-Enhanced Multimodal Confocal Imaging of Brain Cancers

    Science.gov (United States)

    Wirth, Dennis; Snuderl, Matija; Sheth, Sameer; Curry, William; Yaroslavsky, Anna

    2011-04-01

    Background and Significance: Accurate high resolution intraoperative detection of brain tumors may result in improved patient survival and better quality of life. The goal of this study was to evaluate dye enhanced multimodal confocal imaging for discriminating normal and cancerous brain tissue. Materials and Methods: Fresh thick brain specimens were obtained from the surgeries. Normal and cancer tissues were investigated. Samples were stained in methylene blue and imaged. Reflectance and fluorescence signals were excited at 658nm. Fluorescence emission and polarization were registered from 670 nm to 710 nm. The system provided lateral resolution of 0.6 μm and axial resolution of 7 μm. Normal and cancer specimens exhibited distinctively different characteristics. H&E histopathology was processed from each imaged sample. Results and Conclusions: The analysis of normal and cancerous tissues indicated clear differences in appearance in both the reflectance and fluorescence responses. These results confirm the feasibility of multimodal confocal imaging for intraoperative detection of small cancer nests and cells.

  3. Molecular targeted treatment and radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  4. Molecular targeted treatment and radiation therapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marquardt, Friederike; Roedel, Franz; Capalbo, Gianni; Weiss, Christian; Roedel, Claus [Dept. of Radiation Therapy, Univ. of Frankfurt/Main (Germany)

    2009-06-15

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  5. Nanoparticle-enabled terahertz imaging for cancer diagnosis.

    Science.gov (United States)

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

    2009-03-01

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

  6. Breast cancer imaging: A perspective for the next decade

    Energy Technology Data Exchange (ETDEWEB)

    Karellas, Andrew; Vedantham, Srinivasan [Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655 (United States)

    2008-11-15

    Breast imaging is largely indicated for detection, diagnosis, and clinical management of breast cancer and for evaluation of the integrity of breast implants. In this work, a prospective view of techniques for breast cancer detection and diagnosis is provided based on an assessment of current trends. The potential role of emerging techniques that are under various stages of research and development is also addressed. It appears that the primary imaging tool for breast cancer screening in the next decade will be high-resolution, high-contrast, anatomical x-ray imaging with or without depth information. MRI and ultrasonography will have an increasingly important adjunctive role for imaging high-risk patients and women with dense breasts. Pilot studies with dedicated breast CT have demonstrated high-resolution three-dimensional imaging capabilities, but several technological barriers must be overcome before clinical adoption. Radionuclide based imaging techniques and x-ray imaging with intravenously injected contrast offer substantial potential as a diagnostic tools and for evaluation of suspicious lesions. Developing optical and electromagnetic imaging techniques hold significant potential for physiologic information and they are likely to be of most value when integrated with or adjunctively used with techniques that provide anatomic information. Experimental studies with breast specimens suggest that phase-sensitive x-ray imaging techniques can provide edge enhancement and contrast improvement but more research is needed to evaluate their potential role in clinical breast imaging. From the technological perspective, in addition to improvements within each modality, there is likely to be a trend towards multi-modality systems that combine anatomic with physiologic information. We are also likely to transition from a standardized screening, where all women undergo the same imaging exam (mammography), to selection of a screening modality or modalities based an

  7. Current imaging strategies for the evaluation of uterine cervical cancer.

    Science.gov (United States)

    Bourgioti, Charis; Chatoupis, Konstantinos; Moulopoulos, Lia Angela

    2016-04-28

    Uterine cervical cancer still remains an important socioeconomic issue because it largely affects women of reproductive age. Prognosis is highly depended on extent of the disease at diagnosis and, therefore, accurate staging is crucial for optimal management. Cervical cancer is clinically staged, according to International Federation of Gynecology and Obstetrics guidelines, but, currently, there is increased use of cross sectional imaging modalities [computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT)] for the study of important prognostic factors like tumor size, parametrial invasion, endocervical extension, pelvic side wall or adjacent/distal organs involvement and lymph node status. Imaging indications also include cervical cancer follow-up, evaluation of tumor response to treatment and selection of suitable candidates for less radical surgeries like radical trachelectomy for fertility preservation. The preferred imaging method for local cervical cancer evaluation is MRI; CT is equally effective for evaluation of extrauterine spread of the disease. PET-CT shows high diagnostic performance for the detection of tumor relapse and metastatic lymph nodes. The aim of this review is to familiarize radiologists with the MRI appearance of cervical carcinoma and to discuss the indications of cross sectional imaging during the course of the disease in patients with cervical carcinoma.

  8. Portable multispectral imaging system for oral cancer diagnosis

    Science.gov (United States)

    Hsieh, Yao-Fang; Ou-Yang, Mang; Lee, Cheng-Chung

    2013-09-01

    This study presents the portable multispectral imaging system that can acquire the image of specific spectrum in vivo for oral cancer diagnosis. According to the research literature, the autofluorescence of cells and tissue have been widely applied to diagnose oral cancer. The spectral distribution is difference for lesions of epithelial cells and normal cells after excited fluorescence. We have been developed the hyperspectral and multispectral techniques for oral cancer diagnosis in three generations. This research is the third generation. The excited and emission spectrum for the diagnosis are acquired from the research of first generation. The portable system for detection of oral cancer is modified for existing handheld microscope. The UV LED is used to illuminate the surface of oral cavity and excite the cells to produce fluorescent. The image passes through the central channel and filters out unwanted spectrum by the selection of filter, and focused by the focus lens on the image sensor. Therefore, we can achieve the specific wavelength image via fluorescence reaction. The specificity and sensitivity of the system are 85% and 90%, respectively.

  9. Molecular imaging agents for SPECT (and SPECT/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Gnanasegaran, Gopinath [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); Ballinger, James R. [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2014-05-15

    The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

  10. Hyperspectral imaging for cancer surgical margin delineation: registration of hyperspectral and histological images

    Science.gov (United States)

    Lu, Guolan; Halig, Luma; Wang, Dongsheng; Chen, Zhuo G.; Fei, Baowei

    2014-03-01

    The determination of tumor margins during surgical resection remains a challenging task. A complete removal of malignant tissue and conservation of healthy tissue is important for the preservation of organ function, patient satisfaction, and quality of life. Visual inspection and palpation is not sufficient for discriminating between malignant and normal tissue types. Hyperspectral imaging (HSI) technology has the potential to noninvasively delineate surgical tumor margin and can be used as an intra-operative visual aid tool. Since histological images provide the ground truth of cancer margins, it is necessary to warp the cancer regions in ex vivo histological images back to in vivo hyperspectral images in order to validate the tumor margins detected by HSI and to optimize the imaging parameters. In this paper, principal component analysis (PCA) is utilized to extract the principle component bands of the HSI images, which is then used to register HSI images with the corresponding histological image. Affine registration is chosen to model the global transformation. A B-spline free form deformation (FFD) method is used to model the local non-rigid deformation. Registration experiment was performed on animal hyperspectral and histological images. Experimental results from animals demonstrated the feasibility of the hyperspectral imaging method for cancer margin detection.

  11. Radiopharmaceuticals: nanoparticles like multi-functional systems for the obtaining in vivo of molecular images; Radiofarmacos: nanoparticulas como sistemas multifuncionales para la obtencion in vivo de imagenes moleculares

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Ramirez de la Cruz, F. M.; Ocampo G, B. E.; Morales A, E.; Santos C, C. L.; Mendoza S, A. N., E-mail: guillermina.ferro@inin.gob.m [ININ, Departamento de Materiales Radiactivos, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2010-07-01

    The techniques of obtaining direct or indirect molecular images detect and register the space-temporary distribution of molecular or cellular processes for biochemical, biological, diagnostic and therapeutic applications. The advanced techniques of image like the nuclear magnetic resonance, the single photon emission computed tomography, the positron emission tomography and the images of optic fluorescence have been used successfully to detect these processes. On the other hand, the utility of the nanoparticles for any application is dependent of the physicochemical properties that present, being possible to modify their surface when making them react with different biomolecules what allows the formation of conjugates with specific molecular recognition. The joint of various protein molecules, peptides or oligonucleotides to the surface of a nanoparticle produce a multi-functional system able to increase the multivalent joints from the nanoparticles-biomolecules to their receivers for the obtaining of molecular images in vivo. The peptides stimulate, regulate or inhibit numerous functions of the life, acting mainly as information transmitters and activity coordinators of several tissues in the organism. The receivers of regulator peptides are over represented in numerous types of cancer cells and they are protein structures. These receivers have been used as white molecular of marked peptides, to locate primary malignant tumors and their metastasis, using the diagnostic techniques of molecular image mentioned above, which consist basically on the radio peptides use and conjugated peptides to fluoro chromes, to metallic nanoparticles and nano crystals. A summary of the work is presented carried out by the personnel of the Radio-active Materials and Chemistry Departments of the Instituto Nacional de Investigaciones Nucleares in this field. (Author)

  12. Micropapillary Lung Cancer with Breast Metastasis Simulating Primary Breast Cancer due to Architectural Distortion on Images

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kyung Ran; Hong, Eun Kyung; Lee, See Yeon [Center for Breast Cancer, National Cancer Center, Goyang (Korea, Republic of); Ro, Jae Yoon [The Methodist Hospital, Weill Medical College of Cornell University, Houston (United States)

    2012-03-15

    A 47-year-old Korean woman with right middle lobe lung adenocarcinoma, malignant pleural effusion, and multiple lymph node and bone metastases, after three months of lung cancer diagnosis, presented with a palpable right breast mass. Images of the right breast demonstrated architectural distortion that strongly suggested primary breast cancer. Breast biopsy revealed metastatic lung cancer with a negative result for estrogen receptor (ER), progesterone receptor (PR) and mammaglobin, and a positive result for thyroid transcription factor-1 (TTF-1). We present a case of breast metastasis from a case of lung cancer with an extensive micropapillary component, which was initially misinterpreted as a primary breast cancer due to unusual image findings with architectural distortion.

  13. Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Jenny-Maria Jönsson

    Full Text Available OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. RESULTS: 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and

  14. Multiplexed molecular profiling of prostate cancer specimens using semiconductor quantum dot bioconjugates

    Science.gov (United States)

    Xing, Yun; Numora, Takeo; Chung, Leland; Zhau, Haiyen; Nie, Shuming

    2007-02-01

    Quantum dots (QDs) are light emitting semi-conductor nanocrystals with novel optical properties including superior photostability, narrow emission spectra with continuous excitation spectra. These properties make QDs especially suitable for multiplexed fluorescent labeling, live cell imaging, and in vivo animal imaging. The multiplexing potential has been recognized but real applications of biological/clinical significance are few. In this study, we used quantum dots to study epithelial mesenchymal transition (EMT), an important process involved in the bone metastasis of prostate cancer. Two prostate cancer cells lines with distinct molecular profiles, representing the two ends of the EMT process, were selected for this study. Four EMT-related biomarkers including E-cadherin, N-cadherin, Vimentin, and RANKL were stained with QD-antibody conjugates with elongation factor 1alpha as the internal control. Morphological information of the QD-stained cells was obtained by digital-color imaging and quantitative information obtained by spectra analysis using a spectrometer. Two types of analysis were performed: abundance of each biomarker in the same cell line relative to the internal control; and the relative abundance of these markers between the two cell lines. Our results demonstrate the feasibility of QDs for multiplexed profiling of FFPE cells/tissue of clinical significance; however, the standardization and quantification still awaits optimization.

  15. From Bombs to Breast Cancer Imaging: Los Alamos National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Martineau, Rebecca M [Los Alamos National Laboratory

    2012-07-26

    . Currently, there is fierce debate surrounding the age at which breast cancer screening should begin, and once begun, how often it should occur. The American Cancer Society recommends yearly mammograms starting at age 40. On the other hand, the U.S. Preventive Services Task Force recommends against routine so early. Rather, the Task Force recommends biennial mammography screening for women aged 50 to 74 years. The ten-year discrepancy in the onset of screening results from recent data suggesting that the frequent use of X-ray radiation during screenings could potentially increase the likelihood of developing cancer. This danger is increased by the low sensitivity and accuracy of mammograms, which sometimes require multiple screenings to yield results. Furthermore, mammograms are often not only inaccurate, but average appalling misdiagnoses rates: about 80% false positives and 15% false negatives. These misdiagnoses lead to unwarranted biopsies at an estimated health care cost of $2 billion per year, while at the same time, resulting in excessive cases of undetected cancer. As such, the National Cancer Institute recommends more studies on the advantages of types and frequency of screenings, as well as alternative screening options. The UST technology developed at LANL could be an alternative option to greatly improve the specificity and sensitivity of breast cancer screening without using ionizing radiation. LANL is developing high-resolution ultrasound tomography algorithms and a clinical ultrasound tomography scanner to conduct patient studies at the UNM Hospital. During UST scanning, the patient lies face-down while her breast, immersed in a tank of warm water, is scanned by phased-transducer arrays. UST uses recorded ultrasound signals to reconstruct a high-resolution three-dimensional image of the breast, showing the spatial distribution of mechanical properties within the breast. Breast cancers are detected by higher values of mechanical properties compared to

  16. Functionalized bismuth ferrite harmonic nanoparticles for cancer cells labeling and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Passemard, Solène; Staedler, Davide; Sonego, Giona [Ecole Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering (Switzerland); Magouroux, Thibaud [Université de Genève, GAP-Biophotonics (Switzerland); Schneiter, Guillaume Stéphane [Ecole Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering (Switzerland); Juillerat-Jeanneret, Lucienne [University Institute of Pathology, CHUV-UNIL (Switzerland); Bonacina, Luigi [Université de Genève, GAP-Biophotonics (Switzerland); Gerber-Lemaire, Sandrine, E-mail: Sandrine.Gerber@epfl.ch [Ecole Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering (Switzerland)

    2015-10-15

    Bismuth ferrite (BFO) harmonic nanoparticles (NPs) display high nonlinear optical efficiency and excellent biocompatibility profile which make them attractive for the development of diagnostic applications as contrast agents. In this study, we present a general method for the functionalization of this material with chemical ligands targeting cancer molecular biomarkers. In particular, a conjugation protocol based on click reaction between alkynyl-containing targeting ligands and poly(ethylene glycol)-coated BFO NPs (67.7 nm) displaying surface reactive azido groups was developed. Copper-free click reaction allowed fast and efficient conjugation of a covalent inhibitor of prolyl-specific endopeptidases to coated BFO NPs. The ability of these functionalized nanomaterials (134.2 nm) to act as imaging probes for cancer cells was demonstrated by the selective labeling of human lung cancer cells.

  17. Luminescent Nanomaterials for Molecular-Specific Cellular Imaging

    Science.gov (United States)

    Zvyagin, Andrei Vasilyevich; Song, Zhen; Nadort, Annemarie; Sreenivasan, Varun Kumaraswamy Annayya; Deyev, Sergey Mikhailovich

    Imaging of molecular trafficking in cells and biological tissue aided by molecular-specific fluorescent labeling is very attractive, since it affords capturing the key processes in comprehensive biological context. Several shortcomings of the existing organic dye labeling technology, however, call for development of alternative molecular reporters, with improved photostability, reduced cytotoxicity, and an increased number of controllable surface moieties. Such alternative molecular reporters are represented by inorganic luminescent nanoparticles (NP) whose optical, physical, and chemical properties are discussed on the examples of luminescent nanodiamonds (LND) and upconversion nanoparticles (UCNP). The emission origins of these nanomaterials differ markedly. LND emission results from individual nitrogen-vacancy color-centers in a biocompatible nanodiamond host whose properties can be controlled via size and surface groups. Photophysics of UCNP is governed by the collective, nonlinear excitation transfer processes, resulting in conversion of longer-wavelength excitation to the shorter-wavelength emission. The emission/excitation spectral properties of UCNP falling within the biological tissue transparency window open new opportunities of almost complete suppression of the cell/tissue autofluorescence background. The developed surface of these nanoparticles represents a flexible platform populated with biocompatible surface moieties onto which cargo and targeting biomolecules can be firmly docked through a process called bioconjugation. These bioconjugated modules, e.g., nanodiamond-antibody, (quantum dot)-somatostatin, or (upconversion nanoparticle)-(mini-antibody) can gain admission into the cells by initiating the cell-specific, cell-recognized communication protocol. In this chapter, we aim to demonstrate the whole bottom-up bio-nano-optics approach for optical biological imaging capturing luminescent nanoparticle design, surface activation, and bioconjugation

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

    Science.gov (United States)

    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

  19. PET/SPECT molecular imaging in clinical neuroscience: recent advances in the investigation of CNS diseases

    OpenAIRE

    Lu, Feng-Mei; Yuan, Zhen

    2015-01-01

    Molecular imaging is an attractive technology widely used in clinical practice that greatly enhances our understanding of the pathophysiology and treatment in central nervous system (CNS) diseases. It is a novel multidisciplinary technique that can be defined as real-time visualization, in vivo characterization and qualification of biological processes at the molecular and cellular level. It involves the imaging modalities and the corresponding imaging agents. Nowadays, molecular imaging in n...

  20. High-frequency ultrasound imaging for breast cancer biopsy guidance.

    Science.gov (United States)

    Cummins, Thomas; Yoon, Changhan; Choi, Hojong; Eliahoo, Payam; Kim, Hyung Ham; Yamashita, Mary W; Hovanessian-Larsen, Linda J; Lang, Julie E; Sener, Stephen F; Vallone, John; Martin, Sue E; Kirk Shung, K

    2015-10-01

    Image-guided core needle biopsy is the current gold standard for breast cancer diagnosis. Microcalcifications, an important radiogr