WorldWideScience

Sample records for cancer molecular imaging

  1. 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.)

  2. 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

  3. 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.

  4. Acoustic and photoacoustic molecular imaging of cancer.

    Science.gov (United States)

    Wilson, Katheryne E; Wang, Tzu Yin; Willmann, Jürgen K

    2013-11-01

    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed.

  5. Acoustic and Photoacoustic Molecular Imaging of Cancer

    Science.gov (United States)

    Wilson, Katheryne E.; Wang, Tzu Yin; Willmann, Jürgen K.

    2014-01-01

    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed. PMID:24187042

  6. Advanced imaging of colorectal cancer: From anatomy to molecular imaging

    OpenAIRE

    García-Figueiras, Roberto; Baleato-González, Sandra; Padhani, Anwar R.; Marhuenda, Ana; Luna, Antonio; Alcalá, Lidia; Carballo-Castro, Ana; Álvarez-Castro, Ana

    2016-01-01

    Abstract Imaging techniques play a key role in the management of patients with colorectal cancer. The introduction of new advanced anatomical, functional, and molecular imaging techniques may improve the assessment of diagnosis, prognosis, planning therapy, and assessment of response to treatment of these patients. Functional and molecular imaging techniques in clinical practice may allow the assessment of tumour-specific characteristics and tumour heterogeneity. This paper will review recent...

  7. Molecular Imaging of Prostate Cancer: A Concise Synopsis

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2009-03-01

    Full Text Available Prostate cancer is the most common malignancy in men and continues to be a major public health problem. Imaging of prostate cancer remains particularly challenging owing to disease heterogeneity. Molecular imaging can provide unprecedented opportunities for deciphering the molecular mechanisms that are involved in the development and natural progression of prostate cancer from a localized process to the hormone-refractory metastatic disease. Such understanding will be the key for targeted imaging and therapy and for predicting and evaluating treatment response and prognosis. In this article, we review briefly the contribution of multimodality molecular imaging methods for the in vivo characterization of the pathophysiology of prostate cancer.

  8. Multi-modality molecular imaging for gastric cancer research

    Science.gov (United States)

    Liang, Jimin; Chen, Xueli; Liu, Junting; Hu, Hao; Qu, Xiaochao; Wang, Fu; Nie, Yongzhan

    2011-12-01

    Because of the ability of integrating the strengths of different modalities and providing fully integrated information, multi-modality molecular imaging techniques provide an excellent solution to detecting and diagnosing earlier cancer, which remains difficult to achieve by using the existing techniques. In this paper, we present an overview of our research efforts on the development of the optical imaging-centric multi-modality molecular imaging platform, including the development of the imaging system, reconstruction algorithms and preclinical biomedical applications. Primary biomedical results show that the developed optical imaging-centric multi-modality molecular imaging platform may provide great potential in the preclinical biomedical applications and future clinical translation.

  9. Molecular Imaging of Breast Cancer: Role of RGD Peptides.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2015-01-01

    Breast cancer is the leading cause of cancer deaths among women of all ages worldwide. With advances in molecular imaging procedures, it has been possible to detect breast cancer in its early stage, determine the extent of the disease to administer appropriate therapeutic protocol and also monitor the effects of treatment. By accurately characterizing the tumor properties and biological processes involved, molecular imaging can play a crucial role in minimizing the morbidity and mortality associated with breast cancer. The integrin αvβ3 plays an important role in breast cancer angiogenesis and is expressed on tumor endothelial cells as well as on some tumor cells. It is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic acid (RGD) tripeptide sequence and therefore RGD peptides can preferentially bind to integrin αvβ3. In this context, targeting tumor vasculature or tumor cells by RGD-based probes is a promising strategy for molecular imaging of breast cancer. Using RGD-based probes, several preclinical studies have employed different imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound and optical imaging for visualization of integrin αvβ3 expression in breast cancer models. Limited clinical trials using (18)F-labeled RGD peptides have also been initiated for non-invasive detection and staging of breast cancer. Herein, we provide a comprehensive overview of the latest advances in molecular imaging of breast cancer using RGD peptide-based probes and discuss the challenges and opportunities for advancement of the field. The reported strategies for molecular imaging of breast cancer using RGD peptide-based probes holds promise for making clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in improved quality of life for breast cancer patients.

  10. Ultrasound for molecular imaging and therapy in cancer

    OpenAIRE

    Kaneko, Osamu F; Willmann, Jürgen K.

    2012-01-01

    Over the past decade, molecularly-targeted contrast enhanced ultrasound (ultrasound molecular imaging) has attracted significant attention in preclinical research of cancer diagnostic and therapy. Potential applications for ultrasound molecular imaging run the gamut from early detection and characterization of malignancies to monitoring treatment responses and guiding therapies. There may also be a role for ultrasound contrast agents for improved delivery of chemotherapeutic drugs and gene th...

  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 cell-mediated cancer immunotherapy.

    Science.gov (United States)

    Lucignani, Giovanni; Ottobrini, Luisa; Martelli, Cristina; Rescigno, Maria; Clerici, Mario

    2006-09-01

    New strategies based on the activation of a patient's immune response are being sought to complement present conventional exogenous cancer therapies. Elucidating the trafficking pathways of immune cells in vivo, together with their migratory properties in relation to their differentiation and activation status, is useful for understanding how the immune system interacts with cancer. Methods based on tissue sampling to monitor immune responses are inadequate for repeatedly characterizing the responses of the immune system in different organs. A solution to this problem might come from molecular and cellular imaging - a branch of biomedical sciences that combines biotechnology and imaging methods to characterize, in vivo, the molecular and cellular processes involved in normal and pathologic states. The general concepts of noninvasive imaging of targeted cells as well as the technology and probes applied to cell-mediated cancer immunotherapy imaging are outlined in this review.

  13. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas

    2006-01-01

    for molecular imaging of cancer. Especially the possibility of a quick transfer of methods developed in animals to patients (translational research) is an important strength. This article will briefly discuss the newest applications and their importance and perspective in relation to the shift in paradigm......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...

  14. 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

  15. Anatomical and molecular imaging of skin cancer

    OpenAIRE

    Cai, Weibo

    2008-01-01

    Hao Hong1, Jiangtao Sun1, Weibo Cai1,21Departments of Radiology and Medical Physics, School of Medicine and Public Health, University of Wisconsin – Madison, Madison, Wisconsin, USA; 2University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin, USAAbstract: Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼5%) and nonmelanoma (∼95%), which can be further categorized into basal cell...

  16. Molecular Imaging and Therapy of Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Our objective is to develop an arsenic- based radiopharmaceutical platform for IGF1R-targeted imaging and therapy of PCa. The hypothesis is that...arsenic- based , IGF1R-targeted radiopharmaceuticals can allow for PET imaging, IRT, and monitoring the therapeutic response of PCa. Specific Aims: Aim 1: To...models with PET imaging. Aim 3: To monitor the efficacy of 76As- based IRT of PCa with multimodality imaging.

  17. 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.

  18. 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.

  19. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yang eLiu

    2015-08-01

    Full Text Available Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT, magnetic resonance imaging (MRI, positron emission tomography (PET, as well as nanoprobes for photoacoustic tomography (PAT, two-photon photoluminescence (TPL and surface-enhanced Raman spectroscopy (SERS. Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  20. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Bishnu P. Joshi

    2010-06-01

    Full Text Available 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. Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early

    Science.gov (United States)

    2013-07-01

    10-1-0422 TITLE: Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early PRINCIPAL...DATES COVERED 1 July 2010 - 30 June 2013 4. TITLE AND SUBTITLE Targeting Cell Surface Proteins in Molecular 5a. CONTRACT NUMBER Photoacoustic ...upon request). Aim 2) Prioritize ovarian cancer-associated surface proteins for their utility as molecular photoacoustic imaging targets and

  4. Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Arif Sheikh

    2017-02-01

    Full Text Available Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1. A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC.

  5. 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.)

  6. 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.

  7. 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

  8. 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...

  9. Molecular Cancer Imaging with Polymeric Nanoassemblies: From Tumor Detection to Theranostics.

    Science.gov (United States)

    Mi, Peng; Wang, Fang; Nishiyama, Nobuhiro; Cabral, Horacio

    2017-01-01

    Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.

  10. 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.

  11. Earlier Detection of Breast Cancer with Ultrasound Molecular Imaging in a Transgenic Mouse Model

    Science.gov (United States)

    Bachawal, Sunitha V.; Jensen, Kristin C.; Lutz, Amelie M.; Gambhir, Sanjiv S.; Tranquart, Francois; Tian, Lu; Willmann, Jürgen K.

    2013-01-01

    While there is an increasing role of ultrasound for breast cancer screening in patients with dense breast, conventional anatomical-ultrasound lacks sensitivity and specificity for early breast cancer detection. In this study we assessed the potential of molecular-ultrasound imaging, using clinically-translatable vascular endothelial growth factor receptor (VEGFR2)-targeted microbubbles (MBVEGFR2), to improve the diagnostic accuracy of ultrasound in earlier detection of breast cancer and ductal carcinoma in situ (DCIS) in a transgenic mouse model (FVB/N-Tg(MMTV-PyMT)634Mul). In vivo binding specificity studies (n=26 tumors) showed that ultrasound imaging signal was significantly higher (P95% of cases and highly agreed between each other (ICC=0.98; 95% CI, 97, 99). These results suggest that VEGFR2-targeted ultrasound molecular imaging allows highly accurate detection of DCIS and breast cancer in transgenic mice and may be a promising approach for early breast cancer detection in women. PMID:23328585

  12. 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.

  13. 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.......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...

  14. 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.

  15. 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.

  16. Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.

    Science.gov (United States)

    Bachawal, Sunitha V; Jensen, Kristin C; Wilson, Katheryne E; Tian, Lu; Lutz, Amelie M; Willmann, Jürgen K

    2015-06-15

    Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients.

  17. Breast Cancer Detection by B7-H3 Targeted Ultrasound Molecular Imaging

    Science.gov (United States)

    Bachawal, Sunitha V.; Jensen, Kristin C.; Wilson, Katheryne E.; Tian, Lu; Lutz, Amelie M.; Willmann, Jürgen K.

    2015-01-01

    Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T cell co-regulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor and malignant breast pathologies for diagnostic purposes. Through an immunohistochemical analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. PMID:25899053

  18. 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.)

  19. 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.

  20. 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.

  1. The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer

    Directory of Open Access Journals (Sweden)

    Dagmar Högemann-Savellano

    2003-11-01

    Full Text Available Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.

  2. Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

    Science.gov (United States)

    Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

    2016-10-01

    This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

  3. Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy.

    Science.gov (United States)

    Leng, Liang; Wang, Yuebing; He, Ningning; Wang, Di; Zhao, Qianjie; Feng, Guowei; Su, Weijun; Xu, Yang; Han, Zhongchao; Kong, Deling; Cheng, Zhen; Xiang, Rong; Li, Zongjin

    2014-06-01

    The tumor tropism of mesenchymal stem cells (MSCs) makes them an excellent delivery vehicle used in anticancer therapy. However, the exact mechanisms of MSCs involved in tumor microenvironment are still not well defined. Molecular imaging technologies with the versatility in monitoring the therapeutic effects, as well as basic molecular and cellular processes in real time, offer tangible options to better guide MSCs mediated cancer therapy. In this study, an in situ breast cancer model was developed with MDA-MB-231 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP). In mice breast cancer model, we injected human umbilical cord-derived MSCs (hUC-MSCs) armed with a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk), renilla luciferase (Rluc) and red fluorescent protein (RFP) into tumor on day 13, 18, 23 after MDA-MB-231 cells injection. Bioluminescence imaging of Fluc and Rluc provided the real time monitor of tumor cells and hUC-MSCs simultaneously. We found that tumors were significantly inhibited by hUC-MSCs administration, and this effect was enhanced by ganciclovir (GCV) application. To further demonstrate the effect of hUC-MSCs on tumor cells in vivo, we employed the near infrared (NIR) imaging and the results showed that hUC-MSCs could inhibit tumor angiogenesis and increased apoptosis to a certain degree. In conclusion, hUC-MSCs can inhibit breast cancer progression by inducing tumor cell death and suppressing angiogenesis. Moreover, molecular imaging is an invaluable tool in tracking cell delivery and tumor response to hUC-MSCs therapies as well as cellular and molecular processes in tumor.

  4. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2011-07-01

    37ºC water bath and then cut on a disposable cutting board using a 5 mm punch biopsy in order to maintain size consistency. At least two punch...the be z- uist Sampl information ges of HER . Each se , the first im rentially lab eased signa e. This is ssue in the ion depth. een at...tive tissue oshells for 5 image repres 5 μm. 50 µm p by ssues ction m) in f the focal er of thus , one e, or es ents 11

  5. Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon; Nguyen, Vu H. [Chonnam National University Medical School, Gwangju (Korea, Republic of); Gambhir, Sanjiv S. [Stanford University, California(United States)

    2010-04-15

    Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonarrival biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

  6. 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.

  7. 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

  8. Characterization of TCP-1 probes for molecular imaging of colon cancer.

    Science.gov (United States)

    Liu, Zhonglin; Gray, Brian D; Barber, Christy; Bernas, Michael; Cai, Minying; Furenlid, Lars R; Rouse, Andrew; Patel, Charmi; Banerjee, Bhaskar; Liang, Rongguang; Gmitro, Arthur F; Witte, Marlys H; Pak, Koon Y; Woolfenden, James M

    2016-10-10

    Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m ((99m)Tc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). (99m)Tc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling. In vitro saturation binding experiments were performed for (99m)Tc-TCP-1 in human HCT116 colon cancer cells. SCID mice with human HCT116 cancer xenografts were imaged with (99m)Tc-TCP-1 or control peptide using a small-animal SPECT imager: Group I (n=5) received no blockade; Group II (n=5) received a blocking dose of non-radiolabeled TCP-1. Group III (n=5) were imaged with (99m)Tc-labeled control peptide (inactive peptide). SCID mice with human PC3 prostate cancer xenografts (Group IV, n=5) were also imaged with (99m)Tc-TCP-1. Eight additional SCID mice bearing HCT116 xenografts in dorsal skinfold window chambers (DSWC) were imaged by direct positron imaging of (18)F-fluorodeoxyglucose ((18)F-FDG) and fluorescence microscopy of Cy7-TCP-1. In vitro(99m)Tc-HYNIC-TCP-1 binding assays on HCT 116 cells indicated a mean Kd of 3.04±0.52nM. In cancer xenografts, (99m)Tc-TCP-1 radioactivity (%ID/g) was 1.01±0.15 in the absence of blockade and was reduced to 0.26±0.04 (PTCP-1 or HCT116 tumors with inactive peptide. Cy7-TCP-1 activity localized not only in metabolically active tumors, as defined by (18)F-FDG imaging, but also in peritumoral microvasculature. In conclusion, TCP-1 probes may have a distinct targeting mechanism with high selectivity for CRC and tumor-associated vasculature. Molecular imaging with TCP-1 probes appears promising to detect malignant colorectal lesions.

  9. 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.

  10. Ultrasound Molecular Imaging in a Human CD276 Expression-Modulated Murine Ovarian Cancer Model

    Science.gov (United States)

    Lutz, Amelie M.; Bachawal, Sunitha V.; Drescher, Charles W.; Pysz, Marybeth A.; Willmann, Jürgen K.; Gambhir, Sanjiv Sam

    2014-01-01

    Purpose To develop a mouse ovarian cancer model that allows modulating the expression levels of human vascular targets in mouse xenograft tumors and to test whether expression of CD276 during tumor angiogenesis can be visualized by molecularly targeted ultrasound in vivo. Materials and Methods CD276-expressing MS-1 mouse endothelial cells were engineered and used for co-injection with 2008 human ovarian cancer cells for subcutaneous xenograft tumor induction in 15 nude mice. Fourteen control mice were injected with 2008 cells only. After confirming their binding specificity in flow chamber cell attachment studies, anti CD276 antibody-functionalized contrast microbubbles were used for in vivo CD276-targeted contrast-enhanced ultrasound imaging. Results CD276-targeted ultrasound imaging signal was significantly higher (P=0.006) in mixed MS1/2008 tumors compared to control tumors. Compared to control microbubbles the ultrasound signal using CD276-targeted microbubbles was significantly higher (P=0.002) and blocking with purified anti-CD276 antibody significantly decreased (P=0.0096) the signal in mixed MS-1/2008 tumors. Immunofluorescence analysis of the tumor tissue confirmed higher quantitative immunofluorescence signal in mixed MS-1/2008 tumors than in control 2008 only tumors, but showed not significantly different (P=0.54) microvessel density. Conclusion Our novel small animal model allows for modulating the expression of human tumor-associated vascular endothelial imaging targets in a mouse host and these expression differences can be visualized non-invasively by ultrasound molecular imaging. The animal model can be applied to other human vascular targets and may facilitate the preclinical development of new imaging probes such as microbubbles targeted at human vascular markers not expressed in mice. PMID:24389327

  11. Molecular imaging of potential bone metastasis from differentiated thyroid cancer: a case report

    Directory of Open Access Journals (Sweden)

    Arasho Belachew

    2011-10-01

    Full Text Available Abstract Introduction Molecular imaging of the spine is a rarely used diagnostic method for which only a few case reports exist in the literature. Here, to the best of our knowledge we present the first case of a combination of molecular imaging by single photon emission computer tomography and positron emission tomography used in post-operative spinal diagnostic assessment. Case presentation We present the case of a 50-year-old Caucasian woman experiencing progressive spinal cord compression caused by a vertebral metastasis of a less well differentiated thyroid cancer. Following tumor resection and vertebral stabilization, total thyroidectomy was performed revealing follicular thyroid carcinoma pT2 pNxM1 (lung, bone. During follow-up our patient underwent five radioiodine therapy procedures (5.3 to 5.7 GBq each over a two-year period. Post-therapeutic I-131 scans showed decreasing uptake in multiple Pulmonary metastases. However, following an initial decrease, stimulated thyroglobulin remained at pathologically increased levels, indicating further neoplastic activity. F18 Fludeoxyglucose positron emission tomography, which was performed in parallel, showed remaining hypermetabolism in the lungs but no hypermetabolism of the spinal lesions correlating with the stable neurological examinations. While on single photon emission computer tomography images Pulmonary hyperfixation of I-131 disappeared (most likely indicating dedifferentiation, there was persistent spinal hyperfixation at the operated level and even higher fixation at the spinal process of L3. Based on the negative results of the spinal F18 fludeoxyglucose positron emission tomography, a decision was made not to operate again on the spine since our patient was completely asymptomatic and the neurological risk seemed to be too high. During further follow-up our patient remained neurologically stable. Conclusions Molecular imaging by F18 fludeoxyglucose positron emission tomography helps

  12. The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis.

    Science.gov (United States)

    Chowdhury, R; Ganeshan, B; Irshad, S; Lawler, K; Eisenblätter, M; Milewicz, H; Rodriguez-Justo, M; Miles, K; Ellis, P; Groves, A; Punwani, S; Ng, T

    2014-06-01

    Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm.

  13. Characterization of preclinical models of prostate cancer using PET-based molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Belloli, Sara; Moresco, Rosa M.; Picchio, Maria [Scientific Institute H San Raffaele, Department of Nuclear Medicine, Milan (Italy); IBFM, CNR, Milan (Italy); University of Milano-Bicocca, Milan (Italy); Jachetti, Elena [San Raffaele Scientific Institute, Cancer Immunotherapy and Gene Therapy Program, Milan (Italy); University of Vita-Salute, San Raffaele Institute, Fellowship of the Doctorate School of Cellular and Molecular Medicine, Milan (Italy); Lecchi, Michela [University of Milan, Institute of Radiological Sciences, Milan (Italy); Valtorta, Silvia [Scientific Institute H San Raffaele, Department of Nuclear Medicine, Milan (Italy); University of Milan, Fellowship of the Doctorate School of Molecular Medicine, Milan (Italy); Freschi, Massimo [San Raffaele Scientific Institute, Pathological Anatomy Unit, Milan (Italy); Michelini, Rodrigo Hess; Bellone, Matteo [San Raffaele Scientific Institute, Cancer Immunotherapy and Gene Therapy Program, Milan (Italy); Fazio, Ferruccio [Scientific Institute H San Raffaele, Department of Nuclear Medicine, Milan (Italy); University of Milano-Bicocca, Milan (Italy)

    2009-08-15

    Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice spontaneously develop hormone-dependent and hormone-independent prostate cancer (PC) that potentially resembles the human pathological condition. The aim of the study was to validate PET imaging as a reliable tool for in vivo assessment of disease biology and progression in TRAMP mice using radioligands routinely applied in clinical practice: [{sup 18}F]FDG and [{sup 11}C]choline. Six TRAMP mice were longitudinally evaluated starting at week 11 of age to visualize PC development and progression. The time frame and imaging pattern of PC lesions were subsequently confirmed on an additional group of five mice. PET and [{sup 18}F]FDG allowed detection of PC lesions starting from 23 weeks of age. [{sup 11}C]Choline was clearly taken up only by TRAMP mice carrying neuroendocrine lesions, as revealed by post-mortem histological evaluation. PET-based molecular imaging represents a state-of-the-art tool for the in vivo monitoring and metabolic characterization of PC development, progression and differentiation in the TRAMP model. (orig.)

  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)

    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.

  15. 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.

  16. Current status of multimodal molecular imaging of prostate cancer; Multimodale molekulare Bildgebung des Prostatakarzinoms - aktueller Stand

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N. [Universitaetsklinikum Ulm (Germany). Klinik fuer Nuklearmedizin

    2009-06-15

    Prostate carcinoma is the most common life-threatening cancer affecting men in the western world. In Germany about 40 600 new cases have to be expected each year. The mortality is around 10%. The major goals of pretherapeutic imaging are to determine the local extent of prostate carcinoma in terms of intraprostate localisation, extracapsular extension (ECE), seminal vesicle invasion (SVI), tumour infiltration into neurovascular bundles, and if this has taken place, into surrounding tissues and organs in the small pelvis, detection of loco-regional metastases via the lymph nodes and if this so, of distant metastases. Exact pretherapeutic diagnosis and staging are essential, because the tumour treatment must be selected in strict dependence on clinical tumour stage and risk profile. Both anatomic and functional molecular imaging of prostate carcinoma have advanced significantly in recent years. When there are problems with diagnosis, e.g. when prostate punch biopsies are negative while the suspicion of prostate carcinoma persists, C-11/F-18 choline PET/CT and MRI/MRS may be helpful in localising the carcinoma, revealing how the carcinoma relates to the surrounding intra- and extraprostatic structures and organs, and making a targeted repeat biopsy possible. Lymphotropic contrast agents are highly promising for accurate nodal staging of prostate carcinoma, but are not yet available for routine clinical use. In these circumstances, the sensitivity of nodal staging with the widely available imaging modalities remains difficult. There has been particularly substantial progress in the localisation of local relapse, which can be imaged with contrast-enhanced C-11-choline PET/CT and MRI in most cases when PSA is considerably below 1 ng/ml. F-18-fluoride PET/CT has proved accurate in the diagnosis of skeletal metastases from prostate carcinoma. (orig.)

  17. 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.

  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. Nanoparticles in Cancer Imaging

    Directory of Open Access Journals (Sweden)

    Mehrdad Bakhshayeshkaram

    2010-05-01

    Full Text Available Nanotechnology is an interdisciplinary field as a combination of engineering, biology and medicine. It manipulates atoms and molecules to create devices at atomic, molecular and supramolecular levels for potential clinical use. Cancer nanotechnology as the latest trend in cancer diagnosis and treatment has provided nanoscale tools like biosensors, dendrimers, quantum dots and magnetic nanoparticles such as iron oxide with unique optical, magnetic and electronic properties. They are 100 to 1,000-fold smaller than cancer cells and may be conjugated with several functional molecules like imaging probes, specific ligands and antibodies. The capability of transferring through leaky blood vessels, passive and active targeting, intracellular delivery and subcellular localization has made them dual-purpose and multifunctional probes in cancer. Conventional imaging techniques such as CT and MRI using nontargeted contrast agents have limitations in early and accurate diagnosis and monitoring of treatment that may be eventually removed through the use of nanostructures' properties."nCancer diagnosis in an early stage, which influences the patient's survival, is possible earlier than ever imaginable. For example in contrast to mammography, which can detect breast cancer when it has at least 1000,000 cells, these new tools can accurately detect the tumor when it has less than 100 cells. "nThis article is a review on applications of nanotechnology, as a rapidly growing field for cancer imaging in medicine contributing to the early detection of cancer cells through available imaging techniques.

  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. Tumor Molecular Imaging with Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhen Cheng

    2016-03-01

    Full Text Available Molecular imaging (MI can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging imaging techniques. Over the past decade, the utilization of nanotechnology in MI has exhibited many significant advantages and provided new opportunities for the imaging of living subjects. It is expected that multimodality nanoparticles (NPs can lead to precise assessment of tumor biology and the tumor microenvironment. This review addresses topics related to engineered NPs and summarizes the recent applications of these nanoconstructs in cancer optical imaging, ultrasound, photoacoustic imaging, magnetic resonance imaging (MRI, and radionuclide imaging. Key challenges involved in the translation of NPs to the clinic are discussed.

  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. Molecular imaging of a cancer-targeting theragnostics probe using a nucleolin aptamer- and microRNA-221 molecular beacon-conjugated nanoparticle.

    Science.gov (United States)

    Kim, Jin Kyeoung; Choi, Kyung-Ju; Lee, Minhyung; Jo, Mi-hee; Kim, Soonhag

    2012-01-01

    MicroRNAs (miRNA, miR) have been reported as cancer biomarkers that regulate tumor suppressor genes. Hence, simultaneous detecting and inhibiting of miRNA function will be useful as a cancer theragnostics probe to minimize side effects and invasiveness. In this study, we developed a cancer-targeting therangostics probe in a single system using an AS1411 aptamer - and miRNA-221 molecular beacon (miR-221 MB)-conjugated magnetic fluorescence (MF) nanoparticle (MFAS miR-221 MB) to simultaneously target to cancer tissue, image intracellularly expressed miRNA-221 and treat miRNA-221-involved carcinogenesis. AS1411 aptamer-conjugated MF (MFAS) nanoparticles displayed a great selectivity and delivery into various cancer cell lines. The miR-221 MB detached from the MFAS miR-221 MB in the cytoplasm of C6 cells clearly imaged miRNA-221 biogenesis and simultaneously resulted in antitumor therapeutic effects by inhibiting miRNA function, indicating a successful astrocytoma-targeting theragnostics. MFAS miRNA MB can be easily applied to other cancers by simply changing a targeted miRNA highly expressed in cancers.

  4. Recent Design Development in Molecular Imaging for Breast Cancer Detection Using Nanometer CMOS Based Sensors.

    Science.gov (United States)

    Nguyen, Dung C; Ma, Dongsheng Brian; Roveda, Janet M W

    2012-01-01

    As one of the key clinical imaging methods, the computed X-ray tomography can be further improved using new nanometer CMOS sensors. This will enhance the current technique's ability in terms of cancer detection size, position, and detection accuracy on the anatomical structures. The current paper reviewed designs of SOI-based CMOS sensors and their architectural design in mammography systems. Based on the existing experimental results, using the SOI technology can provide a low-noise (SNR around 87.8 db) and high-gain (30 v/v) CMOS imager. It is also expected that, together with the fast data acquisition designs, the new type of imagers may play important roles in the near-future high-dimensional images in additional to today's 2D imagers.

  5. 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.

  6. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-06-15

    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 (Na{sub 2}{sup 10}B{sub 12}H{sub 11}SH,BSH), a {sup 10}B 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.

  8. Choline molecular imaging with small-animal PET for monitoring tumor cellular response to photodynamic therapy of cancer

    Science.gov (United States)

    Fei, Baowei; Wang, Hesheng; Wu, Chunying; Meyers, Joseph; Xue, Liang-Yan; MacLennan, Gregory; Schluchter, Mark

    2009-02-01

    We are developing and evaluating choline molecular imaging with positron emission tomography (PET) for monitoring tumor response to photodynamic therapy (PDT) in animal models. Human prostate cancer (PC-3) was studied in athymic nude mice. A second-generation photosensitizer Pc 4 was used for PDT in tumor-bearing mice. MicroPET images with 11C-choline were acquired before PDT and 48 h after PDT. Time-activity curves of 11C-choline uptake were analyzed before and after PDT. For treated tumors, normalized choline uptake decreased significantly 48 h after PDT, compared to the same tumors pre-PDT (p detect early tumor response to PDT in the animal model of human prostate cancer.

  9. 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.

  10. A Partnership Training Program in Breast Cancer Research Using Molecular Imaging Techniques

    Science.gov (United States)

    2008-07-01

    through a 26- gauge needle attached to a 1-mL hypodermic syringe 8-10 times. Protein concentrations were determined using the BioRad Detergent-Compatible...ratio by detecting the difference in ‘molecular properties’ between cancer and normal tissues (7-9). This should, in theory , allow for detection of...models. In vitro analysis demonstrated that the TfNIR–LipNBD-CA nanocomplex dramatically improved the uptake of CA in monolayer cultures of MDA-MB

  11. Quantitative imaging as cancer biomarker

    Science.gov (United States)

    Mankoff, David A.

    2015-03-01

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

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

    Science.gov (United States)

    Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

    2013-10-01

    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 (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

  13. 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.

  14. Imaging Molecular Signatures of Breast Cancer With X-ray Activated Nano-Phosphors

    Science.gov (United States)

    2011-09-01

    shot-noise limited detection" was assumed to be too low to detect. To calculate the molar concentration, we assumed a spherical 10 nm diameter...Kandarakis et al. !a" Minimum weight concentration !in mg/ml" vs dose !Gy". !b" Minimum molar concentration !in M" vs dose !Gy". a b c d FIG. 5. Agar imaging...Contrast agents: X-ray contrast agents and molecular imaging—A contradiction ?,” Handb Exp Pharmacol 185, 167–175 񓟸#. 3R. Weissleder and M. J. Pittet

  15. 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.

  16. 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.

  17. Development of HER2-targeted nanobodies for molecular optical imaging and therapy of breast cancer

    NARCIS (Netherlands)

    Kijanka, M.M.

    2014-01-01

    Breast cancer is a complex disease and the most prevalent cancer in women worldwide. It has been estimated that 1 in 8 women and 1 in 1,000 men will develop breast cancer. Surgical-, chemical- and radiation based therapies are available to breast cancer patients. Early detection of cancer is crucial

  18. Oncological image analysis: medical and molecular image analysis

    Science.gov (United States)

    Brady, Michael

    2007-03-01

    This paper summarises the work we have been doing on joint projects with GE Healthcare on colorectal and liver cancer, and with Siemens Molecular Imaging on dynamic PET. First, we recall the salient facts about cancer and oncological image analysis. Then we introduce some of the work that we have done on analysing clinical MRI images of colorectal and liver cancer, specifically the detection of lymph nodes and segmentation of the circumferential resection margin. In the second part of the paper, we shift attention to the complementary aspect of molecular image analysis, illustrating our approach with some recent work on: tumour acidosis, tumour hypoxia, and multiply drug resistant tumours.

  19. Molecular Targeted Enhanced Ultrasound Imaging of Flk1 Reveals Diagnosis and Prognosis Potential in a Genetically Engineered Mouse Prostate Cancer Model

    Directory of Open Access Journals (Sweden)

    Jim W. Xuan

    2009-07-01

    Full Text Available Molecular imaging techniques used to detect the initiation of disease have the potential to provide the best opportunity for early treatment and cure. This report aimed at testing the possibility that Flk1+ (vascular endothelial growth factor receptor 2, a crucial angiogenesis factor of most tumor cells, could be a molecular targeted imaging marker for the diagnosis and prognosis of cancer. We performed Flk1-targeted microbubble-enhanced ultrasound (US imaging of prostate cancer in a genetically engineered mouse model with normal-appearing intact US (negative prostates and with three different tumor sizes (small, medium, and large. Higher levels of Flk1+ molecular signals were identified in the intact US (negative prostate group by US-targeted imaging and immunohistochemical analysis. The increase in Flk1+ expression occurred prior to the angiogenesis switch-on phase and vascularity peak. After this peak accumulation stage of Flk1+ molecules, lower and stabilized levels of Flk1+ signals were maintained together with tumor growth from small, to medium, to large size. In a longitudinal observation in a subset (n = 5 of mice with established tumors, elevated Flk1+ signals were observed in tissues surrounding the prostate cancer, for example, the ipsilateral boundary zones between two developing tumor lobes, new tumor blood vessel recruits, the urethra border, and the pelvic node basin. The potential of Flk1-targeted US imaging as a predictive imaging tool was confirmed by correlation studies of three-dimensional US B-mode imaging, gross pathology, and histology analyses. The results of the application in a genetically engineered mouse model with prostate cancer of molecular Flk1-targeted US imaging support the contention that Flk1 can be used as a molecular imaging marker for small tumors undetectable by microimaging and as a molecular diagnostic and prognosis marker for tumor metastasis and progression.

  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-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

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

    Science.gov (United States)

    Retnakumari, Archana; Setua, Sonali; Menon, Deepthy; Ravindran, Prasanth; Muhammed, Habeeb; Pradeep, Thalappil; Nair, Shantikumar; Koyakutty, Manzoor

    2010-02-01

    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 potential of using

  3. 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.

  4. Development and Evaluation of a Fluorescent Antibody-Drug Conjugate for Molecular Imaging and Targeted Therapy of Pancreatic Cancer.

    Directory of Open Access Journals (Sweden)

    Steve Knutson

    Full Text Available Antibodies are widely available and cost-effective research tools in life science, and antibody conjugates are now extensively used for targeted therapy, immunohistochemical staining, or in vivo diagnostic imaging of cancer. Significant advances in site-specific antibody labeling technologies have enabled the production of highly characterized and homogenous conjugates for biomedical purposes, and some recent studies have utilized site-specific labeling to synthesize bifunctional antibody conjugates with both imaging and drug delivery properties. While these advances are important for the clinical safety and efficacy of such biologics, these techniques can also be difficult, expensive, and time-consuming. Furthermore, antibody-drug conjugates (ADCs used for tumor treatment generally remain distinct from conjugates used for diagnosis. Thus, there exists a need to develop simple dual-labeling methods for efficient therapeutic and diagnostic evaluation of antibody conjugates in pre-clinical model systems. Here, we present a rapid and simple method utilizing commercially available reagents for synthesizing a dual-labeled fluorescent ADC. Further, we demonstrate the fluorescent ADC's utility for simultaneous targeted therapy and molecular imaging of cancer both in vitro and in vivo. Employing non-site-specific, amine-reactive chemistry, our novel biopharmaceutical theranostic is a monoclonal antibody specific for a carcinoembryonic antigen (CEA biomarker conjugated to both paclitaxel and a near-infrared (NIR, polyethylene glycol modified (PEGylated fluorophore (DyLight™ 680-4xPEG. Using in vitro systems, we demonstrate that this fluorescent ADC selectively binds a CEA-positive pancreatic cancer cell line (BxPC-3 in immunofluorescent staining and flow cytometry, exhibits efficient internalization kinetics, and is cytotoxic. Model studies using a xenograft of BxPC-3 cells in athymic mice also show the fluorescent ADC's efficacy in detecting tumors in

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

    Science.gov (United States)

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

    2016-01-01

    Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10(th) type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI.

  6. 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.

  7. [Molecular diagnostics and imaging].

    Science.gov (United States)

    Fink, Christian; Fisseler-Eckhoff, Annette; Huss, Ralf; Nestle, Ursula

    2009-01-01

    Molecular diagnostic methods and biological imaging techniques can make a major contribution to tailoring patients' treatment needs with regard to medical, ethical and pharmaco-economic aspects. Modern diagnostic methods are already being used to help identify different sub-groups of patients with thoracic tumours who are most likely to benefit significantly from a particular type of treatment. This contribution looks at the most recent developments that have been made in the field of thoracic tumour diagnosis and analyses the pros and cons of new molecular and other imaging techniques in day-to-day clinical practice.

  8. 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

  9. Molecular imaging I

    Energy Technology Data Exchange (ETDEWEB)

    Semmler, Wolfhard [Deutsches Krebsforschungszentrum, Heidelberg (DE). Abt. fuer Medizinische Physik in der Radiologie (E020) Forschungsschwerpunkt Innovative Krebsdiagnostik und -therapie (E); Schwaiger, Markus (eds.) [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik

    2008-07-01

    The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation. (orig.)

  10. Molecular imaging II

    Energy Technology Data Exchange (ETDEWEB)

    Semmler, Wolfhard [Deutsches Krebsforschungszentrum, Heidelberg (DE). Abt. fuer Medizinische Physik in der Radiologie (E020) Forschungsschwerpunkt Innovative Krebsdiagnostik und -therapie (E); Schwaiger, Markus (eds.) [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik

    2008-07-01

    The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation. (orig.)

  11. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    Science.gov (United States)

    2009-03-01

    Lung Cancer (NSCLC), completed a comprehensive review by our Institutional Review Board (IRB), the US Department of Defense (DoD), Genentech, and Food ...Results of the study constitute an important part in the investigational new drug (IND) application to the Food and Drug Administration (FDA) for their...treatment and survival among patients [6,7]. This results in erroneous clinical trial design/ analysis, enormous wastage of patient and monetary resources

  12. 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.

  13. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    Science.gov (United States)

    2008-03-01

    Figure 3A). Moreover, because our analysis of pNBS1 (phosphorylated Nijmegen breakage syndrome protein, also known as nibrin) foci indicated that...in combination, in NSCLC and identify molecular predictors of response. Figure 22. Gene expression in different tumors treated with SAHA and 5AZ... SAHA (HDAC inhibitor) and 5-Aza-citidine (DNMT inhibitor) treatment. We expected the treatment would activate expression of a panel of genes which

  14. 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...

  15. 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.

  16. Molecular Imaging With Quantum Dots Probing EMT and Prostate Cancer Metastasis in Live Animals

    Science.gov (United States)

    2007-10-01

    Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER...Cancer Res. 1, 1036–1047 (2003). 40. Mora , G.R., Olivier, K.R., Mitchell, R.F., Jenkins, R.B. & Tindall, D.J. Regulation of expression of the early

  17. 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.

  18. High Resolution PET Imaging Probe for the Detection, Molecular Characterization and Treatment Monitoring of Prostate Cancer

    Science.gov (United States)

    2010-07-01

    State Detector Stack for ToF-PET/MR. Nuclear Science Symposium and Medical Imaging Conference Record, 2009; 2798-2799. 27. V.C. Spanoudaki, et al...M. K., McFarlane, N., Lemon , J. A., Boreham, D. R., Maresca, K. P., Brennan, J. D., Babich, J. W., Zubieta, J., and Valliant, J. F. (2004) Bridging

  19. 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...

  20. A Partnership Training Program in Breast Cancer Research Using Molecular Imaging Techniques

    Science.gov (United States)

    2009-07-01

    Opiorphine which is about 3~6 times stronger than morphine and easily metabolized over time. A non-invasive prototype device, monitoring the...genotype effects, but no gender effects, on GFAP-immunopositive astrocytes in the amygdaloid complex and hippocampus . There were no effects on monoamine...High resolution spin echo MRI Spin-echo T2-weighted MRI was used to capture images through the entire brain and hippocampus at scan times of 1.5 h

  1. Photodynamic Molecular Beacons: An Image-Guided Therapeutic Approach to Breast Cancer Vertebral Metastases

    Science.gov (United States)

    2011-03-01

    which will restrict the drug and light doses that can be used safely. MMP PDT beacons potentially address this limitation. We have demonstrated the...Shao, R., Ji, X., Gelovani, J. G., and Li, C. (2007) A novel method for imaging in vivo degradation of poly(L-glutamic acid), a biodegradable drug ...Piwnica-Worms, D. (2003) Quantitative analysis of permeation peptide complexes labeled with Technetium-99m: chiral and sequence-specific effects on net cell

  2. High Resolution PET Imaging Probe for the Detection, Molecular Characterization and Treatment Monitoring of Prostate Cancer

    Science.gov (United States)

    2012-07-01

    detector and uncertainty in the Compton recoil electron path. Coincidence resolution between two silicon detectors operated at 136 V bias is ~50ns FWHM... Compton camera in nuclear medical imaging. IEEE Trans Nucl Sci 2002; 49:812–16. [15] Linhart V, Burdette D, Chessi E, et al. Spectroscopy study of...applications can be recognized in both emission modalities, SPECT and PET. Compton camera is a subspecies of SPECT, where a silicon based scatter as a MR

  3. 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...

  4. 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

  5. Ultrasound Molecular Imaging: Moving Towards Clinical Translation

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K.

    2015-01-01

    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. PMID:25851932

  6. Ultrasound molecular imaging: Moving toward clinical translation.

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V; Willmann, Jürgen K

    2015-09-01

    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.

  7. 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

  8. Imaging in laryngeal cancers

    Directory of Open Access Journals (Sweden)

    Varsha M Joshi

    2012-01-01

    Full Text Available Imaging plays an important complementary role to clinical examination and endoscopic biopsy in the evaluation of laryngeal cancers. A vast majority of these cancers are squamous cell carcinomas (SCC. Cross-sectional imaging with contrast-enhanced computed tomography (CT and magnetic resonance (MR imaging allows excellent depiction of the intricate anatomy of the larynx and the characteristic patterns of submucosal tumor extension. CT, MRI and more recently PET-CT, also provide vital information about the status of cervical nodal disease, systemic metastases and any synchronous malignancies. Additionally, certain imaging-based parameters like tumor volume and cartilaginous abnormalities have been used to predict the success of primary radiotherapy or surgery in these patients. Integration of radiological findings with endoscopic evaluation greatly improves the pretherapeutic staging accuracy of laryngeal cancers, and significantly impacts the choice of management strategies in these patients. Imaging studies also help in the post-therapeutic surveillance and follow-up of patients with laryngeal cancers. In this article, we review the currently used laryngeal imaging techniques and protocols, the key anatomic structures relevant to tumor spread and the characteristic patterns of submucosal extension and invasion of laryngeal cancer. The role of CT, MRI and PET-CT in the evaluation of patients with laryngeal SCC and the impact of imaging findings on prognosis and clinical management is also discussed.

  9. Cancer imaging with radiolabeled antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Goldenberg, D.M. (Center for Molecular Medicine and Immunology, Newark, NJ (US))

    1990-01-01

    This book presents a perspective of the use of antibodies to target diagnostic isotopes to tumors. Antibodies with reasonable specificity can be developed against almost any substance. If selective targeting to cancer cells can be achieved, the prospects for a selective therapy are equally intriguing. But the development of cancer detection, or imaging, with radiolabeled antibodies has depended upon advances in a number of different areas, including cancer immunology and immunochemistry for identifying suitable antigen targets and antibodies to these targets, tumor biology for model systems, radiochemistry for he attachment of radionuclides to antibodies, molecular biology for reengineering the antibodies for safer and more effective use in humans, and nuclear medicine for providing the best imaging protocols and instrumentation to detect minute amounts of elevated radioactivity against a background of considerable noise. Accordingly, this book has been organized to address the advances that are being made in many of these areas.

  10. Molecular imaging applications for immunology.

    Science.gov (United States)

    Hildebrandt, Isabel Junie; Gambhir, Sanjiv Sam

    2004-05-01

    The use of multimodality molecular imaging has recently facilitated the study of molecular and cellular events in living subjects in a noninvasive and repetitive manner to improve the diagnostic capability of traditional assays. The noninvasive imaging modalities utilized for both small animal and human imaging include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT). Techniques specific to small-animal imaging include bioluminescent imaging (BIm) and fluorescent imaging (FIm). Molecular imaging permits the study of events within cells, the examination of cell trafficking patterns that relate to inflammatory diseases and metastases, and the ability to rapidly screen new drug treatments for distribution and effectiveness. In this paper, we will review the current field of molecular imaging assays (especially those utilizing PET and BIm modalities) and examine how they might impact animal models and human disease in the field of clinical immunology.

  11. 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.

  12. Molecular photoacoustic imaging

    OpenAIRE

    Frogh Jafarian Dehkordi; Ali Mahmoud Pashazadeh; Majid Assadi

    2015-01-01

    Background: Hybrid imaging modalities which simultaneously benefit from capabilities of combined modalities provides an opportunity to modify quality of the images which can be obtained by each of the combined imaging systems. One of the imaging modalities, emerged in medical research area as a hybrid of ultrasound imaging and optical imaging, is photoacoustic imaging which apply ultrasound wave generated by tissue, after receiving laser pulse, to produce medical images. Materials and Methods...

  13. 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.

  14. 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.

  15. 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.

  16. [Imaging of cancer prostate].

    Science.gov (United States)

    Ghouadni, Mehdi; Sandoz, Catherine; Eiss, David; Cornud, François; Thiounn, Nicolas; Hélénon, Olivier

    2003-12-31

    Imaging of prostate cancer relies mainly on ultrasonography (US) and magnetic resonance imaging (MRI). It plays a diagnostic role in detecting and staging prostate carcinomas. Prostate biopsies are performed under endorectal US guidance at best with additional colour Doppler information. US also may provide useful information regarding the significance of an abnormal digital rectal examination sometimes related to some benign prostate alterations that can mimic a neoplastic nodule. In all cases imaging studies need to be interpreted in light of clinical and biological data including the results of biopsy especially in staging carcinoma with MR. Finally, CT and scintigraphy are helpful in screening for distant metastases.

  17. 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

  18. Meninges in cancer imaging.

    Science.gov (United States)

    Mahendru, G; Chong, V

    2009-10-02

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

  19. 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.)

  20. Molecular photoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Frogh Jafarian Dehkordi

    2015-04-01

    Full Text Available Background: Hybrid imaging modalities which simultaneously benefit from capabilities of combined modalities provides an opportunity to modify quality of the images which can be obtained by each of the combined imaging systems. One of the imaging modalities, emerged in medical research area as a hybrid of ultrasound imaging and optical imaging, is photoacoustic imaging which apply ultrasound wave generated by tissue, after receiving laser pulse, to produce medical images. Materials and Methods: In this review, using keywords such as photoacoustic, optoacoustic, laser-ultrasound, thermoacoustic at databases such as PubMed and ISI, studies performed in the field of photoacoustic and related findings were evaluated. Results: Photoacoustic imaging, acquiring images with high contrast and desired resolution, provides an opportunity to perform physiologic and anatomic studies. Because this technique does not use ionizing radiation, it is not restricted by the limitation of the ionizing-based imaging systems therefore it can be used noninvasively to make images from cell, vessels, whole body imaging of the animal and distinguish tumor from normal tissue. Conclusion: Photoacoustic imaging is a new method in preclinical researches which can be used in various physiologic and anatomic studies. This method, because of application of non-ionizing radiation, may resolve limitation of radiation based method in diagnostic assessments.

  1. Advances in multimodal molecular imaging.

    Science.gov (United States)

    Auletta, Luigi; Gramanzini, Matteo; Gargiulo, Sara; Albanese, Sandra; Salvatore, Marco; Greco, Adelaide

    2017-03-01

    Preclinical molecular imaging is an emerging field. Improving the ability of scientists to study the molecular basis of human pathology in animals is of the utmost importance for future advances in all fields of human medicine. Moreover, the possibility of developing new imaging techniques or of implementing old ones adapted to the clinic is a significant area. Cardiology, neurology, immunology and oncology have all been studied with preclinical molecular imaging. The functional techniques of photoacoustic imaging (PAI), fluorescence molecular tomography (FMT), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in association with each other or with the anatomic reference provided by computed tomography (CT) as well as with anatomic and functional information provided by magnetic resonance (MR) have all been proficiently applied to animal models of human disease. All the above-mentioned imaging techniques have shown their ability to explore the molecular mechanisms involved in animal models of disease. The clinical translatability of most of the techniques motivates the ongoing study of their possible fields of application. The ability to combine two or more techniques allows obtaining as much information as possible on the molecular processes involved in pathologies, reducing the number of animals necessary in each experiment. Merging molecular probes compatible with various imaging technique will further expand the capability to achieve the best results.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

    Science.gov (United States)

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-02-17

    Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

  8. 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.

  9. Molecular Testing for Gastrointestinal Cancer

    Science.gov (United States)

    Lee, Hye Seung; Kim, Woo Ho; Kwak, Yoonjin; Koh, Jiwon; Bae, Jeong Mo; Kim, Kyoung-Mee; Chang, Mee Soo; Han, Hye Seung; Kim, Joon Mee; Kim, Hwal Woong; Chang, Hee Kyung; Choi, Young Hee; Park, Ji Y.; Gu, Mi Jin; Lhee, Min Jin; Kim, Jung Yeon; Kim, Hee Sung; Cho, Mee-Yon

    2017-01-01

    With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians. PMID:28219002

  10. Evidence-Based Cancer Imaging

    Science.gov (United States)

    Khorasani, Ramin

    2017-01-01

    With the advances in the field of oncology, imaging is increasingly used in the follow-up of cancer patients, leading to concerns about over-utilization. Therefore, it has become imperative to make imaging more evidence-based, efficient, cost-effective and equitable. This review explores the strategies and tools to make diagnostic imaging more evidence-based, mainly in the context of follow-up of cancer patients.

  11. [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.

  12. Molecular Imaging of Pituitary Pathology.

    Science.gov (United States)

    de Herder, Wouter W

    2016-01-01

    The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas.

  13. 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.

  14. 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...

  15. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...... disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates...... of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, (18)F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer...

  16. Translational research of optical molecular imaging for personalized medicine.

    Science.gov (United States)

    Qin, C; Ma, X; Tian, J

    2013-12-01

    In the medical imaging field, molecular imaging is a rapidly developing discipline and forms many imaging modalities, providing us effective tools to visualize, characterize, and measure molecular and cellular mechanisms in complex biological processes of living organisms, which can deepen our understanding of biology and accelerate preclinical research including cancer study and medicine discovery. Among many molecular imaging modalities, although the penetration depth of optical imaging and the approved optical probes used for clinics are limited, it has evolved considerably and has seen spectacular advances in basic biomedical research and new drug development. With the completion of human genome sequencing and the emergence of personalized medicine, the specific drug should be matched to not only the right disease but also to the right person, and optical molecular imaging should serve as a strong adjunct to develop personalized medicine by finding the optimal drug based on an individual's proteome and genome. In this process, the computational methodology and imaging system as well as the biomedical application regarding optical molecular imaging will play a crucial role. This review will focus on recent typical translational studies of optical molecular imaging for personalized medicine followed by a concise introduction. Finally, the current challenges and the future development of optical molecular imaging are given according to the understanding of the authors, and the review is then concluded.

  17. 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 ...

  18. 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.

  19. IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

    Science.gov (United States)

    2016-04-01

    abnormalities in cancer and has succeeded in some tumor types such as chronic myeloid leukemia (CML) (Druker et al., 2004; Druker and Sawyers et al...Proof-of-concept with a reporter/ suicide gene (i.e., HSV-tk) or targeted TNF. 35 Army Award W81XWH-05-2-0027; George Simon, M.D. Final Report...cancer compared to normal cells. It regulates cellular stress responses by acting as a chaperon protein; namely, it preserves the function of proteins

  20. 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.

  1. 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.

  2. 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.)

  3. 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.

  4. Molecular imaging: current status and emerging strategies

    Energy Technology Data Exchange (ETDEWEB)

    Pysz, M.A. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States); Gambhir, S.S. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States); Departments of Bioengineering and Materials Science and Engineering, Stanford University, Stanford, CA (United States); Willmann, J.K., E-mail: willmann@stanford.ed [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States)

    2010-07-15

    In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

  5. 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.

  6. Cancer and molecular biomarkers of phase 2

    DEFF Research Database (Denmark)

    Dalhoff, Kim; Enghusen Poulsen, Henrik

    2005-01-01

    as molecular genetic biomarkers of risk. GSTM(my)1 has been associated with an increased risk of colorectal cancer, lung cancer, and bladder cancer and GSTP(pi)1 with prostate cancer. UGT1A1*28 and *37 are both associated with an increased risk of breast cancer as is SULT1A1*2. The presence of UGT1A1...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Cancer nanomedicine: from drug delivery to imaging.

    Science.gov (United States)

    Chow, Edward Kai-Hua; Ho, Dean

    2013-12-18

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

  13. Molecular therapeutics in pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Vignesh Narayanan; Colin D Weekes

    2016-01-01

    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.

  14. Miniature and Molecularly Specific Optical Screening Technologies for Breast Cancer

    Science.gov (United States)

    2008-10-01

    and molecular contrast in breast cancer V. Millon SR, Provenzano PP, Elicieri, KW, Brown, JQ, Keely, PJ, Ramanujam, N. "Imaging of ALA-induced PpIX...calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms. Appl Opt, 2006. 45(5): p. 1062-71. 4. Baumann, M., C

  15. 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.

  16. Clinical photoacoustic imaging of cancer

    Directory of Open Access Journals (Sweden)

    Keerthi S. Valluru

    2016-10-01

    Full Text Available 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.

  17. Clinical photoacoustic imaging of cancer.

    Science.gov (United States)

    Valluru, Keerthi S; Willmann, Juergen K

    2016-10-01

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

  18. Clinical photoacoustic imaging of cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-15

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

  19. 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

  20. Molecular imaging and sensing using plasmonic nanoparticles

    Science.gov (United States)

    Crow, Matthew James

    Noble metal nanoparticles exhibit unique optical properties that are beneficial to a variety of applications, including molecular imaging. The large scattering cross sections of nanoparticles provide high contrast necessary for biomarkers. Unlike alternative contrast agents, nanoparticles provide refractive index sensitivity revealing information regarding the local cellular environment. Altering the shape and composition of the nanoparticle shifts the peak resonant wavelength of scattered light, allowing for implementation of multiple spectrally distinct tags. In this project, nanoparticles that scatter in different spectral windows are functionalized with various antibodies recognizing extra-cellular receptors integral to cancer progression. A hyperspectral imaging system is developed, allowing for visualization and spectral characterization of cells labeled with these conjugates. Various molecular imaging and microspectroscopy applications of plasmonic nanoparticles are then investigated. First, anti-EGFR gold nanospheres are shown to quantitatively measure receptor expression with similar performance to fluorescence assays. Second, anti-EGFR gold nanorods and novel anti-IGF-1R silver nanospheres are implemented to indicate local cellular refractive indices. Third, because biosensing capabilities of nanoparticle tags may be limited by plasmonic coupling, polarization mapping is investigated as a method to discern these effects. Fourth, plasmonic coupling is tested to monitor HER-2 dimerization. Experiments reveal the interparticle conformation of proximal HER-2 bound labels, required for plasmonic coupling-enhanced dielectric sensing. Fifth, all three functionalized plasmonic tags are implemented simultaneously to indicate clinically relevant cell immunophenotype information and changes in the cellular dielectric environment. Finally, flow cytometry experiments are conducted utilizing the anti-EGFR nanorod tag to demonstrate profiling of receptor expression

  1. Imaging diagnostics in ovarian cancer

    DEFF Research Database (Denmark)

    Fog, Sigrid Marie Kasper Kasper; Dueholm, Margit; Marinovskij, Edvard;

    2017-01-01

    OBJECTIVE: To analyze the ability of magnetic resonance imaging (MRI) and systematic evaluation at surgery to predict optimal cytoreduction in primary advanced ovarian cancer and to develop a preoperative scoring system for cancer staging. STUDY DESIGN: Preoperative MRI and standard laparotomy were...... performed in 99 women with either ovarian or primary peritoneal cancer. Using univariate and multivariate logistic regression analysis of a systematic description of the tumor in nine abdominal compartments obtained by MRI and during surgery plus clinical parameters, a scoring system was designed....... MRI is able to assess ovarian cancer with peritoneal carcinomatosis with satisfactory concordance with laparotomic findings. This scoring system could be useful as a clinical guideline and should be evaluated and developed further in larger studies....

  2. Inorganic Nanoparticles for Multimodal Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Magdalena Swierczewska

    2011-01-01

    Full Text Available Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle-based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...... allows functional assessment with techniques such as diffusion-weighted MRI, MR spectroscopy, and dynamic contrast-enhanced MRI. The most common PET radiotracer, (18)F-fluorodeoxyglucose, is not very useful in prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET...

  4. 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.

  5. 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.

  6. Genetic and molecular changes in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Robert L Hollis; Charlie Gourley

    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.

  7. Molecular Diagnosis in Bladder Cancer

    NARCIS (Netherlands)

    T.C.M. Zuiverloon (Tahlita)

    2013-01-01

    textabstractEpidemiologyBladder cancer (BC) is the most prevalent type of urothelial cancer and is associated with thehighest costs of all cancer types due to intensive patient surveillance. Because bladder tumorsfrequently recur, patients need to be monitored extensively [1-4]. Incidence increases

  8. Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics.

    Science.gov (United States)

    Kaneda, Megan M; Caruthers, Shelton; Lanza, Gregory M; Wickline, Samuel A

    2009-10-01

    A broad array of nanomaterials is available for use as contrast agents for molecular imaging and drug delivery. Due to the lack of endogenous background signal in vivo and the high NMR sensitivity of the (19)F atom, liquid perfluorocarbon nanoemulsions make ideal agents for cellular and magnetic resonance molecular imaging. The perfluorocarbon core material is surrounded by a lipid monolayer which can be functionalized with a variety of agents including targeting ligands, imaging agents and drugs either individually or in combination. Multiple copies of targeting ligands (approximately 20-40 monoclonal antibodies or 200-400 small molecule ligands) serve to enhance avidity through multivalent interactions while the composition of the particle's perfluorocarbon core results in high local concentrations of (19)F. Additionally, lipophilic drugs contained within molecularly targeted nanoemulsions can result in contact facilitated drug delivery to target cells. Ultimately, the dual use of perfluorocarbon nanoparticles for both site targeted drug delivery and molecular imaging may provide both imaging of disease states as well as conclusive evidence that drug delivery is localized to the area of interest. This review will focus on liquid perfluorocarbon nanoparticles as (19)F molecular imaging agents and for targeted drug delivery in cancer and cardiovascular disease.

  9. Molecular imaging of head and neck cancers. Perspectives of PET/MRI; Molekulare Bildgebung bei Kopf-ï]¿Hals-Tumoren. Perspektive der PET-MRT

    Energy Technology Data Exchange (ETDEWEB)

    Stumpp, P.; Kahn, T. [Universitaetsklinikum Leipzig AoeR, Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie, Leipzig (Germany); Purz, S.; Sabri, O. [Universitaetsklinikum Leipzig, Klinik und Poliklinik fuer Nuklearmedizin, Leipzig (Germany)

    2016-07-15

    The {sup 18}F-fluorodeoxyglucose positron emission tomography-computed tomography ({sup 18}F-FDG-PET/CT) procedure is a cornerstone in the diagnostics of head and neck cancers. Several years ago PET-magnetic resonance imaging (PET/MRI) also became available as an alternative hybrid multimodal imaging method. Does PET/MRI have advantages over PET/CT in the diagnostics of head and neck cancers ?The diagnostic accuracy of the standard imaging methods CT, MRI and PET/CT is depicted according to currently available meta-analyses and studies concerning the use of PET/MRI for these indications are summarized. In all studies published up to now PET/MRI did not show superiority regarding the diagnostic accuracy in head and neck cancers; however, there is some evidence that in the future PET/MRI can contribute to tumor characterization and possibly be used to predict tumor response to therapy with the use of multiparametric imaging. Currently, {sup 18}F-FDG-PET/CT is not outperformed by PET/MRI in the diagnostics of head and neck cancers. The additive value of PET/MRI due to the use of multiparametric imaging needs to be investigated in future research. (orig.) [German] Die {sup 18}F-Fluordesoxyglukose-Positronenemissionstomographie-Computertomographie ({sup 18}F-FDG-PET-CT) hat ihren festen Stellenwert in der Diagnostik von Kopf-Hals-Tumoren. Seit einigen Jahren ist die PET-MRT als weitere hybride Bildgebungsmodalitaet verfuegbar. Bringt die PET-MRT Fortschritte bei der Diagnostik von Kopf-Hals-Tumoren ?Darstellung der diagnostischen Genauigkeit der bisherigen Bildgebungsmethoden CT, MRT und PET-CT anhand von Metaanalysen und Zusammenfassung der bisherigen Publikationen zur PET-MRT auf diesem Gebiet. Die PET-MRT zeigt in allen bisherigen Studien keine Ueberlegenheit bzgl. der diagnostischen Genauigkeit von Kopf-Hals-Tumoren. Sie kann jedoch durch die multiparametrische Diagnostik perspektivisch Beitraege zur Tumorcharakterisierung und damit moeglicherweise Voraussagen zum

  10. C-11 radiochemistry in cancer imaging applications.

    Science.gov (United States)

    Tu, Z; Mach, R H

    2010-01-01

    Carbon-11 (C-11) radiotracers are widely used for the early diagnosis of cancer, monitoring therapeutic response to cancer treatment, and pharmacokinetic investigations of anticancer drugs. PET imaging permits non-invasive monitoring of metabolic processes and molecular targets, while carbon-11 radiotracers allow a "hot-for cold" substitution of biologically active molecules. Advances in organic synthetic chemistry and radiochemistry as well as improved automated techniques for radiosynthesis have encouraged investigators in developing carbon-11 tracers for use in oncology imaging studies. The short half-life of carbon-11 (20.38 minutes) creates special challenges for the synthesis of C-11 labeled tracers; these include the challenges of synthesizing C-11 target compounds with high radiochemical yield, high radiochemical purity and high specific activity in a short time and on a very small scale. The optimization of conditions for making a carbon-11 tracer include the late introduction of the C-11 isotope, the rapid formation and purification of the target compound, and the use of automated systems to afford a high yield of the target compound in a short time. In this review paper, we first briefly introduce some basic principles of PET imaging of cancer; we then discuss principles of carbon-11 radiochemistry, focus on specific advances in radiochemistry, and describe the synthesis of C-11 radiopharmaceuticals developed for cancer imaging. The carbon-11 radiochemistry approaches described include the N,O, and S-alkylations of [(11)C]methyl iodide/[(11)C]methyl triflate and analogues of [(11)C]methyl iodide and their applications for making carbon-11 tracers; we then address recent advances in exploring a transmetallic complex mediated [(11)C]carbonyl reaction for oncologic targets.

  11. Genitourinary cancers: molecular determinants for personalized therapies.

    Science.gov (United States)

    Mazzucchelli, Roberta; Gasparrini, Silvia; Galosi, Andrea B; Massari, Francesco; Raspollini, Maria Rosaria; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-09-26

    Recent insights and emerging strategies for individualized therapeutic approaches in patients with genitourinary (GU) cancers are based on patient's genomic and cancer's molecular profiles. This depends on the significant advances made in molecular biology technologies, such as next-generation sequencing and whole-exome sequencing. The rise of such novel techniques has grayly increased our knowledge on cancer cell biology and development, thus allowing to identify complex abnormalities at the genomic level. These findings have paved the way toward what is called precision medicine, thus providing healthcare from an individual perspective in patients with GU tumors.

  12. Quantum dot-based in situ simultaneous molecular imaging and quantitative analysis of EGFR and collagen IV and identification of their prognostic value in triple-negative breast cancer.

    Science.gov (United States)

    Zheng, Hong-Mei; Chen, Chuang; Wu, Xin-Hong; Chen, Jian; Sun, Si; Sun, Jin-Zhong; Wang, Ming-Wei; Sun, Sheng-Rong

    2016-02-01

    Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with high heterogeneity and poor prognosis. Currently, the treatment effect of TNBC has reached a bottleneck, rendering new breakthroughs difficult. Cancer invasion is not an entirely cell-autonomous process, requiring the cells to transmigrate across the surrounding extracellular matrix (ECM) barriers. Developing a new system that integrates key constituents in the tumor microenvironment with pivotal cancer cell molecules is essential for the in-depth investigation of the mechanism of invasion in TNBC. We describe a computer-aided algorithm developed using quantum dot (QD)-based multiplex molecular imaging of TNBC tissues. We performed in situ simultaneous imaging and quantitative detection of epidermal growth factor receptor (EGFR), expressed in the TNBC cell membrane, and collagen IV, the major ECM constituent; calculated the EGFR/collagen IV ratio; and investigated the prognostic value of the EGFR/collagen IV ratio in TNBC. We simultaneously imaged and quantitatively detected EGFR and collagen IV in the TNBC samples. In all patients, quantitative determination showed a statistically significant negative correlation between EGFR and collagen IV. The 5-year disease-free survival (5-DFS) of the high and low EGFR/collagen IV ratio subgroups was significantly different. The EGFR/collagen IV ratio was predictive and was an independent prognostic indicator in TNBC. Compared with EGFR expression, the EGFR/collagen IV ratio had a greater prognostic value for 5-DFS. Our findings open up a new avenue for predicting the clinical outcome in TNBC from the perspective of integrating molecules expressed in both cancer cells and the ECM.

  13. 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.

  14. Molecular imaging of movement disorders

    Institute of Scientific and Technical Information of China (English)

    Karlo J Lizarraga; Alessandra Gorgulho; Wei Chen; Antonio A De Salles

    2016-01-01

    -to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy(PSP) and multiple system atrophy(MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration(CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parietooccipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.

  15. 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.

  16. Terahertz molecular resonance of cancer DNA

    Science.gov (United States)

    Cheon, Hwayeong; Yang, Hee-Jin; Lee, Sang-Hun; Kim, Young A.; Son, Joo-Hiuk

    2016-11-01

    Carcinogenesis involves the chemical and structural alteration of biomolecules in cells. Aberrant methylation of DNA is a well-known carcinogenic mechanism and a common chemical modification of DNA. Terahertz waves can directly observe changes in DNA because the characteristic energies lie in the same frequency region. In addition, terahertz energy levels are not high enough to damage DNA by ionization. Here, we present terahertz molecular resonance fingerprints of DNA methylation in cancer DNA. Methylated cytidine, a nucleoside, has terahertz characteristic energies that give rise to the molecular resonance of methylation in DNA. Molecular resonance is monitored in aqueous solutions of genomic DNA from cancer cell lines using a terahertz time-domain spectroscopic technique. Resonance signals can be quantified to identify the types of cancer cells with a certain degree of DNA methylation. These measurements reveal the existence of molecular resonance fingerprints of cancer DNAs in the terahertz region, which can be utilized for the early diagnosis of cancer cells at the molecular level.

  17. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  18. Microbubbles for Molecular Imaging and Drug Delivery

    NARCIS (Netherlands)

    I. Skachkov (Ilya)

    2016-01-01

    markdownabstractIn my thesis, microbubbles (MBs) for ultrasound (US) imaging, ultrasound molecular imaging, and drug delivery were studied. Microbubbles are gas-encapsulated lipid or polymer shell coated micro-particles, widely used as ultrasound contrast agents (UCA). MBs oscillate in response to t

  19. 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.

  20. The next few years: nuclear medicine and molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Eil, P.J. [Middlesex Hospital Mortimer Street, Institute of Nuclear Medicine, London (United Kingdom)

    2002-10-01

    Nuclear medicine in the future will be integrated in best practice in diagnosis, staging and re-staging of disease, treatment monitoring and indeed specific new therapy. Routine multi modality imaging has clearly arrived whilst some image fusion is still required. Intra and inter modality special registration is in progress. The impact of image fusion especially PET/CT on radiotherapy planning will be major. There are major developments in therapy and especially the treatment of lymphoma with new tracers such as yttrium-90 and iodine 131 labelled anti-CD monoclonal antibodies. New registered tracers are impacting. Cancer profiling will be improved with molecular phenotype with biopsy and imaging and organ staging via imaging technology. (N.C.)

  1. Molecular Imaging of Autoimmune Diseases and Inflammation

    Directory of Open Access Journals (Sweden)

    S. Anna Sargsyan

    2012-05-01

    Full Text Available Molecular imaging methods allow the noninvasive detection and localization of specific molecules. Agents that report on molecular disease biomarkers can be used to diagnose and monitor disease. Many inflammatory diseases have molecular signatures within altered tissues. Although tissue biopsy is still the gold standard for detecting these signatures, several molecular imaging markers have been developed. Pharmacologic agents that block specific immune molecules have recently entered the clinic, and these drugs have already transformed the way we care for patients with immune-mediated diseases. The use of immunomodulatory drugs is usually guided by clinical assessment of the patient's response. Unfortunately, clinical assessment may miss the signs of inflammation, and many of the serologic markers of immune-mediated diseases correlate poorly with the underlying inflammatory activity within target tissues. Molecular imaging methods have the potential to improve our ability to detect and characterize tissue inflammation. We discuss some of the molecular signatures of immune activation and review molecular imaging methods that have been developed to detect active tissue inflammation.

  2. MOLECULAR PROGNOSTIC MARKERS OF URINE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2012-01-01

    Full Text Available Bladder cancer (BC remains a current problem in oncourology. Despite that bladder cancer risk factors have been studied and described in the literature, new molecular and genetic mechanisms have been identified that predisposes to the disease development. There are numerous cellular processes involve in BC pathogenesis. The less-aggressive, non-invasive slow progressing bladder cancer types are defined by Ras-MAPK system activation. Tumors that are more aggressive and have low cancer-specific survival rate are characterized by changes in retinoblastoma genes and p53. Attempts are made to develop prognostic tests to predict tumor behavior, targeted treatment. perspectively, BC patients will be treated using molecular genetic markers allowing the accurate prediction of the patient’s tumor behavior and fitting the treatment tactics on the individual basis.

  3. Molecular breast imaging. An update; Molekulare Brustbildgebung. Ein Update

    Energy Technology Data Exchange (ETDEWEB)

    Pinker, K.; Helbich, T.H.; Magometschnigg, H.; Baltzer, P. [Medizinische Universitaet Wien, Abteilung fuer Molekulare Bildgebung, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria); Fueger, B. [Medizinische Universitaet Wien, Abteilung fuer Molekulare Bildgebung, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria); Medizinische Universitaet Wien, Abteilung fuer Nuklearmedizin, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria)

    2014-03-15

    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 ({sup 1}H-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 ({sup 23}Na-MRI), phosphorus spectroscopy ({sup 31}P-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.) [German] Die molekulare Bildgebung zielt auf die Darstellung, Beschreibung und Quantifizierung biologischer, physiologischer und pathologischer Prozesse auf zellulaerer und molekularer Ebene ab. In den letzten Jahren hat sich die molekulare Bildgebung mit ihren verschiedenen Modalitaeten in der Brustdiagnostik etabliert. Die molekularen Brustbildgebung umfasst derzeit die multiparametrische(MP)-MRT mit funktioneller und morphologischer kontrastmittelverstaerkter MRT (KM-MRT), molekularer diffusionsgewichteter Bildgebung (''diffusion-weighted imaging'', DWI) und metabolischer Protonenspektroskopie ({sup 1}H-MRSI) sowie nuklearmedizinische Verfahren (brustspezifische Gammakamerabildgebung [BSGI], Positronenemissionstomographie [PET], PET

  4. 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.

  5. Molecular and Clinical Markers of Pancreas Cancer

    OpenAIRE

    James L Buxbaum; Eloubeidi, Mohamad A

    2010-01-01

    Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those wi...

  6. 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.

  7. 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.

  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 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.

  10. [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.

  11. Molecular diagnosis of lung cancer: an overview of recent developments.

    Science.gov (United States)

    Mutti, Antonio

    2008-01-01

    Health surveillance of workers occupationally exposed to lung carcinogens calls for screening procedures which may not be fully justified, owing to current uncertainties about the outcome of early detection. Indeed, bias-free designs are difficult to set up, and the effects of lead time, length and screening biases can all result in an overestimation of the benefits of screenings, which certainly increase survival, but without any actual reduction of mortality. A major issue with modern imaging techniques is the very high incidence of discovery of lung nodules, usually false positive, but still calling for additional and sometimes painful examinations. Currently, the differential diagnosis is mainly based on additional imaging approaches, particularly positron emission tomography, which is very expensive and also shows limitations in terms of sensitivity and specificity. Therefore, purely morphological criteria seem to be insufficient to distinguish lung cancer at early stages from benign nodules with sufficient confidence. A molecular approach to the diagnosis of lung cancer through biomarkers measured by non-invasive means could greatly improve the specificity of imaging procedures. Extremely sensitive mass spectrometric techniques and polymerase chain reaction-based methods are available to detect, in accessible media, molecular alterations which characterise lung cancer at an early stage, thereby reducing the rate of false positives. The lessons learnt from decades of screening programmes based on imaging and the future prospects possibly enhanced by using biomarkers are briefly discussed in this overview. (www.actabiomedica.it)

  12. 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

  13. Molecular and Clinical Markers of Pancreas Cancer

    Directory of Open Access Journals (Sweden)

    James L Buxbaum

    2010-11-01

    Full Text Available Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those with hereditary pancreatitis and genetic syndromes which predispose to cancer. Ongoing work to identify early markers of pancreas cancer consists of high throughput discovery methods including gene arrays and proteomics as well as hypothesis driven methods. While several promising candidates have been identified none has yet been convincingly proven to be better than CA 19-9. New methods including endoscopic ultrasound are improving detection of pancreas cancer and are being used to acquire tissue for biomarker discovery.

  14. Molecular imaging of Alzheimer disease pathology.

    Science.gov (United States)

    Kantarci, K

    2014-06-01

    Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents.

  15. 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.

  16. 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

  17. Near-infrared operating lamp for intraoperative molecular imaging of a mediastinal tumor

    OpenAIRE

    2016-01-01

    Background Near-Infrared (NIR) intraoperative molecular imaging is a new diagnostic modality utilized during cancer surgery for the identification of tumors, metastases and lymph nodes. Surgeons typically use headlamps during an operation to increase visible light; however, these light sources are not adapted to function simultaneously with NIR molecular imaging technology. Here, we design a NIR cancelling headlamp and utilize it during surgery to assess whether intraoperative molecular imagi...

  18. 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.)

  19. Ovarian cancer: a molecularly insidious disease.

    Science.gov (United States)

    Mezzanzanica, Delia

    2015-01-01

    In this issue of the Chinese Journal of Cancer, European, American, and Chinese experts review the current management and future perspectives of epithelial ovarian cancer (EOC), the leading cause of gynecological cancer deaths. Although major advances have been made in understanding the cellular and molecular biology of this highly heterogeneous malignancy, the survival rate of women with EOC has changed little since the introduction of platinum-based treatment as a front-line therapy. The papers describe the progress in deciphering the molecular complexity of this disease and the newly available molecular-driven therapies, which have been applied by shifting trial designs toward restricting eligibility to specific subgroups of patients rather than testing agents in unselected populations. These new trial designs provide potential opportunities for improved efficacy in targeted populations. Given the molecular complexity of this disease, patient survival may be increased by searching for new molecular prognostic/predictive signatures as well as by translating the recent insight of microRNA involvement in EOC progression into new, targeted therapies. Particular attention has been given to the issue of fertility sparing for women affected by curable diseases.

  20. 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.)

  1. In Vivo Imaging of Molecularly Targeted Phage

    Directory of Open Access Journals (Sweden)

    Kimberly A. Kelly

    2006-12-01

    Full Text Available Rapid identification of in vivo affinity ligands would have far-reaching applications for imaging specific molecular targets, in vivo systems imaging, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biologic targets of interest in vivo. We directly labeled viable phage clones with far-red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted Protein Acidic and Rich in Cysteine (osteonectin and vascular cell adhesion molecule-1 as model targets, we show that: 1 fluorescently labeled phage retains target specificity on labeling; 2 in vivo distribution can be quantitated (detection thresholds of ~ 300 phage/mm3 tissue throughout the entire depth of the tumor using fluorescent tomographic imaging; and 3 fluorescently labeled phage itself can serve as a replenishable molecular imaging agent. The described method should find widespread application in the rapid in vivo discovery and validation of affinity ligands and, importantly, in the use of fluorochrome-labeled phage clones as in vivo imaging agents.

  2. 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.

  3. 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.

  4. [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.

  5. Towards molecular imaging by means of MRI

    NARCIS (Netherlands)

    Norek, M.

    2008-01-01

    The work presented in the thesis is focused on the design of highly efficient contrast agents for molecular imaging by means of MRI based on the detailed physical characterization of the given material. Specifically, attention is paid on the development of contrast agents for magnetic fields higher

  6. Mesoscopic and Macroscopic Optoacoustic Imaging of Cancer

    NARCIS (Netherlands)

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

    2015-01-01

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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Imaging molecular structure with photoelectron diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Boll, Rebecca

    2014-07-02

    The possibility to study the structure of polyatomic gas-phase molecules by photoelectron diffraction is investigated with the goal of developing a method capable of imaging ultrafast photochemical reactions with femtosecond temporal and sub-Angstroem spatial resolution. The fluorine 1s-level of adiabatically laser-aligned 1-ethynyl-4-fluorobenzene (C{sub 8}H{sub 5}F) molecules was ionized by X-ray pulses from the Linac Coherent Light Source Free-Electron Laser, and the angular distributions of photoelectrons with kinetic energies between 30 and 60 eV were recorded by velocity map imaging. Comparison with density functional theory calculations allows relating the measured distributions to the molecular structure. The results of an IR-pump, X-ray-probe experiment on aligned 1,4-dibromobenzene (C{sub 6}H{sub 4}Br{sub 2})molecules are presented to explore the potential of photoelectron diffraction for time-resolved imaging. The influence of the alignment laser pulse on the pumping and probing step is discussed. Laser-alignment is contrasted with determination of the molecular orientation by photoelectron-photoion coincidences for an exemplary data set on 1-ethynyl-4-fluorobenzene molecules recorded at the PETRA III synchrotron. Both methods are evaluated with respect to their applicability to record time-dependent snapshots of molecular structure. The results obtained in this work indicate possible future avenues for investigating ultrafast molecular dynamics using X-ray Free-Electron Lasers.

  12. Imaging molecular geometry with electron momentum spectroscopy

    Science.gov (United States)

    Wang, Enliang; Shan, Xu; Tian, Qiguo; Yang, Jing; Gong, Maomao; Tang, Yaguo; Niu, Shanshan; Chen, Xiangjun

    2016-12-01

    Electron momentum spectroscopy is a unique tool for imaging orbital-specific electron density of molecule in momentum space. However, the molecular geometry information is usually veiled due to the single-centered character of momentum space wavefunction of molecular orbital (MO). Here we demonstrate the retrieval of interatomic distances from the multicenter interference effect revealed in the ratios of electron momentum profiles between two MOs with symmetric and anti-symmetric characters. A very sensitive dependence of the oscillation period on interatomic distance is observed, which is used to determine F-F distance in CF4 and O-O distance in CO2 with sub-Ångström precision. Thus, using one spectrometer, and in one measurement, the electron density distributions of MOs and the molecular geometry information can be obtained simultaneously. Our approach provides a new robust tool for imaging molecules with high precision and has potential to apply to ultrafast imaging of molecular dynamics if combined with ultrashort electron pulses in the future.

  13. 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.

  14. 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.

  15. 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.

  16. Molecular imaging using sodium iodide symporter (NIS)

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Je Yoel [School of Dentistry, Kyungpook National Univ., Daegu (Korea, Republic of)

    2004-04-01

    Radioiodide uptake in thyroid follicular epithelial cells, mediated by a plasma membrane transporter, sodium iodide symporter (NIS), provides a first step mechanism for thyroid cancer detection by radioiodide injection and effective radioiodide treatment for patients with invasive, recurrent, and/or metastatic thyroid cancers after total thyroidectomy. NIS gene transfer to tumor cells may significantly and specifically enhance internal radioactive accumulation of tumors following radioiodide administration, and result in better tumor control. NIS gene transfers have been successfully performed in a variety of tumor animal models by either plasmid-mediated transfection or virus (adenovirus or retrovirus)-mediated gene delivery. These animal models include nude mice xenografted with human melanoma, glioma, breast cancer of prostate cancer, rats with subcutaneous thyroid tumor implantation, as well as the rat intracranial glioma model. In these animal models, non-invasive imaging of in vivo tumors by gamma camera scintigraphy after radioiodide or technetium injection has been performed successfully, suggesting that the NIS can serve as an imaging reporter gene for gene therapy trials. In addition, the tumor killing effects of I-131, ReO4-188 and At-211 after NIS gene transfer have been demonstrated in in vitro clonogenic assays and in vivo radioiodide therapy studies, suggesting that NIS gene can also serve as a therapeutic requires a more efficient and specific system of gene delivery with better retention of radioiodide in tumor. Results thus far are, however, promising, and suggest that NIS gene transfer followed by radioiodide treatment will allow non-invasive in vivo imaging to assess the outcome of gene therapy and provide a therapeutic strategy for a variety of human diseases.

  17. 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

  18. 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.

  19. Molecular orbital imaging for partially aligned molecules

    Science.gov (United States)

    Qin, Meiyan; Zhu, Xiaosong

    2017-01-01

    We investigate molecular orbital reconstruction using high-order harmonic emissions from partially aligned molecular ensembles. By carrying out the reconstruction procedure using the harmonic sampling with or without the spectral minimum, the roles of the harmonic phase and amplitude modulation due to the partial alignment can be separately studied. It is found that with the prior knowledge of the orbital symmetry, the reconstructed result is very sensitive to the modulation of the harmonic phase for the πg orbital, while in the case of σg orbital, the reconstructed result is mainly determined by the harmonic amplitude. These results can provide an important reference for the future experiment of molecular orbital imaging.

  20. Quantitative, Noninvasive Imaging of DNA Damage in Vivo of Prostate Cancer Therapy by Transurethral Photoacoustic (TUPA) Imaging

    Science.gov (United States)

    2014-10-01

    Photoacoustic (TUPA) Imaging PRINCIPAL INVESTIGATOR: Liangzhong Xiang CONTRACTING ORGANIZATION: The Leland Stanford Junior University Stanford, CA...NUMBER Prostate Cancer Therapy by Transurethral Photoacoustic Imaging 5b. GRANT NUMBER W81XWH-13-1-0481 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S... Photoacoustic (TUPA) Imaging, which utilizing a small catheter into the urethra enabling imaging molecular marker of DNA Damage during prostate radiation

  1. 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

  2. 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

  3. Molecular cytogenetic applications in analysis of the cancer genome.

    Science.gov (United States)

    Rao, Pulivarthi H; Nandula, Subhadra V; Murty, Vundavalli V

    2007-01-01

    Cancer cells exhibit nonrandom and complex chromosome abnormalities. The role of genomic changes in cancer is well established. However, the identification of complex and cryptic chromosomal changes is beyond the resolution of conventional banding methods. The fluorescence microscopy afforded by imaging technologies, developed recently, facilitates a precise identification of these chromosome alterations in cancer. The three most commonly utilized molecular cytogenetics methods comparative genomic hybridization, spectral karyotype, and fluorescence in situ hybridization, that have already become benchmark tools in cancer cytogenetics, are described in this chapter. Comparative genomic hybridization is a powerful tool for screening copy-number changes in tumor genomes without the need for preparation of metaphases from tumor cells. Multicolor spectral karyotype permits visualization of all chromosomes in one experiment permitting identification of precise chromosomal changes on metaphases derived from tumor cells. The uses of fluorescence in situ hybridization are diverse, including mapping of alteration in single copy genes, chromosomal regions, or entire chromosomes. The opportunities to detect genetic alterations in cancer cells continue to evolve with the use of these methodologies both in diagnosis and research.

  4. Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

    Science.gov (United States)

    2015-07-01

    BAG1, ER, PGR, BCL2, SCUBE2, ACTB, GAPDH, RPLPO, GUS, TFRC) to stratify risk of recurrence, and relative benefit of adjuvant chemotherapy. This explosion...and relative benefit of adjuvant chemotherapy. This explosion in biomarkers poses both cost and logical selection challenges. In addition, these...western and qRT-PCR) will be performed in the Borowsky lab at UC Davis. All NanoSIMS imaging, initial image analysis, image segmentation and data output

  5. 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.

  6. A review of NIR dyes in cancer targeting and imaging.

    Science.gov (United States)

    Luo, Shenglin; Zhang, Erlong; Su, Yongping; Cheng, Tianmin; Shi, Chunmeng

    2011-10-01

    The development of multifunctional agents for simultaneous tumor targeting and near infrared (NIR) fluorescence imaging is expected to have significant impact on future personalized oncology owing to the very low tissue autofluorescence and high tissue penetration depth in the NIR spectrum window. Cancer NIR molecular imaging relies greatly on the development of stable, highly specific and sensitive molecular probes. Organic dyes have shown promising clinical implications as non-targeting agents for optical imaging in which indocyanine green has long been implemented in clinical use. Recently, significant progress has been made on the development of unique NIR dyes with tumor targeting properties. Current ongoing design strategies have overcome some of the limitations of conventional NIR organic dyes, such as poor hydrophilicity and photostability, low quantum yield, insufficient stability in biological system, low detection sensitivity, etc. This potential is further realized with the use of these NIR dyes or NIR dye-encapsulated nanoparticles by conjugation with tumor specific ligands (such as small molecules, peptides, proteins and antibodies) for tumor targeted imaging. Very recently, natively multifunctional NIR dyes that can preferentially accumulate in tumor cells without the need of chemical conjugation to tumor targeting ligands have been developed and these dyes have shown unique optical and pharmaceutical properties for biomedical imaging with superior signal-to-background contrast index. The main focus of this article is to provide a concise overview of newly developed NIR dyes and their potential applications in cancer targeting and imaging. The development of future multifunctional agents by combining targeting, imaging and even therapeutic routes will also be discussed. We believe these newly developed multifunctional NIR dyes will broaden current concept of tumor targeted imaging and hold promise to make an important contribution to the diagnosis

  7. 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.

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

    Science.gov (United States)

    Langsner, Robert James

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

  9. 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.

  10. 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.

  11. Clinical Advances in Molecular Biomarkers for Cancer Diagnosis and Therapy

    OpenAIRE

    Sarkar, Fazlul H.; Philip, Philip A.; Seema Sethi; Shadan Ali

    2013-01-01

    Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer...

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

    Science.gov (United States)

    Dehghan Khalilabad, Nastaran; Hassanpour, Hamid

    2017-02-01

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

  13. 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.

  14. Diffusion MR Imaging of the Brain in Patients with Cancer

    Directory of Open Access Journals (Sweden)

    J. Matthew Debnam

    2011-01-01

    Full Text Available Over the last several years, there has been significant advancement in the molecular characterization of intracranial diseases, particularly cerebral neoplasms. While nuclear medicine technology, including PET/CT, has been at the foreground of exploration, new MR imaging techniques, specifically diffusion-weighted and diffusion tensor imaging, have shown interesting applications towards advancing our understanding of cancer involving the brain. In this paper, we review the fundamentals and basic physics of these techniques, and their applications to patient care for both general diagnostic use and in answering specific questions in selection of patients in terms of expected response to treatment.

  15. Molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy.

    Science.gov (United States)

    Yip, Linwah

    2015-01-01

    Molecular markers including gene expression profiles, somatic gene alterations, and circulating peripheral markers have augmented diagnostic, prognostic, and therapeutic options for thyroid cancer patients.

  16. 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.

  17. Radiolabeled nanogels for nuclear molecular imaging.

    Science.gov (United States)

    Singh, Smriti; Bingöl, Bahar; Morgenroth, Agnieszka; Mottaghy, Felix M; Möller, Martin; Schmaljohann, Jörn

    2013-04-12

    An efficient and simple synthesis approach to form stable (68) Ga-labeled nanogels is reported and their fundamental properties investigated. Nanogels are obtained by self-assembly of amphiphilic statistical prepolymers derivatised with chelating groups for radiometals. The resulting nanogels exhibit a well-defined spherical shape with a diameter of 290 ± 50 nm. The radionuclide (68) Ga is chelated in high radiochemical yields in an aqueous medium at room temperature. The phagocytosis assay demonstrates a highly increased internalization of nanogels by activated macrophages. Access to these (68) Ga-nanogels will allow the investigation of general behavior and clearance pathways of nanogels in vivo by nuclear molecular imaging.

  18. Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

    Science.gov (United States)

    2015-07-01

    situ hybridization and subcellular metabolic analysis . The extended applications of MIBI taken with the gains Angelo et al. Page 7 Nat Med. Author...clinical deployment of this technology would extend multiplexed expression analysis typically restricted to flow cytometry of cell suspensions (such as...range of quantitation. We propose to develop assays and analysis tools to evaluate breast cancer tissues using formal fixed and paraffin embedded

  19. Optical imaging for breast cancer prescreening

    Directory of Open Access Journals (Sweden)

    Godavarty A

    2015-07-01

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

  20. 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. Molecular imaging of tumour hypoxia;Imagerie moleculaire de l'hypoxie tumorale

    Energy Technology Data Exchange (ETDEWEB)

    Huchet, A.; Maire, J.P.; Trouette, R. [Hopital Saint-Andre, CHU de Bordeaux, Service d' Oncologie Medicale et de Radiotherapie, 33 - Bordeaux (France); Fernandez, P.; Allard, M. [CHU de Bordeaux, Service de Medecine Nucleaire, 33 - Bordeaux (France); Belkacemi, Y. [Hopital Henri-Mondor, AP-HP, Oncologie-radiotherapie, 94 - Creteil (France); Eimer, S. [CHU de Bordeaux, Service d' Anatomopathologie, 33 - Bordeaux (France); Tourdias, T. [CHU de Bordeaux, Service de Neuroradiologie, 33 - Bordeaux (France); Loiseau, H. [CHU de Bordeaux, Clinique universitaire de Neurochirurgie, 33 - Bordeaux (France); Huchet, A.; Fernandez, P.; Allard, M.; Maire, J.P.; Eimer, S.; Tourdias, T.; Loiseau, H. [Bordeaux-2 Univ., 33 - Bordeaux (France); Belkacemi, Y. [Paris-12 Univ., 94 - Creteil (France)

    2009-12-15

    By allowing an earlier diagnosis and a more exhaustive assessment of extension of the disease, the tomography by emission of positrons (PET) transforms the care of numerous cancers. At present, {sup 18}F-fluorodeoxyglucose ([{sup 18}F]-F.D.G.) imaging appears as the only one available but new molecular markers are being developed. In the next future they would modify the approach of cancers. In this context, the molecular imaging of the hypoxia and especially the {sup 18}Fluoromisonidazole PET ([{sup 18}F]-MISO PET) can give supplementary information allowing the mapping of hypoxic regions within the tumour. Because of the links, which exist between tumour hypoxia and treatment resistance of very numerous cancers, this information can have an interest, for determination of prognosis as well as for the delineation, volumes to be irradiated. Head and neck tumours are doubtless those for which the literature gives the most elements on the therapeutic impact of tumour hypoxia. Targeted therapies, based on hypoxia, already exist and the contribution of the molecular imaging could be decisive in the evaluation of the impact of such treatment. Molecular imaging of brain tumours remains to be developed. The potential contributions of the [{sup 18}F]-MISO PET for the care of these patients need to be confirmed. In this context, we propose a review of hypoxia molecular imaging taking as examples head and neck tumours and glioblastomas (GB), two tumours for which hypoxia is one of the key factors to overcome in order to increase therapeutics results

  2. Review: Receptor Targeted Nuclear Imaging of Breast Cancer.

    Science.gov (United States)

    Dalm, Simone U; Verzijlbergen, John Fred; De Jong, Marion

    2017-01-26

    Receptor targeted nuclear imaging directed against molecular markers overexpressed on breast cancer (BC) cells offers a sensitive and specific method for BC imaging. Currently, a few targets such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), somatostatin receptor (SSTR), and the gastrin releasing peptide receptor (GRPR) are being investigated for this purpose. Expression of these targets is BC subtype dependent and information that can be gained from lesion visualization is dependent on the target; ER-targeting radiotracers, e.g., can be used to monitor response to anti-estrogen treatment. Here we give an overview of the studies currently under investigation for receptor targeted nuclear imaging of BC. Main findings of imaging studies are summarized and (potential) purposes of lesion visualization by targeting these molecular markers are discussed. Since BC is a very heterogeneous disease and molecular target expression can vary per subtype, but also during disease progression or under influence of treatment, radiotracers for selected imaging purposes should be chosen carefully.

  3. Review: Receptor Targeted Nuclear Imaging of Breast Cancer

    Science.gov (United States)

    Dalm, Simone U.; Verzijlbergen, John Fred; De Jong, Marion

    2017-01-01

    Receptor targeted nuclear imaging directed against molecular markers overexpressed on breast cancer (BC) cells offers a sensitive and specific method for BC imaging. Currently, a few targets such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), somatostatin receptor (SSTR), and the gastrin releasing peptide receptor (GRPR) are being investigated for this purpose. Expression of these targets is BC subtype dependent and information that can be gained from lesion visualization is dependent on the target; ER-targeting radiotracers, e.g., can be used to monitor response to anti-estrogen treatment. Here we give an overview of the studies currently under investigation for receptor targeted nuclear imaging of BC. Main findings of imaging studies are summarized and (potential) purposes of lesion visualization by targeting these molecular markers are discussed. Since BC is a very heterogeneous disease and molecular target expression can vary per subtype, but also during disease progression or under influence of treatment, radiotracers for selected imaging purposes should be chosen carefully. PMID:28134770

  4. 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).

  5. Optical imaging of RNAi-mediated silencing of cancer

    Science.gov (United States)

    Ochiya, Takahiro; Honma, Kimi; Takeshita, Fumitaka; Nagahara, Shunji

    2008-02-01

    RNAi has rapidly become a powerful tool for drug target discovery and validation in an in vitro culture system and, consequently, interest is rapidly growing for extension of its application to in vivo systems, such as animal disease models and human therapeutics. Cancer is one obvious application for RNAi therapeutics, because abnormal gene expression is thought to contribute to the pathogenesis and maintenance of the malignant phenotype of cancer and thereby many oncogenes and cell-signaling molecules present enticing drug target possibilities. RNAi, potent and specific, could silence tumor-related genes and would appear to be a rational approach to inhibit tumor growth. In subsequent in vivo studies, the appropriate cancer model must be developed for an evaluation of siRNA effects on tumors. How to evaluate the effect of siRNA in an in vivo therapeutic model is also important. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide cancer inhibition in real time and are sensitive to subtle changes, are crucial for rapid advancement of these approaches. Bioluminescent imaging is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. Ultrasound Imaging Methods for Breast Cancer Detection

    NARCIS (Netherlands)

    Ozmen, N.

    2014-01-01

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

  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. Molecular Imaging to Identify Tumor Recurrence following Chemoradiation in a Hostile Surgical Environment

    Directory of Open Access Journals (Sweden)

    Olugbenga T. Okusanya

    2015-01-01

    Full Text Available Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

  14. Molecular hydrogen polarization images of OMC-1

    Science.gov (United States)

    Burton, Michael G.; Minchin, N. R.; Hough, J. H.; Aspin, C.; Axon, D. J.

    1991-01-01

    An image of the polarization of the shocked H2 v = 1-0 S(1) line emission in the core of OMC-1 has been obtained. Along the molecular outflow of the source, the line is dichroically polarized by a medium of aligned grains located between the earth and the shock fronts. The polarization pattern traces the magnetic field direction, which is parallel to the outflow axis and to the large-scale field direction determined from far-IR continuum measurements. Close to the IR source IRc2, the likely source of the outflow, the aligned vectors twist, indicating that the magnetic field direction changes. Modeling the line ratios of scattered H2 lines in the reflection nebula, it is concluded that the size distribution of grains there is typical of the small grains in the diffuse interstellar medium. By contrast, the scattered continuum radiation from the core region suggests that the grains there are larger than this.

  15. Molecular ultrasound imaging: current status and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Deshpande, N. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California (United States); Needles, A. [Visualsonics, Toronto (Canada); Willmann, J.K., E-mail: willmann@stanford.ed [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California (United States)

    2010-07-15

    Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionising irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of pre-clinical and clinical ultrasound systems, the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic.

  16. 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.

  17. 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.

  18. Molecular Imaging Of Metabolic Reprogramming In Mutant IDH Cells

    Directory of Open Access Journals (Sweden)

    Pavithra eViswanath

    2016-03-01

    Full Text Available Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70-90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutarate (α-KG. Mutations in the enzyme lead to loss of wild-type enzymatic activity and a neomorphic activity that converts α-KG to 2-hydroxyglutarate (2-HG. In turn, 2-HG, which has been termed an oncometabolite, inhibits key α-KG- dependent enzymes, resulting in alterations of the cellular epigenetic profile and, subsequently, inhibition of differentiation and initiation of tumorigenesis. In addition, it is now clear that the IDH mutation also induces a broad metabolic reprogramming that extends beyond 2-HG production, and this reprogramming often differs from what has been previously reported in other cancer types. In this review we will discuss in detail what is known to date about the metabolic reprogramming of mutant IDH cells and how this reprogramming has been investigated using molecular metabolic imaging. We will describe how metabolic imaging has helped shed light on the basic biology of mutant IDH cells and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor mutant IDH tumors in vivo.

  19. 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).

  20. 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.

  1. Near-infrared autofluorescence imaging for colonic cancer detection

    Science.gov (United States)

    Shao, Xiaozhuo; Zheng, Wei; Huang, Zhiwei

    2009-11-01

    We explore an NIR autofluorescence imaging technique for cancer diagnosis and detection. A set of tissue images including NIR white light images, autofluorescence (AF) images and fluorescence polarized images (FPI) (parallel-, and perpendicular- polarization) were acquired in tandem on human colonic tissues. The results show that NIR fluorescence intensity of normal tissue is significantly higher than that of cancer tissue. The perpendicular-polarization image yields the highest diagnostic accuracy 93% compared to other imaging modes. This work demonstrates that Fluorescence polarization imaging (FPI) technique has great potential for cancer diagnosis and detection in the colon.

  2. Click reaction: An applicable radiolabeling method for molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Ji Young; Lee, Byung Chul [Dept. of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Sungnam (Korea, Republic of)

    2015-12-15

    In recent years, the click reaction has found rapidly growing applications in the field of radiochemistry, ranging from a practical labeling method to molecular imaging of biomacromolecules. This present review details the development of highly reliable, powerful and selective click chemistry reactions for the rapid synthesis of new radiotracers for molecular imaging.

  3. Molecular Imaging and Therapy of Merkel Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Volkan Beylergil

    2014-04-01

    Full Text Available Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC, a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

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

    Science.gov (United States)

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

    2016-03-01

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

  5. 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

  6. Polymer nanoassemblies for cancer treatment and imaging.

    Science.gov (United States)

    Lee, Hyun Jin; Ponta, Andrei; Bae, Younsoo

    2010-12-01

    Amphiphilic polymers represented by block copolymers self-assemble into well-defined nanostructures capable of incorporating therapeutics. Polymer nanoassemblies currently developed for cancer treatment and imaging are reviewed in this article. Particular attention is paid to three representative polymer nanoassemblies: polymer micelles, polymer micellar aggregates and polymer vesicles. Rationales, design and performance of these polymer nanoassemblies are addressed, focusing on increasing the solubility and chemical stability of drugs. Also discussed are polymer nanoassembly formation, the distribution of polymer materials in the human body and applications of polymer nanoassemblies for combined therapy and imaging of cancer. Updates on tumor-targeting approaches, based on preclinical and clinical results are provided, as well as solutions for current issues that drug-delivery systems have, such as in vivo stability, tissue penetration and therapeutic efficacy. These are discussed to provide insights on the future development of more effective polymer nanoassemblies for the delivery of therapeutics in the body.

  7. OPTIMIZATION OF DIAGNOSTIC IMAGING IN BREAST CANCER

    Directory of Open Access Journals (Sweden)

    S. A. Velichko

    2015-01-01

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

  8. 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.

  9. Imaging Prostate Cancer (PCa) Phenotype and Evolution

    Science.gov (United States)

    2015-10-01

    it inhibited aconitase activity or expression. On the other hand, no changes were detected at any time in the rate of incorporation of 2-13C-acetate...deplete the tumor of iron. Decreases in tumor iron concentration induced by DFP are expected to be detectable by MRI using spin echo T2 (spin-spin...1 AWARD NUMBER: W81XWH-13-1-0386 TITLE: Imaging Prostate Cancer (PCa) Phenotype and Evolution PRINCIPAL INVESTIGATOR: Jason A. Koutcher

  10. The current state of molecular cytogenetics in cancer diagnosis.

    Science.gov (United States)

    Liehr, Thomas; Othman, Moneeb A K; Rittscher, Katharina; Alhourani, Eyad

    2015-04-01

    Cytogenetics and molecular cytogenetics are and will continue to be indispensable tools in cancer diagnostics. Leukemia and lymphoma diagnostics are still emphases of routine (molecular) cytogenetics and corresponding studies of solid tumors gain more and more prominence. Here, first a historical perspective of molecular tumor cytogenetics is provided, which is followed by the basic principles of the fluorescence in situ hybridization (FISH) approach. Finally the current state of molecular cytogenetics in cancer diagnostics is discussed. Nowadays routine diagnostics includes basic FISH approaches rather than multicolor-FISH. The latter together with modern high-throughput methods have their impact on research to identify new tumor-associated genomic regions.

  11. Functional CT imaging of prostate cancer

    Science.gov (United States)

    Henderson, Elizabeth; Milosevic, Michael F.; Haider, Masoom A.; Yeung, Ivan W. T.

    2003-09-01

    The purpose of this paper is to investigate the distribution of blood flow (F), mean capillary transit time (Tc), capillary permeability (PS) and blood volume (vb) in prostate cancer using contrast-enhanced CT. Nine stage T2-T3 prostate cancer patients were enrolled in the study. Following bolus injection of a contrast agent, a time series of CT images of the prostate was acquired. Functional maps showing the distribution of F, Tc, PS and vb within the prostate were generated using a distributed parameter tracer kinetic model, the adiabatic approximation to the tissue homogeneity model. The precision of the maps was assessed using covariance matrix analysis. Finally, maps were compared to the findings of standard clinical investigations. Eight of the functional maps demonstrated regions of increased F, PS and vb, the locations of which were consistent with the results of standard clinical investigations. However, model parameters other than F could only be measured precisely within regions of high F. In conclusion functional CT images of cancer-containing prostate glands demonstrate regions of elevated F, PS and vb. However, caution should be used when applying a complex tracer kinetic model to the study of prostate cancer since not all parameters can be measured precisely in all areas.

  12. 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.

  13. Photothermal cancer therapy and imaging based on gold nanorods.

    Science.gov (United States)

    Choi, Won Il; Sahu, Abhishek; Kim, Young Ha; Tae, Giyoong

    2012-02-01

    Gold nanorods (GNRs), which strongly absorb near-infrared (NIR) light, have shown great potential in fields of biomedical application. These include photothermal therapy, molecular imaging, biosensing, and gene delivery, especially for the treatment of diseased tissues such as cancer. These biomedical applications of GNRs arise from their various useful properties; photothermal (nanoheater) properties, efficient large scale synthesis, easy functionalization, and colloidal stability. In addition, GNRs do not decompose and have an enhanced scattering signal and tunable longitudinal plasmon absorption which allow them to be used as a stable contrast agent. Therefore, GNRs are also promising theranostic agents, combining both tumor diagnosis and treatment. In this review, we discuss the recent progress of in vitro and in vivo explorations of the diagnostic and therapeutic applications of GNRs as a component of cancer therapy.

  14. 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.

  15. Molecular cytogenetics: recent developments and applications in cancer.

    Science.gov (United States)

    Das, K; Tan, P

    2013-10-01

    Aneuploidy or alteration in chromosome numbers is a characteristic feature in cancer that is generally a consequence of defective chromosome segregation during cell division. Molecular cytogenetic analyses have conferred substantial evidence with regards to the chromosomal architectures in cancer. Most importantly, the fluorescence in situ hybridization (FISH) technique that plays a leading role in diagnostic pathology for its single-cell analysis has provided crucial information regarding genomic variations in malignant cells. Further development of molecular cytogenetic methodologies such as chromosome specific FISH karyotyping and comparative genomic hybridization have also helped in the detection of cryptic genetic changes in cancer. But, the recent advancement of high throughput sequencing technologies have provided a more comprehensive genomic analyses resulting in novel chromosome rearrangements, somatic mutations as well as identification of fusion genes leading to new therapeutic targets. This review highlights the application of early molecular cytogenetics and the recent high throughput genomic approaches in characterizing various cancers and their invaluable support in cancer therapeutics.

  16. Resonance Energy Transfer Molecular Imaging Application in Biomedicine

    Directory of Open Access Journals (Sweden)

    NIE Da-hong1,2;TANG Gang-hua1,3

    2016-11-01

    Full Text Available Resonance energy transfer molecular imaging (RETI can markedly improve signal intensity and tissue penetrating capacity of optical imaging, and have huge potential application in the deep-tissue optical imaging in vivo. Resonance energy transfer (RET is an energy transition from the donor to an acceptor that is in close proximity, including non-radiative resonance energy transfer and radiative resonance energy transfer. RETI is an optical imaging technology that is based on RET. RETI mainly contains fluorescence resonance energy transfer imaging (FRETI, bioluminescence resonance energy transfer imaging (BRETI, chemiluminescence resonance energy transfer imaging (CRETI, and radiative resonance energy transfer imaging (RRETI. RETI is the hot field of molecular imaging research and has been widely used in the fields of biology and medicine. This review mainly focuses on RETI principle and application in biomedicine.

  17. Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer.

    NARCIS (Netherlands)

    Hamakawa, H.; Nakashiro, K.; Sumida, T.; Shintani, S.; Myers, J.N.; Takes, R.P.; Rinaldo, A.; Ferlito, A.

    2008-01-01

    BACKGROUND: Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The a

  18. Bispecific Antibody Pretargeting for Improving Cancer Imaging and Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sharkey, Robert M.

    2005-02-04

    The main objective of this project was to evaluate pretargeting systems that use a bispecific antibody (bsMAb) to improve the detection and treatment of cancer. A bsMAb has specificity to a tumor antigen, which is used to bind the tumor, while the other specificity is to a peptide that can be radiolabeled. Pretargeting is the process by which the unlabeled bsMAb is given first, and after a sufficient time (1-2 days) is given for it to localize in the tumor and clear from the blood, a small molecular weight radiolabeled peptide is given. According to a dynamic imaging study using a 99mTc-labeled peptide, the radiolabeled peptide localizes in the tumor in less than 1 hour, with > 80% of it clearing from the blood and body within this same time. Tumor/nontumor targeting ratios that are nearly 50 times better than that with a directly radiolabeled Fab fragment have been observed (Sharkey et al., ''Signal amplification in molecular imaging by a multivalent bispecific nanobody'' submitted). The bsMAbs used in this project have been composed of 3 antibodies that will target antigens found in colorectal and pancreatic cancers (CEA, CSAp, and MUC1). For the ''peptide binding moiety'' of the bsMAb, we initially examined an antibody directed to DOTA, but subsequently focused on another antibody directed against a novel compound, HSG (histamine-succinyl-glycine).

  19. Luminescence imaging using radionuclides: a potential application in molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Chan [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Il An, Gwang [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Park, Se-Il [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Oh, Jungmin [Korea Basic Science Institute Chuncheon Center, Gangwon-do 200-701 (Korea, Republic of); Kim, Hong Joo [Department of Physics and Energy Science, Kyungpook National University, Daegu 702-710 (Korea, Republic of); Su Ha, Yeong; Wang, Eun Kyung [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Min Kim, Kyeong; Kim, Jung Young [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jaetae [Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Welch, Michael J. [Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Yoo, Jeongsoo, E-mail: yooj@knu.ac.k [Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

    2011-04-15

    Introduction: Nuclear and optical imaging are complementary in many aspects and there would be many advantages when optical imaging probes are prepared using radionuclides rather than classic fluorophores, and when nuclear and optical dual images are obtained using single imaging probe. Methods: The luminescence intensities of various radionuclides having different decay modes have been assayed using luminescence imaging and in vitro luminometer. Radioiodinated Herceptin was injected into a tumor-bearing mouse, and luminescence and microPET images were obtained. The plant dipped in [{sup 32}P]phosphate solution was scanned in luminescence mode. Radio-TLC plate was also imaged in the same imaging mode. Results: Radionuclides emitting high energy {beta}{sup +}/{beta}{sup -} particles showed higher luminescence signals. NIH3T6.7 tumors were detected in both optical and nuclear imaging. The uptake of [{sup 32}P]phosphate in plant was easily followed by luminescence imaging. Radio-TLC plate was visualized and radiochemical purity was quantified using luminescence imaging. Conclusion: Many radionuclides with high energetic {beta}{sup +} or {beta}{sup -} particles during decay were found to be imaged in luminescence mode due mainly to Cerenkov radiation. 'Cerenkov imaging' provides a new optical imaging platform and an invaluable bridge between optical and nuclear imaging. New optical imaging probes could be easily prepared using well-established radioiodination methods. Cerenkov imaging will have more applications in the research field of plant science and autoradiography.

  20. A Molecular Epidemiologic Case-Case Study of Prostate Cancer

    Science.gov (United States)

    2002-03-01

    Receptor Polymorphism and Prostate Cancer Risk 1 Sara S. Strom 2, Qiang Zhang, Yun Gu, Margaret R. Spitz, Peter T. Scardino 3, Christopher J. Logothetis...Taylor, J. A. Vitamin D receptor polymorphisms and prostate cancer. Molecular Carcinogenesis, 27: 18-23, 2000. 6. Ma, J., Stampfer , M. J., Gann, P. H...Margaret R. Spitz, Richard J. Babaian, Christopher Logothetis, Sara S. Strom, University of Texas M.D. Anderson Cancer Center, Houston, TX; The University

  1. Inorganic nanoparticles for cancer imaging and therapy.

    Science.gov (United States)

    Huang, Huang-Chiao; Barua, Sutapa; Sharma, Gaurav; Dey, Sandwip K; Rege, Kaushal

    2011-11-07

    Inorganic nanoparticles have received increased attention in the recent past as potential diagnostic and therapeutic systems in the field of oncology. Inorganic nanoparticles have demonstrated successes in imaging and treatment of tumors both ex vivo and in vivo, with some promise towards clinical trials. This review primarily discusses progress in applications of inorganic nanoparticles for cancer imaging and treatment, with an emphasis on in vivo studies. Advances in the use of semiconductor fluorescent quantum dots, carbon nanotubes, gold nanoparticles (spheres, shells, rods, cages), iron oxide magnetic nanoparticles and ceramic nanoparticles in tumor targeting, imaging, photothermal therapy and drug delivery applications are discussed. Limitations and toxicity issues associated with inorganic nanoparticles in living organisms are also discussed.

  2. 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.

  3. Nanomedicine: Perspective and promises with ligand-directed molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pan Dipanjan [Department of Medicine, Washington University Medical School, St. Louis, MO (United States)], E-mail: dipanjan@wustl.edu; Lanza, Gregory M.; Wickline, Samuel A. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Caruthers, Shelton D. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Philips Healthcare, Andover, MA (United States)], E-mail: scaruthers@cmrl.wustl.edu

    2009-05-15

    Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

  4. Breast cancer imaging; Bildgebende Diagnostik des Mammakarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Funke, M. [Stadtklinik Baden-Baden, Brustzentrum Klinikum Mittelbaden, Radiologische Klinik, Baden-Baden (Germany); Villena, C. [Stadtklinik Baden-Baden, Brustzentrum Klinikum Mittelbaden, Frauenklinik, Baden-Baden (Germany)

    2008-06-15

    Advances in female breast imaging have substantially influenced the diagnosis, therapy, and prognosis of breast cancer in the past few years. Mammography using conventional or digital technique is considered the gold standard for the early detection of breast cancer. Other modalities such as breast ultrasound and contrast-enhanced magnetic resonance imaging of the breast play an important role in diagnostic imaging, staging, and follow-up of breast cancer. Percutaneous needle biopsy is a faster, less invasive, and more cost-effective method than surgical biopsy for verifying the histological diagnosis. New methods such as breast tomosynthesis, contrast-enhanced mammography, and positron emission tomography promise to further improve breast imaging. Further studies are mandatory to adapt these new methods to clinical needs and to evaluate their performance in clinical practice. (orig.) [German] Die Fortschritte bei den bildgebenden Verfahren der weiblichen Brust haben in den letzten Jahren die Diagnostik, die Therapie und die Prognose des Mammakarzinoms erheblich beeinflusst. Die Frueherkennungsmammographie in traditioneller oder digitaler Technik gilt heute als der ''Goldstandard'' fuer die fruehzeitige Detektion von Brustkrebs. Weitere Modalitaeten wie die Mammasonographie und die kontrastmittelgestuetzte MR-Mammographie spielen bei der bildgebenden Diagnostik, im Staging sowie in der Nachsorge des Mammakarzinoms eine wichtige Rolle. Die perkutane Nadelbiopsie stellt eine schnellere, weniger invasive und kostenguenstigere Methode dar als die diagnostische Exzision fuer die histologische Sicherung der Diagnose. Neue Modalitaeten wie Tomosynthese der Brust, kontrastverstaerkte Mammographie und Positronenemissionstomographie erheben den Anspruch, zu einer weiteren Verbesserung der Bildgebung beizutragen. Weitere Studien sind notwendig, um diese neuen Methoden an die klinischen Beduerfnisse zu adaptieren und ihren Stellenwert im klinischen Alltag

  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. 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.

  7. 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.

  8. Molecular imaging of angiogenesis with SPECT.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Boerman, O.C.

    2010-01-01

    Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life th

  9. Imaging biomarker roadmap for cancer studies

    Science.gov (United States)

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

    2017-01-01

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use. PMID:27725679

  10. 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.

  11. Molecular and neuroendocrine mechanisms of cancer cachexia.

    Science.gov (United States)

    Mendes, Maria Carolina S; Pimentel, Gustavo D; Costa, Felipe O; Carvalheira, José B C

    2015-09-01

    Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

  12. Design of optimal collimation for dedicated molecular breast imaging systems

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, Amanda L.; Hruska, Carrie B.; O' Connor, Michael K. [Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, Minnesota 55905 (United States)

    2009-03-15

    Molecular breast imaging (MBI) is a functional imaging technique that uses specialized small field-of-view gamma cameras to detect the preferential uptake of a radiotracer in breast lesions. MBI has potential to be a useful adjunct method to screening mammography for the detection of occult breast cancer. However, a current limitation of MBI is the high radiation dose (a factor of 7-10 times that of screening mammography) associated with current technology. The purpose of this study was to optimize the gamma camera collimation with the aim of improving sensitivity while retaining adequate resolution for the detection of sub-10-mm lesions. Square-hole collimators with holes matched to the pixilated cadmium zinc telluride detector elements of the MBI system were designed. Data from MBI patient studies and parameters of existing dual-head MBI systems were used to guide the range of desired collimator resolutions, source-to-collimator distances, pixel sizes, and collimator materials that were examined. General equations describing collimator performance for a conventional gamma camera were used in the design process along with several important adjustments to account for the specialized imaging geometry of the MBI system. Both theoretical calculations and a Monte Carlo model were used to measure the geometric efficiency (or sensitivity) and resolution of each designed collimator. Results showed that through optimal collimation, collimator sensitivity could be improved by factors of 1.5-3.2, while maintaining a collimator resolution of either {<=}5 or {<=}7.5 mm at a distance of 3 cm from the collimator face. These gains in collimator sensitivity permit an inversely proportional drop in the required dose to perform MBI.

  13. 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...

  14. Deciphering the Molecular Mechanisms of Breast Cancer

    Science.gov (United States)

    2005-03-01

    BRCA1 and BRCA2, by a Signalosome-like Subunit and its Role in DNA Repair. Molecular Cell 12; 1087-1099 (2003). Presentations/Abstracts...BRCA1 and BRCA2, by a Signalosome-like Subunit and its Role in DNA Repair. Molecular Cell 12; 1087-1099. APPENDICIES: CURRICULUM VITAE...Oncogenesis Program Member, Faculty Recruitment Committee Periodic Manuscript Reviews: Cell, Science, Molecular Cell , Molecular and Cellular

  15. 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.

  16. Photoactive Lipid-Gold Nanoconstructs for Molecular Imaging and Photo-Therapy

    Science.gov (United States)

    Farhadi, Arash

    The ubiquitous presence of porphyrins in nature is a testament to their versatility and utility. This thesis examines the utility of novel synthetic porphyrin derivatives, metallo-pyrolipid, as surface-enhanced Raman scattering (SERS) contrast agents for molecular imaging and monitoring of photodynamic therapy (PDT). Chapter 2 illustrates the refinement and optimization of manganese-pyrolipid gold nanoparticles for optical imaging of endothelial growth factor receptor overexpression in early stage lung cancer. In chapter 3, the use of palladium-pyrolipid gold nanoparticles as a new platform for SERS reporting photosensitizers is presented, allowing for real-time PDT and molecular imaging. These nanoparticles are demonstrated to be promising as photobleaching-dependent SERS reporting agents for PDT dosimetry. It is my hope that the studies presented in this thesis will set the stage for the development of simple and multifunctional SERS agents for medical imaging and therapeutic-use relevant to current unmet needs in medicine.

  17. 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

  18. 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.

  19. Photoacoustic imaging of prostate cancer using cylinder diffuse radiation

    Science.gov (United States)

    Xie, Wenming; Li, Li; Li, Zhifang; Li, Hui

    2012-12-01

    Prostate cancer is one of diseases with high mortality in man. Many clinical imaging modalities are utilized for the detection, grading and staging of prostate cancer, such as ultrasound, CT, MRI, etc. But they lacked adequate sensitivity and specificity for finding cancer in transition or central zone of prostate. To overcome these problems, we propose a photoacoustic imaging modality based on cylinder diffuse radiation through urethra for prostate cancer detection. We measure the related parameters about this system like lateral resolution (~2mm) and axial resolution(~333μm). Finally, simulated sample was imaged by our system. The results demonstrate the feasibility for detecting prostate cancer by our system.

  20. [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.

  1. Agents described in the Molecular Imaging and Contrast Agent Database for imaging carbonic anhydrase IX expression.

    Science.gov (United States)

    Sneddon, Deborah; Poulsen, Sally-Ann

    2014-10-01

    Carbonic anhydrase IX (CA IX) is selectively expressed in a range of hypoxic tumours and is a validated endogenous hypoxia marker with prognostic significance; hence, CA IX is of great interest as a molecular imaging target in oncology. In this review, we present an overview of the different imaging agents and imaging modalities that have been applied for the in vivo detection of CA IX. The imaging agents reviewed are all entries in the Molecular Imaging and Contrast Agent Database (MICAD) and comprise antibody, antibody fragments and small molecule imaging agents. The effectiveness of these agents for imaging CA IX in vivo gave variable performance; however, a number of agents proved very capable. As molecular imaging has become indispensable in current medical practice we anticipate that the clinical significance of CA IX will see continued development and improvements in imaging agents for targeting this enzyme.

  2. 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.

  3. 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.

  4. Molecular aspects of magnetic resonance imaging and spectroscopy.

    Science.gov (United States)

    Boesch, C

    1999-01-01

    Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.

  5. Gallic acid: molecular rival of cancer.

    Science.gov (United States)

    Verma, Sharad; Singh, Amit; Mishra, Abha

    2013-05-01

    Gallic acid, a predominant polyphenol, has been shown to inhibit carcinogenesis in animal models and in vitro cancerous cell lines. The inhibitory effect of gallic acid on cancer cell growth is mediated via the modulation of genes which encodes for cell cycle, metastasis, angiogenesis and apoptosis. Gallic acid inhibits activation of NF-κB and Akt signaling pathways along with the activity of COX, ribonucleotide reductase and GSH. Moreover, gallic acid activates ATM kinase signaling pathways to prevent the processes of carcinogenesis. The data so far available, both from in vivo and in vitro studies, indicate that this dietary polyphenol could be promising agent in the field of cancer chemoprevention.

  6. Targets for molecular therapy of skin cancer.

    Science.gov (United States)

    Green, Cheryl L; Khavari, Paul A

    2004-02-01

    Cancers of the skin encompass the first and second most common neoplasms in the United States, epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.

  7. 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.

  8. 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.

  9. Precursor lesions in pancreatic cancer: morphological and molecular pathology.

    Science.gov (United States)

    Scarlett, Christopher J; Salisbury, Elizabeth L; Biankin, Andrew V; Kench, James

    2011-04-01

    Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.

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

    Science.gov (United States)

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

    2010-02-06

    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.

  11. 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

  12. Advances of molecular imaging in epilepsy

    OpenAIRE

    Galovic, M.; Koepp, M.

    2016-01-01

    Positron emission tomography (PET) is a neuroimaging method that offers insights into the molecular functioning of a human brain. It has been widely used to study metabolic and neurotransmitter abnormalities in people with epilepsy. This article reviews the development of several PET radioligands and their application in studying the molecular mechanisms of epilepsy. Over the last decade, tracers binding to serotonin and γ-aminobutyric acid (GABA) receptors have been used to delineate the loc...

  13. Advances of Molecular Imaging in Epilepsy

    OpenAIRE

    Galovic, Marian; Koepp, Matthias

    2016-01-01

    Positron emission tomography (PET) is a neuroimaging method that offers insights into the molecular functioning of a human brain. It has been widely used to study metabolic and neurotransmitter abnormalities in people with epilepsy. This article reviews the development of several PET radioligands and their application in studying the molecular mechanisms of epilepsy. Over the last decade, tracers binding to serotonin and γ-aminobutyric acid (GABA) receptors have been used to delineate the loc...

  14. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

    Science.gov (United States)

    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2016-01-01

    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer. PMID:27920729

  15. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

    Directory of Open Access Journals (Sweden)

    Guillermo de Anda-Jáuregui

    2016-11-01

    Full Text Available Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes.In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples is also inferred and analyzed.Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e. CNR2 or to a particular subtype (such as LCK. Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance.With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

  16. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2016-01-01

    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

  17. Visualization of molecular composition and functionality of cancer cells using nanoparticle-augmented ultrasound-guided photoacoustics

    Science.gov (United States)

    Mallidi, Srivalleesha; Kim, Seungsoo; Karpiouk, Andrei; Joshi, Pratixa P.; Sokolov, Konstantin; Emelianov, Stanislav

    2015-01-01

    Assessment of molecular signatures of tumors in addition to their anatomy and morphology is desired for effective diagnostic and therapeutic procedures. Development of in vivo imaging techniques that can identify and monitor molecular composition of tumors remains an important challenge in pre-clinical research and medical practice. Here we present a molecular photoacoustic imaging technique that can visualize the presence and activity of an important cancer biomarker – epidermal growth factor receptor (EGFR), utilizing the effect of plasmon resonance coupling between molecular targeted gold nanoparticles. Specifically, spectral analysis of photoacoustic images revealed profound changes in the optical absorption of systemically delivered EGFR-targeted gold nanospheres due to their molecular interactions with tumor cells overexpressing EGFR. In contrast, no changes in optical properties and, therefore, photoacoustic signal, were observed after systemic delivery of non-targeted gold nanoparticles to the tumors. The results indicate that multi-wavelength photoacoustic imaging augmented with molecularly targeted gold nanoparticles has the ability to monitor molecular specific interactions between nanoparticles and cell-surface receptors, allowing visualization of the presence and functional activity of tumor cells. Furthermore, the approach can be used for other cancer cell-surface receptors such as human epidermal growth factor receptor 2 (HER2). Therefore, ultrasound-guided molecular photoacoustic imaging can potentially aid in tumor diagnosis, selection of customized patient-specific treatment, and monitor the therapeutic progression and outcome in vivo. PMID:25893171

  18. 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.

  19. 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

    2014-11-06

    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.

  20. 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.

  1. Natural language processing and visualization in the molecular imaging domain.

    Science.gov (United States)

    Tulipano, P Karina; Tao, Ying; Millar, William S; Zanzonico, Pat; Kolbert, Katherine; Xu, Hua; Yu, Hong; Chen, Lifeng; Lussier, Yves A; Friedman, Carol

    2007-06-01

    Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

  2. Enhancing in vivo tumor boundary delineation with structured illumination fluorescence molecular imaging and spatial gradient mapping

    Science.gov (United States)

    Sun, Jessica; Miller, Jessica P.; Hathi, Deep; Zhou, Haiying; Achilefu, Samuel; Shokeen, Monica; Akers, Walter J.

    2016-08-01

    Fluorescence imaging, in combination with tumor-avid near-infrared (NIR) fluorescent molecular probes, provides high specificity and sensitivity for cancer detection in preclinical animal models, and more recently, assistance during oncologic surgery. However, conventional camera-based fluorescence imaging techniques are heavily surface-weighted such that surface reflection from skin or other nontumor tissue and nonspecific fluorescence signals dominate, obscuring true cancer-specific signals and blurring tumor boundaries. To address this challenge, we applied structured illumination fluorescence molecular imaging (SIFMI) in live animals for automated subtraction of nonspecific surface signals to better delineate accumulation of an NIR fluorescent probe targeting α4β1 integrin in mice bearing subcutaneous plasma cell xenografts. SIFMI demonstrated a fivefold improvement in tumor-to-background contrast when compared with other full-field fluorescence imaging methods and required significantly reduced scanning time compared with diffuse optical spectroscopy imaging. Furthermore, the spatial gradient mapping enhanced highlighting of tumor boundaries. Through the relatively simple hardware and software modifications described, SIFMI can be integrated with clinical fluorescence imaging systems, enhancing intraoperative tumor boundary delineation from the uninvolved tissue.

  3. 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

  4. Molecular genetics and genomics progress in urothelial bladder cancer.

    Science.gov (United States)

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  5. Molecular therapy of colorectal cancer: progress and future directions.

    Science.gov (United States)

    Weng, Wenhao; Feng, Junlan; Qin, Huanlong; Ma, Yanlei

    2015-02-01

    Colorectal cancer (CRC) remains one of the most common types of cancer and leading causes of cancer death worldwide. Although the introduction of cytotoxic drugs such as oxaliplatin, irinotecan and fluorouracil has improved the treatment of advanced CRC, the individual response to chemoradiotherapy varies tremendously from one patient to another. However, recent progress in CRC molecular therapies may provide new insight into the treatment of this disease. Currently, components of the EGFR, VEGF, Wnt and NF-kB pathways are the most important targets for CRC therapy. This review chronicles the development of molecular CRC therapies over the past few decades. We also provide an update on the current progress of research concerning the molecular pathways leading to CRC and discuss the possible implications for CRC therapy.

  6. 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...... With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas....

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Diagnosis of skin cancer using image processing

    Science.gov (United States)

    Guerra-Rosas, Esperanza; Álvarez-Borrego, Josué; Coronel-Beltrán, Ángel

    2014-10-01

    In this papera methodology for classifying skin cancerin images of dermatologie spots based on spectral analysis using the K-law Fourier non-lineartechnique is presented. The image is segmented and binarized to build the function that contains the interest area. The image is divided into their respective RGB channels to obtain the spectral properties of each channel. The green channel contains more information and therefore this channel is always chosen. This information is point to point multiplied by a binary mask and to this result a Fourier transform is applied written in nonlinear form. If the real part of this spectrum is positive, the spectral density takeunit values, otherwise are zero. Finally the ratio of the sum of the unit values of the spectral density with the sum of values of the binary mask are calculated. This ratio is called spectral index. When the value calculated is in the spectral index range three types of cancer can be detected. Values found out of this range are benign injure.

  13. Transcriptional networks inferred from molecular signatures of breast cancer.

    Science.gov (United States)

    Tongbai, Ron; Idelman, Gila; Nordgard, Silje H; Cui, Wenwu; Jacobs, Jonathan L; Haggerty, Cynthia M; Chanock, Stephen J; Børresen-Dale, Anne-Lise; Livingston, Gary; Shaunessy, Patrick; Chiang, Chih-Hung; Kristensen, Vessela N; Bilke, Sven; Gardner, Kevin

    2008-02-01

    Global genomic approaches in cancer research have provided new and innovative strategies for the identification of signatures that differentiate various types of human cancers. Computational analysis of the promoter composition of the genes within these signatures may provide a powerful method for deducing the regulatory transcriptional networks that mediate their collective function. In this study we have systematically analyzed the promoter composition of gene classes derived from previously established genetic signatures that recently have been shown to reliably and reproducibly distinguish five molecular subtypes of breast cancer associated with distinct clinical outcomes. Inferences made from the trends of transcription factor binding site enrichment in the promoters of these gene groups led to the identification of regulatory pathways that implicate discrete transcriptional networks associated with specific molecular subtypes of breast cancer. One of these inferred pathways predicted a role for nuclear factor-kappaB in a novel feed-forward, self-amplifying, autoregulatory module regulated by the ERBB family of growth factor receptors. The existence of this pathway was verified in vivo by chromatin immunoprecipitation and shown to be deregulated in breast cancer cells overexpressing ERBB2. This analysis indicates that approaches of this type can provide unique insights into the differential regulatory molecular programs associated with breast cancer and will aid in identifying specific transcriptional networks and pathways as potential targets for tumor subtype-specific therapeutic intervention.

  14. 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.

  15. Molecular imaging of angiogenesis with SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, Ingrid; Boerman, Otto C. [Radboud University Nijmegen Medical Center, Department of Nuclear Medicine, P.O. Box 9101, HB Nijmegen (Netherlands)

    2010-08-15

    Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life than those used for PET. In addition, SPECT is a less expensive technique than PET. Commonly used gamma emitters are: {sup 99m}Tc (E{sub max} 141 keV, T{sub 1/2} 6.02 h), {sup 123}I (E{sub max} 529 keV, T{sub 1/2} 13.0 h) and {sup 111}In (E{sub max} 245 keV, T{sub 1/2} 67.2 h). Compared to clinical SPECT, PET has a higher spatial resolution and the possibility to more accurately estimate the in vivo concentration of a tracer. In preclinical imaging, the situation is quite different. The resolution of microSPECT cameras (<0.5 mm) is higher than that of microPET cameras (>1.5 mm). In this report, studies on new radiolabelled tracers for SPECT imaging of angiogenesis in tumours are reviewed. (orig.)

  16. [New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?].

    Science.gov (United States)

    Dreyer, Chantal; Afchain, Pauline; Trouilloud, Isabelle; André, Thierry

    2016-01-01

    This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.

  17. Intraoperative Assessment of Breast Cancer Margins ex vivo using Aqueous Quantum Dot-Functionalized Molecular Probes

    Science.gov (United States)

    Au, Giang Hoang Thuy

    Breast cancer is increasingly diagnosed at an early stage, allowing the diseased breast to be removed only partially or breast conserving surgery (BCS). Current BCS procedures have no rapid methods during surgery to assess if the surgical margin is clear of cancer, often resulting in re-excision. The current breast cancer re-excision rate is estimated to be 15% to as high as 60%. It would be desirable if there is a rapid and reliable breast cancer margin assessment tool in the operating room to help assess if the surgical margin is clean to minimize unnecessary re-excisions. In this research, we seek to develop an intraoperative, molecular probe-based breast cancer surgical margin assessment tool using aqueous quantum dots (AQDs) coupled with cancer specific biomarkers. Quantum dots (QDs) are photoluminescent semiconductor nanoparticles that do not photobleach and are brighter than organic fluorescent dyes. Aqueous quantum dots (AQDs) such as CdSe and near infrared (NIR) CdPbS developed in Shih's lab emit light longer than 600 nm. We have examined conjugating AQDs with antibodies to cancer specific biomarkers such as Tn antigen, a cancer-associated glycan antigen for epithelial cancers. We showed that AQDs could achieve ~80% antibody conjugation efficiency, i.e., 100 times less antibodies than required by commercial, making such AQD molecular probe surgical margin evaluation economically feasible. By conjugating AQDs with anti-Tn-antigen antibody, the AQDs molecular probe exhibited 94% sensitivity and 92% specificity in identifying breast cancer against normal breast tissues as well as benign breast tumors in 480 tissue blocks from 126 patients. Furthermore, mice model and clinical human studies indicated that AQDs imaging did not interfere with the following pathological staining. More interestingly, we showed that it it possible to directly conjugate one antibody to multiple AQDs, further reduces the required amount of antibodies needed, a feat that could not be

  18. 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.

  19. Clinical variability and molecular heterogeneity in prostate cancer

    Directory of Open Access Journals (Sweden)

    Jonathan Shoag

    2016-01-01

    Full Text Available Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care.

  20. Molecular markers in prostate cancer.Part II:potential roles in management

    Institute of Scientific and Technical Information of China (English)

    Sachin Agrawal; Krishnaji P.Patil; William D.Dunsmuir

    2009-01-01

    Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities.New molecular markers have emerged as potential diagnostic and prognostic indicators;these were summarized in Part I of this review in the Asian Journal of Andrology.A number of molecular markers are now being used to enhance PCa imaging and staging.However,management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed.Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation.Additionally,markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development.This review summarizes the current advances regarding the roles of these markers in the management of PCa.

  1. [Advances of molecular targeted therapy in squamous cell lung cancer].

    Science.gov (United States)

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  2. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    Directory of Open Access Journals (Sweden)

    Bruna Karina Banin Hirata

    2014-01-01

    Full Text Available Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity.

  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. 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.

  5. Advances of Molecular Imaging in Epilepsy.

    Science.gov (United States)

    Galovic, Marian; Koepp, Matthias

    2016-06-01

    Positron emission tomography (PET) is a neuroimaging method that offers insights into the molecular functioning of a human brain. It has been widely used to study metabolic and neurotransmitter abnormalities in people with epilepsy. This article reviews the development of several PET radioligands and their application in studying the molecular mechanisms of epilepsy. Over the last decade, tracers binding to serotonin and γ-aminobutyric acid (GABA) receptors have been used to delineate the location of the epileptic focus. PET studies have examined the role of opioids, cannabinoids, acetylcholine, and dopamine in modulating neuronal hyperexcitability and seizure termination. In vivo analyses of drug transporters, e.g., P-glycoprotein, have increased our understanding of pharmacoresistance that could inform new therapeutic strategies. Finally, PET experiments targeting neuroinflammation and glutamate receptors might guide the development of novel biomarkers of epileptogenesis.

  6. 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.

  7. 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.

  8. Synchronous gynecologic cancer and the use of imaging for diagnosis.

    Science.gov (United States)

    Boaventura, Camila Silva; Galvão, José Lucas Scarpinetti; Soares, Giovanna Milanes Bego; Bitencourt, Almir Galvão Vieira; Chojniak, Rubens; Bringel, Shenia Lauanna Rezende; Brot, Louise De

    2016-04-01

    Endometrial and cervical cancers are the most prevalent gynecologic neoplasms. While endometrial cancer occurs in older women, cervical cancer is more prevalente in young subjects. The most common clinical manifestation in these two gynecological cancers is vaginal bleeding. In the first case, diagnosis is made based on histological and imaging evaluation of the endometrium, while cervical cancers are diagnosed clinically, according to the International Federation of Gynecology and Obstetrics (FIGO). The authors present a case of synchronous gynecological cancer of the endometrium and cervix diagnosed during staging on MRI and confirmed by histological analysis of the surgical specimen.

  9. Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques.

    Science.gov (United States)

    Put, Stéphanie; Westhovens, René; Lahoutte, Tony; Matthys, Patrick

    2014-04-15

    Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ₃ integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.

  10. Molecular imaging: a new approach to nuclear cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Dobrucki, L.W.; Sinusas, A.J. [Yale Univ. School of Medicine, New Haven (United States). Section of Cardiovascular Medicine, Department of Internal Medicine

    2005-03-01

    Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk statification. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well as transporter gene imaging strategies are evolving to meet these new needs, but require the development of an interdisciplinary approach which focuses on molecular processes, as well as the pathogenesis and progression of disease. This progress has been made possible with the availability of transgenic animal models along with many technological advances. Future adaptations of the developing experimental procedures and instrumentations will allow for the smooth translation and application to clinical practice. This review is intended as a brief overview on the subject molecular imaging. Basic concepts and historical perspective of molecular imaging will be reviewed first, followed by description of current technology, and concluding with current applications in cardiology. The emphasis will be on the use of both single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers, although other imaging modalities will be also briefly discussed. The specific approaches presented here will include receptor-based and reporter gene imaging of natural and therapeutical angiogenesis.

  11. Direct Imaging of Laser-driven Ultrafast Molecular Rotation.

    Science.gov (United States)

    Mizuse, Kenta; Fujimoto, Romu; Mizutani, Nobuo; Ohshima, Yasuhiro

    2017-02-04

    We present a method for visualizing laser-induced, ultrafast molecular rotational wave packet dynamics. We have developed a new 2-dimensional Coulomb explosion imaging setup in which a hitherto-impractical camera angle is realized. In our imaging technique, diatomic molecules are irradiated with a circularly polarized strong laser pulse. The ejected atomic ions are accelerated perpendicularly to the laser propagation. The ions lying in the laser polarization plane are selected through the use of a mechanical slit and imaged with a high-throughput, 2-dimensional detector installed parallel to the polarization plane. Because a circularly polarized (isotropic) Coulomb exploding pulse is used, the observed angular distribution of the ejected ions directly corresponds to the squared rotational wave function at the time of the pulse irradiation. To create a real-time movie of molecular rotation, the present imaging technique is combined with a femtosecond pump-probe optical setup in which the pump pulses create unidirectionally rotating molecular ensembles. Due to the high image throughput of our detection system, the pump-probe experimental condition can be easily optimized by monitoring a real-time snapshot. As a result, the quality of the observed movie is sufficiently high for visualizing the detailed wave nature of motion. We also note that the present technique can be implemented in existing standard ion imaging setups, offering a new camera angle or viewpoint for the molecular systems without the need for extensive modification.

  12. 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.

  13. Autofluorescence spectroscopy and imaging for cancer detection in the larynx

    Science.gov (United States)

    Lin, Kan; Zheng, Wei; Huang, Zhiwei

    2009-11-01

    Autofluorescence imaging has shown high sensitivity for early diagnosis and detection of cancer in humans. However, it has a limitation in diagnostic specificity due to high false positive rates. In this work, we apply an integrated fluorescence spectroscopy and endoscopic imaging technique for real-time tissue measurements. The results show that the combined autofluorescence imaging and spectroscopy has the potential for improving laryngeal cancer diagnosis and detection.

  14. 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.

  15. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

    Science.gov (United States)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-01

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  16. 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.

  17. Molecular Characterization of Indolent Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Luo, Ph.D. CONTRACTING ORGANIZATION: Johns Hopkins University Baltimore, MD 21218-2680 REPORT DATE: October 2015 TYPE OF REPORT: Annual...DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual Report 3. DATES COVERED 15 Sep 2014- 14 Sep 2015...detected at biopsy , leading to the contemporary problem of prostate cancer over-diagnosis and over-treatment. The objective of the project is to

  18. Molecular prostate cancer pathology: current issues and achievements.

    NARCIS (Netherlands)

    Schalken, J.A.; Bergh, A. von; Bono, A.V.; Foster, C.; Gospadarowicz, M.; Isaacs, W.B.; Rubin, M.; Schroder, F.H.; Tribukait, B.; Tsukamotot, T.; Wiklund, P.

    2005-01-01

    Recent developments in the field of molecular techniques have provided new tools that have led to the discovery of many new promising biomarkers for prostate cancer. These biomarkers may be instrumental in the development of new tests that will have a high specificity for the diagnosis and prognosis

  19. Molecular imaging probes spy on the body's inner workings: miniaturized microscopes, microbubbles, 7- and 15-T scanners, diffusion-tensor MRI, and other molecular-imaging technologies are pushing molecular imaging into the future.

    Science.gov (United States)

    Mertz, Leslie

    2013-01-01

    Molecular imaging is one of the hot-button areas within medical imaging. This technology employs imaging techniques in concert with molecular probes, or biomarkers, that together noninvasively spy on cellular function and molecular processes. In some cases, this technology may be able to detect the very earliest stages of diseases and eliminate them on the spot. This paper discusses how miniaturized microscopes, microbubbles, 7T and 15T scanners, diffusion-tensor MRI and other molecular imaging technologies are pushing molecular imaging into the future.

  20. Molecular Biology and Prevention of Endometrial Cancer

    Science.gov (United States)

    2009-07-01

    of the oral contraceptive pill (OCP). Project 1: Objectives completed and data previously submitted with 2004 report. Data published this past year...molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC...not been altered appreciably. Despite the known protective effect of oral contraceptives , little has been learned regarding the underlying mechanism

  1. Methodologies in cancer cytogenetics and molecular cytogenetics.

    Science.gov (United States)

    Wang, Nancy

    2002-10-30

    Various types of cytogenetic and molecular cytogenetic approaches, including conventional banding, fluorescence in situ hybridization (FISH), fiber-FISH, comparative genomic hybridization (CGH), matrix array CGH, chromosome microdissection, and microcell-mediated chromosome transfer are summarized. The rationale, advantage, and limitations of each approach are discussed with respect to research and clinical applications in human neoplasia.

  2. Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer.

    Science.gov (United States)

    Clark, Owen; Yen, Katharine; Mellinghoff, Ingo K

    2016-04-15

    IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the "oncometabolite" R(-)-2-hydroxyglutarate (R-2-HG). R-2-HG competitively inhibits α-KG-dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials, and have shown encouraging results in patients with IDH-mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.Clin Cancer Res; 22(8); 1837-42. ©2016 AACR.

  3. Epigenetic Markers for Molecular Detection of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Vera L. Costa

    2007-01-01

    Full Text Available Prostate cancer is a highly prevalent malignancy, which is clinically silent but curable while organ-confined. Because available screening methods show poor sensitivity and specificity, the development of new molecular markers is warranted. Epigenetic alterations, mainly promoter hypermethylation of cancer-related genes, are common events in prostate cancer and might be used as cancer biomarkers. Moreover, the development of quantitative, high-throughput techniques to assess promoter methylation enabled the simultaneous screening of multiple clinical samples. From the numerous cancer-related genes hypermethylated in prostate cancer only a few proved to be strong candidates to become routine biomarkers. This small set of genes includes GSTP1, APC, RARβ2, Cyclin D2, MDR1, and PTGS2. Single and/or multigene analyses demonstrated the feasibility of detecting early prostate cancer, with high sensitivity and specificity, in body fluids (serum, plasma, urine, and ejaculates and tissue samples. In addition, quantitative hypermethylation of several genes has been associated with clinicopathologic features of tumor aggressiveness, and also reported as independent prognostic factor for relapse. The identification of age-related methylation at specific loci and the differential frequency of methylation among ethnical groups, also provided interesting data linking methylation and prostate cancer risk. Although large trials are needed to validate these findings, the clinical use of these markers might be envisaged for the near future.

  4. 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.

  5. Nanomedicines for image-guided cancer therapy (Conference Presentation)

    Science.gov (United States)

    Zheng, Jinzi

    2016-09-01

    Imaging technologies are being increasingly employed to guide the delivery of cancer therapies with the intent to increase their performance and efficacy. To date, many patients have benefited from image-guided treatments through prolonged survival and improvements in quality of life. Advances in nanomedicine have enabled the development of multifunctional imaging agents that can further increase the performance of image-guided cancer therapy. Specifically, this talk will focus on examples that demonstrate the benefits and application of nanomedicine in the context of image-guide surgery, personalized drug delivery, tracking of cell therapies and high precision radiotherapy delivery.

  6. 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.

  7. Advances of Molecular Targeted Therapy in Squamous Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2013-12-01

    Full Text Available Squamous cell lung cancer (SQCLC is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR inhibitors or anaplastic lymphoma kinase (ALK inhibitors that show exquisite activity in lungadenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1 gene, the discoidin domain receptor 2 (DDR2 gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lungcancer assessing the value of novel therapeutics addressing these targets.

  8. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Mathieu Salaün

    Full Text Available Several matrix metalloproteinases (MMPs are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma.K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors.In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27, but in none of the non-invasive (0/4 (p=0.001.MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.

  9. 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

  10. Molecular imaging with dynamic contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Miles, K.A., E-mail: k.a.miles@bsms.ac.u [Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton (United Kingdom)

    2010-07-15

    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.

  11. MIPortal: A High Capacity Server for Molecular Imaging Research

    Directory of Open Access Journals (Sweden)

    Misha Pivovarov

    2005-10-01

    Full Text Available The introduction of novel molecular tools in research and clinical medicine has created a need for more refined information management systems. This article describes the design and implementation of such a new information platform: the Molecular Imaging Portal (MIPortal. The platform was created to organize, archive, and rapidly retrieve large datasets using Web-based browsers as access points. The system has been implemented in a heterogeneous, academic research environment serving Macintosh, Unix, and Microsoft Windows clients and has been shown to be extraordinarily robust and versatile. In addition, it has served as a useful tool for clinical trials and collaborative multi-institutional small-animal imaging research.

  12. Radiomic analysis reveals DCE-MRI features for prediction of molecular subtypes of breast cancer

    Science.gov (United States)

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

    2017-01-01

    The purpose of this study was to investigate the role of features derived from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to incorporated clinical information to predict the molecular subtypes of breast cancer. In particular, 60 breast cancers with the following four molecular subtypes were analyzed: luminal A, luminal B, human epidermal growth factor receptor-2 (HER2)-over-expressing and basal-like. The breast region was segmented and the suspicious tumor was depicted on sequentially scanned MR images from each case. In total, 90 features were obtained, including 88 imaging features related to morphology and texture as well as dynamic features from tumor and background parenchymal enhancement (BPE) and 2 clinical information-based parameters, namely, age and menopausal status. An evolutionary algorithm was used to select an optimal subset of features for classification. Using these features, we trained a multi-class logistic regression classifier that calculated the area under the receiver operating characteristic curve (AUC). The results of a prediction model using 24 selected features showed high overall classification performance, with an AUC value of 0.869. The predictive model discriminated among the luminal A, luminal B, HER2 and basal-like subtypes, with AUC values of 0.867, 0.786, 0.888 and 0.923, respectively. An additional independent dataset with 36 patients was utilized to validate the results. A similar classification analysis of the validation dataset showed an AUC of 0.872 using 15 image features, 10 of which were identical to those from the first cohort. We identified clinical information and 3D imaging features from DCE-MRI as candidate biomarkers for discriminating among four molecular subtypes of breast cancer. PMID:28166261

  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...

  14. Prototype of Microwave Imaging System for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Zhurbenko, Vitaliy

    2009-01-01

    Microwave imaging for breast-cancer detection has received the attention of a large number of research groups in the last decade. In this paper, the imaging system currently being developed at the Technical university of Denmark is presented. This includes a description of the antenna system......, the microwave hardware, and the imaging algorithm....

  15. 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...

  16. 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.)

  17. 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.

  18. 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.

  19. Simultaneous molecular and anatomical imaging of the mouse in vivo.

    Science.gov (United States)

    Goertzen, Andrew L; Meadors, A Ken; Silverman, Robert W; Cherry, Simon R

    2002-12-21

    Non-invasive imaging technologies are opening up new windows into mouse biology. We have developed a mouse imaging system that integrates positron emission tomography (PET) with x-ray computed tomography (CT), allowing simultaneous anatomic and molecular imaging in vivo with the potential for precise registration of the two image volumes. The x-ray system consists of a compact mini-focal x-ray tube and an amorphous selenium flat panel x-ray detector with a low-noise CMOS readout. The PET system uses planar arrays of lutetium oxyorthosilicate scintillator coupled to position-sensitive photomultiplier tubes. We describe the design of this dual-modality imaging system and show, for the first time, simultaneously acquired PET and CT images in a phantom and in mice.

  20. 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.

  1. Molecular Determinants of Hormone Refractory Prostate Cancer

    Science.gov (United States)

    2013-07-01

    to known prostate cancer oncogenes, Never In Mitosis A (NIMA) related kinase 6 (NEK6) reproducibly yielded androgen-independent tumors in female...constitutively active MEK, RAF1, ERBB2, AKT1, PIM1 and PIM2), overexpression of the Never In Mitosis A (NIMA) related kinase 6 (NEK6) reproducibly yielded...Never In Mitosis A (NIMA) related kinase 6 (NEK6), and nemo-like kinase (NLK). Aim 1. Elucidating the role of NIMA-related kinase 6 (NEK6) and nemo

  2. Specific survivin dual fluorescence resonance energy transfer molecular beacons for detection of human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang WANG; Jun ZHAO; Jin ZENG; Kai-jie WU; Yu-le CHEN; Xin-ya ng WANG; Luke S CHANG; Da-lin HE

    2011-01-01

    Survivin molecular beacons can be used to detectbladder cancer cells in urine samples non-invasively.The aim of this study is to improve the specificity of detection of bladder cancer cells using survivin dual fluorescence resonance energy transfer molecular beacons (FRET MBs) that have fluorophores forming one donor-acceptor pair.Methods:Survivin-targeting dual fluorescence resonance energy transfer molecular beacons with unique target sequences were designed,which had no overlap with the other genes in the apoptosis inhibitor protein family.Human bladder cancer cell lines 5637,253J and T24,as well as the exfoliated cells in the urine of healthy adults and patients with bladder cancer were examined.Images of cells were taken using a laser scanning confocal fluorescence microscope.For assays using dual FRET MBs,the excitation wavelength was 488 nm,and the emission detection wavelengths were 520+20 nm and 560+20 nm,respectively.Results:The human bladder cancer cell lines and exfoliated cells in the urine of patients with bladder cancer incubated with the survivin dual FRET MBs exhibited strong fluorescence signals.In contrast,no fluorescence was detected in the survivin-negative human dermal fibroblasts-adult (HDF-a) cells or exfoliated cells in the urine of healthy adults incubated with the survivin dual FRET MBs.Conclusion:The results suggest that the survivin dual FRET MBs may be used as a specific and non-invasive method for early detection and follow-up of patients with bladder cancer.

  3. Molecular imaging of cyclooxygenase-2 in canine transitional cell carcinomas in vitro and in vivo.

    Science.gov (United States)

    Cekanova, Maria; Uddin, Md Jashim; Bartges, Joseph W; Callens, Amanda; Legendre, Alfred M; Rathore, Kusum; Wright, Laura; Carter, Amanda; Marnett, Lawrence J

    2013-05-01

    The enzyme COX-2 is induced at high levels in tumors but not in surrounding normal tissues, which makes it an attractive target for molecular imaging of cancer. We evaluated the ability of novel optical imaging agent, fluorocoxib A to detect urinary bladder canine transitional cell carcinomas (K9TCC). Here, we show that fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show specific uptake of fluorocoxib A by COX-2-expressing K9TCC xenograft tumors in vivo. Fluorocoxib A uptake by COX-2-expressing xenograft tumors was blocked by 70% (P dogs diagnosed with TCC. Fluorocoxib A specifically detected COX-2-expressing K9TCC during cystoscopy in vivo but was not detected in normal urothelium. Taken together, our findings show that fluorocoxib A selectively bound to COX-2-expressing primary K9TCC cells in vitro, COX-2-expressing K9TCC xenografts tumors in nude mice, and heterogeneous canine TCC during cystoscopy in vivo. Spontaneous cancers in companion animals offer a unique translational model for evaluation of novel imaging and therapeutic agents using primary cancer cells in vitro and in heterogeneous cancers in vivo.

  4. In vitro derby imaging of cancer biomarkers using quantum dots.

    Science.gov (United States)

    Ko, Mee Hyang; Kim, Soonhag; Kang, Won Jun; Lee, Jung Hwan; Kang, Hyungu; Moon, Sung Hwan; Hwang, Do Won; Ko, Hae Young; Lee, Dong Soo

    2009-05-01

    Semiconductor quantum dots (QDs), which have broad absorption with narrow emission spectra, are useful for multiplex imaging. Here, fluorescence derby imaging using dual color QDs conjugated by the AS1411 aptamer (targeting nucleolin) and the arginine-glycine-aspartic acid (targeting the integrin alpha(v)beta(3)) in cancer cells is reported. Simultaneous fluorescence imaging of cellular distribution of nucleolin and integrin alpha(v)beta(3) using QDs enables easy monitoring of separate targets in the cancer cells and the normal healthy cells. These results suggest the feasibility of a concurrent visualization of QD-based multiple cancer biomarkers using small molecules such as aptamer or peptide ligands.

  5. Prostate Cancer: The Role of Multiparametric Magnetic Resonance Imaging.

    Science.gov (United States)

    Dias, João Lopes; Pina, João Magalhães; João, Raquel; Fialho, Joana; Carmo, Sandra; Leal, Cecília; Bilhim, Tiago; Marques, Rui Mateus; Pinheiro, Luís Campos

    2015-01-01

    Multiparametric magnetic resonance imaging has been increasingly used for detection, localization and staging of prostate cancer over the last years. It combines high-resolution T2 weighted-imaging and at least two functional techniques, which include dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging, and magnetic resonance imaging spectroscopy. Although the combined use of a pelvic phased-array and an endorectal coil is considered the state-of-the-art for magnetic resonance imaging evaluation of prostate cancer, endorectal coil is only absolute mandatory for magnetic resonance imaging spectroscopy at 1.5 T. Sensitivity and specificity levels in cancer detection and localization have been improving with functional technique implementation, compared to T2 weighted-imaging alone. It has been particularly useful to evaluate patients with abnormal PSA and negative biopsy. Moreover, the information added by the functional techniques may correlate to cancer aggressiveness and therefore be useful to select patients for focal radiotherapy, prostate sparing surgery, focal ablative therapy and active surveillance. However, more studies are needed to compare the functional techniques and understand the advantages and disadvantages of each one. This article reviews the basic principles of prostatic mp-magnetic resonance imaging, emphasizing its role on detection, staging and active surveillance of prostate cancer.

  6. The molecular mechanisms between metabolic syndrome and breast cancer.

    Science.gov (United States)

    Chen, Yi; Wen, Ya-yuan; Li, Zhi-rong; Luo, Dong-lin; Zhang, Xiao-hua

    2016-03-18

    Metabolic syndrome, which is extremely common in developed and some developing countries, is a clustering of at least three of five of the following medical conditions: abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. It has been proved that there is a strong association between metabolic syndrome and breast cancer. Metabolic syndrome could increase the risk of breast cancer and influence the prognosis of the breast cancer patients. Some characteristic of metabolic syndrome such as obesity and lack of physical exercise are all risk factors for developing breast cancer. The metabolic syndrome mainly include obesity, type 2 diabetes, hypercholesterolemia and nonalcoholic fatty liver disease, and each of them impacts the risk of breast cancer and the prognosis of the breast cancer patients in different ways. In this Review, we focus on recently uncovered aspects of the immunological and molecular mechanisms that are responsible for the development of this highly prevalent and serious disease. These studies bring new insight into the complex associations between metabolic syndrome and breast cancer and have led to the development of novel therapeutic strategies that might enable a personalized approach in the management of this disease.

  7. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy.

  8. 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

  9. 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.

  10. Feasibility study of the optical imaging of a breast cancer lesion labeled with upconversion nanoparticle biocomplexes.

    Science.gov (United States)

    Grebenik, Ekaterina A; Nadort, Annemarie; Generalova, Alla N; Nechaev, Andrei V; Sreenivasan, Varun K A; Khaydukov, Evgeny V; Semchishen, Vladimir A; Popov, Alexey P; Sokolov, Viktor I; Akhmanov, Aleksandr S; Zubov, Vitali P; Klinov, Dmitry V; Panchenko, Vladislav Y; Deyev, Sergey M; Zvyagin, Andrei V

    2013-07-01

    Innovative luminescent nanomaterials, termed upconversion nanoparticles (UCNPs), have demonstrated considerable promise as molecular probes for high-contrast optical imaging in cells and small animals. The feasibility study of optical diagnostics in humans is reported here based on experimental and theoretical modeling of optical imaging of an UCNP-labeled breast cancer lesion. UCNPs synthesized in-house were surface-capped with an amphiphilic polymer to achieve good colloidal stability in aqueous buffer solutions. The scFv4D5 mini-antibodies were grafted onto the UCNPs via a high-affinity molecular linker barstar:barnase (Bs:Bn) to allow their specific binding to the human epidermal growth factor receptor HER2/neu, which is overexpressed in human breast adenocarcinoma cells SK-BR-3. UCNP-Bs:Bn-scFv4D5 biocomplexes exhibited high-specific immobilization on the SK-BR-3 cells with the optical contrast as high as 10:1 benchmarked against a negative control cell line. Breast cancer optical diagnostics was experimentally modeled by means of epi-luminescence imaging of a monolayer of the UCNP-labeled SK-BR-3 cells buried under a breast tissue mimicking optical phantom. The experimental results were analyzed theoretically and projected to in vivo detection of early-stage breast cancer. The model predicts that the UCNP-assisted cancer detection is feasible up to 4 mm in tissue depth, showing considerable potential for diagnostic and image-guided surgery applications.

  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. Optical imaging of breast tumors and of gastrointestinal cancer by laser-induced fluorescence.

    Science.gov (United States)

    Ebert, Bernd; Grosenick, Dirk

    2013-01-01

    Optical imaging offers a high potential for noninvasive detection of cancer in humans. Recent advances in instrumentation for diffuse optical imaging have led to new capabilities for the detection of cancer in highly scattering tissue such as the female breast. We review recent developments in the detection of breast cancer in humans by fluorescent contrast agents. So far, the unspecific contrast agents indocyanine green (ICG) and omocyanine have been applied, whereas molecular probes for direct targeted imaging of this disease are still in preclinical research. We discuss recent improvements in the differentiation of malignant and benign lesions with ICG based on its enhanced extravasation in breast cancer. Whereas fluorescence imaging in thick tissue layers is hampered by strong light scattering, tissue surfaces can be investigated with high spatial resolution. As an example for superficial tumors, lesions of the gastrointestinal tract (GI) are discussed. In these investigations, protoporphyrin IX is used as a tumor-specific (due to its strong enhancement in tumor cells) target for spectroscopic identification and imaging. We present a time-gated method for fluorescence imaging and spectroscopy with strong suppression of tissue autofluorescence and show results on patients with Barrett's esophagus and with colitis ulcerosa.

  13. Body Image in Younger Breast Cancer Survivors: A Systematic Review

    Science.gov (United States)

    Paterson, Carly; Lengacher, Cecile A.; Donovan, Kristine A.; Kip, Kevin E.; Tofthagen, Cindy S.

    2015-01-01

    Background Body image is a complex issue with the potential to impact many aspects of cancer survivorship, particularly for the younger breast cancer survivor. Objective The purpose of this review is to synthesize the current state of the science for body image in younger women with breast cancer. Intervention/Methods Combinations of the terms “body image,” “sexuality intervention,” “women,” “younger women,” and “breast cancer” were searched in the PubMed, PsycInfo, CINAHL, Web of Knowledge and Science Direct databases through January 2014. Inclusion criteria for this review were: 1) original research; 2) published in English from the year 2000 forward; 3) measuring body image as an outcome variable; and 4) results included reporting of age-related outcomes. Results Thirty-six articles met the inclusion criteria. The majority of studies were cross-sectional, with extensive variation in body image assessment tools. Age and treatment type had a significant impact on body image, and poorer body image was related to physical and psychological distress, sex and intimacy, and the partnered relationship among younger women. Only one intervention study found a significant improvement in body image post-intervention. Conclusions Findings suggest body image is a complex post-treatment concern for breast cancer survivors, particularly younger women. The findings of this review are limited by the high level of variation in the methods for assessing body image. Implications for Practice Further research of interventions to address body image concerns following treatment for breast cancer is warranted. Improvement of body image may improve the quality of life of younger breast cancer survivors. PMID:25881807

  14. 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

  15. Molecular targeting of acid ceramidase: implications to cancer therapy.

    Science.gov (United States)

    Zeidan, Youssef H; Jenkins, Russell W; Korman, John B; Liu, Xiang; Obeid, Lina M; Norris, James S; Hannun, Yusuf A

    2008-08-01

    Increasingly recognized as bioactive molecules, sphingolipids have been studied in a variety of disease models. The impact of sphingolipids on cancer research facilitated the entry of sphingolipid analogues and enzyme modulators into clinical trials. Owing to its ability to regulate two bioactive sphingolipids, ceramide and sphingosine-1-phosphate, acid ceramidase (AC) emerges as an attractive target for drug development within the sphingolipid metabolic pathway. Indeed, there is extensive evidence supporting a pivotal role for AC in lipid metabolism and cancer biology. In this article, we review the current knowledge of the biochemical properties of AC, its relevance to tumor promotion, and its molecular targeting approaches.

  16. Molecular damage in cancer: an argument for mTOR-driven aging.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2011-12-01

    Despite common belief, accumulation of molecular damage does not play a key role in aging. Still, cancer (an age-related disease) is initiated by molecular damage. Cancer and aging share a lot in common including the activation of the TOR pathway. But the role of molecular damage distinguishes cancer and aging. Furthermore, an analysis of the role of both damage and aging in cancer argues against "a decline, caused by accumulation of molecular damage" as a cause of aging. I also discuss how random molecular damage, via rounds of multiplication and selection, brings about non-random hallmarks of cancer.

  17. Novelty detection for breast cancer image classification

    Science.gov (United States)

    Cichosz, Pawel; Jagodziński, Dariusz; Matysiewicz, Mateusz; Neumann, Łukasz; Nowak, Robert M.; Okuniewski, Rafał; Oleszkiewicz, Witold

    2016-09-01

    Using classification learning algorithms for medical applications may require not only refined model creation techniques and careful unbiased model evaluation, but also detecting the risk of misclassification at the time of model application. This is addressed by novelty detection, which identifies instances for which the training set is not sufficiently representative and for which it may be safer to restrain from classification and request a human expert diagnosis. The paper investigates two techniques for isolated instance identification, based on clustering and one-class support vector machines, which represent two different approaches to multidimensional outlier detection. The prediction quality for isolated instances in breast cancer image data is evaluated using the random forest algorithm and found to be substantially inferior to the prediction quality for non-isolated instances. Each of the two techniques is then used to create a novelty detection model which can be combined with a classification model and used at the time of prediction to detect instances for which the latter cannot be reliably applied. Novelty detection is demonstrated to improve random forest prediction quality and argued to deserve further investigation in medical applications.

  18. 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

  19. 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.

  20. 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.)

  1. Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging.

    Science.gov (United States)

    Ciccarelli, Olga; Barkhof, Frederik; Bodini, Benedetta; De Stefano, Nicola; Golay, Xavier; Nicolay, Klaas; Pelletier, Daniel; Pouwels, Petra J W; Smith, Seth A; Wheeler-Kingshott, Claudia A M; Stankoff, Bruno; Yousry, Tarek; Miller, David H

    2014-08-01

    The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood-brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.

  2. 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

  3. Embryonic stem cell biology: insights from molecular imaging.

    Science.gov (United States)

    Sallam, Karim; Wu, Joseph C

    2010-01-01

    Embryonic stem (ES) cells have therapeutic potential in disorders of cellular loss such as myocardial infarction, type I diabetes and neurodegenerative disorders. ES cell biology in living subjects was largely poorly understood until incorporation of molecular imaging into the field. Reporter gene imaging works by integrating a reporter gene into ES cells and using a reporter probe to induce a signal detectable by normal imaging modalities. Reporter gene imaging allows for longitudinal tracking of ES cells within the same host for a prolonged period of time. This has advantages over postmortem immunohistochemistry and traditional imaging modalities. The advantages include expression of reporter gene is limited to viable cells, expression is conserved between generations of dividing cells, and expression can be linked to a specific population of cells. These advantages were especially useful in studying a dynamic cell population such as ES cells and proved useful in elucidating the biology of ES cells. Reporter gene imaging identified poor integration of differentiated ES cells transplanted into host tissue as well as delayed donor cell death as reasons for poor long-term survival in vivo. This imaging technology also confirmed that ES cells indeed have immunogenic properties that factor into cell survival and differentiation. Finally, reporter gene imaging improved our understanding of the neoplastic risk of undifferentiated ES cells in forming teratomas. Despite such advances, much remains to be understood about ES cell biology to translate this technology to the bedside, and reporter gene imaging will certainly play a key role in formulating this understanding.

  4. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-12-1-0168 TITLE: Imaging prostatic lipids to distinguish aggressive prostate cancer PRINCIPAL INVESTIGATOR: Jackilen...Imaging prostatic lipids to distinguish aggressive prostate Cancer 5a. CONTRACT NUMBER W81XWH-12-1-0168 5b. GRANT NUMBER PC110361 5c. PROGRAM...Mechanisms linking fatty acid synthase overexpression, lipid accumulation, lipid oxidation, and tumor aggressiveness will be explored using

  5. 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.

  6. 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

  7. The central role of imaging for breast cancer patients

    NARCIS (Netherlands)

    Barentsz, M.W.

    2015-01-01

    This thesis describes the essential role of imaging in breast cancer diagnostics and treatment. Part I describes the impact of same-day diagnosis for breast cancer. Same-day diagnosis was introduced in the University Medical Center Utrecht in November 2011 with the aim to reduce patient anxiety by

  8. Prostate cancer magnetic resonance imaging (MRI): multidisciplinary standpoint.

    Science.gov (United States)

    Li, Liang; Wang, Liang; Feng, Zhaoyan; Hu, Zhiquan; Wang, Guoping; Yuan, Xianglin; Wang, He; Hu, Daoyu

    2013-04-01

    Prostate cancer is the most common cancer diagnosed in men and a leading cause of death. Accurate assessment is a prerequisite for optimal clinical management and therapy selection of prostate cancer. There are several parameters and nomograms to differentiate between patients with clinically insignificant disease and patients in need of treatment. Magnetic resonance imaging (MRI) is a technique which provides more detailed anatomical images due to high spatial resolution, superior contrast resolution, and multiplanar capability. State-of-the-art MRI techniques, such as diffusion weighted imaging (DWI), MR spectroscopic imaging (MRSI), dynamic contrast enhanced MRI (DCE-MRI), improve interpretation of prostate cancer imaging. In this article, we review the major role of MRI in the advanced management of prostate cancer to noninvasively improve tumor staging, biologic potential, treatment planning, therapy response, local recurrence, and to guide target biopsy for clinical suspected cancer with previous negative biopsy. Finally, future challenges and opportunities in prostate cancer management in the area of functional MRI are discussed as well.

  9. Molecular epidemiology, cancer-related symptoms, and cytokines pathway.

    Science.gov (United States)

    Reyes-Gibby, Cielito C; Wu, Xifeng; Spitz, Margaret; Kurzrock, Razelle; Fisch, Michael; Bruera, Eduardo; Shete, Sanjay

    2008-08-01

    The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalized and more effective therapies for persistent symptoms.

  10. Cellular and molecular effects of yeast probiotics on cancer.

    Science.gov (United States)

    Saber, Amir; Alipour, Beitollah; Faghfoori, Zeinab; Yari Khosroushahi, Ahmad

    2017-02-01

    The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.

  11. 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.

  12. 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.

  13. Biomedical nanomaterials for imaging-guided cancer therapy

    Science.gov (United States)

    Huang, Yuran; He, Sha; Cao, Weipeng; Cai, Kaiyong; Liang, Xing-Jie

    2012-09-01

    To date, even though various kinds of nanomaterials have been evaluated over the years in order to develop effective cancer therapy, there is still significant challenges in the improvement of the capabilities of nano-carriers. Developing a new theranostic nanomedicine platform for imaging-guided, visualized cancer therapy is currently a promising way to enhance therapeutic efficiency and reduce side effects. Firstly, conventional imaging technologies are reviewed with their advantages and disadvantages, respectively. Then, advanced biomedical materials for multimodal imaging are illustrated in detail, including representative examples for various dual-modalities and triple-modalities. Besides conventional cancer treatment (chemotherapy, radiotherapy), current biomaterials are also summarized for novel cancer therapy based on hyperthermia, photothermal, photodynamic effects, and clinical imaging-guided surgery. In conclusion, biomedical materials for imaging-guided therapy are becoming one of the mainstream treatments for cancer in the future. It is hoped that this review might provide new impetus to understand nanotechnology and nanomaterials employed for imaging-guided cancer therapy.

  14. 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.)

  15. Detection of Melanoma Skin Cancer in Dermoscopy Images

    Science.gov (United States)

    Eltayef, Khalid; Li, Yongmin; Liu, Xiaohui

    2017-02-01

    Malignant melanoma is the most hazardous type of human skin cancer and its incidence has been rapidly increasing. Early detection of malignant melanoma in dermoscopy images is very important and critical, since its detection in the early stage can be helpful to cure it. Computer Aided Diagnosis systems can be very helpful to facilitate the early detection of cancers for dermatologists. In this paper, we present a novel method for the detection of melanoma skin cancer. To detect the hair and several noises from images, pre-processing step is carried out by applying a bank of directional filters. And therefore, Image inpainting method is implemented to fill in the unknown regions. Fuzzy C-Means and Markov Random Field methods are used to delineate the border of the lesion area in the images. The method was evaluated on a dataset of 200 dermoscopic images, and superior results were produced compared to alternative methods.

  16. 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.

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

    Science.gov (United States)

    Xu, Jiehua; Teng, I-Ting; Zhang, Liqin; Delgado, Stefanie; Champanhac, Carole; Cansiz, Sena; Wu, Cuichen; Shan, Hong; Tan, Weihong

    2015-01-01

    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.

  18. 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

  19. 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.

  20. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    OpenAIRE

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reacti...

  1. 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.

  2. 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.

  3. 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...

  4. 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

  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. 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.

  7. Contrast ultrasound molecular imaging of inflammation in cardiovascular disease.

    Science.gov (United States)

    Lindner, Jonathan R

    2009-11-01

    The cellular immune response plays an important role in almost every major form of cardiovascular disease. The ability to image the key aspects of the immune response in the clinical setting could be used to improve diagnostic information, to provide important prognostic or risk information, and to customize therapy according to disease phenotype. Accordingly, targeted imaging probes for assessing inflammation have been developed for essentially all forms of medical imaging. Molecular imaging of inflammation with contrast ultrasound relies on the detection of targeted microbubble or other gas-filled particle contrast agents. These agents are confined to the vascular space and, hence, have been targeted to either activated leucocytes or endothelial cell adhesion molecules that are upregulated in inflammation and mediate leucocyte recruitment and adhesion. This review focuses on the inflammation-targeting strategies for ultrasound contrast agents and how they have been matched to cardiovascular disease states such as myocardial ischaemia, infarction, atherosclerosis, transplant rejection, and arteriogenesis.

  8. 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.

  9. Quantification and confocal imaging of protein specific molecularly imprinted polymers

    OpenAIRE

    Hawkins, DM; Trache, A; Ellis, EA; Stevenson, D.; Holzenburg, A.; Meininger, GA; Reddy, Subrayal M

    2006-01-01

    We have employed FITC-albumin as the protein template molecule in an aqueous phase molecular imprinted polymer (HydroMIP) strategy. For the first time, the use of a fluorescently labelled template is reported, with subsequent characterisation of the smart material to show that the HydroMIP possess a significant molecular memory in comparison to that of the nonimprinted control polymer (HydroNIP). The imaging of the FITC-albumin imprinted HydroMIP using confocal microscopy is described, with t...

  10. Microwave Imaging for Breast Cancer Detection

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Fhager, Andreas; Jensen, Peter Damsgaard

    2011-01-01

    Still more research groups are promoting microwave imaging as a viable supplement or substitution to more conventional imaging modalities. A widespread approach for microwave imaging of the breast is tomographic imaging in which one seeks to reconstruct the distributions of permittivity and condu...

  11. Predictive and prognostic molecular markers for cancer medicine.

    Science.gov (United States)

    Mehta, Sunali; Shelling, Andrew; Muthukaruppan, Anita; Lasham, Annette; Blenkiron, Cherie; Laking, George; Print, Cristin

    2010-03-01

    Over the last 10 years there has been an explosion of information about the molecular biology of cancer. A challenge in oncology is to translate this information into advances in patient care. While there are well-formed routes for translating new molecular information into drug therapy, the routes for translating new information into sensitive and specific diagnostic, prognostic and predictive tests are still being developed. Similarly, the science of using tumor molecular profiles to select clinical trial participants or to optimize therapy for individual patients is still in its infancy. This review will summarize the current technologies for predicting treatment response and prognosis in cancer medicine, and outline what the future may hold. It will also highlight the potential importance of methods that can integrate molecular, histopathological and clinical information into a synergistic understanding of tumor progression. While these possibilities are without doubt exciting, significant challenges remain if we are to implement them with a strong evidence base in a widely available and cost-effective manner.

  12. Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation.

    Science.gov (United States)

    Abou, D S; Pickett, J E; Thorek, D L J

    2015-10-01

    Molecular imaging provides considerable insight into biological processes for greater understanding of health and disease. Numerous advances in medical physics, chemistry and biology have driven the growth of this field in the past two decades. With exquisite sensitivity, depth of detection and potential for theranostics, radioactive imaging approaches have played a major role in the emergence of molecular imaging. At the same time, developments in materials science, characterization and synthesis have led to explosive progress in the nanoparticle (NP) sciences. NPs are generally defined as particles with a diameter in the nanometre size range. Unique physical, chemical and biological properties arise at this scale, stimulating interest for applications as diverse as energy production and storage, chemical catalysis and electronics. In biomedicine, NPs have generated perhaps the greatest attention. These materials directly interface with life at the subcellular scale of nucleic acids, membranes and proteins. In this review, we will detail the advances made in combining radioactive imaging and NPs. First, we provide an overview of the NP platforms and their properties. This is followed by a look at methods for radiolabelling NPs with gamma-emitting radionuclides for use in single photon emission CT and planar scintigraphy. Next, utilization of positron-emitting radionuclides for positron emission tomography is considered. Finally, recent advances for multimodal nuclear imaging with NPs and efforts for clinical translation and ongoing trials are discussed.

  13. Imaging molecular shapes with molecular-frame photoelectron angular distributions from core hole ionization

    Science.gov (United States)

    Trevisan, C. S.; McCurdy, C. W.; Rescigno, T. N.

    2012-10-01

    We demonstrate, for a class of molecules containing a single heavy atom, the striking result that molecular-frame photoelectron angular distributions resulting from core-level ionization can be used to obtain three-dimensional images of the target molecule at low photoelectron energies. We demonstrate this finding with the results of theoretical calculations on methane, ammonia and water.

  14. [Molecular-targeted therapy for hormone-refractory prostate cancer].

    Science.gov (United States)

    Nishimura, Kazuo; Takayama, Hitoshi; Nakayama, Masashi; Nonomura, Norio; Okuyama, Akihiko

    2006-06-01

    Molecular-targeted therapy is to treat pathologic pathways specifically in tumor cell or tumor microenvironment. Specific molecular-targeted therapeutic agents for hormone-refractory prostate cancer (HRPC) include endothelin-A receptor antagonist, EGF receptor (EGFR) inhibitor, platelet derived growth factor receptor (PDGFR) inhibitor, nuclear factor of kappaB (NF-kappaB) inhibitor, cyclooxygenase-2 (COX2) inhibitor, and active form of Vitamin D. These agents have been investigated in clinical trials. So far, none of the above-mentioned agent has shown a sufficient clinical efficacy alone. However, docetaxel-based combinations with thalidomide or calcitriol have promising clinical activities. Further investigations are needed to optimize the molecular-targeted agents in the combinations with chemotherapeutic agents for the treatment of HRPC.

  15. 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.

  16. 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.

  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. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available BACKGROUND: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. METHODS AND FINDINGS: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. CONCLUSIONS: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive

  3. 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

  4. Various diffusion magnetic resonance imaging techniques for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Meng-Yue Tang; Xiao-Ming Zhang; Tian-Wu Chen; Xiao-Hua Huang

    2015-01-01

    Pancreatic cancer is one of the most common malignanttumors and remains a treatment-refractory cancer with a poor prognosis. Currently, the diagnosis of pancreatic neoplasm depends mainly on imaging and which methods are conducive to detecting small lesions. Compared to the other techniques, magnetic resonance imaging(MRI) has irreplaceable advantages and can provide valuable information unattainable with other noninvasive or minimally invasive imaging techniques. Advances in MR hardware and pulse sequence design have particularly improved the quality and robustness of MRI of the pancreas. Diffusion MR imaging serves as one of the common functional MRI techniques and is the only technique that can be used to reflect the diffusion movement of water molecules in vivo. It is generally known that diffusion properties depend on the characterization of intrinsic features of tissue microdynamics and microstructure. With the improvement of the diffusion models, diffusion MR imaging techniques are increasingly varied, from the simplest and most commonly used technique to the more complex. In this review, the various diffusion MRI techniques for pancreatic cancer are discussed, including conventional diffusion weighted imaging(DWI), multi-b DWI based on intra-voxel incoherent motion theory, diffusion tensor imaging and diffusion kurtosis imaging. The principles, main parameters, advantages and limitations of these techniques, as well as future directions for pancreatic diffusion imaging are also discussed.

  5. Ratiometric Photoacoustic Molecular Imaging for Methylmercury Detection in Living Subjects.

    Science.gov (United States)

    Liu, Yi; Wang, Sheng; Ma, Ying; Lin, Jing; Wang, Hai-Yan; Gu, Yueqing; Chen, Xiaoyuan; Huang, Peng

    2017-02-22

    Photoacoustic molecular imaging is an emerging and promising diagnostic tool for heavy metal ions detection. Methylmercury (MeHg(+) ) is one of the most potent neurotoxins, which damages the brain and nervous system of human beings through fish consumption. The development of a selective and sensitive method for MeHg(+) detection is highly desirable. In this Communication, we develope a chemoselective photoacoustic sensor (LP-hCy7) composed of the liposome (LP) and MeHg(+) -responsive near-infrared (NIR) cyanine dye (hCy7) for MeHg(+) detection within living subjects, such as zebrafish and mouse. The as-prepared LP-hCy7 nanoprobe displays unique dual-shift NIR absorbance peaks and produces a normalized turn-on response after the reaction of MeHg(+) and hCy7 through a mercury-promoted cyclization reaction. The absorbance intensities of LP-hCy7 nanoprobe at 690 and 860 nm are decreased and increased, respectively. The ratiometric photoacoustic signal (PA860/PA690) is noticeably increased in the presence of MeHg(+) . These findings not only provide a ratiometric photoacoustic molecular imaging probe for the detection of metal ions in vivo, but also provides a tool for spectroscopic photoacoustic molecular imaging.

  6. 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.

  7. Hyperspectral imaging fluorescence excitation scanning for colon cancer detection

    Science.gov (United States)

    Leavesley, Silas J.; Walters, Mikayla; Lopez, Carmen; Baker, Thomas; Favreau, Peter F.; Rich, Thomas C.; Rider, Paul F.; Boudreaux, Carole W.

    2016-10-01

    Optical spectroscopy and hyperspectral imaging have shown the potential to discriminate between cancerous and noncancerous tissue with high sensitivity and specificity. However, to date, these techniques have not been effectively translated to real-time endoscope platforms. Hyperspectral imaging of the fluorescence excitation spectrum represents new technology that may be well suited for endoscopic implementation. However, the feasibility of detecting differences between normal and cancerous mucosa using fluorescence excitation-scanning hyperspectral imaging has not been evaluated. The goal of this study was to evaluate the initial feasibility of using fluorescence excitation-scanning hyperspectral imaging for measuring changes in fluorescence excitation spectrum concurrent with colonic adenocarcinoma using a small pre-pilot-scale sample size. Ex vivo analysis was performed using resected pairs of colorectal adenocarcinoma and normal mucosa. Adenocarcinoma was confirmed by histologic evaluation of hematoxylin and eosin (H&E) permanent sections. Specimens were imaged using a custom hyperspectral imaging fluorescence excitation-scanning microscope system. Results demonstrated consistent spectral differences between normal and cancerous tissues over the fluorescence excitation range of 390 to 450 nm that could be the basis for wavelength-dependent detection of colorectal cancers. Hence, excitation-scanning hyperspectral imaging may offer an alternative approach for discriminating adenocarcinoma from surrounding normal colonic mucosa, but further studies will be required to evaluate the accuracy of this approach using a larger patient cohort.

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

    Directory of Open Access Journals (Sweden)

    Maneesha Amrita Rajora

    2016-09-01

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

  10. 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.

  11. Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

    Science.gov (United States)

    2013-09-01

    Molecular Imaging and Radiochemistry core would synthesize the FDHT agent needed for these studies using previously reported methods. Based on their...recommendation, rather than pursuing a new precursor synthesis we elected to purchase the FDHT precursor from the Radiochemistry & Molecular

  12. 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.

  13. Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jesal C. Patel

    2013-01-01

    Full Text Available Androgen deprivation therapy (ADT with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700, and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.

  14. PET-based molecular nuclear neuro-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Ho [Gil Medical Center, Gachon (Korea, Republic of)

    2004-04-01

    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.

  15. Advancing Molecular Therapies through In Vivo Bioluminescent Imaging

    Directory of Open Access Journals (Sweden)

    Anton McCaffrey

    2003-04-01

    Full Text Available Effective development of therapeutics that target the molecular basis of disease is dependent on testing new therapeutic moieties and delivery strategies in animal models of human disease. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide data in real time and are sensitive to the subtle changes, are crucial for rapid advancement of these approaches. Modalities based on optics are rapid, sensitive, and accessible methods for in vivo analyses with relatively low instrumentation costs. In vivo bioluminescent imaging (BLI is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity. BLI is based on the use of light-emitting enzymes as internal biological light sources that can be detected externally as biological indicators. BLI has been used to test spatio-temporal expression patterns of both target and therapeutic genes in living laboratory animals where the contextual influences of whole biological systems are preserved. BLI has also been used to analyze gene delivery, immune cell therapies, and the in vivo efficacy of inhibitory RNAs. New tools for BLI are being developed that will offer greater flexibility in detection and analyses. BLI can be used to accelerate the evaluation of experimental therapeutic strategies and whole body imaging offers the opportunity of revealing the effects of novel approaches on key steps in disease processes.

  16. Guidance for laboratories performing molecular pathology for cancer patients.

    Science.gov (United States)

    Cree, Ian A; Deans, Zandra; Ligtenberg, Marjolijn J L; Normanno, Nicola; Edsjö, Anders; Rouleau, Etienne; Solé, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J Han

    2014-11-01

    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here.

  17. 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.

  18. 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)

  19. Multiphoton microscopy as a diagnostic imaging modality for lung cancer

    Science.gov (United States)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Peters, Rachel M.; Weiss, Robert S.; Webb, Watt W.

    2010-02-01

    Lung cancer is the leading killer among all cancers for both men and women in the US, and is associated with one of the lowest 5-year survival rates. Current diagnostic techniques, such as histopathological assessment of tissue obtained by computed tomography guided biopsies, have limited accuracy, especially for small lesions. Early diagnosis of lung cancer can be improved by introducing a real-time, optical guidance method based on the in vivo application of multiphoton microscopy (MPM). In particular, we hypothesize that MPM imaging of living lung tissue based on twophoton excited intrinsic fluorescence and second harmonic generation can provide sufficient morphologic and spectroscopic information to distinguish between normal and diseased lung tissue. Here, we used an experimental approach based on MPM with multichannel fluorescence detection for initial discovery that MPM spectral imaging could differentiate between normal and neoplastic lung in ex vivo samples from a murine model of lung cancer. Current results indicate that MPM imaging can directly distinguish normal and neoplastic lung tissues based on their distinct morphologies and fluorescence emission properties in non-processed lung tissue. Moreover, we found initial indication that MPM imaging differentiates between normal alveolar tissue, inflammatory foci, and lung neoplasms. Our long-term goal is to apply results from ex vivo lung specimens to aid in the development of multiphoton endoscopy for in vivo imaging of lung abnormalities in various animal models, and ultimately for the diagnosis of human lung cancer.

  20. 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.

  1. 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”.

  2. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Science.gov (United States)

    Hong, Hao; Sun, Jiangtao; Cai, Weibo

    2008-01-01

    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”. PMID:19578524

  3. 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.

  4. Challenges and opportunities in international molecular cancer prevention research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report.

    Science.gov (United States)

    Epplein, Meira; Bostick, Roberd M; Mu, Lina; Ogino, Shuji; Braithwaite, Dejana; Kanetsky, Peter A

    2014-11-01

    The International Agency for Research on Cancer estimates that over half of the new cancer cases and almost two-thirds of the cancer deaths in 2012 occurred in low and middle income countries. To discuss the challenges and opportunities to reducing the burden of cancer worldwide, the Molecular Epidemiology and the Environment and the International Issues in Cancer Special Interest Groups joined forces to hold a session during the 38th Annual Meeting of the American Society of Preventive Oncology (March 2014, Arlington, Virginia). The session highlighted three topics of particular interest to molecular cancer prevention researchers working internationally, specifically: 1) biomarkers in cancer research; 2) environmental exposures and cancer; and 3) molecular pathological epidemiology. A major factor for successful collaboration illuminated during the discussion was the need for strong, committed, and reliable international partners. A key element of establishing such relationships is to thoroughly involve individual international collaborators in the development of the research question; engaged international collaborators are particularly motivated to champion and shepherd the project through all necessary steps, including issues relating to institutional review boards, political sensitivity, laboratory-based assays, and tumor subtyping. Also essential is allotting time for the building, maintaining, and investing in such relationships so that successful international collaborations may take root and bloom. While there are many challenges inherent to international molecular cancer research, the opportunities for furthering the science and prevention of cancer worldwide are great, particularly at this time of increasing cancer incidence and prevalence in low and middle income countries.

  5. 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.

  6. 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

  7. 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.

  8. Molecular Link between Vitamin D and Cancer Prevention

    Directory of Open Access Journals (Sweden)

    William B. Grant

    2013-09-01

    Full Text Available The metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (also known as calcitriol, is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D3 signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol in modulating cellular growth and development. Vitamin D (calcitriol acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise—yet where sunlight and, hence, vitamin D may be easily acquired—adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence.

  9. 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).

  10. Review of Histopathological and Molecular Prognostic Features in Colorectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marzouk, Ola; Schofield, John, E-mail: john.schofield@nhs.net [Department of Cellular Pathology, Maidstone Hospital, Hermitage Lane, Maidstone, Kent ME16 9QQ (United Kingdom)

    2011-06-23

    Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer.

  11. Review of Histopathological and Molecular Prognostic Features in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    John Schofield

    2011-06-01

    Full Text Available Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer.

  12. Mangiferin in cancer chemoprevention and treatment: pharmacokinetics and molecular targets.

    Science.gov (United States)

    Rajendran, Peramaiyan; Rengarajan, Thamaraiselvan; Nandakumar, Natarajan; Divya, H; Nishigaki, Ikuo

    2015-02-01

    A variety of bioactive food components have been shown to modulate inflammatory responses and to attenuate carcinogenesis. Polyphenols isolated several years ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments. Mangiferin, a unique, important, and highly investigated polyphenol, has attracted much attention of late for its potential as a chemopreventive and chemotherapeutic agent against various types of cancer. Mangiferin has been shown to target multiple proinflammatory transcription factors, cell- cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of mangiferin by inhibiting the initiation, promotion, and metastasis of cancer. This review not only summarizes the diverse molecular targets of mangiferin, but also gives the results of various preclinical studies that have been performed in the last decade with this promising polyphenol.

  13. 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.

  14. Nanoshell bioconjugates for integrated imaging and therapy of cancer

    Science.gov (United States)

    Loo, Christopher H.; Lee, Min-Ho; Hirsch, Leon R.; West, Jennifer L.; Halas, Naomi J.; Drezek, Rebekah A.

    2004-06-01

    Currently, separate diagnostic and therapeutic modalities are required for the diagnosis and treatment of cancer. In many cases, the present standard of care requires invasive surgical procedures and/or other treatments associated with significant side effect profiles, high cost, and poor clinical outcome. A single technology with dual diagnostic/therapeutic capabilities would potentially yield significant savings in the time and cost associated with diagnosing and treating many cancers. In this paper, we discuss gold nanoshell bioconjugates and their role in the development of an integrated cancer imaging and therapy application. Nanoshells are a novel class of nanomaterials that have unique properties including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. Here, we describe the development of an integrated cancer imaging and therapy application using near-infrared (NIR) gold nanoshell bioconjugates.

  15. 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.

  16. Biomarker, Molecular, and Technologic Advances in Urologic Pathology, Oncology, and Imaging.

    Science.gov (United States)

    Ellis, Carla L; Harik, Lara R; Cohen, Cynthia; Osunkoya, Adeboye O

    2017-04-01

    Urologic pathology is evolving rapidly. Emerging trends include the expanded diagnostic utility of biomarkers and molecular testing, as well as adapting to the plethora of technical advances occurring in genitourinary oncology, surgical practice, and imaging. We illustrate those trends by highlighting our approach to the diagnostic workup of a few selected disease entities that pathologists may encounter, including newly recognized subtypes of renal cell carcinoma, pheochromocytoma, and prostate cancer, some of which harbor a distinctive chromosomal translocation, gene loss, or mutation. We illustrate applications of immunohistochemistry for differential diagnosis of needle core renal biopsies, intraductal carcinoma of the prostate, and amyloidosis and cite encouraging results from early studies using targeted gene expression panels to predict recurrence after prostate cancer surgery. At our institution, pathologists are working closely with urologic surgeons and interventional radiologists to explore the use of intraoperative frozen sections for margins and nerve sparing during robotic prostatectomy, to pioneer minimally invasive videoscopic inguinal lymphadenectomy, and to refine image-guided needle core biopsies and cryotherapy of prostate cancer as well as blue-light/fluorescence cystoscopy. This collaborative, multidisciplinary approach enhances clinical management and research, and optimizes the care of patients with urologic disorders.

  17. Terahertz imaging applied to cancer diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Brun, M-A; Formanek, F; Yasuda, A [Life Science Laboratory, Advanced Materials Laboratories, Sony Corporation, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510 (Japan); Sekine, M; Ando, N; Eishii, Y, E-mail: florian.formanek@jp.sony.co [Department of Human Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510 (Japan)

    2010-08-21

    We report on terahertz (THz) time-domain spectroscopy imaging of 10 {mu}m thick histological sections. The sections are prepared according to standard pathological procedures and deposited on a quartz window for measurements in reflection geometry. Simultaneous acquisition of visible images enables registration of THz images and thus the use of digital pathology tools to investigate the links between the underlying cellular structure and specific THz information. An analytic model taking into account the polarization of the THz beam, its incidence angle, the beam shift between the reference and sample pulses as well as multiple reflections within the sample is employed to determine the frequency-dependent complex refractive index. Spectral images are produced through segmentation of the extracted refractive index data using clustering methods. Comparisons of visible and THz images demonstrate spectral differences not only between tumor and healthy tissues but also within tumors. Further visualization using principal component analysis suggests different mechanisms as to the origin of image contrast.

  18. Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

    Science.gov (United States)

    Zhang, Jialing; Feider, Clara L.; Nagi, Chandandeep; Yu, Wendong; Carter, Stacey A.; Suliburk, James; Cao, Hop S. Tran; Eberlin, Livia S.

    2017-02-01

    Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed.

  19. Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer

    DEFF Research Database (Denmark)

    Stoffel, Elena M; Erichsen, Rune; Frøslev, Trine;

    2016-01-01

    BACKGROUND AND AIMS: Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy....... METHODS: We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (d...

  20. An introduction to molecular imaging in radiation oncology: a report by the AAPM Working Group on Molecular Imaging in Radiation Oncology (WGMIR).

    Science.gov (United States)

    Munley, Michael T; Kagadis, George C; McGee, Kiaran P; Kirov, Assen S; Jang, Sunyoung; Mutic, Sasa; Jeraj, Robert; Xing, Lei; Bourland, J Daniel

    2013-10-01

    Molecular imaging is the direct or indirect noninvasive monitoring and recording of the spatial and temporal distribution of in vivo molecular, genetic, and/or cellular processes for biochemical, biological, diagnostic, or therapeutic applications. Molecular images that indicate the presence of malignancy can be acquired using optical, ultrasonic, radiologic, radionuclide, and magnetic resonance techniques. For the radiation oncology physicist in particular, these methods and their roles in molecular imaging of oncologic processes are reviewed with respect to their physical bases and imaging characteristics, including signal intensity, spatial scale, and spatial resolution. Relevant molecular terminology is defined as an educational assist. Current and future clinical applications in oncologic diagnosis and treatment are discussed. National initiatives for the development of basic science and clinical molecular imaging techniques and expertise are reviewed, illustrating research opportunities in as well as the importance of this growing field.

  1. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer

    OpenAIRE

    Antonelli,Giovanna; Libra, Massimo; PANEBIANCO, VINCENZO; Russo,Alessia Erika; Vitale, Felice Vito; COLINA, PAOLO; D'Angelo,Alessandro; ROSSELLO, ROSALBA; Ferraù, Francesco

    2015-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared wit...

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

    Science.gov (United States)

    Pu, Yang

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

  3. 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

  4. Molecular imaging in traditional Chinese medicine therapy for neurological diseases.

    Science.gov (United States)

    Wang, Zefeng; Wan, Haitong; Li, Jinhui; Zhang, Hong; Tian, Mei

    2013-01-01

    With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer's disease, Parkinson's disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM.

  5. In Situ Correlated Molecular Imaging of Chemically Communicating Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

    Bohn, Paul W. [Univ. of Notre Dame, IN (United States); Shrout, J. D. [Univ. of Notre Dame, IN (United States); Sweedler, J. V. [Univ. of Illinois, Urbana-Champaign, IL (United States); Farrand, S. [Univ. of Illinois, Urbana-Champaign, IL (United States)

    2016-01-25

    This document constitutes the final technical report for DE-SC0006642, In Situ Correlated Molecular Imaging of Chemically Communicating Microbial Communities, a project carried out collaboratively by investigators at Notre Dame and UIUC. The work carried out under DOE support in this project produced advances in two areas: development of new highly sophisticated correlated imaging approaches and the application of these new tools to the growth and differentiation of microbial communities under a variety of environmental conditions. A significant effort involved the creation of technical enhancements and sampling approaches to allow us to advance heterocorrelated mass spectrometry imaging (MSI) and correlated Raman microscopy (CRM) from bacterial cultures and biofilms. We then exploited these measurement advances in heterocorrelated MS/CRM imaging to determine relationship of signaling molecules and excreted signaling molecules produced by P. aeruginosa to conditions relevant to the rhizosphere. In particular, we: (1) developed a laboratory testbed mimic for the rhizosphere to enable microbial growth on slides under controlled conditions; (2) integrated specific measurements of (a) rhamnolipids, (b) quinolone/quinolones, and (c) phenazines specific to P. aeruginosa; and (3) utilized the imaging tools to probe how messenger secretion, quorum sensing and swarming behavior are correlated with behavior.

  6. Molecular imaging in neurological diseases; Molekulare Bildgebung bei neurologischen Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Reimold, M.; Fougere, C. la [Universitaetsklinikum Tuebingen, Abteilung Nuklearmedizin und Klinische Molekulare Bildgebung, Department Radiologie, Tuebingen (Germany)

    2016-07-15

    In neurodegeneration and in neuro-oncology, the standard imaging procedure, m