Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide), which can selectively target plasma membrane of cells based on lower extracellular pH. 20 pairs of clinically normal and abnormal biopsies were obtained from consenting patients at UCDMC. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG and Alexa-647 labeled pHLIP was measured non-invasively by widefield imaging and confocal microscope. Uptake of propargyl choline was measured after topical delivery using confocal microscope. The results of all three molecular imagine probes were further correlated with pathological diagnosis. The imaging results of clinical biopsies demonstrated that 2-NBDG, propargyl choline and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. Topical application of the contrast agents generated significantly higher fluorescence signal intensity in all neoplastic tissues as compared to clinically normal biopsies irrespective of the anatomic location or patient. This unpaired comparison across all the cancer patients in this study highlights the specificity of the imaging approach. Furthermore, the results indicated that changes in intracellular glucose, choline metabolism and cancer acidosis are initiated in the early stages of cancer and these changes are correlated with the progression of the disease. In conclusion, these novel optical molecular imaging approaches to measure multiple biomarkers in cancer have significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

This review volume integrates the advances in cancer biology, molecular imaging techniques and imaging probes for visualization and quantitative measurement of anatomical, functional, and molecular profiles of cancer. The volume also presents a comprehensive summary of the state-of-the-art technology in molecular imaging probe design and applications in radionuclide (PET and SPECT), magnetic resonance (MR), optical (fluorescence, Raman, photoacoustic), ultrasound, CT, and multimodality imaging. Bringing together the fundamentals of molecular imaging, and the basic principles of each molecular imaging modality in this volume, readers' understanding in this field is further enhanced. With a strong emphasis on the chemistry of the design of appropriate molecular imaging probes for early cancer detection, therapy-response monitoring, and anti-cancer drug development, the process of translating novel cancer imaging probes from bench to bedside is extensively discussed.

With molecular imaging becoming one the fastest growing topics in medical schools, Informa Healthcare presents Molecular Imaging in Oncology, the first comprehensive reference on molecular imaging in oncology.Giving clinicians and researchers a greater understanding of the current field, this text covers:instrumentation and techniquescancer imaging

To describe principles of optical imaging including chemistry and physics of fluorescence, limitations/advantages of optical imaging compared to metabolic and anatomic imaging. Describe hardware adapted for small animal imaging and for clinical applications: endoscopes and operative microscopes. Outline FDA approved and newer optical imaging probes. Include discussion of chemistry and linkage to other proteins. Review current techniques to image cancer and the development of techniques to specifically image cancer cells. Review use of exploiting differences in tissue autofluorescence to diagnose and treat cancer. Include agents such as 5-aminoleculinic acid. Review mechanisms that require proteolytic processing within the tumor to become active fluorophores. Review use of cancer selective proteins to localize probes to cancer cells: include toxins, antibodies, and minibodies. Introduction of plasmids, viruses or other genetic material may be used to express fluorescent agents in vivo. This chapter will review multiple vectors and delivery mechanisms of optical imaging cassettes.Preclinical investigations into the use of optical contrast agents for the detection of primary tumors in conventional and orthotopic models will be discussed. Preclinical investigations into the use of optical contrast agents for the detection of metastatic tumors in mouse models will be discussed. Use of targeted and non-specific optical contrast agents have been used for the detection of sentinel lymph node detection. These applications and how they differ from other applications will be discussed. Because of the unique difficulty of identifying tumor from normal tissue in brain tissue, a separate chapter would be needed. More clinical data is available for this cancer type than any other. Discussion of potential clinical applications for optical imaging and an assessment of the potential market.

This book provides an in-depth description and discussion of different multi-modal diagnostic techniques for cancer detection and treatment using exact optical methods, their comparison, and combination. Coverage includes detailed descriptions of modern state of design for novel methods of optical non-invasive cancer diagnostics; multi-modal methods for earlier cancer diagnostic enhancing the probability of effective cancer treatment; modern clinical trials with novel methods of clinical cancer diagnostics; medical and technical aspects of clinical cancer diagnostics, and long-term monitoring. Biomedical engineers, cancer researchers, and scientists will find the book to be an invaluable resource. Introduces optical imaging strategies; Focuses on multimodal optical diagnostics as a fundamental approach; Discusses novel methods of optical non-invasive cancer diagnostics.

The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing steadily. Many innovative molecular imaging probes have already entered clinical practice, and there is no doubt that the future emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation. This handbook addresses all aspects of molecular imaging in oncology, from basic research to clinical applications. 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.

The inclusion of oncogene-driven reprogramming of energy metabolism within the list of cancer hallmarks (Hanahan and Weinberg, Cell 2000, 2011) has provided major impetus to further investigate the existence of a much wider metabolic rewiring in cancer cells, which not only includes deregulated cellular bioenergetics, but also encompasses multiple links with a more comprehensive network of altered biochemical pathways. This network is currently held responsible for redirecting carbon and phosphorus fluxes through the biosynthesis of nucleotides, amino acids, lipids and phospholipids and for the production of second messengers essential to cancer cells growth, survival and invasiveness in the hostile tumor environment. The capability to develop such a concerted rewiring of biochemical pathways is a versatile tool adopted by cancer cells to counteract the host defense and eventually resist the attack of anticancer treatments. Integrated efforts elucidating key mechanisms underlying this complex cancer metabolic reprogramming have led to the identification of new signatures of malignancy that are providing a strong foundation for improving cancer diagnosis and monitoring tumor response to therapy using appropriate molecular imaging approaches. In particular, the recent evolution of positron emission tomography (PET), magnetic resonance spectroscopy (MRS), spectroscopic imaging (MRSI), functional MR imaging (fMRI) and optical imaging technologies, combined with complementary cellular imaging approaches, have created new ways to explore and monitor the effects of metabolic reprogramming in cancer at clinical and preclinical levels. Thus, the progress of high-tech engineering and molecular imaging technologies, combined with new generation genomic, proteomic and phosphoproteomic methods, can significantly improve the clinical effectiveness of image-based interventions in cancer and provide novel insights to design and validate new targeted therapies. The Frontiers in Oncology Research Topic “Exploring Cancer Metabolic Reprogramming Through Molecular Imaging” focusses on current achievements, challenges and needs in the application of molecular imaging methods to explore cancer metabolic reprogramming, and evaluate its potential impact on clinical decisions and patient outcome. A series of reviews and perspective articles, along with original research contributions on humans and on preclinical models have been concertedly included in the Topic to build an open forum on perspectives, present needs and future challenges of this cutting-edge research area.

Ch. 1. The optical detection of cancer: an introduction / Toby Steele and Arlen Meyers -- ch. 2. Optical coherence tomography in oral cancer / Shahareh Sabet and Petra Wilder-Smith -- ch. 3. Optical coherence tomography in laryngeal cancer / Marcel Kraft and Christoph Arens -- ch. 4. Fluorescence imaging of the upper aerodigestive tract / Christian Stephan Betz, Andreas Leunig and Christoph Arens -- ch. 5. Photodynamic diagnosis and photodynamic therapy techniques / Zheng Huang -- ch. 6. OCT detection of lung cancer / S. Murgu and M. Brenner -- ch. 7. Diffuse optical spectroscopy and imaging in breast cancer / Albert E. Cerussi and Bruce J. Tromberg -- ch. 8. OCT for skin cancer / Gordon McKenzie and Adam Meekings

The continuous progress in the understanding of molecular processes of disease formation and progression attributes an increasing importance to biomedical molecular imaging methods. The purpose of this workshop was to discuss and overview multiple applications and emerging technologies in the area of diagnostic imaging including its fundamental capabilities in preclinical research, the opportunities for medical care, and the options involving therapeutic concepts. The book provides the reader with state-of-the-art information on the different aspects of diagnostic imaging, illuminating new developments in molecular biology, imaging agents and molecular probe design, and therapeutic techniques.

This is an interdisciplinary book that presents the applications of novel laser spectroscopy and imaging techniques for the detection of cancers recently developed by some of the world's most renown researchers. The book consists of three parts and a total of 16 chapters. Each chapter is written by leading experts who are actively seeking to develop novel spectroscopic and analytical methods for cancer detection and diagnosis.In Part I, the authors present fundamentals on optics, atoms and molecules, biophysics, cancer and machine learning. These chapters are intended for those who are not experts in the field but wish to learn about fundamentals' aspects of some of the key topics that are addressed in this book. Particular attention has been given to providing key references for those who wish to go further into the fundamental aspects of atoms and molecules, light-matter interaction, optical instrumentation, machine learning and cancer.In Part II, the authors present key applications of various laser spectroscopic methods in cancer diagnosis. They have provided recent progress in cancer diagnostics obtained by combining laser spectroscopy and machine learning for the analysis of the spectra acquired from biomedical tissues and biofluids.In Part III, the authors present chapters that discuss key developments in the applications of various laser imaging techniques for cancer detection.This is one of the few books that addresses cancer detection and diagnosis using laser spectroscopic and imaging tools with an eye on providing the reader the scientific tools, including machine learning ones.