Matrix Metalloproteinases (MMPs), a family of over 20 types of enzymes, collectively are capable of degrading all the components of the extracellular matrix. MMP-2 and MMP-9 (also known as gelatinases) are specifically thought to play critical roles in tumor cell invasion and are frequently co-expressed in breast cancer. Cyclic peptides containing the sequence HWGF have been described as selective inhibitors of MMP-2 and MMP-9. We tested the hypothesis that gelatinase expression may provide a target for in vivo tumor imaging using a radiolabeled gelatinase inhibitor. The peptide, DOTA-CTTHWGFTLC (DOTA-CTT), was labeled with Cu-64 T 1/2 1/2% = l2.7 h.%, which has a decay scheme suitable for both PET imaging and cancer therapy. This conjugate maintained MMP-2 inhibitory activity comparable to %Ilomastat, a broad-range inhibitor of MMPs. An increase in the MMP-2/9 activity of human metastatic breast cancer MDA-MB-435 tumors in nude mice was observed from 4 to 10 weeks post-implantation. MicroPET images of Cu-64-DOTA-CTT in the tumor-bearing nude mice showed tumor uptake at 8-wk post-implantation; however, the same mouse with 5-wk palpable tumors showed no uptake of the tracer, suggesting that the MMP-2 and MMP-9 activity is related to the stage of tumor growth. These data suggest the potential of radiolabeled gelatinase inhibitors as markers for imaging the metastatic capability of human breast cancer.

Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

While simultaneous breakthroughs occurring in molecular biology and nanoscience/technology will ultimately revolutionize all of medicine, it is with our efforts to prevent, diagnose, and treat cancer that many of the most dramatic advances will occur. In support of this potential, the U.S. National Cancer Institute (NCI) established the Alliance fo

Cell Surface Proteases provides a comprehensive overview of these important enzymes that catalyze the hydrolysis of a protein as it degrades to a simpler substance. In the 1990s, an explosion of new discoveries shed light on the role of cell surface proteases and extended it beyond degradation of extracellular matrix components to include its influence on growth factors, cell signaling, and other cellular events. This volume unites the scientific literature from across disciplines and teases out unified themes of interactions between cell surface proteases and interconnecting cell surface-related systems -- including integrins and other adhesion molecules. Scientists and students involved in developmental biology, cell biology and disease processes will find this an indispensable resource. * Provides an overview of the entire field of cell surface proteases in a single volume* Presents major issues and astonishing discoveries at the forefront of modern developmental biology and developmental medicine * A thematic volume in the longest-running forum for contemporary issues in developmental biology with over 30 years of coverage

This second of two volumes on Cancer Imaging covers the three major topics of imaging instrumentation, general imaging applications, and imaging of a number of human cancer types. Where the first volume emphasized lung and breast carcinomas, Volume 2 focuses on prostate, colorectal, ovarian, gastrointestinal, and bone cancers. Although cancer therapy is not the main subject of this series, the crucial role of imaging in selecting the type of therapy and its post-treatment assessment are discussed. The major emphasis in this volume is on cancer imaging; however, differentiation between benign tumors and malignant tumors is also discussed. This volume is sold individually, and Cancer Imaging, Volume 1 [ISBN: 978-0-12-370468-9] sells separately for $189 and also as part of a two volume set [ISBN: 978-0-12-374212-4] for $299. • Concentrates on the application of imaging technology to the diagnosis and prognosis of prostate, colorectal, ovarian, gastrointestinal, and bone cancers• Addresses relationship between radiation dose and image quality • Discusses the role of molecular imaging in identifying changes for the emergence and progression of cancer at the cellular and/or molecular levels

This book is a comprehensive guide to radiopharmaceutical chemistry. The stunning clinical successes of nuclear imaging and targeted radiotherapy have resulted in rapid growth in the field of radiopharmaceutical chemistry, an essential component of nuclear medicine and radiology. However, at this point, interest in the field outpaces the academic and educational infrastructure needed to train radiopharmaceutical chemists. For example, the vast majority of texts that address radiopharmaceutical chemistry do so only peripherally, focusing instead on nuclear chemistry (i.e. nuclear reactions in reactors), heavy element radiochemistry (i.e. the decomposition of radioactive waste), or solely on the clinical applications of radiopharmaceuticals (e.g. the use of PET tracers in oncology). This text fills that gap by focusing on the chemistry of radiopharmaceuticals, with key coverage of how that knowledge translates to the development of diagnostic and therapeutic radiopharmaceuticals for the clinic. The text is divided into three overarching sections: First Principles, Radiochemistry, and Special Topics. The first is a general overview covering fundamental and broad issues like “The Production of Radionuclides” and “Basics of Radiochemistry”. The second section is the main focus of the book. In this section, each chapter’s author will delve much deeper into the subject matter, covering both well established and state-of-the-art techniques in radiopharmaceutical chemistry. This section will be divided according to radionuclide and will include chapters on radiolabeling methods using all of the common nuclides employed in radiopharmaceuticals, including four chapters on the ubiquitously used fluorine-18 and a “Best of the Rest” chapter to cover emerging radionuclides. Finally, the third section of the book is dedicated to special topics with important information for radiochemists, including “Bioconjugation Methods,” “Click Chemistry in Radiochemistry”, and “Radiochemical Instrumentation.” This is an ideal educational guide for nuclear medicine physicians, radiologists, and radiopharmaceutical chemists, as well as residents and trainees in all of these areas.

The biopharmaceutical market has come along way since 1982 when the first biopharmaceutical product, recombinant human insulin, was launched. Over 120 such products are currently being marketed around the world including nine blockbuster drugs. The global market for biopharmaceuticals, which is currently valued at US$41 billion, has been growing at an impressive compound annual growth rate of 21% over the previous five years. With over one third of all pipe-line products in active development are biopharmaceuticals, this segment is set to continue outperforming the total pharmaceutical market and could easily reach US$100 billion by the end of this decade.