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Development Of Psma Targeted Imaging Agents For Prostate Cancer
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Book Synopsis Development of PSMA-targeted Imaging Agents for Prostate Cancer by : Tanushree Ganguly
Download or read book Development of PSMA-targeted Imaging Agents for Prostate Cancer written by Tanushree Ganguly and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Our SPECT-based radioagent exhibited increasing uptake in the PSMA(+) LNCaP cells over time both in vitro and in vivo. More importantly, it was found that it was rapidly internalized into LNCaP cells, presumably through the PSMA enzyme-inhibitor complex. In addition, a convergent approach for generating the radio-agent was explored.
Book Synopsis Development of PSMA-targeted Spect Imaging Agents for Prostate Cancer by : Jessie R. Nedrow-Byers
Download or read book Development of PSMA-targeted Spect Imaging Agents for Prostate Cancer written by Jessie R. Nedrow-Byers and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: More importantly, it was found that it was rapidly internalized into LNCaP cells, presumably through the PSMA enzyme-inhibitor complex. The 2 nd generation SPECT imaging agents focused on two objectives: 1) Modular technology for assembly and 2) Evaluating the effects of mode of binding on uptake and internalization. It was found that our 2nd generation SPECT imaging agents based on an irreversible PSMA inhibitor core, exhibited greater uptake and internalization than 2nd generation SPECT imaging agent constructed from a slowly-reversible PSMA inhibitor core. This work demonstrates the successful development of PSMA-targeted SPECT imaging agents using phosphoramidate and phosphate inhibitors modified to deliver 99mTc, a SPECT radionuclide. In addition, our 2nd generation PSMA-targeted SPECT agent demonstrated that it can be assembled efficiently using copper-less click chemistry, supporting a modular approach for the assembly of PSMA-targeted imaging and therapeutic agents.
Book Synopsis PSMA-Activated Imaging Agents for Prostate Cancer by :
Download or read book PSMA-Activated Imaging Agents for Prostate Cancer written by and published by . This book was released on 2008 with total page 12 pages. Available in PDF, EPUB and Kindle. Book excerpt: In preliminary studies, a potent TG analog (12ADT) was coupled to a series of pentapeptides composed of varying combinations of Asp and Glu to create PSMA-activated prodrugs. One of these prodrugs with the sequence 12ADT-Asp-Glu*Glu*Glu*Glu was efficiently hydrolyzed by PSMA and resulted in accumulation of high levels of the cleaved product in tumor tissue compared to normal tissue. The goal of this study is to take advantage of this selective accumulation of the TG analog to make a prostate cancer specific PSMA targeted imaging agent. Specific Aims: The specific aims of the study are: (1) To synthesize and characterize the cytotoxicity of a series of Iodide labeled Asp- or Glu-containing TG analogs. (2) To synthesize iodinated PSMA prodrugs and characterize PSMA-selective activation and cytotoxicity to PSMA-producing prostate cancer cells. (3) To determine the in vivo efficacy toxicity, pharmacokinetics and biodistribution of 125-I labeled PSMA-activated prodrugs in non-tumor bearing mice and mice bearing PSMA positive tumor human prostate cancer xenografts; (4) To evaluate added therapeutic efficacy produced by 131-I labeling of the PSMA-activated prodrug in vivo against PSMA producing xenografts. Progress: Over the past year we have developed a 14-step synthesis to generate precursor phenolic TG analog. We documented the analogs ability to bind to the SERCA pump target. We then developed methods to couple the analog to the carrier peptide and confirmed cleavage by PSMA. Finally we developed methods to synthesize and purify the iodinated PSMA-activated agent. This compound is now under evaluation in vivo in biodistribution and imaging studies.
Book Synopsis Targeted Molecular Imaging by : Michael J. Welch
Download or read book Targeted Molecular Imaging written by Michael J. Welch and published by Taylor & Francis. This book was released on 2012-02-24 with total page 378 pages. Available in PDF, EPUB and Kindle. Book excerpt: Targeted Molecular Imaging covers the development of novel diagnostic approaches that use an imaging probe and agent to noninvasively visualize cellular processes in normal and disease states. It discusses the concept, development, preclinical studies, and, in many cases, translation to the clinic of targeted imaging agents. The many case studies t
Book Synopsis Development of a Biologic Basis for PSMA Targeting in Prostate Cancer by :
Download or read book Development of a Biologic Basis for PSMA Targeting in Prostate Cancer written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: We are going to define the biology of PSMA in order to enhance our ability to use PSMA as a target and to generate anti-tumor agents that will be specific and selective for PSMA protein. There is a PSMA-like protein that is similar to PSMA. We will identify that protein so we can develop agents that will be selective for the prostate PSMA protein. We want to know whether the binding of drugs that bind to PSMA are transported into the tumor or whether they stay at the cell surface as it will alter the strategy for drug development. We are going to develop potential ligands (drugs or molecules that bind to PSMA) that will serve as a guide to the chemicals that bind to the active site of enzymatic activity of the PSMA, the "substrate pocket" to identify the 3D structure of the PSMA. The identification of the 3D structure of the PSMA will greatly enhance the potential for rapid development of selective agents. We will also use phage display to identify small peptide ligands that could service as drug delivery vehicles and to aid to identify ligands that will differentiate between PSMA and PSMA-like protein.
Book Synopsis Encyclopedia of Cancer by : Manfred Schwab
Download or read book Encyclopedia of Cancer written by Manfred Schwab and published by Springer Science & Business Media. This book was released on 2008-09-23 with total page 3307 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive encyclopedic reference provides rapid access to focused information on topics of cancer research for clinicians, research scientists and advanced students. Given the overwhelming success of the first edition, which appeared in 2001, and fast development in the different fields of cancer research, it has been decided to publish a second fully revised and expanded edition. With an A-Z format of over 7,000 entries, more than 1,000 contributing authors provide a complete reference to cancer. The merging of different basic and clinical scientific disciplines towards the common goal of fighting cancer makes such a comprehensive reference source all the more timely.
Book Synopsis Radiopharmaceutical Chemistry by : Jason S. Lewis
Download or read book Radiopharmaceutical Chemistry written by Jason S. Lewis and published by Springer. This book was released on 2019-04-02 with total page 648 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Investigations Into Controlled Release Strategies for PSMA-Targeted Therapuetics by : Brian Scott Backer
Download or read book Investigations Into Controlled Release Strategies for PSMA-Targeted Therapuetics written by Brian Scott Backer and published by . This book was released on 2019 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer (CaP) is the third leading cause of cancer related death in American males. Treatments for CaP have historically suffered from off targeting and lack of specificity which, translate into loss of treatment efficacy and/or quality of life for patients. Efforts in the field of CaP therapy have focused upon the principle of targeted deployment of potent cytotoxic agents to diseased tissues in order to elicit controlled therapeutic responses. Prostate-specific membrane antigen (PSMA) is a cancer associated biomarker, which is restricted to the membrane of cancerous tissue. The selective expression to cancerous cells has made it an ideal biomarker for targeting via various small molecule ligands, anti-bodies, imaging agents, radiotherapeutics, and small-molecule drug conjugates. Current research efforts by our lab and reported herein, outline our efforts to develop a new modular scaffold that contains: 1) a potent cytotoxic agent 2) a novel pH-sensitive linker and 3) a small molecule ligand for PSMA. The Kozikowski and Low groups have spent considerable efforts in developing small-molecule drug conjugate (SMDC) platforms that target PSMA to selectively treat CaP cells with known chemotherapeutics to initiate cell death. Recent works by our group have elucidated the pH-sensitivity the P-N bond of phosphoramidates in proximity of ionizable groups at various pH values relevant to homeostatic and disease states. It was our intent to design a modular prodrug scaffold that allows for ease of synthesis, late stage diversification, and without sacrificing affinity for PSMA. This work demonstrates the selectivity and effectiveness of the first generation of pH-triggered phosphoramidate-based SMDCs against PSMA(+) cell lines, synthesis of a third generation of constrained phosphoramidate-based pH-cleavable linkers, the development of a cell culture model to assess the performance pH-sensitive SMDC candidates at reduced pH, and finally discovery of new targeting moieties for PSMA to extend the application of this platform.
Book Synopsis Radioguided Surgery by : Giuliano Mariani
Download or read book Radioguided Surgery written by Giuliano Mariani and published by Springer Science & Business Media. This book was released on 2010-05-10 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: This multidisciplinary textbook is designed to be the standard on the subject and is geared for use by physicians who are involved in the care and/or diagnosis of cancer patients. Comprehensive coverage is provided on all aspects of radioguided surgery. Practical information is readily accessible and throughout there is an emphasis on improved decision making. Tables present the indications, performance, and interpretation of procedures at a glance. A wealth of illustrations, including a full-color insert, enhances the application of new concepts.
Book Synopsis PET/CT in Prostate Cancer by : Gary Cook
Download or read book PET/CT in Prostate Cancer written by Gary Cook and published by Springer. This book was released on 2017-07-24 with total page 73 pages. Available in PDF, EPUB and Kindle. Book excerpt: This pocket book explains the significant and well-documented impact that PET/CT can have on the management of prostate cancer through the provision of high-quality evidence regarding function and structure. Up-to-date information is supplied on the relevance of PET/CT to diagnosis, treatment planning, and therapy, including the emerging role of PET/CT with PSMA. Readers will also find clear explanation of the relation of the clinical and pathological background to imaging and the value of PET/CT compared with conventional radiological imaging. The book will be an excellent asset for referring clinicians, nuclear medicine/radiology physicians, radiographers/technologists, and nurses who routinely work in nuclear medicine and participate in multidisciplinary meetings. It is published within the Springer series Clinicians’ Guides to Radionuclide Hybrid Imaging, which presents contributions from professionals worldwide who share a common purpose in promoting nuclear medicine as an important imaging specialty for the diagnosis and management of oncological and non-oncological conditions.
Book Synopsis Development of PSMA Inhibitors for Molecular Imaging and Radio-guided Surgery of Prostate Cancer by : Stephanie Robu
Download or read book Development of PSMA Inhibitors for Molecular Imaging and Radio-guided Surgery of Prostate Cancer written by Stephanie Robu and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis PSMA-Targeted Nano-Conjugates as Dual-Modality (MRI/PET) Imaging Probes for the Non-Invasive Detection of Prostate Cancer by :
Download or read book PSMA-Targeted Nano-Conjugates as Dual-Modality (MRI/PET) Imaging Probes for the Non-Invasive Detection of Prostate Cancer written by and published by . This book was released on 2010 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of this project is to develop dual modality imaging probes for the detection of prostate cancer by doping radioisotopes to iron oxide nanoparticles, so that the sensitivity and specificity of prostate cancer diagnosis could be significantly improved. During the funding period, a facile approach was developed to prepare gamma- or positron emitting nuclides incorporated SPIO nanoparticles (NUSPIONs) for dual modality imaging of prostate cancer. In this three-month extension, we successfully developed the logistics of importing 74As/GeO2 targets from Europe and developed a standardized operation protocol for the isotope separation and 74AsI3 preparation. Using 74AsI3, we have applied our developed methodology to synthesize 74As incorporated detxtran-coated iron oxide nanoparticles (~ 20 nm) and performed PET-CT and MRI evaluation in a PC-3 tumor mouse model. The PET/MRI dual modality imaging results clearly demonstrated the practicality of the methodology conceived and developed in this project for non-invasive detection of prostate cancer. Further research is warranted to move this project forward.
Book Synopsis Development of Novel Site-specific Imaging Probes for Prostate Cancer Detection by : Hang Xu
Download or read book Development of Novel Site-specific Imaging Probes for Prostate Cancer Detection written by Hang Xu and published by . This book was released on 2017 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular imaging is believed to play a pivotal role in decreasing cancer mortality and improving prognosis in the new era. It relies on molecular probes to image cellular or molecular abnormalities in living body. The primary objective of this research is to develop novel multimodal molecular imaging probes, via nanotechnology and peptide conjugation chemistry, for site-specific targeting and imaging of human prostate cancers. A novel nanoparticle based bimodal MRI/fluorescence molecular imaging probe was developed, characterized, and studied for its capacity to target gastrin releasing peptide receptor (GRPr) which is overexpressed in human prostate cancer. Synthesized USPIO(Cy7.5)-BBN nanoparticles have a small core size (5 nm), a high MRI relaxivity, and a superior binding affinity and specificity to the GRPr overexpressed on human prostate cancer in vitro and in vivo. Furthermore, SIO-AF750-BBN, a silica-coated iron oxide nanoparticle loaded with near infrared fluorescence (NIRF) dyes and bombesin, was developed as a tri-modal photoacoustic (PA), NIRF and MRI imaging probe. SIO-AF750-BBN displayed a high binding affinity and specificity to the GRPr expressed prostate cancer cells in vitro and in vivo. SIO-AF750-BBN demonstrated a significant photoacoustic contrast enhancement in tumor tissues, i.e. 3 and 5-fold as compared to the receptor-blocking control group and the peptide analog AF750-BBN without attachment to a nanoparticle, respectively, after intravenous tail vein injection in tumor bearing mice. In addition to bombesin agonist as the targeting moiety, bombesin antagonist is also explored. A series of bombesin antagonists with three different NIRF dyes and three pharmacokinetic modifiers were synthesized and characterized. Of those, three bombesin antagonist analogs, AF750-G-pip-Sta-BBN, AF750-GSG-Sta-BBN, and AF750-6Ahx-Sta-BBN, exhibited high NIRF imaging efficacy, high binding specificity and affinity, and antagonism to human PC-3 prostate cancer cells both in vitro and in vivo. In conclusion, this Ph.D. work addresses the issues of discovery and development of novel site-specific and multi-modality molecular probes for cancer targeted imaging. USPIO(Cy7.5)-BBN displayed the capacity to generate imaging contrast enhancement for prostate tumors in living bodies on MRI/NIRF. The SIO-AF750-BBN demonstrated tumor specific photoacoustic signal enhancement, as well as near-infrared fluorescent imaging enhancement after intravenous administration of this agent in human prostate cancer animal model. Finally, AF750 labeled bombesin antagonist analogs were developed and demonstrated to have a high binding affinity and selectivity to the GRPr and a desirable in vivo bio-distribution profile, indicating their high potentials to be translated to clinical use for imaging-guided surgery and therapy.
Book Synopsis Technical Aspects of Focal Therapy in Localized Prostate Cancer by : Eric Barret
Download or read book Technical Aspects of Focal Therapy in Localized Prostate Cancer written by Eric Barret and published by Springer. This book was released on 2015-01-29 with total page 252 pages. Available in PDF, EPUB and Kindle. Book excerpt: Focal therapy is a promising option for selected patients who have localized low or intermediate-risk prostate cancer, providing a compelling alternative between active surveillance and radical therapies by targeting the index lesion and preserving as much tissue as possible. Numerous cohort studies have already investigated multiple focal techniques, such as cryotherapy, high-intensity focused ultrasound, brachytherapy, photodynamic therapy, laser therapy, irreversible electroporation and cyberknife methods, all of which have demonstrated positive oncological outcomes with 70 to 90 % negative follow-up biopsy. These various ablative techniques have produced only minor side-effects concerning urinary function, a low rate of erectile dysfunction, and have demonstrated a limited rectal toxicity. As a result, the primary end-point has now shifted and a new strategy needs to be established for patient follow-up and for defining treatment failure. Written by international experts in the field, this book is mainly focused on new techniques, all of which are amply illustrated. Technical Aspects of Focal Therapy in Localized Prostate Cancer will be of great practical value to all urologists and oncologists.
Book Synopsis A High-affinity [18F]-labeled Phosphoramidate Peptidomimetic PSMA-targeted Inhibitor for PET Imaging of Prostate Cancer by :
Download or read book A High-affinity [18F]-labeled Phosphoramidate Peptidomimetic PSMA-targeted Inhibitor for PET Imaging of Prostate Cancer written by and published by . This book was released on 2015 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt: Here in this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated. p-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [18F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA( - ) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or without blocking agent. The crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [18F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA( - ) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h. In conclusion, we have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [18F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa.
Book Synopsis Small-Animal SPECT Imaging by : Matthew A. Kupinski
Download or read book Small-Animal SPECT Imaging written by Matthew A. Kupinski and published by Springer Science & Business Media. This book was released on 2007-05-27 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: Small-Animal SPECT Imaging is an edited work derived from the first workshop on Small-Animal SPECT Imaging held January 14-16, 2004 at the University of Arizona, Tucson, AZ, USA. The overall goal of the meeting and therefore this volume is to promote information exchange and collaboration between the research groups developing systems for small-animal applications. Topics include the biomedical significance of small-animal imaging, an overview of detector technologies including scintillation cameras and semi-conductor arrays, imager design and data acquisition systems, animal handling and anesthesia issues, objective assessment of image quality, and system modeling and reconstruction algorithms.
Book Synopsis Development of a Biological Basis for PSMA Targeting in Prostate Cancer by :
Download or read book Development of a Biological Basis for PSMA Targeting in Prostate Cancer written by and published by . This book was released on 2002 with total page 52 pages. Available in PDF, EPUB and Kindle. Book excerpt: PSMA is a strongly expressed protein in prostate cancer, and it is a type-two membrane protein with the bulk of the molecule and enzymatic activity outside of the cell and thus is accessible to therapeutic attack. We discovered that PSMA has activity as a unique folate hydrolase, being a glutamate carboxypeptidase. We also observed that cells expressing PSMA were sensitive to killing by polygammaglutamated methotrexate while non-PSMA expressing cells were resistant. We therefore proposed to explore the biologic potential of PSMA as a therapeutic target in terms of transport and prodrug activation. Because PSMA appeared to be a broadly active carboxypeptidase we proposed to examine polygammaglutamated derivatives of cytotoxics as potential agents that then might be transported into the cell or as prodrugs that would be activated by the enzymatic activity of PSMA releasing the drug from the polygammaglutamated- linked cytotoxic at the site of the tumor.
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