The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)最新文献

{"title":"Imaging cell death in vivo.","authors":"F Blankenberg,&nbsp;C Mari,&nbsp;H W Strauss","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A technique to image programmed cell death would be useful both in clinical care and in drug development. The most widely studied agent for the in vivo study of apoptosis is radiolabeled annexin V, an endogenous protein labeled with technectium-99m, now undergoing clinical trials in both Europe and the United States. While annexin V has been studied extensively in humans the precise mechanism(s) of uptake this agent in vivo is unclear and needs further study. Other agents are also under development, including radiolabeled forms of Z-VAD.fmk, a potent inhibitor of the enzymatic cascade intimately associated with apoptosis. In addition other technologies, such as diffusion weighted magnetic resonance imaging and magnetic resonance imaging with contrast agents, such as small paramagnetic iron oxide particles coated with peptides have also been advocated as methods to monitor apoptotic cell death. The potential applications of imaging apoptosis as a marker of early response to therapy in cancer, acute cerebral and myocardial ischemic injury and infarction, immune mediated inflammatory disease and transplant rejection are reviewed.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"337-48"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24402353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The developing role of peptide radiopharmaceuticals in the study of chronic inflammation: new techniques for novel therapeutic options.","authors":"M Chianelli,&nbsp;M G Parisella,&nbsp;C D'Alessandria,&nbsp;F Corsetti,&nbsp;F Scopinaro,&nbsp;A Signore","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chronic inflammatory diseases usually lead to fibrosis of the target organ and consequent hypo function. They are often relapsing, invalidating and require life-long treatment. In this class of patients it is very important to try and achieve specific immune suppression to extinguish the immune process with the aim of preventing the disease, preventing or delaying complications and avoiding disease relapse, often requiring surgical intervention. It is important that, while attempting to improve the quality of life of these patients by means of anti-inflammatory drugs, side effects are reduced to a minimum via the use of specific immune therapies that block as selectively as possible the pathologic mechanism responsible for the disease. New therapeutic options are being developed for specific targeted therapies. Several trials are being performed to assess the efficacy and safety of this approach. All of them, however, rely on the clinical assessment of the patients to evaluate the effect of treatment. It would be important to use an objective and reliable method to highlight directly the immune process underlying the individual disease. This manuscript reviews the radiopharmaceuticals available or recently developed for imaging chronic inflammatory diseases and their use for therapy decision making and follow-up.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"256-69"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24401883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-oncologic applications of radiolabeled peptides in nuclear medicine.","authors":"L C Knight","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Radiolabeled peptides have been investigated for diagnostic imaging in a variety of non-oncologic diseases. For imaging thromboembolic disease, peptides which bind to various components of thrombi have been tested. For targeting the fibrin component of thrombi, peptide analogues of fibrin or fragments of fibronectin which have a distinct binding domain for fibrin have been studied. For targeting activated platelets within thrombi, linear and cyclic peptide antagonists of the glycoprotein IIb/IIIa receptor on platelets have been studied, as well as naturally occurring antagonists of this receptor which are found in venoms. Analogues of laminin and thrombospondin which bind to other receptors on platelets have also been tested. There is an approach which uses a peptide to target thrombin which is sequestered within a fibrin clot. Another area of investigation has been to develop an improved radiopharmaceutical for imaging sites of infection and/or inflammation. Peptides which would bind to leukocytes in vivo, such as antagonists to the tuftsin receptor, chemotactic peptides, interleukin-8, or a platelet factor 4 analogue, have been radiolabeled for this purpose. These agents would enable imaging of both infection and inflammation. Development of a radiopharmaceutical for specifically imaging infection has focused on antimicrobial peptides such as human neutrophil defensin, ubiquicidin, human lactoferrin and alafosfalin, which are expected to bind selectively to microorganisms and not to leukocytes. Radiolabeled peptides are also being explored as agents for assessing unstable atherosclerotic plaque (endothelin), amyloid deposits (amyloid beta peptides), and the consequences of diabetes mellitus (human C-peptide).</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"279-91"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24402350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Pathophysiologic mapping\" of venous thromboembolism: opportunities for radiolabeled peptides.","authors":"M P Bernarducci","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The serious clinical and economic impact of venous thromboembolic (VTE) disease is undisputed. What concerns practitioners and researchers alike is the seeming inability to truly mitigate the ramifications of VTE. Ironically, the current approaches to the diagnostic evaluation of suspected VTE patients tends to favor the application of anatomic modalities, which by virtue of their principles of detection, seemingly ignore the extensive knowledge base of VTE pathophysiology and natural history. In other words, are we seeking the appropriate types of information in patients with suspected VTE? Research in nuclear medicine techniques for detecting VTE began approximately 25 years ago. Recently, the emergence of the radiolabeled peptides as a clinically applicable technology platform has encouraged a different way of evaluating VTE. Many radiolabeled peptide candidates are undergoing preclinical and clinical research. Currently, only one, (99m)Tc-apcitide (AcuTect), has been approved (since 1998) for clinical use, specifically in the United States. Its availability this time has fueled ongoing clinical research to further elucidate the benefits of this unique peptide technology. Consequently, significant insight has been gained from large prospective clinical trials. Furthermore, this insight has kindled increasing interest in (99m)Tc-apcitide and potential new entrants into this special \"diagnostic class\". Unlike the more popular modalities, radiolabeled peptides circumvent many of the clinical and anatomic challenges to objectively and accurately diagnosing VTE. The importance of an objective and accurate diagnosis is understood, because it is paramount to a cost-effective treatment strategy. In addition to describing the current activities concerning the development for and use of radiolabeled peptides for clinical practice, this manuscript is intended to promulgate a thought-provoking argument for changing our current approach to the diagnostic evaluation of VTE. Despite technological and medical advances, we continue to debate controversial issues in VTE, which seemingly and arguably disproportionately, focus on treatment (i.e., who?, when?, how much? and for how long?). Should we not adopt a more robust approach to VTE problem-solving, which would logically start with the diagnosis? Perhaps the validated and perceived advantages of the radiolabeled peptides are all the rationale we need to advance beyond the status quo? Only time and continued research will tell.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"292-320"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24402351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiolabelling of peptides for diagnosis and therapy of non-oncological diseases.","authors":"J Sosabowsky,&nbsp;L Melendez-Alafort,&nbsp;S Mather","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Radiolabelled peptides have significant potential as radiopharmaceuticals for the diagnosis and therapy of receptor-expressing diseases. Methods have been developed for labelling peptides with a variety of radionuclides having a broad range of chemical and physical properties. These methods include both direct (where the radionuclide is bound directly to one or more atoms of the peptide structure) and indirect techniques in which bifunctional coupling agents are employed. Although most commonly applied to date in the field of oncology, a significant number of applications in non-oncological diseases have also been proposed and these can be expected to expand as the technology progresses. An overview is presented of some peptide-receptor systems in radiopharmaceutical development and the techniques which have been employed to radiolabel these peptides with isotopes of iodine, yttrium, indium, gallium, copper and technetium. While many of the examples employed are derived from cancer related indications, identical radiopharmaceutical chemistry can also be applied to peptides with applications in the fields of immunology, infection and other inflammatory conditions.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"223-37"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24401880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"99mTc-antimicrobial peptides: promising candidates for infection imaging.","authors":"A Lupetti,&nbsp;E K J Pauwels,&nbsp;P H Nibbering,&nbsp;M M Welling","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This review presents the state of the art of imaging of bacterial and fungal infections in laboratory animals using antimicrobial peptides labelled with technetium-99m ((99m)Tc). The mechanistic basis of this approach is that these peptides accumulate at sites of infection, but not in sterile inflammatory lesions, because of their preferential binding to bacteria and fungi over mammalian cells. For practical reasons, such as production of large amounts of peptides under good laboratory practice conditions and favourable pharmacokinetics, synthetic peptides representing such binding domains of natural antimicrobial peptides are preferred. On the basis of their preferential in vitro and in vivo binding to microorganisms over human cells, fast and easy penetration into the target area, and rapid clearance from the circulation via the urinary tract, various (99m)Tc-antimicrobial peptides were identified. Next, it was determined whether these radiopharmaceuticals distinguish infectious foci from sites of sterile inflammation. Further experiments with (99m)Tc-ubiquicidin-derived peptides in infected laboratory animals have revealed that the radioactivity at the infectious site correlated well with the number of viable bacteria present, indicating that these (99m)Tc-labelled peptides may enable the monitoring of the efficacy of antimicrobial therapy. Together, (99m)Tc-labelled synthetic peptides derived from human ubiquicidin are promising candidates for imaging of bacterial and fungal infections in nuclear medicine.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"238-45"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24401881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of octreotide scintigraphy in rheumatoid arthritis and sarcoidosis.","authors":"V A S H Dalm,&nbsp;P M van Hagen,&nbsp;E P Krenning","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Somatostatin receptors are widely expressed on cells and tissues throughout the human body. Apart from their expression in the physiological target organs of the peptide, somatostatin receptors are also expressed in various tumours. The expression of somatostatin receptors on neuroendocrine tumours led to the development of somatostatin receptor scintigraphy using [(111)In-DTPA-D-Phe(1)]-octreotide ((111)In-pentetreotide) in order to visualize somatostatin receptor positive tumours and their metastases in vivo. Previous studies reported the expression of somatostatin receptors in both normal and pathological cells and tissues of the human immune system as well. Somatostatin receptors have been demonstrated in Hodgkin's and non-Hodgkin's lymphomas and sst scintigraphy has shown to be a useful tool in diagnosis and staging of these diseases. Moreover, sst expression has also been detected in granulomateus diseases, like sarcoidosis and auto-immune diseases, like rheumatoid arthritis. In this paper we discuss the (possible) role of somatostatin receptor scintigraphy in diagnosis, staging or follow-up of patients suffering from sarcoidosis and rheumatoid arthritis.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"270-8"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24402349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiolabelled peptides and low molecular weight proteins in metabolic diseases.","authors":"C Aprile","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>During the last decade there has been a tremendous effort to develop labelled peptides for diagnosis and therapy. The main goal has been to develop tumor imaging/therapeutic agents, as well as peptides directed to the study of thrombosis and infection. Relatively few efforts have been made to develop peptides directed to the study of metabolic diseases. Ideally, a peptide suitable for the study of metabolism should be constructed keeping in mind the following characteristics: a) preserved affinity constant, b) preserved or improved specificity for its binding site, c) increased biological half-life in comparison with the parent peptide, d) labelling with a g or positron emitter whose physical half-life fits with the biological half-life, e) strong binding of the nuclide to the molecule so that it cannot be released after internalization. In this paper some of the peptides or low molecular weight proteins along with some analogues which have been employed in experimental studies and in humans are reviewed, with major emphasis on amyloid seekers, insulin and leptin. Many of these radiopharmaceuticals have been labelled with iodine isotopes, however their in vivo application suffer of severe limitations due to rapid release of iodine after internalization. On the other hand, new perspectives are opened by new radiofluorination techniques, which offer the unique advantage to quantify organ uptake and kinetics, parameters which are of paramount importance in metabolic studies.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"321-36"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24402352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of labeled Annexin A5 in imaging of programmed cell death. From animal to clinical imaging.","authors":"B L J H Kietselaer,&nbsp;L Hofstra,&nbsp;E A W Dumont,&nbsp;C P M Reutelingsperger,&nbsp;G A K Heidendal","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Programmed cell death plays a critical role in embryology, homeostasis and disease. However, until recently no non-invasive imaging modality has been able to visualize this process directly. Annexin A5 binds to cells undergoing programmed cell death. When labeling this protein, Annexin A5 becomes a tool for the detection of programmed cell death in vitro and in vivo. Labeled Annexin A5 has enabled our group and others to detect programmed cell death non-invasively in animals and patients. This review will highlight the development of this imaging modality in cellular and animal models. Furthermore, we will discuss Annexin A5 imaging in human disease. We will focus on the clinical applications and their relevance, limitations and future perspectives of non-invasive imaging of programmed cell death using labeled Annexin A5.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"349-61"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24402354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiolabeled chemotactic cytokines: new agents for scintigraphic imaging of infection and inflammation.","authors":"J E M van Eerd,&nbsp;O C Boerman,&nbsp;F H M Corstens,&nbsp;W J G Oyen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Several radiopharmaceuticals are currently used for diagnosis of inflammatory and infectious diseases in patients. Most inflammatory and infectious processes can be visualized with radiolabeled autologous leukocytes, currently considered to be the most appropriate radiopharmaceutical for this purpose. This agent is very well capable to delineate most inflammatory and infectious foci in a relatively short time after injection. The time-consuming and intricate labeling procedure and the handling of potentially contaminated blood, however cause that there is a great interest in the development of new radiopharmaceuticals comprising the same imaging qualities but without these disadvantages. Besides radiolabeled leukocytes several other radiopharmaceuticals, such as (67)Ga-citrate, radiolabeled anti-granulocyte antibodies and FDG are used to image infection and inflammation. These agents accumulate in infectious and inflammatory lesions in a non-specific manner or have suboptimal diagnostic characteristics. Nowadays, there is a great interest in the development of radiolabeled chemotactic and chemokinetic cytokines that accumulate and are retained in infectious and inflammatory foci by specific interaction with infiltrated inflammatory cells. In this review we describe the specific characteristics of the chemotactic and chemokinetic compounds that are currently studied as potential radiopharmaceutical to visualize infectious and inflammatory foci. The characteristics of a series of cytokines (IL-1, IL-2), chemokines (IL-8, PF-4, MCP-1, NAP-2), complement factors (C5a, C5adR), chemotactic peptides (fMLF) and other chemotactic factors (LTB4) are described. The potentials of these compounds to serve as an imaging agent are discussed.</p>","PeriodicalId":79384,"journal":{"name":"The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)","volume":"47 4","pages":"246-55"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24401882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}