{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:35:50Z","timestamp":1790760950835,"version":"4.1.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Amyloid deposition is a cause of restrictive cardiomyopathy. Patients who present with cardiac disease can be evaluated for transthyretin (TTR)-associated cardiac amyloidosis using nuclear imaging with <jats:sup>99m<\/jats:sup>Tc-labeled pyrophosphate (PYP); however, light chain-associated (AL) cardiac amyloid is generally not detected using this tracer. As an alternative, the amyloid-binding peptide p5+14 radiolabeled with iodine-124 has been shown to be an effective pan-amyloid radiotracer for PET\/CT imaging. Here, a <jats:sup>99m<\/jats:sup>Tc-labeled form of p5+14 peptide has been prepared to facilitate SPECT\/CT imaging of cardiac amyloidosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>A synthesis method suitable for clinical applications has been used to prepare <jats:sup>99m<\/jats:sup>Tc-labeled p5+14 and tested for peptide purity, product bioactivity, radiochemical purity and stability. The product was compared with<jats:sup>99m<\/jats:sup>Tc-PYP for cardiac SPECT\/CT imaging in a mouse model of AA amyloidosis and for reactivity with human tissue sections from AL and TTR patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The <jats:sup>99m<\/jats:sup>Tc p5+14 tracer was produced with &gt;95% yields in radiopurity and bioactivity with no purification steps required and retained over 95% peptide purity and &gt;90% bioactivity for &gt;3 h. In mice, the tracer detected hepatosplenic AA amyloid as well as heart deposits with uptake ~5 fold higher than <jats:sup>99m<\/jats:sup>Tc-PYP. <jats:sup>99m<\/jats:sup>Tc p5+14 effectively bound human amyloid deposits in the liver, kidney and both AL- and ATTR cardiac amyloid in tissue sections in which <jats:sup>99m<\/jats:sup>Tc-PYP binding was not detectable.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p><jats:sup>99m<\/jats:sup>Tc-p5+14 was prepared in minutes in &gt;20 mCi doses with good performance in preclinical studies making it suitable for clinical SPECT\/CT imaging of cardiac amyloidosis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0301756","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T16:08:36Z","timestamp":1712333316000},"page":"e0301756","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Preclinical evaluation of Tc-99m p5+14 peptide for SPECT detection of cardiac amyloidosis"],"prefix":"10.1371","volume":"19","author":[{"given":"Stephen J.","family":"Kennel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1572-6907","authenticated-orcid":true,"given":"Joseph W.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Stuckey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Richey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Wall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"key":"pone.0301756.ref001","article-title":"Systemic amyloidosis from A (AA) to T (ATTR): a review","author":"E Muchtar","year":"2020","journal-title":"J Intern Med"},{"issue":"4","key":"pone.0301756.ref002","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.hlc.2019.11.019","article-title":"Amyloid Cardiomyopathy","volume":"29","author":"NK Bart","year":"2020","journal-title":"Heart Lung Circ"},{"issue":"12","key":"pone.0301756.ref003","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.jacc.2016.06.053","article-title":"AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy","volume":"68","author":"RH Falk","year":"2016","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"pone.0301756.ref004","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00059-020-04904-4","article-title":"Amyloid cardiomyopathy","volume":"45","author":"AV Kristen","year":"2020","journal-title":"Herz"},{"issue":"22","key":"pone.0301756.ref005","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1016\/j.jacc.2019.04.003","article-title":"Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review","volume":"73","author":"FL Ruberg","year":"2019","journal-title":"J Am Coll Cardiol"},{"issue":"12","key":"pone.0301756.ref006","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/s11886-019-1230-9","article-title":"Amyloid and the Heart","volume":"21","author":"AM Wolfson","year":"2019","journal-title":"Curr Cardiol Rep"},{"key":"pone.0301756.ref007","doi-asserted-by":"crossref","first-page":"22695","DOI":"10.1038\/srep22695","article-title":"Comparative evaluation of p5+14 with SAP and peptide p5 by dual-energy SPECT imaging of mice with AA amyloidosis","volume":"6","author":"EB Martin","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0301756.ref008","article-title":"Dual-Energy SPECT and the Development of Peptide p5+14 for Imaging Amyloidosis","volume":"16","author":"JS Wall","year":"2017","journal-title":"Mol Imaging"},{"issue":"3","key":"pone.0301756.ref009","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s11307-021-01681-2","article-title":"First in Human Evaluation and Dosimetry Calculations for Peptide (124)I-p5+14-a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET\/CT Imaging","volume":"24","author":"JS Wall","year":"2022","journal-title":"Mol Imaging Biol"},{"issue":"5","key":"pone.0301756.ref010","doi-asserted-by":"crossref","first-page":"7657","DOI":"10.3390\/molecules20057657","article-title":"Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis","volume":"20","author":"JS Wall","year":"2015","journal-title":"Molecules"},{"issue":"Supp 1","key":"pone.0301756.ref011","first-page":"3127","article-title":"Time resolved biodistribution of peptide 124I-p5+14 in patients with systemic AL amyloidosis","volume":"61","author":"A Stuckey","year":"2020","journal-title":"Journal of Nuclear Medicine"},{"issue":"Supp 1","key":"pone.0301756.ref012","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1182\/blood-2019-128850","article-title":"Preliminary Phase 1 Data on the Safety and Efficacy of a Novel PET Radiotracer, 124I-p5+14, for Imaging Systemic Amyloidosis","volume":"134","author":"JS Wall","year":"2019","journal-title":"Blood"},{"issue":"2","key":"pone.0301756.ref013","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1161\/CIRCIMAGING.112.000132","article-title":"(99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses","volume":"6","author":"S Bokhari","year":"2013","journal-title":"Circ Cardiovasc Imaging"},{"issue":"1","key":"pone.0301756.ref014","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12350-016-0610-4","article-title":"Standardization of (99m)Technetium pyrophosphate imaging methodology to diagnose TTR cardiac amyloidosis","volume":"25","author":"S Bokhari","year":"2018","journal-title":"J Nucl Cardiol"},{"issue":"8","key":"pone.0301756.ref015","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1001\/jamacardio.2016.2839","article-title":"Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for Patients With ATTR Cardiac Amyloidosis","volume":"1","author":"A Castano","year":"2016","journal-title":"JAMA Cardiol"},{"issue":"22","key":"pone.0301756.ref016","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1016\/j.jacc.2020.04.022","article-title":"Cardiac Scintigraphy With Technetium-99m-Labeled Bone-Seeking Tracers for Suspected Amyloidosis: JACC Review Topic of the Week","volume":"75","author":"M Hanna","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"pone.0301756.ref017","article-title":"(99m)Tc-PYP SPECT and SPECT\/CT quantitation for diagnosing cardiac transthyretin amyloidosis","author":"KJ Nichols","year":"2022","journal-title":"J Nucl Cardiol"},{"issue":"2","key":"pone.0301756.ref018","doi-asserted-by":"crossref","first-page":"e221082","DOI":"10.1148\/radiol.221082","article-title":"(99m)Tc Bone-Avid Tracer Cardiac Scintigraphy: Role in Noninvasive Diagnosis of Transthyretin Cardiac Amyloidosis","volume":"306","author":"YM Khor","year":"2023","journal-title":"Radiology"},{"issue":"5","key":"pone.0301756.ref019","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.carpath.2016.07.001","article-title":"Varying levels of small microcalcifications and macrophages in ATTR and AL cardiac amyloidosis: implications for utilizing nuclear medicine studies to subtype amyloidosis","volume":"25","author":"MA Stats","year":"2016","journal-title":"Cardiovasc Pathol"},{"issue":"1","key":"pone.0301756.ref020","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1532\/IJH97.05126","article-title":"Marked hepatomegaly due to AA type amyloidosis in a case with Castleman\u2019s disease","volume":"84","author":"N Yamagata","year":"2006","journal-title":"Int J Hematol"},{"issue":"1","key":"pone.0301756.ref021","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0002-9343(94)00054-9","article-title":"Prospective and serial study of primary amyloidosis with serum amyloid P component scintigraphy: from diagnosis to prognosis","volume":"101","author":"E Hachulla","year":"1996","journal-title":"Am J Med"},{"issue":"4","key":"pone.0301756.ref022","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.amjmed.2005.08.043","article-title":"Diagnostic performance of 123I-labeled serum amyloid P component scintigraphy in patients with amyloidosis","volume":"119","author":"BP Hazenberg","year":"2006","journal-title":"Am J Med"},{"issue":"11","key":"pone.0301756.ref023","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.jacc.2022.11.022","article-title":"2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee","volume":"81","author":"MM Kittleson","year":"2023","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"pone.0301756.ref024","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s11307-015-0914-9","article-title":"Tc-99m Radiolabeled Peptide p5 + 4 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis","volume":"18","author":"SJ Kennel","year":"2016","journal-title":"Mol Imaging Biol"},{"issue":"2","key":"pone.0301756.ref025","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1021\/bc060291m","article-title":"In vivo evaluation of cysteine-based chelators for attachment of 99mTc to tumor-targeting Affibody molecules","volume":"18","author":"T Tran","year":"2007","journal-title":"Bioconjug Chem"},{"issue":"42","key":"pone.0301756.ref026","doi-asserted-by":"crossref","first-page":"14101","DOI":"10.1021\/bi991131j","article-title":"Thermodynamic instability of human lambda 6 light chains: correlation with fibrillogenicity","volume":"38","author":"J Wall","year":"1999","journal-title":"Biochemistry"},{"issue":"1","key":"pone.0301756.ref027","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3109\/13506120108993811","article-title":"Micro-method to isolate and purify amyloid proteins for chemical characterization","volume":"8","author":"B Kaplan","year":"2001","journal-title":"Amyloid"},{"key":"pone.0301756.ref028","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0076-6879(06)12011-X","article-title":"Micro-imaging of amyloid in mice","volume":"412","author":"JS Wall","year":"2006","journal-title":"Methods Enzymol"},{"issue":"1","key":"pone.0301756.ref029","first-page":"79","article-title":"An improved Congo red method for amyloid","volume":"33","author":"G. Stokes","year":"1976","journal-title":"Med Lab Sci"},{"issue":"4","key":"pone.0301756.ref030","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1172\/JCI105784","article-title":"The characterization of soluble amyloid prepared in water","volume":"47","author":"M Pras","year":"1968","journal-title":"J Clin Invest"},{"issue":"4","key":"pone.0301756.ref031","doi-asserted-by":"crossref","DOI":"10.3390\/ph16040629","article-title":"Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide (124)I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET\/CT Imaging","volume":"16","author":"EB Martin","year":"2023","journal-title":"Pharmaceuticals (Basel)"},{"issue":"1","key":"pone.0301756.ref032","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1001\/jama.2020.5493","article-title":"Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review","volume":"324","author":"MA Gertz","year":"2020","journal-title":"JAMA"},{"issue":"8","key":"pone.0301756.ref033","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2174\/1573405615666191210103452","article-title":"Role of Nuclear Imaging in Cardiac Amyloidosis Management: Clinical Evidence and Review of Literature","volume":"16","author":"V Frantellizzi","year":"2020","journal-title":"Curr Med Imaging"},{"issue":"Suppl 1","key":"pone.0301756.ref034","first-page":"42","article-title":"Imaging of cardiac amyloidosis by (99m)Tc-PYP scintigraphy","volume":"18","author":"V Papantoniou","year":"2015","journal-title":"Hell J Nucl Med"},{"issue":"9","key":"pone.0301756.ref035","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.2967\/jnumed.118.221770","article-title":"Early Detection of Multiorgan Light-Chain Amyloidosis by Whole-Body (18)F-Florbetapir PET\/CT","volume":"60","author":"EC Ehman","year":"2019","journal-title":"J Nucl Med"},{"issue":"11","key":"pone.0301756.ref036","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/ehjci\/jeu107","article-title":"Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis","volume":"15","author":"DF Hutt","year":"2014","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"pone.0301756.ref037","article-title":"Technetium-99m radiopharmaceuticals\u2014Radiochemistry and radiolabeling","author":"J Cleynhens","year":"2021","journal-title":"Reference Module in Biomedical Sciences"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0301756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T16:09:02Z","timestamp":1712333342000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0301756"}},"subtitle":[],"editor":[{"given":"Alexander","family":"Hohn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,5]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0301756","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,5]]}}}