{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T23:49:07Z","timestamp":1778888947878,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Several studies investigated the use of 99mTc-labelled Aprotinin as an amyloid seeker some years ago. In vitro tests showed high binding affinity for several types of amyloid fibrils accompanied by an excellent specificity. Initial human studies demonstrated good accuracy in detecting cardiac involvement. Scintigraphy results were confirmed in a group of 28 endomyocardial biopsies. Unfortunately, clinical studies were halted because of a temporary suspension of the vector protein (Trasylol) and public health concerns over prion contamination of the bovine origin compound. To obviate these limitations, efforts have been made to label a recombinant Aprotinin with 99mTc, which exhibits the same affinity for h-insulin fibrils. With the aim of developing a PET tracer, the same recombinant protein was labeled with Gallium. The introduction of a bifunctional chelator did not affect fibril affinity. Finally, a synthetic peptidic fragment, the cyclic 30-51 SS, was synthetized. After direct technetium labeling, an impressive increase in affinity was demonstrated. This peptide appears to be a potential candidate for Gallium labeling through a bifunctional chelator for PET imaging.<\/jats:p>","DOI":"10.3390\/biomedicines10061377","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T10:25:12Z","timestamp":1654856712000},"page":"1377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Narrative Review of 99mTc-Aprotinin in the Diagnosis of Cardiac Amyloidosis and a New Life for an Unfairly Abandoned Drug"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4243-6289","authenticated-orcid":false,"given":"Carlo","family":"Aprile","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Policlinico San Matteo, Nuclear Medicine Unit, I-27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Lodola","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Policlinico San Matteo, Nuclear Medicine Unit, I-27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1056\/NEJM199008233230803","article-title":"Evaluation of systemic amyloidosis by scintigraphy with I-123\u2014labelled serum amyloid P component","volume":"325","author":"Hawkins","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/BF00803246","article-title":"99mTc-aprotinin: A new tracer for kidney morphology and function","volume":"9","author":"Bianchi","year":"1984","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/BF01791147","article-title":"Cardiac and pleuropulmonary AL amyloid imaging with technetium-99m labeled aprotinin","volume":"22","author":"Aprile","year":"1995","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1056\/NEJMoa0802395","article-title":"A comparison of aprotinin and lysine analogues in high-risk cardiac surgery","volume":"358","author":"Fergusson","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jtcvs.2012.07.018","article-title":"Putting the record straight on aprotinin as safe and effective: Results from a mixed treatment meta-analysis of trials of aprotinin","volume":"145","author":"Howell","year":"2013","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_6","unstructured":"(2022, March 15). EMA\/CHMP\/119704\/2012 European Medicines Agency Recommends Lifting Suspension of Aprotinin. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/press-release\/european-medicines-agency-recommends-lifting-suspension-aprotinin_en.pdf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.15252\/emmm.201505357","article-title":"A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis","volume":"7","author":"Marcoux","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.1016\/j.jmb.2016.08.021","article-title":"The kinetic stability of a full-length antibody light chain dimer determines whether endoproteolysis can release amyloidogenic variable domains","volume":"428","author":"Morgan","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1046\/j.1432-1327.2000.01237.x","article-title":"Aprotinin binding to amyloid fibrils","volume":"267","author":"Cardoso","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1399-3011.1997.tb01200.x","article-title":"Technetium-99m labeled epidermal growth factor-tumor imaging in mice","volume":"50","author":"Rusckowski","year":"1997","journal-title":"J. Pept. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijpharm.2004.07.049","article-title":"Accumulation of radiolabelled low molecular peptides and proteins in experimental inflammation","volume":"291","author":"Komarek","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_12","first-page":"22","article-title":"99mTc-aprotinin: Comparison with 99mTc-DMSA in normal and diseased kidneys","volume":"23","author":"Aprile","year":"1984","journal-title":"Nuklearmedizin"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/00006231-200506000-00009","article-title":"Pharmacokinetics and normal scintigraphic appearance of 99mTc aprotinin","volume":"26","author":"Sojan","year":"2005","journal-title":"Nucl. Med. Commun."},{"key":"ref_14","unstructured":"Deutsch, E., Nicolini, M., and Wagner, H.N. (1983). Aprotinin-99 m Tc: A new radiopharmaceutical for the study of kidney morphology and function. Technetium in Chemistry and Nuclear Medicine, Cortina International."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.nucmedbio.2005.06.006","article-title":"An improved (99m)Tc-aprotinin kit formulation: Quality control analysis of radiotracer stability and cold kit shelf life","volume":"32","author":"Smyth","year":"2005","journal-title":"Nucl. Med. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1080\/13506129.2021.1994386","article-title":"Tissue biopsy for the diagnosis of amyloidosis: Experience from some centres","volume":"29","author":"Benson","year":"2022","journal-title":"Amyloid"},{"key":"ref_17","first-page":"177","article-title":"99mTc-Aprotinin scintigraphy in amyloidosis","volume":"44","author":"Schaadt","year":"2003","journal-title":"J. Nucl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1600-0609.2007.00963.x","article-title":"Preliminary experience of 99mTc-Aprotinin scintigraphy in amyloidosis","volume":"79","author":"Han","year":"2007","journal-title":"Eur. J. Haematol."},{"key":"ref_19","unstructured":"B\u00e9ly, M., and \u00c1gnes Ap\u00e1thy, \u00c1. (2001). Accuracy of 99mTc-Aprotinin scintigraphy for the detection of myocardial amyloidosis: Long term follow-up of 78 patients. Amyloid and Amyloidosis 2001. The Proceedings of the IXth International Symposium on Amyloidosis. Budapest, Hungary, PXP Els\u0151 Magyar Digit\u00e1lis Nyomda Rt."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s12350-019-01868-9","article-title":"Performance of 99mTc-aprotinin scintigraphy for diagnosing light chain (AL) cardiac amyloidosis confirmed by endomyocardial biopsy","volume":"27","author":"Awaya","year":"2020","journal-title":"J. Nucl. Cardiol."},{"key":"ref_21","first-page":"A117","article-title":"Technetium-99m Aprotinin Scintigraphy in Amyloidosis: A Pilot Study","volume":"36","author":"Johnston","year":"2006","journal-title":"Intern. Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bergmann, H., Kohn, H., and Sinziger, H. (1999). Aprotinin 99m Tc myocardial scan: Risk stratification of cardiac events in patients with AL\/ATTR amyloidosis. Radioactive Isotopes in Clinical Medicine and Research XXIII, Birkhauser Verlag.","DOI":"10.1007\/978-3-0348-8782-3"},{"key":"ref_23","first-page":"261","article-title":"Re-evaluating the potentials and limitations of (99m)Tc-aprotinin scintigraphy for amyloid imaging","volume":"3","author":"Minamimoto","year":"2013","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1109\/TMI.2011.2169981","article-title":"Improved regional activity quantitation in nuclear medicine using a new approach to correct for tissue partial volume and spillover effects","volume":"31","author":"Moore","year":"2012","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1118\/1.3031110","article-title":"Diminishing the impact of the partial volume effect in cardiac SPECT perfusion imaging","volume":"36","author":"Pretorius","year":"2009","journal-title":"Med. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1109\/TNS.2007.912874","article-title":"Spillover Compensation in the Presence of Respiratory Motion Embedded in SPECT Perfusion Data","volume":"55","author":"Pretorius","year":"2008","journal-title":"IEEE Trans. Nucl. Sci."},{"key":"ref_27","first-page":"A235","article-title":"A new approach to the detection of dialysis related amyloidosis (DRA) with 99 m Tc-aprotinin","volume":"11","author":"Aprile","year":"1996","journal-title":"Nephrol Dial Transplant."},{"key":"ref_28","first-page":"56","article-title":"Labeling peptides with technetium-99m using a bifunctional chelator of a N-hydroxysuccinimide ester of mercaptoacetyltriglycine","volume":"39","author":"Hnatowich","year":"1998","journal-title":"J. Nucl. Med."},{"key":"ref_29","unstructured":"SMPC (2022, March 15). Aprotinin 10,000 KIU\/mL Injection BP-SPC 19th November 2020. Available online: https:\/\/www.medicines.org.uk\/emc\/product\/2472\/smpc\/print."},{"key":"ref_30","first-page":"257","article-title":"Transmissible spongiform encephalopathies (TSE): Minimizing the risk of transmission by biological\/biopharmaceutical products: An industry perspective","volume":"88","author":"Kozak","year":"1996","journal-title":"Dev. Biol Stand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biologicals.2004.10.002","article-title":"Use of substances of animal origin in pharmaceutics and compliance with the TSE-risk guideline\u2014A market survey","volume":"33","author":"Berger","year":"2005","journal-title":"Biologicals"},{"key":"ref_32","first-page":"S148","article-title":"Recombinant Aprotinin (tobacco): Technetium Labelling and Amyloid Fibrils Affinity","volume":"34","author":"Aprile","year":"2007","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_33","first-page":"S145","article-title":"A 99mTc-Labeled Synthetic Cyclic Peptide (Aprotinin Analogue) with High Affinity for Amyloid Fibrils","volume":"38","author":"Aprile","year":"2011","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_34","first-page":"S26","article-title":"A new PET radiopharmaceutical with high affinity for amyloid fibrils","volume":"1","author":"Buroni","year":"2013","journal-title":"Clin. Transl. Imaging"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1007\/s00259-019-04325-4","article-title":"Time for new imaging and therapeutic approaches in cardiac amyloidosis","volume":"46","author":"Slart","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Saeed, S., Saad, J.M., Ahmed, A.I., Han, Y., and Al-Mallah, M.H. (2021). The utility of positron emission tomography in cardiac amyloidosis. Heart Fail. Rev., Epub ahead of print.","DOI":"10.1007\/s10741-021-10183-w"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1007\/s12350-015-0261-x","article-title":"Serial scanning with technetium pyrophosphate (99mTc-PYP) in advanced ATTR cardiac amyloidosis","volume":"23","author":"DeLuca","year":"2016","journal-title":"J. Nucl. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1515\/cipms-2015-0077","article-title":"In vitro study: Binding of 99mTc-DPD to synthetic amyloid fibrils","volume":"28","author":"Buroni","year":"2015","journal-title":"Curr. Issues Pharm. Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ijcard.2022.01.036","article-title":"Cardiac microcalcifications in transthyretin (ATTR) amyloidosis","volume":"352","author":"Thelander","year":"2022","journal-title":"Int. J. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s12350-018-1260-5","article-title":"Significance of 11C-PIB PET\/CT in cardiac amyloidosis compared with 99mTc-aprotinin scintigraphy: A pilot study","volume":"27","author":"Minamimoto","year":"2020","journal-title":"J. Nucl. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wall, J.S., Martin, E.B., Endsley, A., Stuckey, A.C., Williams, A.D., Powell, D., Whittle, B., Hall, S., Lambeth, T.R., and Julian, R.R. (2021). 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. Mol. Imaging Biol., Online ahead of print.","DOI":"10.1007\/s11307-021-01681-2"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/S0735-1097(22)02175-1","article-title":"Detection of Cardiac Amyloidosis In Patients With Systemic AlL and ATTR Amyloidosis Using Iodine Evuzamitide PET\/CT Imaging and The Correlation With Serum NT-proBNP","volume":"79","author":"Wall","year":"2022","journal-title":"JACC"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1007\/s12350-019-01917-3","article-title":"99mTc-aprotinin imaging in cardiac amyloidosis. Make an old tool new again?","volume":"27","author":"Slart","year":"2020","journal-title":"J. Nucl. Cardiol."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/6\/1377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:50Z","timestamp":1760138870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/6\/1377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["biomedicines10061377"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines10061377","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}