Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging
There are at least 20 distinct types of systemic amyloidosis, all of which result in the organ-compromising accumulation of extracellular amyloid deposits. Amyloidosis is challenging to diagnose due to the heterogeneity of the clinical presentation, yet early detection is critical for favorable pati...
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/4/629 |
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| author | Emily B. Martin Alan Stuckey Dustin Powell Ronald Lands Bryan Whittle Craig Wooliver Sallie Macy James S. Foster Spencer Guthrie Stephen J. Kennel Jonathan S. Wall |
| author_facet | Emily B. Martin Alan Stuckey Dustin Powell Ronald Lands Bryan Whittle Craig Wooliver Sallie Macy James S. Foster Spencer Guthrie Stephen J. Kennel Jonathan S. Wall |
| author_sort | Emily B. Martin |
| collection | DOAJ |
| description | There are at least 20 distinct types of systemic amyloidosis, all of which result in the organ-compromising accumulation of extracellular amyloid deposits. Amyloidosis is challenging to diagnose due to the heterogeneity of the clinical presentation, yet early detection is critical for favorable patient outcomes. The ability to non-invasively and quantitatively detect amyloid throughout the body, even in at-risk populations, before clinical manifestation would be invaluable. To this end, a pan-amyloid-reactive peptide, p5+14, has been developed that is capable of binding all types of amyloid. Herein, we demonstrate the ex vivo pan-amyloid reactivity of p5+14 by using peptide histochemistry on animal and human tissue sections containing various types of amyloid. Furthermore, we present clinical evidence of pan-amyloid binding using iodine-124-labeled p5+14 in a cohort of patients with eight (<i>n</i> = 8) different types of systemic amyloidosis. These patients underwent PET/CT imaging as part of the first-in-human Phase 1/2 clinical trial evaluating this radiotracer (NCT03678259). The uptake of <sup>124</sup>I-p5+14 was observed in abdominothoracic organs in patients with all types of amyloidosis evaluated and was consistent with the disease distribution described in the medical record and literature reports. On the other hand, the distribution in healthy subjects was consistent with radiotracer catabolism and clearance. The early and accurate diagnosis of amyloidosis remains challenging. These data support the utility of <sup>124</sup>I-p5+14 for the diagnosis of varied types of systemic amyloidosis by PET/CT imaging. |
| first_indexed | 2024-03-11T04:37:55Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T04:37:55Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-0c7a66e5b85e4db4a58eeeaf99099fad2023-11-17T20:51:38ZengMDPI AGPharmaceuticals1424-82472023-04-0116462910.3390/ph16040629Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT ImagingEmily B. Martin0Alan Stuckey1Dustin Powell2Ronald Lands3Bryan Whittle4Craig Wooliver5Sallie Macy6James S. Foster7Spencer Guthrie8Stephen J. Kennel9Jonathan S. Wall10Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USADepartment of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USADepartment of Radiology, University of Tennessee Medical Center, Knoxville, TN 37920, USADepartment of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USADepartment of Radiology, University of Tennessee Medical Center, Knoxville, TN 37920, USADepartment of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USADepartment of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USADepartment of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USAAttralus Inc., South San Francisco, CA 94133, USADepartment of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USADepartment of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USAThere are at least 20 distinct types of systemic amyloidosis, all of which result in the organ-compromising accumulation of extracellular amyloid deposits. Amyloidosis is challenging to diagnose due to the heterogeneity of the clinical presentation, yet early detection is critical for favorable patient outcomes. The ability to non-invasively and quantitatively detect amyloid throughout the body, even in at-risk populations, before clinical manifestation would be invaluable. To this end, a pan-amyloid-reactive peptide, p5+14, has been developed that is capable of binding all types of amyloid. Herein, we demonstrate the ex vivo pan-amyloid reactivity of p5+14 by using peptide histochemistry on animal and human tissue sections containing various types of amyloid. Furthermore, we present clinical evidence of pan-amyloid binding using iodine-124-labeled p5+14 in a cohort of patients with eight (<i>n</i> = 8) different types of systemic amyloidosis. These patients underwent PET/CT imaging as part of the first-in-human Phase 1/2 clinical trial evaluating this radiotracer (NCT03678259). The uptake of <sup>124</sup>I-p5+14 was observed in abdominothoracic organs in patients with all types of amyloidosis evaluated and was consistent with the disease distribution described in the medical record and literature reports. On the other hand, the distribution in healthy subjects was consistent with radiotracer catabolism and clearance. The early and accurate diagnosis of amyloidosis remains challenging. These data support the utility of <sup>124</sup>I-p5+14 for the diagnosis of varied types of systemic amyloidosis by PET/CT imaging.https://www.mdpi.com/1424-8247/16/4/629amyloidosis<sup>124</sup>I-p5+14p5+14 peptideAT-01systemic amyloidosisPET/CT imaging |
| spellingShingle | Emily B. Martin Alan Stuckey Dustin Powell Ronald Lands Bryan Whittle Craig Wooliver Sallie Macy James S. Foster Spencer Guthrie Stephen J. Kennel Jonathan S. Wall Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging Pharmaceuticals amyloidosis <sup>124</sup>I-p5+14 p5+14 peptide AT-01 systemic amyloidosis PET/CT imaging |
| title | Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging |
| title_full | Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging |
| title_fullStr | Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging |
| title_full_unstemmed | Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging |
| title_short | Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide <sup>124</sup>I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging |
| title_sort | clinical confirmation of pan amyloid reactivity of radioiodinated peptide sup 124 sup i p5 14 at 01 in patients with diverse types of systemic amyloidosis demonstrated by pet ct imaging |
| topic | amyloidosis <sup>124</sup>I-p5+14 p5+14 peptide AT-01 systemic amyloidosis PET/CT imaging |
| url | https://www.mdpi.com/1424-8247/16/4/629 |
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