ISSN Print 2500–1094
ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
Copyright: © 2025 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).
ORIGINAL RESEARCH
Comparative pharmacokinetics and biodistribution of HAEE and HASS peptides
About authors
Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia
Correspondence should be addressed: Anna V. Ivanova
Ostrovityanova, 1, str. 1, Moscow, 117513, Russia; ur.xednay@tirofsof.repus
About paper
Funding: the study was conducted under the State Assignment “Development of a Radiopharmaceutical for the Diagnosis of Alzheimer's disease Using the HAEE Tetrapeptide as a Vector Molecule”, EGISU R&D registration number 1024110600012-8-3.2.25;3.2.26;3.2.12.
Author contribution: Ivanova AV — literature review, BALB/с mouse model experimental research, ensuring transcardiac perfusion of all organs, manuscript writing; Lazareva PA — BALB/с mouse model experimental research, ensuring transcardiac perfusion of all organs, analysis of the results, manuscript writing; Kuzmichev IA — synthesis of HAEEGGGGK-Cy5 and HASSGGGGGK-Cy5 fluorescent peptides; Vadekhina VV — intravenous tail vein injection of HAEEGGGGK-Cy5 and HASSGGGGGK-Cy5 peptides, ensuring transcardiac perfusion of all organs; Kosykh AV — fixation, histology slide preparation for microscopic imaging, imaging and manuscript writing; Gurskaya NG — imaging using the fluorescence microscope and analysis, manuscript writing; Abakumov MA — goal setting, developing the study design, manuscript writing; all the authors contributed to preparation of the paper equally, they confirmed compliance of their authorship with the international ICMJE criteria.
Compliance with ethical standards: the study approved by the Ethics Committee of the Pirogov Russian National Research Medical University (protocol 03/2025 dated 23 January 2025) was conducted in accordance with the principles of Good Laboratory Practice (Order of the Ministry of Health of the Russian Federation No. 708n dated 23.08.2010, Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes).
Received: 2025-07-10
Accepted: 2025-07-24
Published online: 2025-07-31
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Due to the limited availability of advanced methods to diagnose Alzheimer's disease, small molecules and short peptides capable of specifically biniding β-amyloid are of special interest. The study aimed to perform comparative assessment of pharmacokinetics and biodistribution of two model peptides, HAEE (His-Ala-Glu-Glu) and HASS (His-Ala-Ser-Ser), as potential platforms for the development of diagnostic kits, as well as to determine the relationship between the peptide structure and organotropism. The study involving BALB/c mice (n = 10) was conducted using the fluorescence labeled compounds. We used in vivo IVIS imaging, ex vivo fluorescence microscopy, and pharmacokinetic analysis. The results showed fundamental differences: the negatively charged HAEE was accumulated mainly in the kidney (T½β = 4.39 h) due to tubular reabsorption, while neutral HASS was soon captured by the liver (T½β = 2.76 h). The data obtained demonstrate the key role of amino acid composition in determining organotropism and open prospects for the development of organ-specific peptide systems.
Keywords: HAEE peptide, HASS peptide, BALB/c healthy mice, HAEE pharmacokinetics, HASS pharmacokinetics, in vivo fluorescence imaging (IVIS), blood brain barrier, HAEE biodistribution, HASS biodistribution