Copyright: © 2025 by the authors. Licensee: Pirogov University.
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ORIGINAL RESEARCH

Comparative pharmacokinetics and biodistribution of HAEE and HASS peptides

Ivanova AV, Lazareva PA, Kuzmichev IA, Vadekhina VV, Kosykh AV, Gurskaya NG, Abakumov MA
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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Fig. 1. In vivo fluorescence kinetic curves of the studied HAEE (r2= 0.94) and HASS (r2= 0.95) peptides
Fig. 2. Comparative kinetics of the HAEE and HASS peptide elimination
Fig. 3. Ex vivo assessment of the HAEE and HASS accumulation in the organs 24 h after intravenous administration. * — p < 0.05, significance of intergroup differences based on the Mann–Whitney U-test
Fig. 4. Histological analysis of the mouse kidney tissue after the HAEE and HASS systemic administration. А, B. Localization of the Су5-labeled НАЕЕ (red) in the mouse kidney 24 h after intravenous administration. А. Giant section of the mouse kidney. B. Accumulation of fluorescent granules in epithelial cells of the renal proximal tubules. C, D. Localization of the Су5-labeled HASS (red) in the mouse kidney 24 h after intravenous administration. C. Giant section of the mouse kidney. D. Accumulation of fluorescent granules in epithelial cells of the renal proximal tubules. E, F. Kidney of the control mice 24 h after intravenous administration of saline. E. Giant section of the kidney. F. Magnified image of the kidney tissue obtained by superimposing red and blue fluorescence. The nuclei are DAPI stained (blue). Scale bar 200 µm
Fig. 5. HAEE and HASS organ specificity within 24 h (IVIS). White arrow points to the kidneys with maximum buildup. Color scale: from blue (min) to red (max)
Table 1. Dynamic changes in the mean fluorescence intensity (p/sec/cm2/sr) injection of the HAEE and HASS fluorescence peptides
Note: * — the data are presented as the mean ± standard deviation (Mean ± SD) for n = 4
Table 2. Comparison of the HAEE and HASS pharmacokinetic parameters after intravenous administration