In Vivo evaluation of newly synthesized 213 Bi-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptide analogues in melanocortin-1 receptor (MC1-R) positive experimental melanoma model.

Autor: Kálmán-Szabó I; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Gyula Petrányi Doctoral School of Clinical Immunology and Allergology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Képes Z; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary. Electronic address: kepes.zita@med.unideb.hu., Fekete A; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Vágner A; Scanomed Ltd., Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Nagy G; Scanomed Ltd., Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Szücs D; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Department of Physical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem square 1, H-4032 Debrecen, Hungary; Doctoral School of Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem square 1, H-4032 Debrecen, Hungary., Gyuricza B; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Doctoral School of Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem square 1, H-4032 Debrecen, Hungary., Arató V; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Doctoral School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Varga J; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Kárpáti L; Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Hőgyes Endre St. 7, H-1092 Budapest, Hungary., Garai I; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Scanomed Ltd., Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Mándity I; Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Hőgyes Endre St. 7, H-1092 Budapest, Hungary; Artificial Transporters Research Group, Research Centre for Natural Sciences, Magyar tudósok boulevard 2, H-1117 Budapest, Hungary., Bruchertseifer F; European Commission, Joint Research Centre (JRC), Karlsruhe, Germany., Elek J; Department of Inorganic and Analytical Chemistry, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Science Port Ltd., Debrecen, Elek St. 166, H-4225 Debrecen, Hungary., Szikra D; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Trencsényi G; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Gyula Petrányi Doctoral School of Clinical Immunology and Allergology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2023 May 30; Vol. 229, pp. 115374. Date of Electronic Publication: 2023 Mar 28.
DOI: 10.1016/j.jpba.2023.115374
Abstrakt: Given the rising pervasiveness of melanocortin-1 receptor (MC1-R) positive melanoma malignum (MM) and pertinent metastases, radiolabelled receptor-affine alpha-melanocyte stimulating hormone-analogue (α-MSH analogue) imaging probes would be of crucial importance in timely tumor diagnostic assessment. Herein we aimed at investigating the biodistribution and the MM targeting potential of newly synthesized 213 Bi-conjugated MC1-R specific peptide-based radioligands with the establishment of MC1-R overexpressing MM preclinical model. DOTA-conjugated NAP, -HOLD, -FOLD, -and MARSamide were labelled with 213 Bi. Ex vivo biodistribution studies were conducted post-administration of 3.81 ± 0.32 MBq [ 213 Bi]Bi-DOTA conjugated deriva-tives into twenty B16-F10 tumor-bearing C57BL/6 J and healthy mice. Organ Level Internal Dose Assessment (OLINDA) and IDAC-Dose were used to calculate translational data-based absorbed radiation dose in human organs. Moderate or low %ID/g uptake of [ 213 Bi]Bi-DOTA conjugated NAP, -HOLD, -and MARSamide and significantly increased [ 213 Bi]Bi-DOTA-FOLDamide accumulation was observed in the thoracic and abdominal organs (p ≤ 0.01). High [ 213 Bi]Bi-DOTA-NAP (%ID/g:3.76 ± 0.96), -and FOLDamide (%ID/g:3.28 ± 0.95) tumor tracer activity confirmed their MC1-R-affinity. The bladder wall received the highest radiation absorbed dose followed by the kidneys (bladder wall: 1.95·10 -2 and 8.97·10 -2 mSv/MBq; kidneys: 7.47·10 -3 vs. 5.88·10 -2 mSv/MBq measured by IDAC and OLINDA; respectively) indicating the suitability of the NAPamide derivative for clinical use. These novel [ 213 Bi]Bi-DOTA-linked peptide probes displaying meaningful MC1-R affinity could be promising molecular probes in MM imaging.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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