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Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection

Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to (99m)Tc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of ly...

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Autores principales: Papasavva, Afroditi, Shegani, Antonio, Kiritsis, Christos, Roupa, Ioanna, Ischyropoulou, Myrto, Makrypidi, Konstantina, Pilatis, Irineos, Loudos, George, Pelecanou, Maria, Papadopoulos, Minas, Pirmettis, Ioannis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400719/
https://www.ncbi.nlm.nih.gov/pubmed/34443384
http://dx.doi.org/10.3390/molecules26164797
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author Papasavva, Afroditi
Shegani, Antonio
Kiritsis, Christos
Roupa, Ioanna
Ischyropoulou, Myrto
Makrypidi, Konstantina
Pilatis, Irineos
Loudos, George
Pelecanou, Maria
Papadopoulos, Minas
Pirmettis, Ioannis
author_facet Papasavva, Afroditi
Shegani, Antonio
Kiritsis, Christos
Roupa, Ioanna
Ischyropoulou, Myrto
Makrypidi, Konstantina
Pilatis, Irineos
Loudos, George
Pelecanou, Maria
Papadopoulos, Minas
Pirmettis, Ioannis
author_sort Papasavva, Afroditi
collection PubMed
description Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to (99m)Tc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with (99m)Tc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10–500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac-[(99m)Tc(CO)(3)](+) synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, (99m)Tc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified.
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spelling pubmed-84007192021-08-29 Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection Papasavva, Afroditi Shegani, Antonio Kiritsis, Christos Roupa, Ioanna Ischyropoulou, Myrto Makrypidi, Konstantina Pilatis, Irineos Loudos, George Pelecanou, Maria Papadopoulos, Minas Pirmettis, Ioannis Molecules Article Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to (99m)Tc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with (99m)Tc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10–500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac-[(99m)Tc(CO)(3)](+) synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, (99m)Tc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified. MDPI 2021-08-07 /pmc/articles/PMC8400719/ /pubmed/34443384 http://dx.doi.org/10.3390/molecules26164797 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Papasavva, Afroditi
Shegani, Antonio
Kiritsis, Christos
Roupa, Ioanna
Ischyropoulou, Myrto
Makrypidi, Konstantina
Pilatis, Irineos
Loudos, George
Pelecanou, Maria
Papadopoulos, Minas
Pirmettis, Ioannis
Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection
title Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection
title_full Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection
title_fullStr Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection
title_full_unstemmed Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection
title_short Comparative Study of a Series of (99m)Tc(CO)(3) Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection
title_sort comparative study of a series of (99m)tc(co)(3) mannosylated dextran derivatives for sentinel lymph node detection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400719/
https://www.ncbi.nlm.nih.gov/pubmed/34443384
http://dx.doi.org/10.3390/molecules26164797
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