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Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals
The organometallic technetium-99m tricarbonyl core, [(99m)Tc][Tc(CO)(3)(H(2)O)(3)](+), is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the (99m)Tc-tricarbonyl core is its lipophilicity, which can influence the pharmac...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321340/ https://www.ncbi.nlm.nih.gov/pubmed/32527027 http://dx.doi.org/10.3390/molecules25112680 |
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author | Giammei, Carolina Balber, Theresa Benčurová, Katarina Cardinale, Jens Berroterán-Infante, Neydher Brandt, Marie Jouini, Nedra Hacker, Marcus Mitterhauser, Markus Mindt, Thomas L. |
author_facet | Giammei, Carolina Balber, Theresa Benčurová, Katarina Cardinale, Jens Berroterán-Infante, Neydher Brandt, Marie Jouini, Nedra Hacker, Marcus Mitterhauser, Markus Mindt, Thomas L. |
author_sort | Giammei, Carolina |
collection | PubMed |
description | The organometallic technetium-99m tricarbonyl core, [(99m)Tc][Tc(CO)(3)(H(2)O)(3)](+), is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the (99m)Tc-tricarbonyl core is its lipophilicity, which can influence the pharmacokinetic properties of the SPECT imaging probe. Addition of polar pharmacological modifiers to (99m)Tc-tricarbonyl conjugates holds the promise to counteract this effect and provide tumor-targeting radiopharmaceuticals with improved hydrophilicities, e.g., resulting in a favorable fast renal excretion in vivo. We applied the “Click-to-Chelate” strategy for the assembly of a novel (99m)Tc-tricarbonyl labeled conjugate made of the tumor-targeting, modified bombesin binding sequence [Nle(14)]BBN(7–14) and the carbohydrate sorbitol as a polar modifier. The (99m)Tc-radiopeptide was evaluated in vitro with PC-3 cells and in Fox-1(nu) mice bearing PC-3 xenografts including a direct comparison with a reference conjugate lacking the sorbitol moiety. The glycated (99m)Tc-tricarbonyl peptide conjugate exhibited an increased hydrophilicity as well as a retained affinity toward the Gastrin releasing peptide receptor and cell internalization properties. However, there was no significant difference in vivo in terms of pharmacokinetic properties. In particular, the rate and route of excretion was unaltered in comparison to the more lipophilic reference compound. This could be attributed to the intrinsic properties of the peptide and/or its metabolites. We report a novel glycated (sorbitol-containing) alkyne substrate for the “Click-to-Chelate” methodology, which is potentially of general applicability for the development of (99m)Tc-tricarbonyl based radiotracers displaying an enhanced hydrophilicity. |
format | Online Article Text |
id | pubmed-7321340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73213402020-06-29 Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals Giammei, Carolina Balber, Theresa Benčurová, Katarina Cardinale, Jens Berroterán-Infante, Neydher Brandt, Marie Jouini, Nedra Hacker, Marcus Mitterhauser, Markus Mindt, Thomas L. Molecules Article The organometallic technetium-99m tricarbonyl core, [(99m)Tc][Tc(CO)(3)(H(2)O)(3)](+), is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the (99m)Tc-tricarbonyl core is its lipophilicity, which can influence the pharmacokinetic properties of the SPECT imaging probe. Addition of polar pharmacological modifiers to (99m)Tc-tricarbonyl conjugates holds the promise to counteract this effect and provide tumor-targeting radiopharmaceuticals with improved hydrophilicities, e.g., resulting in a favorable fast renal excretion in vivo. We applied the “Click-to-Chelate” strategy for the assembly of a novel (99m)Tc-tricarbonyl labeled conjugate made of the tumor-targeting, modified bombesin binding sequence [Nle(14)]BBN(7–14) and the carbohydrate sorbitol as a polar modifier. The (99m)Tc-radiopeptide was evaluated in vitro with PC-3 cells and in Fox-1(nu) mice bearing PC-3 xenografts including a direct comparison with a reference conjugate lacking the sorbitol moiety. The glycated (99m)Tc-tricarbonyl peptide conjugate exhibited an increased hydrophilicity as well as a retained affinity toward the Gastrin releasing peptide receptor and cell internalization properties. However, there was no significant difference in vivo in terms of pharmacokinetic properties. In particular, the rate and route of excretion was unaltered in comparison to the more lipophilic reference compound. This could be attributed to the intrinsic properties of the peptide and/or its metabolites. We report a novel glycated (sorbitol-containing) alkyne substrate for the “Click-to-Chelate” methodology, which is potentially of general applicability for the development of (99m)Tc-tricarbonyl based radiotracers displaying an enhanced hydrophilicity. MDPI 2020-06-09 /pmc/articles/PMC7321340/ /pubmed/32527027 http://dx.doi.org/10.3390/molecules25112680 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Giammei, Carolina Balber, Theresa Benčurová, Katarina Cardinale, Jens Berroterán-Infante, Neydher Brandt, Marie Jouini, Nedra Hacker, Marcus Mitterhauser, Markus Mindt, Thomas L. Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals |
title | Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals |
title_full | Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals |
title_fullStr | Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals |
title_full_unstemmed | Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals |
title_short | Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of (99m)Tc-Tricarbonyl-Based Radiopharmaceuticals |
title_sort | sorbitol as a polar pharmacological modifier to enhance the hydrophilicity of (99m)tc-tricarbonyl-based radiopharmaceuticals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321340/ https://www.ncbi.nlm.nih.gov/pubmed/32527027 http://dx.doi.org/10.3390/molecules25112680 |
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