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In vivo and in vitro studies of [M(η$^6$-pseudoerlotinib)$_2$]$^+$ sandwich complexes (M = Re, 99m$_T$$_c$)


Battistin, Federica; Fernandes, Célia; Raposinho, Paula D; Blacque, Olivier; Paulo, Antonio; Alberto, Roger (2023). In vivo and in vitro studies of [M(η$^6$-pseudoerlotinib)$_2$]$^+$ sandwich complexes (M = Re, 99m$_T$$_c$). Dalton Transactions, 52(43):15757-15766.

Abstract

The pursuit of molecular imaging for tumors has led to endeavors focused on targeting epidermal growth factor receptors (EGFR) through monoclonal antibodies or radionuclide-labelled EGF analogs with 99mTc, 111In, or 131I. In this context, various 99mTc-labeled EGFR inhibitors using quinazoline structures have been reported based on the so-called pendant approach and on two types of complexes and labelling strategies: “4 + 1” mixed ligand complexes and fac-tricarbonyl complexes. Apart from this approach, which alters lead structures by linking pharmacophores to chelator frameworks through different connectors, the integrated incorporation of topoisomerase and tyrosine kinase inhibitors into Re and 99mTc complexes has not been explored. Here we present [M(η6-inhibitor)2]+ (M = Re, 99mTc) and [Re(η6-bz)(η6-inhibitor)]+ complexes, where the core structure of an EGFR tyrosine kinase inhibitor binds directly to the metal center. These complexes exhibit potential for tumor imaging: initial biological investigations highlight the influence of one versus two bound inhibitors on the metal center.

Abstract

The pursuit of molecular imaging for tumors has led to endeavors focused on targeting epidermal growth factor receptors (EGFR) through monoclonal antibodies or radionuclide-labelled EGF analogs with 99mTc, 111In, or 131I. In this context, various 99mTc-labeled EGFR inhibitors using quinazoline structures have been reported based on the so-called pendant approach and on two types of complexes and labelling strategies: “4 + 1” mixed ligand complexes and fac-tricarbonyl complexes. Apart from this approach, which alters lead structures by linking pharmacophores to chelator frameworks through different connectors, the integrated incorporation of topoisomerase and tyrosine kinase inhibitors into Re and 99mTc complexes has not been explored. Here we present [M(η6-inhibitor)2]+ (M = Re, 99mTc) and [Re(η6-bz)(η6-inhibitor)]+ complexes, where the core structure of an EGFR tyrosine kinase inhibitor binds directly to the metal center. These complexes exhibit potential for tumor imaging: initial biological investigations highlight the influence of one versus two bound inhibitors on the metal center.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > Inorganic Chemistry
Uncontrolled Keywords:Inorganic Chemistry
Language:English
Date:12 October 2023
Deposited On:18 Feb 2024 15:07
Last Modified:19 Jul 2024 10:15
Publisher:Royal Society of Chemistry
ISSN:1477-9226
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1039/d3dt03011c
PubMed ID:37846621
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)