Facile reactivity of hydrazides and aldehydes was explored as potential coupling partners for incorporation into M(CO)(3) (M = Re, (99m)Tc) based radiopharmaceuticals. Both 'click, then chelate' and 'prelabel, then click' synthetic routes produced identical products in high yields and lacked metal-hydrazide/-hydrazone interactions, highlighting the potential of this click strategy.
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http://dx.doi.org/10.1039/c1cc15451f | DOI Listing |
ACS Omega
September 2024
Department of Chemistry, University of Missouri, 601 South College Avenue, Columbia, Missouri 65211, United States.
1,4,7-Triazacyclononane (TACN)-based chelators, such as NOTA and NODAGA, have shown great promise as bifunctional chelators for [M(CO)] cores (M = Tc and Re) in radiopharmaceutical development. Previous investigations of TACN-based chelators bearing pendent acid and ester arms demonstrated the important role the pendent arms have in successful coordination of the [M(CO)] core with the TACN backbone nitrogens. In this work, we introduce three TACN-based bifunctional chelators bearing amide, alcohol, and ketone pendent arms and evaluate their (radio)labeling efficiency with the [M(CO)] core as well as the stability and hydrophilicity of the resulting radiometal complexes.
View Article and Find Full Text PDFDalton Trans
January 2024
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
The - rearrangements in [MX(CO)] (M = Re, Tc) induced by a pincer-type ligand (PNP) and a "halide scavenger" are reported. The reactions of -[Tc(CO)(OH)] or [TcO] in saline both yield -[Tc(PNP)(CO)], the first example of a -{Tc(CO)} type complex. In contrast, reactions with terpyridine (terpy) only gave the facial κ-terpy complexes with Re and Tc.
View Article and Find Full Text PDFInorg Chem
December 2023
Department of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.
Metal complexes with the general formula [M(CO)(k-L)], where M = Re, Re, or Tc and L = 1,4,7-triazacyclononane (TACN), NOTA, or NODAGA chelators, have previously been conjugated to peptide-based biological targeting vectors and investigated as potential theranostic radiopharmaceuticals. The promising results demonstrated by these bioconjugate complexes prompted our exploration of other TACN-based chelators for suitability for (radio)labeling with the [M(CO)] core. In this work, we investigated the role of the TACN pendant arms in complexation of the [M(CO)] core through (radio)labeling of TACN chelators bearing acid, ester, mixed acid-ester, or no pendant functional groups.
View Article and Find Full Text PDFNucl Med Biol
June 2022
Research Reactor Center, University of Missouri, Columbia, MO 65211, United States; Department of Chemistry, University of Missouri, Columbia, MO 65211, United States. Electronic address:
Introduction: With the goal of developing theranostic agents for application in radiopharmaceutical chemistry, in this work, we studied p-NCS-Bn-NODAGA (1) as a bifunctional chelator for the fac-[M(CO)] core (M = Re, Re, Tc). Specifically, we studied complexes of the formula [M(CO)(L)], where L denotes either Bn-NODAGA-Pyr (2) or Bn-NODAGA-Ser-Ser-RM2 (3).
Methods: The model bioconjugate molecule 2 was synthesized by conjugating pyrrolidine with 1, while 3 was derived from the conjugation of the gastrin-releasing peptide receptor (GRPR)-targeting peptide Ser-Ser-RM2 with 1.
Invest New Drugs
June 2022
Institute of Biosciences & Applications, National Centre for Scientific Research "Demokritos", 15310, Athens, Greece.
To address the major medical need for effective chemotherapeutics/diagnostics for brain cancer, in this work three cyclopentadienyl M(CO) (M = Re, Tc) complexes, which cross the blood-brain barrier (BBB) in high % and are designed to mimic the anticancer agent 2-phenylbenzothiazole, are in vitro and in vivo evaluated for anticancer action. The study includes cytotoxicity and uptake studies in cancer and healthy neuronal cell lines, mechanistic investigation of potential anticancer pathways, and biodistribution studies in mice bearing glioblastoma xenografts. The stable Re complexes exhibit selective uptake and significant antiproliferative effect, particularly against U-251 MG glioblastoma cells, with no significant toxicity in healthy neurons, demonstrating the suitability of this type of complexes to serve as selective therapeutic/imaging agents for brain cancer.
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