Issue 105, 2016

Synthesis and characterization of lipophilic cationic Ga(iii) complexes based on the H2CHXdedpa and H2dedpa ligands and their 67/68Ga radiolabeling studies

Abstract

68 Ga is an attractive isotope for incorporation into a positron-emission tomography (PET) imaging agent, and is finding use as an alternative generator-produced isotope to 99mTc particularly in imaging of myocardial perfusion. We have synthesized six new chelating ligands based on our previously reported H2dedpa and H2CHXdedpa scaffolds (CHX = cyclohexyl, H2dedpa = 1,2-[[carboxypyridin-2-yl]methylamino]ethane). These ligands are designed to incorporate several lipophilic appendages at the secondary nitrogens, and upon coordination to 68Ga(III) will form lipophilic, cationic complexes designed to mimic the properties of other clinically relevant myocardial perfusion imaging agents. The non-radioactive Ga(III) complexes were prepared and characterized by NMR spectroscopy; each ligand retained its predicted hexadentate N4O2 binding to Ga(III). The radiolabeling properties of the six ligands were assessed using the longer-lived 68Ga surrogate, 67Ga. The absence of ‘free’ uncomplexed 67Ga in the HPLC radio-chromatograms indicated >99% radiochemical yields (10 minutes at ambient temperature, ligand concentrations of 10−4 M). However, the N,N′-benzyl functionalized derivatives displayed multiple peaks corresponding to the presence of additional 67Ga-complexes which complicated further study. Selected 67Ga-CHXdedpa complexes were tested for in vitro stability against the metal-binding protein apo-transferrin, and were found to be sufficiently stable (>80%) in a 2 h challenge assay, suggesting that alternative N,N′-alkylated derivatives which introduce more lipophilic character will be of interest in future studies.

Graphical abstract: Synthesis and characterization of lipophilic cationic Ga(iii) complexes based on the H2CHXdedpa and H2dedpa ligands and their 67/68Ga radiolabeling studies

Supplementary files

Article information

Article type
Paper
Submitted
28 Sep 2016
Accepted
19 Oct 2016
First published
19 Oct 2016

RSC Adv., 2016,6, 103763-103773

Synthesis and characterization of lipophilic cationic Ga(III) complexes based on the H2CHXdedpa and H2dedpa ligands and their 67/68Ga radiolabeling studies

C. F. Ramogida, D. Schindler, C. Schneider, Y. L. K. Tan, S. Huh, C. L. Ferreira, M. J. Adam and C. Orvig, RSC Adv., 2016, 6, 103763 DOI: 10.1039/C6RA24070D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements