A new class of macrocyclic lanthanide complexes for cell labeling and magnetic resonance imaging applications

Quan Zheng, Houquan Dai, Matthew E. Merritt, Craig Malloy, Cai Yuan Pan, Wen Hong Li

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Lanthanide complexes have wide applications in biochemical research and biomedical imaging. We have designed and synthesized a new class of macrocyclic lanthanide chelates, Ln/DTPA-PDA-Cn, for cell labeling and magnetic resonance imaging (MRI) applications. Two lipophilic Gd3+ complexes, Gd/DTPA-PDA-Cn (n = 10,12), labeled a number of cultured mammalian cells noninvasively at concentrations as low as a few micromolar. Cells took up these agents rapidly and showed robust intensity increases in T1-weighed MR images. Labeled cells showed normal morphology and doubling time as control cells. In addition to cultured cells, these agents also labeled primary cells in tissues such as dissected pancreatic islets. To study the mechanism of cellular uptake, we applied the technique of diffusion enhanced fluorescence resonance energy transfer (DEFRET) to determine the cellular localization of these lipophilic lanthanide complexes. After loading cells with a luminescent complex, Tb/DTPA-PDA-C10, we observed DEFRET between the Tb3+ complex and extracellular, but not intracellular, calcein. We concluded that these cyclic lanthanide complexes label cells by inserting two hydrophobic alkyl chains into cell membranes with the hydrophilic metal binding site facing the extracellular medium. As the first imaging application of these macrocyclic lanthanide chelates, we labeled insulin secreting β-cells with Gd/DTPA-PDA-C12. Labeled cells were encapsulated in hollow fibers and were implanted in a nude mouse. MR imaging of implanted β-cells showed that these cells could be followed in vivo for up to two weeks. The combined advantages of this new class of macrocyclic contrast agents ensure future imaging applications to track cell movement and localization in different biological systems.

Original languageEnglish (US)
Pages (from-to)16178-16188
Number of pages11
JournalJournal of the American Chemical Society
Volume127
Issue number46
DOIs
StatePublished - Nov 23 2005

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Lanthanoid Series Elements
Magnetic resonance
Rare earth elements
Labeling
Personal digital assistants
Magnetic Resonance Imaging
Imaging techniques
Pentetic Acid
Gadolinium DTPA
Cells
Fluorescence Resonance Energy Transfer
Insulin
Biological systems
Binding sites
Cell membranes
Contrast Media
Labels
Cultured Cells
Metals
Binding Sites

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

A new class of macrocyclic lanthanide complexes for cell labeling and magnetic resonance imaging applications. / Zheng, Quan; Dai, Houquan; Merritt, Matthew E.; Malloy, Craig; Pan, Cai Yuan; Li, Wen Hong.

In: Journal of the American Chemical Society, Vol. 127, No. 46, 23.11.2005, p. 16178-16188.

Research output: Contribution to journalArticle

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