Fluorous-Soluble Metal Chelate for Sensitive Fluorine-19 Magnetic Resonance Imaging Nanoemulsion Probes

Amin Haghighat Jahromi, Chao Wang, Stephen R. Adams, Wenlian Zhu, Kazim Narsinh, Hongyan Xu, Danielle L. Gray, Roger Y. Tsien, Eric T. Ahrens

Research output: Contribution to journalArticle

Abstract

Fluorine-19 MRI is an emerging cellular imaging approach, enabling lucid, quantitative "hot-spot" imaging with no background signal. The utility of 19 F-MRI to detect inflammation and cell therapy products in vivo could be expanded by improving the intrinsic sensitivity of the probe by molecular design. We describe a metal chelate based on a salicylidene-tris(aminomethyl)ethane core, with solubility in perfluorocarbon (PFC) oils, and a potent accelerator of the 19 F longitudinal relaxation time (T 1 ). Shortening T 1 can increase the 19 F image sensitivity per time and decrease the minimum number of detectable cells. We used the condensation between the tripodal ligand tris-1,1,1-(aminomethyl)ethane and salicylaldehyde to form the salicylidene-tris(aminomethyl)ethane chelating agent (SALTAME). We purified four isomers of SALTAME, elucidated structures using X-ray scattering and NMR, and identified a single isomer with high PFC solubility. Mn 4+ , Fe 3+ , Co 3+ , and Ga 3+ cations formed stable and separable chelates with SALTAME, but only Fe 3+ yielded superior T 1 shortening with modest line broadening at 3 and 9.4 T. We mixed Fe 3+ chelate with perfluorooctyl bromide (PFOB) to formulate a stable paramagnetic nanoemulsion imaging probe and assessed its biocompatibility in macrophages in vitro using proliferation, cytotoxicity, and phenotypic cell assays. Signal-to-noise modeling of paramagnetic PFOB shows that sensitivity enhancement of nearly 4-fold is feasible at clinical magnetic field strengths using a 19 F spin-density-weighted gradient-echo pulse sequence. We demonstrate the utility of this paramagnetic nanoemulsion as an in vivo MRI probe for detecting inflammation macrophages in mice. Overall, these paramagnetic PFC compounds represent a platform for the development of sensitive 19 F probes.

Original languageEnglish (US)
Pages (from-to)143-151
Number of pages9
JournalACS Nano
Volume13
Issue number1
DOIs
StatePublished - Jan 22 2019

Keywords

  • F
  • MRI
  • inflammation
  • macrophage
  • metal chelate
  • nanoemulsion
  • perfluorocarbon

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Jahromi, A. H., Wang, C., Adams, S. R., Zhu, W., Narsinh, K., Xu, H., Gray, D. L., Tsien, R. Y., & Ahrens, E. T. (2019). Fluorous-Soluble Metal Chelate for Sensitive Fluorine-19 Magnetic Resonance Imaging Nanoemulsion Probes. ACS Nano, 13(1), 143-151. https://doi.org/10.1021/acsnano.8b04881