Solid MRI contrast agents for long-term, quantitative in vivo oxygen sensing

Abstract

Targeted MRI contrast agents have proven useful in research and clinical studies for highlighting specific metabolites and biomarkers [Davies GL, et al. (2013) Chem Commun (Camb) 49(84):9704-9721] but their applicability in serial imaging is limited owing to a changing concentration postinjection. Solid enclosures have previously been used to keep the local concentration of contrast agent constant, but the need to surgically implant these devices limits their use [Daniel K, et al. (2009) Biosens Bioelectron 24(11):3252-3257]. This paper describes a novel class of contrast agent that comprises a responsive material for contrast generation and an injectable polymeric matrix for structural support. Using this principle, we have designed a contrast agent sensitive to oxygen, which is composed of dodecamethylpentasiloxane as the responsive material and polydimethylsiloxane as the matrix material. A rodent inspired-gas model demonstrated that these materials are functionally stable in vivo for at least 1 mo, which represents an order of magnitude improvement over an injection of liquid siloxane [Kodibagkar VD, et al. (2006)

A review of responsive MRI contrast agents: 2005–2014

“…As a straightforward example, hyperpolarized [1‐ 13 C]‐dehydrascorbate can be reduced to vitamin C, which changes the 13 C chemical shift by 3.8 ppm . The incorporation of O 2 into a siloxane polymeric matrix causes a change in electronic state of the polymer, causing a decrease in T 1 relaxation time constant of the system . As a more complex example, a Eu(III) chelate with an N ‐methylquinolinium ligand or an anthryl ligand can be reduced, which causes a change in the electron density at the coordinating ligand.…”

Oxygen‐Sensing Methods in Biomedicine from the Macroscale to the Microscale

“…The most commonly used siloxane is hexamethyldisiloxane (HMDSO), although similar compounds have also been investigated 106. 107 HMDSO was chosen as an optimal PISTOL contrast agent largely owing to its similarity to the known HFB, which is used in 19 F relaxometry. The molecular symmetry of the siloxane and the lower electronegativity of silicon provide a single NMR signal that is spectrally well separated from those arising from tissue.…”

“…For example, Liu et al. recently demonstrated that embedded contrast agents chemically directed to target organs can achieve longer retention times for longitudinal tissue oxygenation monitoring 107…”

“…)o fp rotons in siloxane and the local pO 2 value.T he most commonly used siloxane is hexamethyldisiloxane (HMDSO), although similar compounds have also been investigated. [106,107] HMDSO was chosen as an optimal PISTOL contrast agent largely owing to its similarity to the known HFB,which is used in 19 Frelaxometry.T he molecular symmetry of the siloxane and the lower electronegativity of silicon provide as ingle NMR signal that is spectrally well separated from those arising from tissue.This allows HMDSO to be easily identified while suppressing signals arising from water and fat. HMDSO exhibits ad ynamic range capable of sensing physiological oxygen levels at body temperatures,and has been reported to be inert and non-toxic.…”

“…Recent developments in PISTOL have focused on the design of optimal delivery vehicles for siloxanes.F or example,Liu et al recently demonstrated that embedded contrast agents chemically directed to target organs can achieve longer retention times for longitudinal tissue oxygenation monitoring. [107]…”