Quantitative “magnetic resonance immunohistochemistry” with ligand‐targeted ¹⁹F nanoparticles

Abstract

Unstable atherosclerotic plaques exhibit microdeposits of fibrin that may indicate the potential for a future rupture. However, current methods for evaluating the stage of an atherosclerotic lesion only involve characterizing the level of vessel stenosis, without delineating which lesions are beginning to rupture. Previous work has shown that fibrin-targeted, liquid perfluorocarbon nanoparticles, which carry a high payload of gadolinium, have a high sensitivity and specificity for detecting fibrin with clinical 1 H MRI. In this work, the perfluorocarbon content of the targeted nanoparticles is exploited for the purposes of 19 F imaging and spectroscopy to demonstrate a method for quantifiable molecular imaging of fibrin in vitro at 4.7 T. Additionally, the quantity of bound nanoparticles formulated with different perfluorocarbon species was calculated using spectroscopy. Results indicate that the high degree of nanoparticle binding to fibrin clots and the lack of background 19 F signal allow accurate quantification using spectroscopy at 4.7 T, as corroborated with proton relaxation rate measurements at 1.5 T and trace element (gadolinium) analysis. Finally, the extension of these techniques to a clinically relevant application, the evaluation of the fibrin burden within an ex vivo human carotid endarterectomy sample, demonstrates the potential use of these particles for uniquely identifying unstable atherosclerotic lesions in vivo.

Fluorine‐19 MRI for visualization and quantification of cell migration in a diabetes model

“…19 F has low background biological abundance and is a sensitive nucleus, where the gyromagnetic ratios of 1 H and 19 F differ by only about 6%, and the relative sensitivity is 0.83. Previously, 19 F MRI and perfluorocarbons have been used for several extracellular applications, including blood volume measurements (24), measurements of tissue oxygenation (25)(26)(27)(28)(29)(30)(31)(32), and the detection of atherosclerotic plaques (33,34).…”

Imaging of Vx‐2 rabbit tumors with ανβ3‐integrin‐targeted 111In nanoparticles

“…Moreover, the perfluorocarbon core of the NP can provide a 19 F MR signal, which indicates the spatial location of the 111 In a m b 3 -NP at the tumor site. 23,24 In summary, a m b 3 -targeted 111 In NP were developed and studied for use as sensitive beacons of angiogenesis in nascent tumors. 111 In a m b 3 -NP provided a high tumor signal, which was better for the formulations with 10 nuclides per particle than 1.…”

Gd‐enhanced MR images of substrates other than water

“…These procedures are often indicated as spectroscopic imaging and refer to endogenous substrates like lactate, choline, creatine, etc. (4-6), although images of exogenous substrates (mainly 19 F-containing molecules) have also been reported (7)(8)(9).…”