Perfluoro-tert-butanol: a cornerstone for high performance fluorine-19 magnetic resonance imaging

Abstract

As a valuable complement to its proton-based counterpart (1H MRI/NMR), fluorine-based magnetic resonance imaging/spectroscopy (19F MRI/NMR) provides quantitative images or spectroscopy without background interference, which has become an extensively used...

Nanotechnology as a Versatile Tool for 19F-MRI Agent’s Formulation: A Glimpse into the Use of Perfluorinated and Fluorinated Compounds in Nanoparticles

“…After being drawn up by RES, PFC emulsions are diffused back into the blood, where they dissolve in plasma lipids and are carried to the lungs to be expelled out mainly through exhalation by the lungs [56,73,82]. Even though PFC is intrinsically inert, there are reports of severe retention of PFCs in the liver, spleen, and lungs [83][84][85], and the effect of the PFC when stayed too long in vivo or their intracellular fate is currently undetermined [53,86]. In general, nanosystems of size less than 10 nm, exceedingly are devoured by the renal clearance system, 20 to 100 nm by far, is the optimal size range to avoid physiological barriers, 100 to 200 nm particles have extended potential for prolonged circulation, and size greater than 200 nm is retreated almost certainly to spleen and liver and has the possibility for capillary clogging [87].…”

“…Even after four decades into the research of 19 F MRI, none of the PFC formulations have gained clinical approval [83]. Umpteen requisites should be actualized to extend a formulation into the clinic.…”

19F MRI Probes for Multimodal Imaging**

“…Proposed 19 F/OFI agents have possessed 5–40 % F and 1–108 chemically equivalent fluorine atoms per molecule, although structural variations mean that these values are not proportional. In other words, the number of fluorine atoms must be adjusted to the overall size of the agent: single F atom or −CF 3 groups may be sufficient for smaller molecules whereas perfluoro‐ tert ‐butanol or multiple −CF 3 groups are used with larger agents [30] . An important consideration is the low solubility of highly fluorinated agents in aqueous environment.…”

“…19 F MRI contrast agents have not been used clinically so far except in the case of perfluorinated gases for lung imaging [150] . Currently, only 6 agents are in clinical trials [30,151] . Among them, perfluoropropane has passed phase II for chronic obstructive pulmonary disorder [30] .…”

“…In other words, the number of fluorine atoms must be adjusted to the overall size of the agent: single F atom or À CF 3 groups may be sufficient for smaller molecules whereas perfluoro-tert-butanol or multiple À CF 3 groups are used with larger agents. [30] An important consideration is the low solubility of highly fluorinated agents in aqueous environment. For example, the effect of substituting BODIPY-based emitters with various 19 concentration was a minimum for 19 F MRI and only 50 μM for fluorescence but an organic solvent was necessary as the probe was not soluble in water.…”