Fluorine (¹⁹F) MRS and MRI in biomedicine

Abstract

Shortly after the introduction of 1 H MRI, fluorinated molecules were tested as MR-detectable tracers or contrast agents. Many fluorinated compounds, which are nontoxic and chemically inert, are now being used in a broad range of biomedical applications, including anesthetics, chemotherapeutic agents, and molecules with high oxygen solubility for respiration and blood substitution. These compounds can be monitored by fluorine ( 19 F) MRI and/or MRS, providing a noninvasive means to interrogate associated functions in biological systems. As a result of the lack of endogenous fluorine in living organisms, 19 F MRI of 'hotspots' of targeted fluorinated contrast agents has recently opened up new research avenues in molecular and cellular imaging. This includes the specific targeting and imaging of cellular surface epitopes, as well as MRI cell tracking of endogenous macrophages, injected immune cells and stem cell transplants.

19F-MRI for monitoring human NK cellsin vivo

“…Usage of 19 F is an appealing labeling approach for in vivo imaging of NK cells (or other cell therapies) because (1) it is the only naturally occurring isotope of fluorine and does not decay, (2) does not require phagocytosis to enter the cell, (3) is a component of the chemical structure of over a dozen FDAapproved drugs and thus has a long safety record in humans, 15 and (4) perfluorocarbons have already been successfully used in clinical trials for decades in artificial blood substitutes. 45 Moreover, using 19 F-MRI is an attractive technique as it provides positive contrast, and the high-resolution anatomical 1 H clinical images can be registered and superimposed with the highly sensitive 19 F hotspot images to create a precise mapping of where the 19 F-labeled NK cells exist in relation to the patient's tumor.…”

“…14 Radiofrequency MRI coils can then be tuned to detect and image these fluorine atoms enabling tracking of cellular fate post-infusion. 15 In preclinical models, optical imaging using fluorescent and bioluminescent models have provided valuable insight into NK cell trafficking patterns after adoptive transfer, [16][17][18] but these techniques assume murine NK cells traffic similarly to human NK cells, do not give high resolution of the live gross anatomical structures where the NK cells traffic to, and most importantly, are not available in the clinic. Radiolabeling of NK cells with clinically available isotopes, like 18 F, 11 C or 111 In, offers high sensitivity but also lacks high resolution of anatomical structures, exposes the patient to ionizing radiation, and is limited by radioactive decay of the isotope (typically hours to days) preventing detection of long-term NK cell persistence.…”

“…19 In the past decade, very promising MRI techniques have been developed to monitor and quantify immune cells in vivo using the non-radioactive nucleus 19 F as an MRI contrast agent. 14,20,21 Because there are trace amounts of fluorine in the body (mainly in the bone matrix and teeth) that exhibit a very CONTACT Christian M. Capitini ccapitini@pediatrics.wisc.edu short spin-spin relaxation time, 15 there is minimal background "noise" and infusions of 19 F-labeled cells could be easily identified at a high contrast to noise ratio. 22 With a high gyromagnetic ratio similar to that of 1 H, 19 F has favorable physical properties that improve inherent receptivity and sensitivity, requiring only millimolar quantities per voxel for detection.…”

Cell-Based Therapeutic Strategies in Multiple Sclerosis

“…[84][85][86] Additionally, in vivo perfluorocarbon emulsion infusion followed by 19 F MRI has been shown to preferentially detect areas of inflammation both in the CNS and systemically via preferential uptake by CD68+ macrophages, providing a non-invasive measure of disease activity in murine models of inflammatory disease. [87][88][89][90] Thus, the advantage of these labelling modalities includes the ability to directly visualise (and potentially in an EAE mouse model in which human MSCs engineered to express a myelin oligodendrocyte glycoprotein-specific receptor were intranasally delivered and found to significantly improve EAE symptoms better than non-engineered human MSCs, and prevented further EAE induction.…”

Double-tuned Radiofrequency Coil for 19F and 1H Imaging

“…1,2 Most 19 F imaging studies have been conducted using tunable singletuned radiofrequency (RF) coils developed for 19 F/ 1 H imaging because the gyromagnetic ratios of 19 F nuclei (40.05 MHz/T) and 1 H nuclei (42.58 MHz/T) are very close. [3][4][5] However, retuning the RF coil during in vivo animal experiments is time consuming, and differing distributions of the RF fields between 19 F and 1 H are inconvenient for quantifying 19 F distribution using the 1 H sensitivity map.…”