A characterization of ABL-101 as a potential tracer for clinical fluorine-19 MRI.
Emeline DarçotRoberto ColottiDavid BrennanGraeme A DeucharCelestine SantoshRuud B van HeeswijkPublished in: NMR in biomedicine (2019)
The two main challenges that prevent the translation of fluorine-19 (19 F) MRI for inflammation monitoring or cell tracking into clinical practice are (i) the relatively low signal-to-noise ratio generated by the injected perfluorocarbon (PFC), which necessitates long scan times, and (ii) the need for regulatory approval and a high biocompatibility of PFCs that are also suitable for MRI. ABL-101, an emulsion of perfluoro(t-butylcyclohexane), is a third-generation PFC that is already used in clinical trials, but has not yet been used for 19 F MRI. The objective of this study was therefore to assess the performance of ABL-101 as a 19 F MRI tracer. At magnetic field strengths of 3, 9.4 and 14.1 T, the CF3 groups of ABL-101 generated a large well-separated singlet with T2 /T1 ratios of >0.27, >0.14 and > 0.05, respectively. All relaxation times decreased with the increase in magnetic field strength. The detection limit of ABL-101 in a 0.25 mm3 voxel at 3 T, 37°C and with a 3-minute acquisition time was 7.21mM. After intravenous injection, the clearance half-lives of the ABL-101 19 F MR signal in mouse (n = 3) spleen and liver were 6.85 ± 0.45 and 3.20 ± 0.35 days, respectively. These results demonstrate that ABL-101 has 19 F MR characteristics that are similar to those of PFCs developed specifically for MRI, while it has clearance half-lives similar to PFCs that have previously been used in large doses in non-MRI clinical trials. Overall, ABL-101 is thus a very promising candidate tracer for future clinical trials that use 19 F MRI for cell tracking or the monitoring of inflammation.
Keyphrases
- contrast enhanced
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- diffusion weighted imaging
- positron emission tomography
- computed tomography
- oxidative stress
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- randomized controlled trial
- clinical practice
- stem cells
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- low dose
- transcription factor
- mesenchymal stem cells
- air pollution
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- climate change
- human health
- double blind