Abstract
Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission tomography (PET) imaging with 18F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. Due to its small size, Macroflor is excreted renally, a prerequisite for imaging with the isotope flourine-18. The particle’s short blood half-life, measured in three species, including a primate, enables macrophage imaging in inflamed cardiovascular tissues. Macroflor enriches in cardiac and plaque macrophages, thereby increasing PET signal in murine infarcts and both mouse and rabbit atherosclerotic plaques. In PET/magnetic resonance imaging (MRI) experiments, Macroflor PET imaging detects changes in macrophage population size while molecular MRI reports on increasing or resolving inflammation. These data suggest that Macroflor PET/MRI could be a clinical tool to non-invasively monitor macrophage biology.
Highlights
Tissue macrophage numbers vary during health versus disease
Most available evidence focuses on blood monocytes, which are macrophage precursors that are easy to assay with existing technology
Macroflor synthesis relied on the commercial building blocks carboxymethylated polyglucose and L-lysine crosslinked through amide bond formation (Fig. 1a)
Summary
Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. We describe positron emission tomography (PET) imaging with 18F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. The long circulation times precluded the use of the clinically facile 18F PET isotope for nanoparticle tracking, because the radioisotope decays faster (T1/2 110 min) than nanoparticles exit from the blood pool adjacent to the imaging target, that is, diseased cardiovascular tissues. To solve these problems, we shrank nanoparticles to a size below the renal excretion threshold[6] and optimized biological behaviour through biocompatible chemistries. In a number of imaging experiments, this approach provides quantitative and specific PET data on inflammation in atherosclerotic plaque and ischaemic myocardium
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