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J Nucl Cardiol. 2019 Oct 28. doi: 10.1007/s12350-019-01929-z. [Epub ahead of print]

Dissecting the target leukocyte subpopulations of clinically relevant inflammation radiopharmaceuticals.

Author information

1
Department of Nuclear Medicine, Hannover Medical School, Carl Neuberg-Str. 1, 30625, Hannover, Germany.
2
Department of Radiopharmaceutical Chemistry, Technical University of Munich, Munich, Germany.
3
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
4
Department of Nuclear Medicine, Hannover Medical School, Carl Neuberg-Str. 1, 30625, Hannover, Germany. Thackeray.James@mh-hannover.de.

Abstract

BACKGROUND:

Leukocyte subtypes bear distinct pro-inflammatory, reparative, and regulatory functions. Imaging inflammation provides information on disease prognosis and may guide therapy, but the cellular basis of the signal remains equivocal. We evaluated leukocyte subtype specificity of characterized clinically relevant inflammation-targeted radiotracers.

METHODS AND RESULTS:

Leukocyte populations were purified from blood- and THP-1-derived macrophages were polarized into M1-, reparative M2a-, or M2c-macrophages. In vitro uptake assays were conducted using tracers of enhanced glucose or amino acid metabolism and molecular markers of inflammatory cells. Both 18F-deoxyglucose (18F-FDG) and the labeled amino acid 11C-methionine (11C-MET) displayed higher uptake in neutrophils and monocytes compared to other leukocytes (P = 0.005), and markedly higher accumulation in pro-inflammatory M1-macrophages compared to reparative M2a-macrophages (P < 0.001). Molecular tracers 68Ga-DOTATATE targeting the somatostatin receptor type 2 and 68Ga-pentixafor targeting the chemokine receptor type 4 (CXCR4) exhibited broad uptake by leukocyte subpopulations and polarized macrophages with highest uptake in T-cells/natural killer cells and B-cells compared to neutrophils. Mitochondrial translocator protein (TSPO)-targeted 18F-flutriciclamide selectively accumulated in monocytes and pro-inflammatory M1 macrophages (P < 0.001). Uptake by myocytes and fibroblasts tended to be higher for metabolic radiotracers.

CONCLUSIONS:

The different in vitro cellular uptake profiles may allow isolation of distinct phases of the inflammatory pathway with specific inflammation-targeted radiotracers. The pathogenetic cell population in specific inflammatory diseases should be considered in the selection of an appropriate imaging agent.

KEYWORDS:

Inflammation; cardiovascular disease; leukocytes; macrophages; positron emission tomography; uptake assay

PMID:
31659697
DOI:
10.1007/s12350-019-01929-z

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