Open AccessRetention of 64Cu-FLFLF, a Formyl Peptide Receptor 1-Specific PET Probe, Correlates with Macrophage and Neutrophil Abundance in Lung Granulomas from Cynomolgus Macaques
Author(s) -
Joshua T. Mattila,
Wissam Beaino,
Alexander G. White,
Lea Nyiranshuti,
Pauline Maiello,
Jaime Tomko,
L. James Frye,
Daniel Fillmore,
Charles A. Scanga,
Philana Ling Lin,
JoAnne L. Flynn,
Carolyn J. Anderson
Publication year - 2021
Publication title -
acs infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.324
H-Index - 39
ISSN - 2373-8227
DOI - 10.1021/acsinfecdis.0c00826
Subject(s) - avidity , tuberculosis , macrophage , lung , mycobacterium tuberculosis , pathology , inflammation , immunology , biology , granuloma , receptor , peptide , medicine , antigen , biochemistry , in vitro
Neutrophilic inflammation correlates with severe tuberculosis (TB), a disease caused by Mycobacterium tuberculosis ( Mtb ). Granulomas are lesions that form in TB, and a PET probe for following neutrophil recruitment to granulomas could predict disease progression. We tested the formyl peptide receptor 1 (FPR1)-targeting peptide FLFLF in Mtb -infected macaques. Preliminary studies in mice demonstrated specificity for neutrophils. In macaques, 64 Cu-FLFLF was retained in lung granulomas and analysis of lung granulomas identified positive correlations between 64 Cu-FLFLF and neutrophil and macrophage numbers (R 2 = 0.8681 and 0.7643, respectively), and weaker correlations for T cells and B cells (R 2 = 0.5744 and 0.5908, respectively), suggesting that multiple cell types drive 64 Cu-FLFLF avidity. By PET/CT imaging, we found that granulomas retained 64 Cu-FLFLF but with less avidity than the glucose analog 18 F-FDG. These studies suggest that neutrophil-specific probes have potential PET/CT applications in TB, but important issues need to be addressed before they can be used in nonhuman primates and humans.