Retention of 64Cu-FLFLF, a Formyl Peptide Receptor 1-Specific PET Probe, Correlates with Macrophage and Neutrophil Abundance in Lung Granulomas from Cynomolgus Macaques

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

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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, 64Cu-FLFLF was retained in lung granulomas and analysis of lung granulomas identified positive correlations between 64Cu-FLFLF and neutrophil and macrophage numbers (R2 = 0.8681 and 0.7643, respectively), and weaker correlations for T cells and B cells (R2 = 0.5744 and 0.5908, respectively), suggesting that multiple cell types drive 64Cu-FLFLF avidity. By PET/CT imaging, we found that granulomas retained 64Cu-FLFLF but with less avidity than the glucose analog 18F-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.

Original languageEnglish
Pages (from-to)2264-2276
Number of pages13
JournalACS infectious diseases
Issue number8
Publication statusPublished - 13 Aug 2021

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