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

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Retention of 64Cu-FLFLF, a Formyl Peptide Receptor 1-Specific PET Probe, Correlates with Macrophage and Neutrophil Abundance in Lung Granulomas from Cynomolgus Macaques
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2021-07-13 , DOI: 10.1021/acsinfecdis.0c00826
Joshua T Mattila _{1,

2} , Wissam Beaino ₃ , Alexander G White ₄ , Lea Nyiranshuti ₅ , Pauline Maiello ₄ , Jaime Tomko ₄ , L James Frye ₄ , Daniel Fillmore ₄ , Charles A Scanga _{2,

4} , Philana Ling Lin _{2,

6} , JoAnne L Flynn _{2,

5} , Carolyn J Anderson _{3,

5,

7,

8,

9}

Affiliation

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.

中文翻译：

甲酰基肽受体 1 特异性 PET 探针 64Cu-FLFLF 的保留与食蟹猴肺肉芽肿中巨噬细胞和中性粒细胞的丰度相关

中性粒细胞炎症与严重结核病 (TB) 相关，这是一种由结核分枝杆菌( Mtb ) 引起的疾病。肉芽肿是结核病中形成的病变，中性粒细胞募集到肉芽肿后的 PET 探针可以预测疾病进展。我们在感染Mtb的猕猴中测试了甲酰基肽受体 1 (FPR1) 靶向肽 FLFLF。对小鼠的初步研究证明了对中性粒细胞的特异性。在猕猴中， ⁶⁴ Cu-FLFLF 保留在肺肉芽肿中，对肺肉芽肿的分析发现⁶⁴ Cu-FLFLF 与中性粒细胞和巨噬细胞数量呈正相关（分别为 R ² = 0.8681 和 0.7643），而与 T 细胞和 B 细胞的相关性较弱（R ²分别 = 0.5744 和 0.5908），表明多种细胞类型驱动⁶⁴ Cu-FLFLF 亲合力。通过 PET/CT 成像，我们发现肉芽肿保留了⁶⁴ Cu-FLFLF，但亲和力低于葡萄糖类似物¹⁸ F-FDG。这些研究表明，中性粒细胞特异性探针在结核病中具有潜在的 PET/CT 应用，但在将其用于非人类灵长类动物和人类之前，需要解决一些重要问题。

更新日期：2021-08-13

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