124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection,Molecular Imaging and Biology

当前位置： X-MOL 学术 › Mol. Imaging Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection
Molecular Imaging and Biology ( IF 3.0 ) Pub Date : 2021-08-23 , DOI: 10.1007/s11307-021-01638-5
Camilo A Ruiz-Bedoya _{1,

2,

3} , Filipa Mota _{1,

2,

3} , Alvaro A Ordonez _{1,

2,

3} , Catherine A Foss _{1,

4} , Alok K Singh ₃ , Monali Praharaj ₅ , Farina J Mahmud _{1,

2,

3} , Ali Ghayoor ₆ , Kelly Flavahan _{1,

2,

3} , Patricia De Jesus _{1,

2,

3} , Melissa Bahr _{1,

2,

3} , Santosh Dhakal ₇ , Ruifeng Zhou ₇ , Clarisse V Solis ₈ , Kathleen R Mulka ₈ , William R Bishai ₃ , Andrew Pekosz _{7,

8} , Joseph L Mankowski ₈ , Jason Villano ₈ , Sabra L Klein ₇ , Sanjay K Jain _{1,

2,

3,

4}

Affiliation

Purpose

Molecular imaging has provided unparalleled opportunities to monitor disease processes, although tools for evaluating infection remain limited. Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by lung injury that we sought to model. Activated macrophages/phagocytes have an important role in lung injury, which is responsible for subsequent respiratory failure and death. We performed pulmonary PET/CT with ¹²⁴I-iodo-DPA-713, a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by activated macrophages cells, to evaluate the local immune response in a hamster model of SARS-CoV-2 infection.

Procedures

Pulmonary ¹²⁴I-iodo-DPA-713 PET/CT was performed in SARS-CoV-2-infected golden Syrian hamsters. CT images were quantified using a custom-built lung segmentation tool. Studies with DPA-713-IRDye680LT and a fluorescent analog of DPA-713 as well as histopathology and flow cytometry were performed on post-mortem tissues.

Results

Infected hamsters were imaged at the peak of inflammatory lung disease (7 days post-infection). Quantitative CT analysis was successful for all scans and demonstrated worse pulmonary disease in male versus female animals (P < 0.01). Increased ¹²⁴I-iodo-DPA-713 PET activity co-localized with the pneumonic lesions. Additionally, higher pulmonary ¹²⁴I-iodo-DPA-713 PET activity was noted in male versus female hamsters (P = 0.02). DPA-713-IRDye680LT also localized to the pneumonic lesions. Flow cytometry demonstrated a higher percentage of myeloid and CD11b + cells (macrophages, phagocytes) in male versus female lung tissues (P = 0.02).

Conclusion

¹²⁴I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, ¹²⁴I-Iodo-DPA-713 PET could serve as a noninvasive, clinically translatable approach to monitor SARS-CoV-2-associated pulmonary inflammation and expedite the development of novel therapeutics for COVID-19.

中文翻译：

SARS-CoV-2 感染仓鼠模型中的 124I-Iodo-DPA-713 正电子发射断层扫描

目的

分子成像为监测疾病过程提供了无与伦比的机会，尽管用于评估感染的工具仍然有限。由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的冠状病毒病 (COVID-19) 是由我们试图模拟的肺损伤介导的。活化的巨噬细胞/吞噬细胞在肺损伤中起重要作用，肺损伤是随后呼吸衰竭和死亡的原因。我们使用¹²⁴ I-iodo-DPA-713（一种被活化的巨噬细胞选择性捕获的低分子量吡唑并嘧啶配体）进行了肺部 PET/CT，以评估 SARS-CoV-2 感染仓鼠模型中的局部免疫反应。

程序

在感染 SARS-CoV-2 的金色叙利亚仓鼠中进行肺^{124 I-iodo-DPA-713 PET/CT。}使用定制的肺部分割工具对 CT 图像进行量化。对死后组织进行了 DPA-713-IRDye680LT 和 DPA-713 的荧光类似物以及组织病理学和流式细胞术的研究。

结果

感染的仓鼠在炎症性肺病的高峰期（感染后 7 天）成像。所有扫描的定量 CT 分析均成功，并证明雄性动物比雌性动物的肺部疾病更严重 ( P < 0.01)。增加的¹²⁴ I-iodo-DPA-713 PET 活性与肺炎病变共定位。此外，雄性仓鼠与雌性仓鼠相比肺部^{124 I-iodo-DPA-713 PET 活性更高 (}P = 0.02)。DPA-713-IRDye680LT 也定位于肺病灶。流式细胞术显示男性肺组织与女性肺组织相比，骨髓和 CD11b + 细胞（巨噬细胞、吞噬细胞）的百分比更高 ( P = 0.02)。