Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study

Tianxiong Ji; Chunfang Zan; Lina Li; Jianbo Cao; Yao Su; Hongliang Wang; Zhifang Wu; Min-Fu Yang; Kefei Dou; Sijin Li

doi:10.1007/s11307-024-01919-9

Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study

Mol Imaging Biol. 2024 Apr 25. doi: 10.1007/s11307-024-01919-9. Online ahead of print.

Authors

Tianxiong Ji^#^{1

2}, Chunfang Zan^#^{1

2

3

4}, Lina Li⁵, Jianbo Cao^{1

2

3}, Yao Su⁵, Hongliang Wang^{1

2

3}, Zhifang Wu^{6

7

8}, Min-Fu Yang^{9

10}, Kefei Dou^{11

12}, Sijin Li^{13

14

15}

Affiliations

¹ Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, China.
² Shanxi Key Laboratory of Molecular Imaging, Shanxi Medical University, Taiyuan, 030001, China.
³ Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, 030001, China.
⁴ College of Medical Imaging, Shanxi Medical University, Taiyuan, 030001, China.
⁵ Department of Nuclear Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
⁶ Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, China. wuzhifang01@163.com.
⁷ Shanxi Key Laboratory of Molecular Imaging, Shanxi Medical University, Taiyuan, 030001, China. wuzhifang01@163.com.
⁸ Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, 030001, China. wuzhifang01@163.com.
⁹ Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, 030001, China. minfuyang@126.com.
¹⁰ Department of Nuclear Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. minfuyang@126.com.
¹¹ State Key Laboratory of Cardiovascular Disease, Beijing, 100037, China. drdoukefei@126.com.
¹² Cardiometabolic Medicine Center, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China. drdoukefei@126.com.
¹³ Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, China. lisjnm123@163.com.
¹⁴ Shanxi Key Laboratory of Molecular Imaging, Shanxi Medical University, Taiyuan, 030001, China. lisjnm123@163.com.
¹⁵ Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, 030001, China. lisjnm123@163.com.

^# Contributed equally.

PMID: 38664355
DOI: 10.1007/s11307-024-01919-9

Abstract

Aim: Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis.

Methods: New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al¹⁸F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al¹⁸F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al¹⁸F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed.

Results: The rabbit carotid and abdominal atherosclerosis model was established. Al¹⁸F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al¹⁸F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al¹⁸F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques.

Conclusions: We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al¹⁸F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques.

Keywords: Atherosclerosis; Fibroblast activation protein; Fibroblast activation protein inhibitor; PET/CT imaging; Plaque.

Abstract

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