Staging Liver Fibrosis by Fibroblast Activation Protein Inhibitor PET in a Human-Sized Swine Model

The Journal of Nuclear Medicine

article

Ali Pirasteh¹  Sarvesh Periyasamy²  Jennifer Jean Meudt³  Yongjun Liu⁴  Laura M. Lee⁵  Kyle M. Schachtschneider⁶  Lawrence B. Schook⁷  Ron C. Gaba⁸  Lu Mao⁹  Adnan Said^1,10  Alan Blair McMillan¹  Paul F. Laeseke²  Dhanansayan Shanmuganayagam³ 

[1] Radiology and Medical Physics, University of Wisconsin–Madison;Radiology and Biomedical Engineering, University of Wisconsin–Madison;Animal and Dairy Sciences, University of Wisconsin–Madison;Pathology and Laboratory Medicine, University of Wisconsin–Madison;Research Animal Resources and Compliance, University of Wisconsin–Madison;Radiology and Biochemistry and Molecular Genetics, University of Illinois at Chicago;Animal Sciences, University of Illinois at Chicago;Radiology/Interventional Radiology, University of Illinois at Chicago;Biostatistics and Medical Informatics, University of Wisconsin–Madison;Medicine, Gastroenterology, and Hepatology, University of Wisconsin–Madison;Surgery, University of Wisconsin–Madison;Center for Biomedical Swine Research and Innovation, University of Wisconsin–Madison

关键词: fibroblast activation protein inhibitor;    liver fibrosis;    PET;    MRI;    swine;   

DOI  :  10.2967/jnumed.121.263736

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Current methods of staging liver fibrosis have notable limitations. We investigated the utility of PET in staging liver fibrosis by correlating liver uptake of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) with histology in a human-sized swine model. Methods: Five pigs underwent baseline 68Ga-FAPI-46 (68Ga-FAPI) PET/MRI and liver biopsy, followed by liver parenchymal embolization, 8 wk of oral alcohol intake, endpoint 68Ga-FAPI PET/MRI, and necropsy. Regions of interest were drawn on baseline and endpoint PET images, and SUVmean was recorded. At the endpoint, liver sections corresponding to regions of interest were identified and cut out. Fibrosis was histologically evaluated using a modified METAVIR score for swine liver and quantitatively using collagen proportionate area (CPA). Box-and-whisker plots and linear regression were used to correlate SUVmean with METAVIR score and CPA, respectively. Results: Liver 68Ga-FAPI uptake strongly correlated with CPA (r = 0.89, P < 0.001). 68Ga-FAPI uptake was significantly and progressively higher across F2 and F3/F4 fibrosis stages, with a respective median SUVmean of 2.9 (interquartile range [IQR], 2.7–3.8) and 7.6 (IQR, 6.7–10.2) (P < 0.001). There was no significant difference between 68Ga-FAPI uptake of baseline liver and endpoint liver sections staged as F0/F1, with a respective median SUVmean of 1.7 (IQR, 1.3–2.0) and 1.7 (IQR, 1.5–1.8) (P = 0.338). Conclusion: The strong correlation between liver 68Ga-FAPI uptake and the histologic stage of liver fibrosis suggests that 68Ga-FAPI PET can play an impactful role in noninvasive staging of liver fibrosis, pending validation in patients.

【 授权许可】

CC BY