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

Ali Pirasteh, Sarvesh Periyasamy, Jennifer Jean Meudt, Yongjun Liu, Laura M. Lee, Kyle M. Schachtschneider, Lawrence B. Schook, Ron C. Gaba, Lu Mao, Adnan Said, Alan Blair McMillan, Paul F. Laeseke, Dhanansayan Shanmuganayagam

Research output: Contribution to journalArticlepeer-review

Abstract

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 5 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 respectivemedian SUVmean of 1.7 (IQR, 1.3 2.0) and 1.7 (IQR, 1.5 1.8) (P 5 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.

Original languageEnglish (US)
Pages (from-to)1956-1961
Number of pages6
JournalJournal of Nuclear Medicine
Volume63
Issue number12
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • MRI
  • PET
  • fibroblast activation protein inhibitor
  • liver fibrosis
  • swine

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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