PT  - JOURNAL ARTICLE
AU  - Ali Pirasteh
AU  - Sarvesh Periyasamy
AU  - Jennifer Jean Meudt
AU  - Yongjun Liu
AU  - Laura M Lee
AU  - Kyle M Schachtschneider
AU  - Lawrence B Schook
AU  - Ron C Gaba
AU  - Lu Mao
AU  - Adnan Said
AU  - Alan B McMillan
AU  - Paul F Laeseke
AU  - Dhanansayan Shanmuganayagam
TI  - Staging Liver Fibrosis by Fibroblast Activation Protein Inhibitor Positron Emission Tomography in a Human-sized Swine Model
AID  - 10.2967/jnumed.121.263736
DP  - 2022 Apr 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.121.263736
4099  - http://jnm.snmjournals.org/content/early/2022/04/28/jnumed.121.263736.short
4100  - http://jnm.snmjournals.org/content/early/2022/04/28/jnumed.121.263736.full
AB  - Rationale: Current methods of staging liver fibrosis have notable limitations. We investigated the utility of positron emission tomography (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 FAPI PET/MRI and liver biopsy, followed by liver parenchymal embolization, 8 weeks of oral alcohol intake, endpoint FAPI PET/MRI, and necropsy. Regions of interest (ROIs) were drawn on baseline and endpoint PET images and standardized uptake values (SUVs) were recorded. At endpoint, liver sections corresponding to ROIs were identified and cut out. Histologic evaluation of fibrosis was performed using a modified METAVIR score for swine liver and quantitatively using collagen proportionate area (CPA). Box-and-whisker plot and linear regression were used to correlate SUV with METAVIR score and CPA, respectively. Results: Liver FAPI uptake strongly correlated with CPA (Pearson correlation coefficient, r=0.89, P<0.001). FAPI uptake was significantly and progressively higher across F2 and F3/F4 fibrosis stages, respective median SUVs [interquartile range, IQR] of 2.9 [2.7 – 3.8] and 7.6 [6.7 – 10.2] (P<0.001). There was no significant difference between FAPI uptake of baseline liver and endpoint liver sections staged as F0/F1, respective median SUVs [IQR] of 1.7 [1.3 – 2.0] and 1.7 [1.5 – 1.8] (P = 0.338). Conclusion: The strong correlation between liver FAPI uptake and the histologic stage of liver fibrosis suggests FAPI PET is a promising tool that can achieve noninvasive and accurate staging of fibrosis throughout the entire liver, pending validation in patients.