Application of TSPO-Specific Positron Emission Tomography Radiotracer as an Early Indicator of Acute Liver Failure Induced by Propacetamol, a Prodrug of Paracetamol

Daehee Kim, Hye Won Lee, Sun Mi Park, Ji Eun Lee, Sang Ju Lee, Bom Sahn Kim, Seung Jun Oh, Byung Seok Moon, Hai Jeon Yoon

Research output: Contribution to journalArticlepeer-review

Abstract

Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24–72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [18F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [18F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUVav) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [18F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUVav compared to controls (p = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [18F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET’s potential as a non-invasive imaging biomarker for early-stage ALF.

Original languageEnglish
Article number5942
JournalInternational Journal of Molecular Sciences
Volume25
Issue number11
DOIs
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • TSPO
  • [F]GE180
  • hepatic failure
  • positron emission tomography
  • propacetamol

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