Quantitative imaging using [18F]F-TZ3108 to assess metabolic-associated fatty liver disease progression and low-carbohydrate diet efficacy.

OBJECTIVE

The Sigma-1 receptor (Sig-1R), located in the mitochondrion-associated membranes (MAMs), is an important biomarker for endoplasmic reticulum (ER) stress and plays a crucial role in the advancement of metabolic-associated fatty liver disease (MAFLD). Despite its significance, current methods to monitor MAFLD progression and treatment response are limited. This study aims to address this gap by utilizing [18F]F-TZ3108, an effecient tracer targeting Sig-1R, to quantitatively assess MAFLD progression and the efficacy of a low-carbohydrate diet (LCD) as a potential therapeutic intervention.

METHODS

The C57 BL/6 J mice were fed either a high-fat diet (HFD) or regular diet (CTR) for 12 weeks, and the progression of MAFLD was continuously monitored at 0, 4, 8, 12 weeks via [18F]F-TZ3108 positron emission tomography/computed tomography (PET/CT) and ex vivo assessment. After confirming successful induction, LDC intervention was administered in the HFD group for 2 weeks. And relevant post-treatment evaluations were also performed.

RESULTS

PET/CT revealed a continuous decline in the hepatic binding potential (BPND) of [18F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BPND in the CTR group. This reduction was significant after the 4th week of induction (p < 0.05). Furthermore, following intervention with LCD, there was a significant improvement in BPND (LCD vs HFD, p = 0.001).

CONCLUSIONS

The results of this study demonstrate that LCD therapy effectively mitigates MAFLD progression. Furthermore, the use of PET imaging with [18F]F-TZ3108 provides a reliable, non-invasive method for monitoring the progression and treatment response of MAFLD, offering significant potential for early detection and personalized treatment evaluation.