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

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.

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.

PET/CT revealed a continuous decline in the hepatic binding potential (BP_ND) of [¹⁸F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BP_ND 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 BP_ND (LCD vs HFD, p = 0.001).

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.