Frontiers in immunology · 2026
Development and evaluation of a peptide-based radiotracer for targeting TIM-3 in preclinical models.
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Bao Guangfa, Zhang Jianfang, Cui Yeqian, Li Dan, Lu Menglin, Lu Rencai, Xv Dongdong, Wu Mingkang, Wang Shaobo
Аннотация
INTRODUCTION: T cell immunoglobulin mucin-3 (TIM-3) plays a critical role in the T cell exhaustion and there have been already many related inhibitory antibodies in clinical trial. However, in vivo non-invasive visualization of TIM-3 is lagging in comparison to the development of therapeutic antibodies. This study aims to develop a positron emission tomography/computed tomography (PET/CT) imaging tracer targeting TIM-3 and explore its ability to visualize tumor lesions.
METHODS: A cysteine-modified, NOTA-conjugated peptide, NOTA-P24, was synthesized and radiolabeled with fluorine-18. Its stability and specificity were evaluated in vivo using uptake, competition, and efflux studies. Furthermore, PET/CT imaging and biodistribution studies were performed on tumor bearing animals.
RESULTS: [18F]AlF-NOTA-P24 showed high specificity and affinity to TIM-3-expressing cells in vitro and in vivo. Biodistribution studies on tumor-bearing mice demonstrated high tumoral uptake of the tracer and fast body clearance, resulting in high-contrast images and negligible exposure of healthy tissue to radiation.
CONCLUSIONS: The work developed a peptide-based probe [18F]AlF-NOTA-P24 targeting TIM-3, with favorable specificity and affinity. This approach has the potential for noninvasive evaluation of TIM-3.
METHODS: A cysteine-modified, NOTA-conjugated peptide, NOTA-P24, was synthesized and radiolabeled with fluorine-18. Its stability and specificity were evaluated in vivo using uptake, competition, and efflux studies. Furthermore, PET/CT imaging and biodistribution studies were performed on tumor bearing animals.
RESULTS: [18F]AlF-NOTA-P24 showed high specificity and affinity to TIM-3-expressing cells in vitro and in vivo. Biodistribution studies on tumor-bearing mice demonstrated high tumoral uptake of the tracer and fast body clearance, resulting in high-contrast images and negligible exposure of healthy tissue to radiation.
CONCLUSIONS: The work developed a peptide-based probe [18F]AlF-NOTA-P24 targeting TIM-3, with favorable specificity and affinity. This approach has the potential for noninvasive evaluation of TIM-3.