基于PCTA的代谢转换试剂用于检测细胞外乳酸盐使用CESTMRI
Remy Chiaffarelli1,2,3, Pedro F Cruz4, Jonathan Cotton1,2
1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen 72076, Germany.
JACS Au
|February 28, 2025
概括
新的转移试剂 (SRs) 通过化学交换和转移 (CEST) MRI 来检测细胞外乳酸. 这一进步为癌症代谢概况和分期提供了更安全,非侵入性的方法.
科学领域:
- 生物医学成像技术 生物医学成像技术
- 分子成像学分子成像学
- 代谢成像 - 代谢成像
背景情况:
- 乳酸是癌症的关键代谢驱动因素,由于高调的无氧糖解,它经常在瘤微环境中积累.
- 目前用于检测细胞外乳酸的方法在灵敏度,特异性和安全性方面存在局限性.
- 开发用于乳酸检测的新型探针对于推进癌症代谢概况和分期至关重要.
研究的目的:
- 引入一种新的基于宏循环的转移试剂 (SRs) 家族,用于使用CEST MRI检测细胞外乳酸.
- 评估这些新型SRs在复杂的生物环境中的有效性和特异性.
- 评估这些药物在体内成像中的安全性和非侵入性潜力.
主要方法:
- 基于PCTA-配体的新型转移试剂 (Yb-PCTA和Eu-PCTA) 的合成和表征.
- 在体外CESTMRI实验中,评估在存在竞争性代谢物时的乳酸检测.
- 在小鼠体内临床前CESTMRI研究,以评估Yb-PCTA在非侵入性乳酸检测中的安全性和有效性.
主要成果:
- Yb-PCTA和Eu-PCTA有效地在CEST光谱中转移了乳酸OH信号.
- 在体外研究证实了细胞外乳酸的特定成像,即使有干扰血液代谢物.
- 在体内研究表明,安全的Yb-PCTA静脉注射和成功的非侵入性检测细胞外乳酸盐.
结论:
- 基于PCTA连接体的转移试剂有效地通过CESTMRI检测细胞外乳酸.
- 这些新型药物显示出特定和非侵入性癌症代谢成像的潜力.
- PCTA 支架是开发用于精密医学的先进分子和代谢成像传感器的有希望的平台.
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