Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.
Biomedical MRI/MoSAIC, Department of Imaging and Pathology, Katholieke Universiteit Leuven, Herestraat 49, B3000 Leuven, Belgium.
J Am Chem Soc. 2023 Jul 5;145(26):14276-14287. doi: 10.1021/jacs.3c02520. Epub 2023 Jun 20.
We report an innovative approach to producing bacteriochlorins (bacs) via formal cycloaddition by subjecting a porphyrin to a trimolecular reaction. Bacs are near-infrared probes with the intrinsic ability to serve in multimodal imaging. However, despite their ability to fluoresce and chelate metal ions, existing bacs have thus offered limited ability to label biomolecules for target specificity or have lacked chemical purity, limiting their use in bio-imaging. In this work, bacs allowed a precise and controlled appending of clickable linkers, lending the porphyrinoids substantially more chemical stability, clickability, and solubility, rendering them more suitable for preclinical investigation. Our bac probes enable the targeted use of biomolecules in fluorescence imaging and Cerenkov luminescence for guided intraoperative imaging. Bacs' capacity for chelation provides opportunities for use in non-invasive positron emission tomography/computed tomography. Herein, we report the labeling of bacs with Hs1a, a (NaV1.7)-sodium-channel-binding peptide derived from the Chinese tarantula to yield Bac-Hs1a and radiolabeled Hs1a, which shuttles our bac sensor(s) to mouse nerves. In vivo, the bac sensor allowed us to observe high signal-to-background ratios in the nerves of animals injected with fluorescent Bac-Hs1a and radiolabeled Hs1a in all imaging modes. This study demonstrates that Bac-Hs1a and [Cu]Cu-Bac-Hs1a accumulate in peripheral nerves, providing contrast and utility in the preclinical space. For the chemistry and bio-imaging fields, this study represents an exciting starting point for the modular manipulation of bacs, their development and use as probes for diagnosis, and their deployment as formidable multiplex nerve-imaging agents for use in routine imaging experiments.
我们报告了一种通过将卟啉进行三聚反应来制备细菌叶绿素（bac）的创新方法。bac 是近红外探针，具有进行多模态成像的固有能力。然而，尽管它们具有荧光和螯合金属离子的能力，但现有的 bac 标记生物分子的靶向特异性能力有限，或者缺乏化学纯度，限制了它们在生物成像中的应用。在这项工作中，bac 允许精确和受控地添加点击连接子，使卟啉类化合物具有更高的化学稳定性、点击性和溶解性，使其更适合临床前研究。我们的 bac 探针能够在荧光成像和 Cerenkov 发光中靶向使用生物分子，用于引导术中成像。bac 的螯合能力为非侵入性正电子发射断层扫描/计算机断层扫描的应用提供了机会。在此，我们报告了 bac 与源自中国狼蛛的（NaV1.7）-钠离子通道结合肽 Hs1a 的标记，得到 Bac-Hs1a 和放射性标记的 Hs1a，后者将我们的 bac 传感器输送到小鼠神经。在体内，bac 传感器允许我们在注射荧光 Bac-Hs1a 和放射性标记 Hs1a 的动物的神经中观察到高信号与背景的比值。在所有成像模式下。这项研究表明，Bac-Hs1a 和 [Cu]Cu-Bac-Hs1a 积聚在外周神经中，为临床前空间提供对比度和实用性。对于化学和生物成像领域，这项研究代表了 bac 的模块化操作、作为诊断探针的开发和使用以及作为强大的多通道神经成像剂的部署的令人兴奋的起点，用于常规成像实验。
