Bimodal Imaging of Mouse Peripheral Nerves with Chlorin Tracers.

Bimodal Imaging of Mouse Peripheral Nerves with Chlorin Tracers.
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用二氢卟酚示踪剂对小鼠周围神经进行双峰成像。

DOI:
10.1021/acs.molpharmaceut.0c00946
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发表时间:
2021-03-01
影响因子:
4.9
通讯作者:
Reiner T
Reiner T
中科院分区:
医学2区
文献类型:
--
作者:
Gonzales J;Hernández-Gil J;Wilson TC;Adilbay D;Cornejo M;Demétrio de Souza Franca P;Guru N;Schroeder CI;King GF;Lewis JS;Reiner T

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Almost 17 million Americans have a history of cancer, a number expected to reach over 22 million by 2030. Cancer patients often undergo chemotherapy in the form of antineoplastic agents such as cis-platin and paclitaxel. Though effective, these agents can induce debilitating side effects; the most common neurotoxic effect, chemotherapy-induced peripheral neuropathy (CIPN), can endure long after treatment ends. Despite the widespread and chronic nature of the dysfunction, no tools exist to quantitatively measure chemotherapy-induced peripheral neuropathy. Such a tool would not only benefit patients but their stratification could also save significant financial and social costs associated with neuropathic pain. In our first step toward addressing this unmet clinical need, we explored a novel dual approach to localize peripheral nerves: Cerenkov luminescence imaging (CLI) and fluorescence imaging (FI). Our approach revolves around the targeting and imaging of voltage-gated sodium channel subtype NaV1.7, highly expressed in peripheral nerves from both harvested human and mouse tissues. For the first time, we show that Hsp1a, a radiolabeled NaV1.7-selective peptide isolated from Homoeomma spec. Peru, can serve as a targeted vector for delivering a radioactive sensor to the peripheral nervous system. In situ, we observe high signal-to-noise ratios in the sciatic nerves of animals injected with fluorescently labeled Hsp1a and radiolabeled Hsp1a. Moreover, confocal microscopy on fresh nerve tissue shows the same high ratios of fluorescence, corroborating our in vivo results. This study indicates that fluorescently labeled and radiolabeled Hsp1a tracers could be used to identify and demarcate nerves in a clinical setting.
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