Noninvasive cell tracking in vivo has the potential to advance stem cell-based therapies into the clinic. Magnetic resonance imaging (MRI) provides an excellent image-guidance platform; however, existing MR cell labeling agents are fraught with limited specificity. To address this unmet need, we developed a highly efficient manganese porphyrin contrast agent, MnEtP, using a two-step synthesis. In vitro MRI at 3 Tesla on human embryonic stem cells (hESCs) demonstrated high labeling efficiency at a very low dose of 10 µM MnEtP, resulting in a four-fold lower T 1 relaxation time. This extraordinarily low dose is ideal for labeling large cell numbers required for large animals and humans. Cell viability and differentiation capacity were unaffected. Cellular manganese quantification corroborated MRI findings, and the agent localized primarily on the cell membrane. In vivo MRI of transplanted hESCs in a rat demonstrated excellent sensitivity and specificity of MnEtP for noninvasive stem cell tracking.

中文翻译：

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用于在MRI上标记和跟踪人类胚胎干细胞的高效T 1造影剂。

体内非侵入性细胞追踪具有将基于干细胞的疗法推向临床的潜力。磁共振成像（MRI）提供了出色的图像指导平台；然而，现有的MR细胞标记剂的特异性有限。为了满足这一未满足的需求，我们使用两步合成技术开发了一种高效的锰卟啉造影剂MnEtP。在人类胚胎干细胞（hESCs）上3 Tesla的体外MRI显示，在非常低的10 µM MnEtP剂量下具有很高的标记效率，从而使T 1弛豫时间降低了四倍。这种极低的剂量非常适合标记大型动物和人类所需的大细胞数量。细胞活力和分化能力不受影响。细胞锰定量证实了MRI结果，药剂主要定位在细胞膜上 大鼠体内移植的hESC的体内MRI显示了MnEtP对非侵入性干细胞追踪的出色敏感性和特异性。