A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells.
A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells.
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DOI：
10.1038/s41598-017-15417-2
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发表时间：
2017-11-09
影响因子：
4.6
通讯作者：
Devoogdt N
中科院分区：
文献类型：
--
作者：
Balhuizen A;Massa S;Mathijs I;Turatsinze JV;De Vos J;Demine S;Xavier C;Villate O;Millard I;Egrise D;Capito C;Scharfmann R;In't Veld P;Marchetti P;Muyldermans S;Goldman S;Lahoutte T;Bouwens L;Eizirik DL;Devoogdt N
目前还没有可靠的方法来量化体内内分泌细胞质量（ECM），这妨碍了对糖尿病或胰岛移植后进行性β细胞损失的准确理解。为了解决这一未满足的需求，我们将人类胰岛的RNA测序与系统生物学方法相结合，以鉴定内分泌胰腺的新生物标志物。二肽基肽酶6（DPP 6）被鉴定为靶点，其mRNA表达在人胰岛中比周围组织高至少25倍，并且不被促炎细胞因子改变。在蛋白质水平上，DPP 6仅定位于胰腺内的β和α细胞中。我们接下来产生了靶向人DPP 6的高亲和力骆驼科单域抗体（纳米抗体）。对纳米抗体进行放射性标记，并在免疫缺陷小鼠中进行体内SPECT/CT成像和生物分布研究，这些小鼠移植了表达DPP 6的Kelly神经母细胞瘤细胞或产生胰岛素的人EndoC-βH1细胞。在两种模型中，表达人DPP 6的细胞都清晰可见。总之，我们已经确定了一种新的β和α细胞生物标志物，并开发了一种用于人胰岛素分泌细胞体内成像的示踪剂。这提供了一个有用的工具，以非侵入性地跟进肌内植入的胰岛素分泌细胞。
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines. At the protein level, DPP6 localizes only in beta and alpha cells within the pancreas. We next generated a high-affinity camelid single-domain antibody (nanobody) targeting human DPP6. The nanobody was radiolabelled and in vivo SPECT/CT imaging and biodistribution studies were performed in immunodeficient mice that were either transplanted with DPP6-expressing Kelly neuroblastoma cells or insulin-producing human EndoC-βH1 cells. The human DPP6-expressing cells were clearly visualized in both models. In conclusion, we have identified a novel beta and alpha cell biomarker and developed a tracer for in vivo imaging of human insulin secreting cells. This provides a useful tool to non-invasively follow up intramuscularly implanted insulin secreting cells.
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作者：
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影响因子：
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作者：
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通讯作者：
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