Saudek Frantisek, Brogren Carl-Henrik, Manohar Srirang
Diabetes Center, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech Republic.
Rev Diabet Stud. 2008 Spring;5(1):6-12. doi: 10.1900/RDS.2008.5.6. Epub 2008 May 10.
Diabetes is a disorder characterized by beta-cell loss or exhaustion and insulin deficiency. At present, knowledge is lacking on the underlying causes and for the therapeutic recovery of the beta-cell mass. A better understanding of diabetes pathogenesis could be obtained through exact monitoring of the fate of beta-cells under disease and therapy conditions. This could pave the way for a new era of intervention by islet replacement and regeneration regimens. Monitoring the beta-cell mass requires a reliable method for noninvasive in vivo imaging. Such a method is not available at present due to the lack of a beta-cell-specific contrast agent. The only existing method to monitor islet cells in vivo consists of labeling islet transplants with iron nanoparticles prior to transplantation and visualization of the transplanted islets by magnetic resonance imaging (MRI). Therefore, accurate assessment of the native beta-cell mass is still limited to autopsy studies. Endeavors to find a biological structure specific for beta-cells led to the discovery of potential candidates that have been tested for noninvasive imaging. Among them are the ligand to the vesicular monoamine transporter type 2 (VMAT-2), which is called dihydrotetrabenazine (DTBZ), antibodies to zinc transporter (ZnT-8) and the monoclonal antibody IC2. While DTBZ and antibodies to ZnT-8 showed binding activities to more than beta-cells, the anti-IC2 monoclonal antibody showed binding properties exclusively to insulin-producing beta-cells. This effect was demonstrated in many previous investigations, and has been further substantiated more recently. Thus, at present, IC2 seems to be the only useful marker for noninvasive functional imaging of native beta-cells. Experiments with a radioisotope-chelated IC2 structure on pancreas ex vivo showed that the tracer specifically bound to the beta-cell surface and could be detected by nuclear imaging. In the near future, these promising findings may offer a new way to monitor the beta-cell mass in vivo under disease and therapy conditions so that we can learn more about diabetes pathogenesis and options for disease prevention.
糖尿病是一种以β细胞丢失或耗竭以及胰岛素缺乏为特征的疾病。目前，对于其潜在病因以及β细胞团的治疗性恢复仍缺乏了解。通过精确监测疾病和治疗条件下β细胞的命运，有望更好地理解糖尿病的发病机制。这可能为胰岛替代和再生方案的干预新时代铺平道路。监测β细胞团需要一种可靠的非侵入性体内成像方法。由于缺乏β细胞特异性造影剂，目前尚无此类方法。目前唯一可用于体内监测胰岛细胞的方法是在移植前用铁纳米颗粒标记胰岛移植体，并通过磁共振成像（MRI）对移植的胰岛进行可视化。因此，对天然β细胞团的准确评估仍仅限于尸检研究。寻找β细胞特异性生物结构的努力导致发现了一些已用于非侵入性成像测试的潜在候选物。其中包括囊泡单胺转运体2型（VMAT-2）的配体二氢丁苯那嗪（DTBZ）、锌转运体（ZnT-8）抗体和单克隆抗体IC2。虽然DTBZ和ZnT-8抗体对多种细胞都有结合活性，但抗IC2单克隆抗体仅对产生胰岛素的β细胞有结合特性。这一效应在许多先前的研究中得到了证实，最近又得到了进一步证实。因此，目前IC2似乎是用于天然β细胞非侵入性功能成像的唯一有用标记物。对离体胰腺进行的放射性同位素螯合IC2结构实验表明，该示踪剂特异性结合到β细胞表面，可通过核成像检测到。在不久的将来，这些有前景的发现可能会提供一种新方法，用于在疾病和治疗条件下体内监测β细胞团，从而使我们能够更多地了解糖尿病发病机制和疾病预防方案。
