de Oliveira Cristiane, Patel Krutika, Mishra Vivek, Trivedi Ram N, Noel Pawan, Singh Abhilasha, Yaron Jordan R, Singh Vijay P
Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2016 Feb 22;11(2):e0149073. doi: 10.1371/journal.pone.0149073. eCollection 2016.
Studying the uptake of 2-deoxy glucose (2-DG) analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG) is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP) is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor) during mild and severe biliary AP.
Wistar rats (300 g; 8-12/group) were administered NIR 2-DG (10 nM; I.V.). Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL) alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g) within 10 minutes of giving NIR 2-DG. Controls (CON) only received NIR 2-DG. Imaging was done every 5-10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer) using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP.
NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP concentrations and mortality, which were not predicted by the blood parameters.
In-vivo fluorescent imaging of a non-radioactive near infrared 2-DG optical probe can predict the AP severity early during the disease.
研究2-脱氧葡萄糖（2-DG）类似物如2-脱氧-2-[18F]氟葡萄糖（FDG）的摄取是识别和监测恶性肿瘤以及最近慢性炎症的常用方法。虽然胰腺炎是人类使用FDG进行胰腺癌研究时假阳性结果的常见原因，但这些发现与急性胰腺炎（AP）的相关性尚不清楚。FDG半衰期短。因此，为了实时准确地描述AP期间胰腺的代谢需求，我们研究了非放射性近红外荧光标记的2-脱氧葡萄糖类似物IRDye® 800CW 2-DG探针（NIR 2-DG；Li-Cor）在轻度和重度胆源性AP中的摄取情况。
给Wistar大鼠（300 g；每组8 - 12只）静脉注射NIR 2-DG（10 nM）。轻度和重度胆源性AP分别通过单独的胆胰管结扎（DL）或在给予NIR 2-DG后10分钟内同时注入甘油三亚油酸酯（GTL；50 μL/100 g）诱导。对照组（CON）仅接受NIR 2-DG。在3小时内每5 - 10分钟进行一次成像。使用IVIS 200体内成像系统（PerkinElmer）和Living Image®软件在胰腺上测量平均辐射效率[p/s/cm²/sr]/[μW/cm²]，并在离体胰腺中进行验证。在AP过程中测量血淀粉酶、脂肪酶以及胰腺水肿、坏死情况。
在最初的一小时内，NIR 2-DG的摄取不受AP诱导的影响。然而，虽然对照组和轻度AP大鼠的信号下降，但在GTL诱导的胰腺炎大鼠中，1小时后胰腺中NIR 2-DG的保留量显著更高。GTL组比对照组增加了3倍以上，并且在离体胰腺中得到验证。在体外，暴露于GTL的胰腺腺泡NIR 2-DG摄取也有类似增加，随后腺泡坏死逐渐加重。体内NIR 2-DG保留量增加与胰腺坏死加重、ATP浓度降低和死亡率相关，而这些情况无法通过血液参数预测。
非放射性近红外2-DG光学探针的体内荧光成像可以在疾病早期预测AP的严重程度。
