title: Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  In-vivo fluorescent imaging of a non-radioactive near infrared 2-DG optical probe can predict the AP severity early during the disease.
authors.affiliation: Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Krutika
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mishra
authors.affiliation: Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Ram N
authors.initials: RN
authors.lastname: Trivedi
authors.affiliation: Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Pawan
authors.initials: P
authors.lastname: Noel
authors.affiliation: Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Yaron
authors.affiliation: Department of Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Singh
mesh_terms: D000208:Acute Disease; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D061848:Optical Imaging / Q000379:methods*; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology*; D051381:Rats
chemical_list: C427728:IRDye800; D007211:Indoles; D003847:Deoxyglucose