Förster resonance energy transfer (FRET)-Labeled nanoprobe enables real-time diagnosis of pancreatic juice activation due to postoperative pancreatic fistula

Objectives: Postoperative pancreatic fistula (POPF) subsequent to pancreatectomy often causes activation of pancreatic juice, resulting in serious complications. In POPF, the types of pancreatic juices found are active and inactive, and the identification of these two types of pancreatic juice greatly contributes to the development of postoperative management after pancreatectomy. This study reports favorable results of the clinical application of the Förster resonance energy transfer (FRET) nanoprobe that was independently developed to distinguish between the active and inactive types of pancreatic juice. Methods: The FRET nanoprobe developed was a nanoprotein capsule. It exuded a red color when the capsule structure was maintained. When activated protease in the pancreatic juice acts on it, the capsules are reduced quantitatively and FRET is abolished, resulting in a change in color from red to green. Pancreatic juice activation can be measured by the FRET signal. A total of 117 drainage fluid samples from 16 postpancreatoduodenectomy cases were obtained and evaluated. Results: The diagnosis of pancreatic juice activation was possible using the FRET signal with a cut-off value of 1.6. Pancreatic juice activation was not associated with drainage fluid amylase (AMY) levels. The results demonstrated that pancreatic juice was activated when drainage fluid was infected. Conclusion: The use of a FRET nanoprobe enabled real-time detection of the presence or absence of pancreatic juice activation in pancreatic fistula after pancreatic surgery. There was an adequate correlation between infection and pancreatic juice activation regardless of drain AMY levels.