Multimodal Imaging Probe Development for Pancreatic β Cells: From Fluorescence to PET
Nam-Young Kang, Jung Yeol Lee, Sang‐Hee Lee, In Ho Song, Yong Hwa Hwang, Min Jun Kim, Wut Hmone Phue, Bikram Keshari Agrawalla, Si Yan Diana Wan, Janise Lalic, Sung Jin Park, Jong-Jin Kim, Haw‐Young Kwon, So Hee Im, Myung Ae Bae, Jin Hee Ahn, Chang Siang Lim, Adrian Kee Keong Teo, Sunyou Park, Sang Eun Kim, Byung Chul Lee, Dong Yun Lee, Young‐Tae Chang
Abstract
Pancreatic β cells are responsible for insulin secretion and are important for glucose regulation in a healthy body and diabetic disease patient without prelabeling of islets. While the conventional biomarkers for diabetes have been glucose and insulin concentrations in the blood, the direct determination of the pancreatic β cell mass would provide critical information for the disease status and progression. By combining fluorination and diversity-oriented fluorescence library strategy, we have developed a multimodal pancreatic β cell probe PiF for both fluorescence and for PET (positron emission tomography). By simple tail vein injection, PiF stains pancreatic β cells specifically and allows intraoperative fluorescent imaging of pancreatic islets. PiF-injected pancreatic tissue even facilitated an antibody-free islet analysis within 2 h, dramatically accelerating the day-long histological procedure without any fixing and dehydration step. Not only islets in the pancreas but also the low background of PiF in the liver allowed us to monitor the intraportal transplanted islets, which is the first in vivo visualization of transplanted human islets without a prelabeling of the islets. Finally, we could replace the built-in fluorine atom in PiF with radioactive 18F and successfully demonstrate in situ PET imaging for pancreatic islets.