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Multimodal Imaging Probe Development for Pancreatic beta Cells: From Fluorescence to PET

Multimodal Imaging Probe Development for Pancreatic beta Cells: From Fluorescence to PET
Kang, Nam-YoungLee, Jung YeolLee, Sang HeeSong, In HoHwang, Yong HwaKim, Min JunPhue, Wut HmoneAgrawalla, Bikram KeshariWan, Si Yan DianaLalic, JanisePark, Sung-JinKim, Jong-JinKwon, Haw-YoungIm, So HeeBae, Myung AeAhn, Jin HeeLim, Chang SiangTeo, Adrian Kee KeongPark, SunyouKim, Sang EunLee, Byung ChulLee, Dong YunChang, Young-Tae
Date Issued
Pancreatic beta 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 beta 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 beta cell probe PiF for both fluorescence and for PET (positron emission tomography). By simple tail vein injection, PiF stains pancreatic beta 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.
Cells; Cytology; Glucose; Insulin; Positron emission tomography; Probes; Direct determination; Fluorescent imaging; Glucose regulation; Insulin concentrations; Insulin secretion; Multi-modal imaging; Pancreatic beta cells; Tail vein injections; Fluorescence imaging; fluorescent dye; fluorine 18; insulin; pancreatic islet fluorinated probe; unclassified drug; animal cell; animal experiment; animal model; animal tissue; Article; cell density; cell viability; controlled study; drug distribution; drug stability; drug synthesis; fat pad; fluorescence; fluorescence activated cell sorting; fluorescence imaging; gene expression; histology; human; human cell; image analysis; in vitro study; in vivo study; insulin dependent diabetes mellitus; kidney; live cell imaging; liver; mouse; nonhuman; pancreas; pancreas islet beta cell; positron emission tomography; rat; spleen; streptozotocin-induced diabetes mellitus
Article Type
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 142, no. 7, page. 3430 - 3439, 2020-02
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