120th General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Exhibition Hall 2+3
Time 10월 19일 (목요일) 11:00~12:30
Code MEDI.P-339
Subject Validation of Carbonic Anhydrase-IX as a Target of Anticancer Using PET Imaging of [18F]-Acetazolamide
Authors KUNAL MORE, JEONG HOON PARK1, Dong-Jo Chang*
Department of Pharmacy, Suncheon National University, Korea
1Korea Atomic Energy Research Institute, Korea
Abstract Hypoxia is salient feature of broad numbers of solid tumors with more aggressive behavior leading poor prognosis, resistance to cancer treatments, increased metastasis and altered metabolism. Carbonic anhydrases (CA) are key enzymes involved in hypoxia induced stress, and regulated by transcriptional factor HIF 1/2 (hypoxia-inducible factor). Among 15 isozymes of CA, Carbonic anhydrase-IX (CAIX) a cell surface anchored enzyme is most prominently overexpressed in hypoxic condition. Overexpressed CAIX involved in several cancers as breast, lung, kidney, ovarian, brain, colon, head and neck cancers. Small molecules with sulfonamide pharmacophore are well known as CAIX inhibitor to achieve reduction of primary growth of cancers and distant metastasis. The clinically approved acetazolamide CAIX inhibitor is also emerged as promising biomarker for clinical imaging of CAIX expressing hypoxic tumors. The known acetazolamide biomarkers used for CAIX imaging are performed well predominantly for renal cancer cell line SKRC-52. Thus, further target validation of CAIX for development of clinically used biomarker is required to be performed. In this study, [18F] radioisotope was introduced to acetazolamide by CuAAC click to synthesize [18F]-Acetazolamide and imaging study was performed by PET in xenograft mouse model bearing 4T1 and HT-29 cell lines as well as metastatic tumor models.
E-mail djchang@sunchon.ac.kr