Acetazolamide-based [F-18]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors

作者：More Kunal N; Lee Jun Young; Kim Dong Yeon; Cho Nam Chul; Pyo Ayoung; Yun Misun; Kim Hyeon Sik; Kim Hangun; Ko Kwangseok; Park Jeong Hoon^*; Chang Dong Jo^*

来源：Bioorganic & Medicinal Chemistry Letters, 2018, 28(5): 915-921.

DOI：10.1016/j.bmcl.2018.01.060

• Carbonic anhydrase IX
• Acetazolamide
• Hypoxic tumor
• PET imaging
• Target validation

Carbonic anhydrase IX is overexpressed in many solid tumors including hypoxic tumors and is a potential target for cancer therapy and diagnosis. Reported imaging agents targeting CA-IX are successful mostly in clear cell renal carcinoma as SKRC-52 and no candidate was approved yet in clinical trials for imaging of CA-IX. To validate CA-IX as a valid target for imaging of hypoxic tumor, we designed and synthesized novel [F-18]-PET tracer (1) based on acetazolamide which is one of the well-known CA-IX inhibitors and performed imaging study in CA-IX expressing hypoxic tumor model as 4T1 and HT-29 in vivo models kother than SKRC-52. [F-18]-acetazolamide (1) was found to be insufficient for the specific accumulation in CA-IX expressing tumor. This study might be useful to understand in vivo behavior of acetazolamide PET tracer and can contribute to the development of successful PET imaging agents targeting CA-IX in future. Additional study is needed to understand the mechanism of poor targeting of CA-IX, as if CA-IX is not reliable as a sole target for imaging of CA-IX expressing hypoxic solid tumors.

• 出版日期2018-3-1