1. Acetazolamide-based [ 18 F]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors.
- Author
-
More KN, Lee JY, Kim DY, Cho NC, Pyo A, Yun M, Kim HS, Kim H, Ko K, Park JH, and Chang DJ
- Subjects
- Acetazolamide chemical synthesis, Acetazolamide pharmacokinetics, Animals, Carbonic Anhydrase IX biosynthesis, Carbonic Anhydrase IX metabolism, Carbonic Anhydrase Inhibitors chemical synthesis, Carbonic Anhydrase Inhibitors pharmacokinetics, Carcinoma, Renal Cell diagnosis, Fluorine Radioisotopes, Humans, Kidney Neoplasms diagnosis, Mice, Mice, Inbred BALB C, Neoplasms, Experimental diagnosis, Neoplasms, Experimental enzymology, Tissue Distribution, Acetazolamide chemistry, Carbonic Anhydrase IX analysis, Carbonic Anhydrase Inhibitors chemistry, Carcinoma, Renal Cell enzymology, Kidney Neoplasms enzymology, Positron-Emission Tomography
- Abstract
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 [
18 F]-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 other than SKRC-52. [18 F]-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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF