Synthesis and Preliminary Evaluation of Peptide Compounds Targeting CA IX

Abstract

In order to synthesize a peptide-based carbonic anhydrase IX (CA IX) imaging probe 68Ga-DOTA-CA IX-P1-4-10, the labeling and quality control methods were developed. The effects of reaction pH and concentration of the peptide DOTA-CA IX-P1-4-10 on the labeling yield were studied. The reaction conditions were confirmed as: pH value 4.0 to 5.0 (n=6), peptide DOTA-CA IX-P1-4-10 concentration 15.0 to 40.0 mg/L (n=6), reaction temperature 100 ℃, and reaction time 10 min. The product was clear, colorless liquid, with no visible particles. The pH of the product was 5 to 7 (n=6), the radiochemical purity of 68Ga-DOTA-CA IX-P1-4-10 was >99.0% (n=6), and the specific activity of 68Ga-DOTA-CA IX-P1-4-10 was 1.0-5.0 GBq/μmol (end of synthesis) (n=6). The lipid-water partition coefficient of the probe was -2.07±0.01 (n=6) which indicated 68Ga-DOTA-CA IX-P1-4-10 was favorable hydrophilicity. 68Ga-DOTA-CA IX-P1-4-10 showed good in vitro stability in saline and fetal bovine serum at 37 ℃, and the radiochemical purity was >95.0% after 4 hours. White mice did not have abnormal behaviors in undue toxicity experiments. Preliminary results of the study showed that the probe 68Ga-DOTA-CA IX-P1-4-10 is worthy of further study with a simple labeling method, high radiochemical purity, good in vitro stability and favorable biosecurity.

Keywords

• 68ga-labeling
• peptide