To investigate the effects of different labeling conditions on the yield of Al¹⁸F-labeled 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA)-prostate specific membrane antigen (PSMA)-137, and to determine the experimental condition for obtaining Al¹⁸F-PSMA-137 probe in high yield.

The effects of different pH values, buffer systems (acetic acid-sodium acetate buffer system and potassium hydrogen phthalate (KHP) buffer system), AlCl₃-ligand ratios, ligand amounts, ethanol volumes and reaction temperatures on the labeling rate were investigated in detail.

The pH value of the reaction solution had a significant effect on the labeling rate, and the optimal range was 4.0-4.5. When the pH value was higher than 4.5, the labeling rate decreased significantly. Both the acetic acid-sodium acetate buffer system and the KHP buffer system could be used to label NOTA-PSMA-137 with Al¹⁸F, and the KHP buffer system obtained higher labeling rate. The ratio of AlCl₃-ligand affected the labeling rate, and the highest labeling rate could be obtained when the ratio of AlCl₃-ligand was 0.54-0.62. When the ratio of AlCl₃-ligand was fixed, increasing the amount of ligand could improve the labeling yield. Adding hydrophilic organic solvent ethanol to the reaction system could significantly increase yield, with the highest labeling rate being achieved at a volume of 100 μl ethanol. The most suitable reaction temperature was 100 ℃, and when the temperature raised to 110 ℃, the labeling rate decreased significantly. The most suitable labeling conditions for NOTA-PSMA-137 were as following: 25 μl KHP buffer (0.50 mol/L, pH=4.0), 7.0 μl AlCl₃ solution (20 mmol/L), 200 μl Na¹⁸F solution (74-80 MBq) and 230 μg ligand NOTA-PSMA-137 were mixed in a vial, then stood for 5 min and 100 μl ethanol was added, and all reagents were heated at 100 ℃ for 10 min. The yield of Al¹⁸F-PSMA-137 under above conditions were 85.7%-88.5%.

Optimization of labeling condition can improve the yield of Al¹⁸F-PSMA-137 and the stability of the labeling.

Prostatic neoplasms; Prostate-specific membrane antigen; Positron-emission tomography; Amino acids, diamino; Isotope labeling; Fluorine radioisotopes