Abstract

Background: Radiopharmaceuticals labeled with [⁶⁸Ga] from positron emission tomography (PET) radionuclides are utilized in nuclear medicine for non-invasive in vivo molecular imaging. Buffer solutions for radiolabeling play an important role as choosing the right buffer for the reaction helps to obtain high yield radiopharmaceuticals. Zwitterionic organic buffer 4-(2- hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), sodium acetate (CH₃COONa), sodium bicarbonate (NaHCO₃) buffers are widely used for labeling of peptides with [⁶⁸Ga]Cl₃. They can be used for peptide labelings with the acidic [⁶⁸Ga]Cl₃ precursor of triethanolammonium (TEA) buffer. The cost and toxicity of TAE buffer are relatively low.

Method: For [⁶⁸Ga]GaPSMA-HBED-CC and [⁶⁸Ga]GaDOTA-TATE labeling, the effectiveness of TEA buffer without chemical impurities in radiolabeling reactions and QC parameters in successful labeling was investigated.

Results: The method used to label [⁶⁸Ga]Cl₃ with PSMA-HBED-CC peptide in the presence of TEA buffer was successful when applied at room temperature. High purity radiosynthesis suitable for clinical use was performed to obtain DOTA-TATE peptide with the addition of 363K temperature and radical scavenger. Quality control tests with R-HPLC have shown that this method is suitable for clinical use.

Conclusion: We present an alternative procedure for labeling PSMA-HBED-CC and DOTATATE peptides with [⁶⁸GaCl₃] to obtain high radioactive doses of final radiopharmaceutical products used in nuclear medicine clinical applications. We have provided a quality-controlled final product that can be used in clinical diagnostic procedures. With the use of an alternative buffer, these methods could be adapted to semi-automatic or automated modules routinely used in nuclear medicine laboratories to label [⁶⁸Ga]-based radiopharmaceuticals.

Graphical Abstract