An automated synthesis method for 68Ga-labelled ubiquicidin 29–41

Abstract

Published methods for radiolabelling of 1,4,7-triazacyclononane-1,4,7-triacetic acid ubiquicidin (NOTA-UBI) 29-41 to date describe manual or kit-based procedures. The purpose of this study was to develop an automated synthesis method for the synthesis of [ 68 Ga]Ga-NOTA-UBI. NOTA-UBI was successfully labelled with gallium-68 using the three different automated procedures. The use of radical scavengers to improve radiochemical purity is also discussed. The automated procedures showed a high degree of robustness and repeatability. The validated automated synthesis protocols using a Scintomics GRP Module will contribute to provide GMP-compliant [ 68 Ga]Ga-NOTA-UBI for clinical infection imaging.

Production of [68Ga]Ga‐PSMA: Comparing a manual kit‐based method with a module‐based automated synthesis approach

“…The entire method is preprogramed on the system as a standard peptide labeling method with gallium‐68 (ABX advanced biochemical compounds GmbH [Radeberg, Germany]). The system eluted the 68 Ge/ 68 Ga generator with 10‐ml 0.6M HCl and purified it with a PS‐H + ‐matrix‐based cation exchange chromatography as described previously 15,16 . Purified [ 68 Ga]GaCl 3 was recovered from the cartridge using a 5.0M sodium chloride solution and added to the reaction vial containing 10 μg of PSMA‐11 dissolved in HEPES buffer.…”

“…The automated synthesis unit is programmed to rinse the SEP‐Pak C‐18 cartridge with 2 ml of 50% v/v water and ethanol, and the final volume of the reaction mixture is 17 ml. A calculation was done to ensure that a safe amount of ethanol is in the final product because the acceptable threshold of ethanol (10% v /v) can never be exceeded 15 …”

“…Ethical approval (application number X19/08/031) was waived by Stellenbosch University (South Africa Ga generator with 10-ml 0.6M HCl and purified it with a PS-H + -matrix-based cation exchange chromatography as described previously. 15,16 Purified [ 68 Ga]GaCl 3 was recovered from the cartridge using a 5.0M sodium chloride solution and added to the reaction vial containing 10 μg of PSMA-11 dissolved in HEPES buffer. The average starting activity of gallium-68 used was 1314 ± 230 MBq.…”

“…A calculation was done to ensure that a safe amount of ethanol is in the final product because the acceptable threshold of ethanol (10% v/v) can never be exceeded. 15 Radiochemical and chemical characteristics were determined by HPLC and ITLC. ITLC utilized a glass microfiber stationary phase impregnated with silica gel.…”

“…A portable testing system (Endosafe PTS, Charles Rivers, Wilmington, MA, USA) was used for rapid endotoxin testing as described previously. 15 Sterility testing was performed on the retention samples by the National Health Laboratory Services (Cape Town, South Africa) and NTP Radioisotopes SOC (Pelindaba, South Africa), respectively. Aerobic, anaerobic, and fungal growth were tested according to standard methods described previously.…”