Cationic eluate pretreatment for automated synthesis of [68Ga]CPCR4.2

René Martin, Steffen Jüttler, Marco Müller, Hans-Jürgen Wester

09.10.2013 [Original Artikel]

Fostered by the clinical success of sst-ligands, the development and evaluation of 68Ga-labeled peptides have become a very active field in radiopharmaceutical chemistry. Consequently, various new peptide tracers have been developed, e.g. [68Ga]CPCR4.2 for in vivo imaging of solid and haematological tumors or [68Ga]TRAP(RGD)3 for imaging of αvβ3 integrin expression. As a consequence of different matrices (TiO2, SnO2, polymers) exploited in commercial 68Ge/68Ga-generators, HCl of different concentrations (0.05…1.0 M) is used to obtain 68Ga as starting material for automated syntheses. We have developed a purification method which reduces the eluate volume and adjusts the HCl concentration. The method may potentially allow standardization of the eluate composition of different commercial generators prior to labeling. Recently, a cationic purification process has been reported which allows the pre-fixation of 68Ga on a Varian SCX cation exchange cartridge and subsequent elution of 68Ga with acidified NaCl solutions. As part of the development of ready-to-use cassettes for the automated production of 68Ga-CPCR4.2 using a SCINTOMICS GRP module and an iThemba Labs generator that is eluted with 0.6…1.0 M HCl, we tested and compared the 68Ga-trapping efficiency of various commercial available cation exchange cartridges, the efficiency of subsequent 68Ga-elution from these cartridges by means of various protocols and the influence of these variations on the labeling efficiency of [68Ga]CPCR4.2, [68Ga]TRAP(RGD)3 and [68Ga]DOTATATE/[68Ga]DOTANOC. Finally, we transferred the optimized method to the automated, cassette based synthesis of [68Ga]CPCR4.2 and the aforementioned peptides. From seven tested cation exchange cartridges, Chromafix PS-H+ gave the best extraction results (> 95%). Moreover, we observed that acidified solutions of 5 M NaCl or 2.5 M CaCl2 can be used for efficient cartridge elution. Using a disposable cGMP-compliant cassette system, we obtained [68Ga]CPCR4.2 in 80% decay-corrected yield and > 99% purity. These data were confirmed by the production of [68Ga]DOTATATE, [68Ga]DOTANOC and [68Ga]TRAP(RGD)3 on the otherwise identical cassette system.