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

Fostered by the clinical success of sst-ligands, the development and evaluation of Ga-68-labeled peptides have become a very active field in radiopharmaceutical chemistry. Consequently, various new peptide tracers have been developed, e.g. [Ga-68]CPCR4.2 for in vivo imaging of solid and haematological tumors or [Ga-68] TRAP(RGD)(3) for imaging of alpha(v)beta(3) integrin expression. As a consequence of different matrices (TiO2, SnO2, polymers) exploited in commercial Ge-68/Ga-68-generators, HCl of different concentrations (0.05...1.0 M) is used to obtain Ga-68 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 Ga-68 on a Varian SCX cation exchange cartridge and subsequent elution of Ga-68 with acidified NaCI solutions. As part of the development of ready-to-use cassettes for the automated production of Ga-68-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 Ga-68-trapping efficiency of various commercial available cation exchange cartridges, the efficiency of subsequent (68)Gaelution from these cartridges by means of various protocols and the influence of these variations on the labeling efficiency of [Ga-68]CPCR4.2, [Ga-68]TRAP(RGD)(3) and [Ga-68]DOTATATE/[Ga-68]DOTANOC. Finally, we transferred the optimized method to the automated, cassette based synthesis of [Ga-68]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 NaCI or 2.5 M CaCl2 can be used for efficient cartridge elution. Using a disposable cGMP-compliant cassette system, we obtained [Ga-68] CPCR4.2 in 80% decay-corrected yield and >99% purity. These data were confirmed by the production of [Ga-68] DOTATATE, [Ga-68]DOTANOC and [Ga-68]TRAP(RGD)(3) on the otherwise identical cassette system. (C) 2014 Elsevier Inc. All rights reserved.