title: Cationic eluate pretreatment for automated synthesis of [⁶⁸Ga]CPCR4.2.
abstract: Fostered by the clinical success of sst-ligands, the development and evaluation of (68)Ga-labeled peptides have become a very active field in radiopharmaceutical chemistry. Consequently, various new peptide tracers have been developed, e.g. [(68)Ga]CPCR4.2 for in vivo imaging of solid and haematological tumors or [(68)Ga]TRAP(RGD)₃ for imaging of α(v)β₃ integrin expression. As a consequence of different matrices (TiO₂, SnO₂, polymers) exploited in commercial (68)Ge/(68)Ga-generators, HCl of different concentrations (0.05...1.0 M) is used to obtain (68)Ga 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 (68)Ga on a Varian SCX cation exchange cartridge and subsequent elution of (68)Ga with acidified NaCl solutions. As part of the development of ready-to-use cassettes for the automated production of (68)Ga-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 (68)Ga-trapping efficiency of various commercial available cation exchange cartridges, the efficiency of subsequent (68)Ga-elution from these cartridges by means of various protocols and the influence of these variations on the labeling efficiency of [(68)Ga]CPCR4.2, [(68)Ga]TRAP(RGD)₃ and [(68)Ga]DOTATATE/[(68)Ga]DOTANOC. Finally, we transferred the optimized method to the automated, cassette based synthesis of [(68)Ga]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 [(68)Ga]CPCR4.2 in 80% decay-corrected yield and >99% purity. These data were confirmed by the production of [(68)Ga]DOTATATE, [(68)Ga]DOTANOC and [(68)Ga]TRAP(RGD)3 on the otherwise identical cassette system.
authors.affiliation: ABX advanced biochemical compounds, Heinrich-Glaeser-Str. 10-14, 01454 Radeberg, Germany. Electronic address: rene.martin@abx.de.
authors.forename: René
authors.initials: R
authors.lastname: Martin
authors.forename: Steffen
authors.initials: S
authors.lastname: Jüttler
authors.forename: Marco
authors.initials: M
authors.lastname: Müller
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
mesh_terms: D001331:Automation; D060326:Chemistry Techniques, Synthetic; D002851:Chromatography, High Pressure Liquid; D005710:Gallium Radioisotopes; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005710:Gallium Radioisotopes; D010455:Peptides
keywords: Automated production; Cationic purification; Gallium; Generator; Peptides