The status and potential of new radionuclide generators providing positron emitters to synthesize new targeting vectors for PET

The 68Ge/Ga generator (68Ge, T1/2 = 270.8 d) provides a cyclotron independent source of positron emitting 68Ga (TT1/2 = 68 min, ββ+ branching = 89%), which can be used for coordinative labelling. Recently, tumour imaging using 68Ga labelled DOTA conjugated peptides became one of the most exciting approaches to diagnose neuroendocrine and other tumours and metastases because (i) octreotide derivatives with high affinity and selectivity to somatostatin receptor expressing tumour cells are available, (ii) syntheses of DOTA conjugated targeting vectors are straightforward due to the kit type labelling, and (iii) PET/CT scanners perfectly correlate morphological and functional parameters. However, for labelling of biomolecules via bifunctional chelators, 68Ga(III) as eluted initially needs to be preconcentrated and purified from 68Ge(IV), Zn(II), Ti(IV) and Fe(III). The paper describes a system for the simple and efficient handling of the 68Ge/68Ga generator eluates with a microchromatography column filled with about 50 mg of a cation exchange resin. Chemical purification and volume concentration of 68Ga are carried out in an 80% acetone/0.15M HCl solution. Finally, more than 97% of 68Ga is obtained in 400 μL of a 98% acetone/0.05M HCl solution. The initial 68Ge contamination of the eluate was reduced by a factor of 1000. Contents of Zn(II), Fe(III) and Ti(IV) were reduced significantly. Consequently, the processed fraction can be used directly for the synthesis of radiopharmaceuticals. The developed system represents a simple and efficient way of labelling DOTA conjugated biomolecules with generator produced 68Ga(III). [68Ga]DOTATOC and [68Ga]DOTANOC were successfully used in a series of human somatostatin receptor expressing tumour diagnoses with PET/CT. (author)