Efficient post-processing of aqueous generator eluates facilitates Ga-68-labelling under anhydrous conditions

摘要

The present study reports a convenient method for Ga-68-labelling under anhydrous conditions using solid-phase derived gallium-68-acetylacetonate ([Ga-68[Ga(acac)(3)) in a microwave-enhanced radiosynthesis. Commercial Ge-68/Ga-68-radionuclide generators utilizing TiO2 to adsorb Ge-68(IV) (Obninsk-generators) were used. The initial aqueous generator eluate was transferred online onto a cation exchange resin and Ga-68 was absorbed quantitatively. From this resin, Ga-68 was eluted with different acetone-based, non-aqueous solvent systems. More than 95% of the generator-eluted Ga-68 was obtained from the cation exchange resin with 600 pi of a 98% acetone/2% acetylacetone mixture providing n.c.a. [Ga-68]Ga(acac)(3) as labelling agent. Water-insoluble macrocyclic polypyrrole derivatives were chosen as model compounds for a proof-of-principle labelling of lipophilic compounds with Ga-68. Labelling of two different porphyrin derivatives, meso-tetraphenyl-porphyrin (Tpp) and (3-(1-hydroxyheptyl)deuteroporphyrin dimethylester (HHDPD) was performed in chloroform in a focused microwave synthesis system in yields of up to 90% within 5 min using phenol as co-ligand. Moreover, new co-ligands were investigated to be more effective and significantly less toxic than phenol. Among the phenol alternatives, gentisic acid (2,5-dihydroxy benzoic acid, DHB, 5 mg) emerged as the most useful, non-toxic phenol substitute. It facilitates reducing the load of co-ligand by 95%, while providing an increased labeling yield of 97%. Ga-68-labelled porphyrins may facilitate the medical application for molecular imaging via positron emission tomography.