Processing of generator-produced 68Ga for medical application.

UNLABELLED: The (68)Ge/(68)Ga generator provides an excellent source of positron-emitting (68)Ga. However, newly available "ionic" (68)Ge/(68)Ga radionuclide generators are not necessarily optimized for the synthesis of (68)Ga-labeled radiopharmaceuticals. The eluates have rather large volumes, a high concentration of H(+) (pH of 1), a breakthrough of (68)Ge, increasing with time or frequency of use, and impurities such as stable Zn(II) generated by the decay of (68)Ga, Ti(IV) as a constituent of the column material, and Fe(III) as a general impurity.
METHODS: We have developed an efficient route for the processing of generator-derived (68)Ga eluates, including the labeling and purification of biomolecules. Preconcentration and purification of the initial generator eluate are performed using a miniaturized column with organic cation-exchanger resin and hydrochloric acid/acetone eluent. The purified fraction was used for the labeling of nanomolar amounts of octreotide derivatives either in pure aqueous solution or in buffers.
RESULTS: Using the generator post-eluate processing system, >97% of the initially eluated (68)Ga activity was obtained within 4 min as a 0.4-mL volume of a hydrochloric acid/acetone fraction. The initial amount of (68)Ge(IV) was decreased by a factor of 10(4), whereas initial amounts of Zn(II), Ti(IV), and Fe(III) were reduced by factors of 10(5), 10(2), and 10, respectively. The processed (68)Ga fraction was directly transferred to solutions containing labeling precursors-for example, DOTA-dPhe(1)-Tyr(3)-octreotide (DOTATOC) (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid). Labeling yields of >95% were achieved within 10 min. Overall yields reached 70% at 20 min after generator elution relative to the eluted (68)Ga activity, not corrected for decay. Specific activities of (68)Ga-DOTATOC were 50 MBq/nmol using a standard protocol, reaching 450 MBq/nmol under optimized conditions.
CONCLUSION: Processing on a cation-exchanger in hydrochloric acid/acetone media represents an efficient strategy for the concentration and purification of generator-derived (68)Ga(III) eluates. The developed scheme guarantees high yields and safe preparation of injectable (68)Ga-labeled radiopharmaceuticals for routine application and is easy to automate. Thus, it is being successfully used in clinical environments and might contribute to a new direction for clinical PET, which could benefit significantly from the easy and safe availability of the radionuclide generator-derived metallic positron-emitter (68)Ga.