Ga Generator Research Articles

Processing of Generator-Produced 68Ga for Medical Application

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. 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. 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. 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.

Microwave-supported preparation of (68)Ga bioconjugates with high specific radioactivity.

The generator-produced positron-emitting (68)Ga (T(1/2) = 68 min) is of potential interest for clinical PET. (68)Ga as a metallic cation is suitable for complexation reactions with chelators, naked or conjugated, with peptides or other macromolecules. Large (68)Ga generator eluate volumes, metal traces from the generator column material, or reaction reagents, however, disturb a fast, reliable, and quantitative labeling procedure. In this paper we describe a simple technique, based on anion exchange, aiming first, to increase the (68)Ga concentration, second to purify it from competing impurities, and third to obtain a fast and quantitative (68)Ga-labeled peptide conjugate that can be applied in humans without further purification. Within 5 min one can obtain from the original 6 mL generator eluate a 200 microL (68)Ga preparation (volume reduction by a factor 30) that is suitable for direct and quantitative labeling of peptide conjugates. DOTATOC (DOTA-D-Phe(1)-Tyr(3)-octreotide, DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was used as a test tracer for comparing the labeling properties of the different (68)Ga preparations. In combination with microwave heating, peptide conjugates of 0.5-1 nmol quantities could be labeled within 10 min with the full (68)Ga activity of a generator. Further purification of the (68)Ga-labeled peptide conjugate was no longer required since the nuclide incorporation was quantitative. The specific radioactivity (with respect to the peptide) was improved by a factor approximately 100 compared to the previously applied techniques using the original generator eluate. The commercial (68)Ge/(68)Ga generator from Obninsk in combination with this system for purification and concentration with an integrated microwave-supported labeling technology resulted in a kitlike technology for (68)Ga-tracer production. The first automated prototype using this technology is being tested.

Effects of Annealing on the Interface Properties between Ni and p-GaN

The effects of annealing on the interface properties between p-GaN and Ni were investigated by ultra-violet photoemission spectroscopy. Photoemission spectra of p-GaN showed the existence of oxidized Ga, however, the oxidized Ga disappeared by Ni deposition. In addition, photoemission spectra of Ni/p-GaN after annealing showed the generation of metal-like Ga and the formation of Ni islands. These results indicate that the Ni deposition on GaN and subsequent annealing have an effect of making clean surface of GaN. Such cleaning effect and the island formation may play an important role in ohmic contact formation.

Effects of Annealing on the Interface Properties between Ni and p-GaN

The effects of annealing on the interface properties between p-GaN and Ni were investigated by ultra-violet photoemission spectroscopy. Photoemission spectra of p-GaN showed the existence of oxidized Ga, however, the oxidized Ga disappeared by Ni deposition. In addition, photoemission spectra of Ni/p-GaN after annealing showed the generation of metal-like Ga and the formation of Ni islands. These results indicate that the Ni deposition on GaN and subsequent annealing have an effect of making clean surface of GaN. Such cleaning effect and the island formation may play an important role in ohmic contact formation.

Improvedp/n junctions in Ge-doped GaAs grown by molecular beam epitaxy

p/n junctions in Ge-doped GaAs consisting ofp-type layers with extremely smooth surfaces and low compensationn-type layers were fabricated by molecular beam epitaxy (MBE). During growth the site occupancy of Ge was controlled by varying the substrate temperature fromTs 600°C (p-type layers) at aconstant As4 to Ga flux ratio of 2. This yields stable growth conditions for the generation of Ga and As vacancies, respectively.

Thermally converted surface layers in semi-insulating GaAs

Charge carrier transport in thermally converted surface layers in semi-insulating GaAs depends on the generation, diffusion, and occupancy of Ga and As vacancies. The amphoteric nature of C in GaAs can significantly alter the density and the distribution of donors and acceptors in the vicinity of the specimen surface and the surface layer may become either p type or n type depending on the thermal treatment conditions.