Gallium-68 Separation
68Ga labeled tracers are increasingly used in PET imaging-based diagnosis especially due to the fact that a number of cold kits are now available and that it might very favorably be paired with radionuclides used in therapy such as 177Lu and 225Ac [1]. It is also very conveniently available through 68Ga/68Ge generators. Limitations on the 68Ge supply and the cost of 68Ga/68Ge generators have led to an increased interest in the direct production of 68Ga using cyclotrons, especially using liquid 68Zn targets [1]. ZR Resin may be used, in combination with TK200 Resin for the separation of 68Ga from liquid targets, as well as from solid targets (Figures 13, 14). Riga et al. [2] have shown that the combination of ZR Resin and TK200 allows for obtaining 68Ga with an average chemical yield of 80 ± 2% and high radionuclidic purity (99.976 ± 0.002) % after separation. Delivery and separation of the 68Ga wire finished 40 min after EOB.
68Ga eluted from the 68Ga/68Ge generator typically requires additional purification prior to chelation to biolocalization agents[3]. Typically, the generator is eluted with dilute HCl and passed directly through a small cartridge of strong acid cation exchange silica (SCX). The 68Ga is retained on the SCX, while traces 68Ge and some other metal ion impurities are removed. The 68Ga is then recovered using HCl + NaCl, buffered and then chelated to a biolocalization agent. The 68Ga-chelated compound is then further purified by passing through a cartridge of weak acid cation exchange silica (WCX or CM) to remove any unbound 68Ga.
References
[1] INTERNATIONAL ATOMIC ENERGY AGENCY, Gallium-68 Cyclotron Production, IAEA-TECDOC-1863, IAEA, Vienna (2019).
[2] Riga, G. Cicoria, D. Pancaldi, F. Zagni, S. Vichi, M. Dassenno, L. Mora, F. Lodi, M. P. Morigi, M. Marengo. Production of Ga-68 with a General Electric PETtrace cyclotron by liquid target. Physica Medica, 55, 2018, 116-126
[3] Tworowska, I., Ranganathan, D., THamake, S., Delpassand, E., Mojtahedi, A., Schultz, M., Zhernosekov, K., Marx, S., (2016). Radiosynthesis of clinical doses of 68Ga-DOTATATE (GalioMedixTM) and validation of organic-matrix-based 68Ge/68Ge generators, Nuclear Medicine and Biology, 43, 19-26.