Providing isotopes that can pinpoint disease in the body

President Eisenhower’s “atoms for Peace” initiative started the movement to explore peaceful uses of radioactive atoms, and today one use of radioactivity is to diagnose and treat diseases. Radioactive atoms are unstable atoms that decay by characteristic half-lives, and their decay involves the release of energy in the form of a gamma, X-ray, or a particle such as a positron (a positive electron), beta (electron) or alpha particle (Helium atom). Germanium-68 (68Ge) has a half-life of 271 days, and decays to Gallium-68 (68Ga) with a half-life of 68 minutes. The isotope pair is used to make a medical isotope generator that separates 68Ga from 68Ge, and the pure 68Ga can be used in radiopharmaceuticals. These molecules can be used to identify disease in the body and evaluate the effectiveness of a treatment (Atlas of Science, December 2, 2015). A second use of 68Ge /68Ga is in the calibration of Positron Emission Tomography cameras which are used to image positron emitting isotopes on the radiopharmaceuticals. The production and use of 68Ge is summarized in Figure 1.

Fig. 1. Production and use of Germanium-68. PET = Positron Imaging Tomography.

Brookhaven and Los Alamos National Laboratories use a linear accelerator to accelerate protons to energies >100MeV. The proton beam passes through a target stack containing: rubidium chloride targets for production of Strontium-82 at proton energies from 42-90 MeV then a gallium target for production of 68Ge at proton energies less than 40 MeV. The gallium target contains approximately 65 grams of natural gallium of which only a small amount of the gallium is converted to microgram quantities of 68Ge. Natural gallium has two stable isotopes; gallium-69 and gallium-71, with natural abundances of 60.1% and 39.9%. Both gallium isotopes have a high “cross section” to capture the proton and be converted to 68Ge. The cross section is a measure of the probability of such an encounter.. The nuclear reaction to produce 68Ge is represented as 69Ga(p,2n)68Ge. The nucleus of the 69Ga atom is excited by absorbed kinetic energy from the incident proton and deexcites with the release of two neutrons to produce 68Ge. The cross section of the reaction peaks around a proton energy of 22 MeV. During the irradiation of natural gallium, Zinc-65 (65Zn) is coproduced in a ratio of ~4 to 1 of 68Ge to 65Zn.

The purification of 68Ge involves a three step process: leaching to remove 68Ge  from the bulk of the natural gallium, an anion ion exchange resin to capture 65Zn and a Sephadex©G25 resin to purify 68Ge from residual natural gallium. During the leaching process hydrogen peroxide and 4 M hydrochloric acid are repeatedly used to recover 68Ge and 65Zn from the liquefied gallium. During this process we have found >95% of 68Ge is removed from the gallium metal and from 0.5-3.5grams of natural gallium is present in the pooled leached solutions. To capture 65Zn the solution is diluted to approximately 1.5 M hydrochloric acid, and the solution is passed through an anion exchange resin. The 65Zn forms a negatively charged zinc complex which is retained by the anion exchange resin, and Gallium and 68Ge species are not retained. The 65Zn is eluted with water or nitric acid, the solution dried, re-dissolved in 0.1 M HCl and distributed to researchers. Citric acid is added to the 68Ge solution to prevent the formation of insoluble gallium species [Ga(OH)3], and the pH is raised to ~12.5 with sodium hydroxide. The solution is added to Sephadex©G25 resin; the 68Ge is retained, and gallium is eluted. Pure 68Ge is eluted from the resin with 0.1 M HCl and can be used in various nuclear medicine imaging applications.

Jonathan Fitzsimmons

 

Publication

Production scale separation of Ge-68 and Zn-65 from irradiated gallium metal.
Fitzsimmons JM, Mausner L.
Applied Radiation and Isotopes. 2015

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