7.2. Ga(71)[v,l~-]Ge(71): A Radiochemical Detector
for the Solar Neutrino
7.1. Ge(68)--*Ga(68) Generator in Biomedical Research
Positron emission tomography (PET), which noninvasively provides information regarding blood flow and metabolism in patients, is a common procedure in clinical nuclear medicine. The detection of the two positron-annihilation photons (511 keV) in coincidence results in a significant reduction in background radiation, thus providing sharp tomographic images. The use of very short half-life positron emitters for PET studies provides sufficient levels of radioactivity to permit adequate statistical sampling in the reconstruction of the cross-sectional images while minimizing the radiation dose to the patient.
The availability of short-lived radionuclides from radionuclide generators provides an inexpensive and convenient alternative to in-house radioisotope production facilities such as cyclotrons. Gallium-68, which has all of the physical characteristics desirable for PET, is produced from the decay of 270-d 68Ge (100%
EC).
In the form of a radioisotope generator, 68Ga is separated from its long-lived parent and used as needed.Gallium-68 decays with a 68 min half-life to'stable Zn with 100% I~ + emission. A simplified decay scheme of the 68Ge---,68Ga system is shown in Fig. 7.1. Production'of 68Ge was discussed in some detail in Sect. 3.
Over the past three decades, a number of 68Ge--*68Ga generators have been developed in an attempt to provide high yield of 68Ga and low breakthrough of 68Ge.
The efforts in this field have been reviewed by Lambrecht. 243'244 Due to the simplicity of the operation, chromatographic-based generators have been the method of choice,
S. MIRZADEH, R. M. LAMBRECFIT: RADIOCHEMISTRY OF GERMANIUM
(2+)
(2+)
(2+) (o*)
(2+)
(2+)
0+ 0.O
270.8 d
Eo.,~.O~c.11, /
1+ 9,~ ~( 68.1 rain
.~ . / - ~,Ge=
~_ . ~ 0.0094%
/I-<+" 0.8,1,
I ~ i
,+,~ o . @ ~ / o.~,,%
II .~%~Y"" /
ll" -'
o o o,~1 l l i ~ 1077.36 g
0.0 / ~+ 88.0%, EC 8.94%, Eft+ mex= 1899
Figure 7.1 Decay scheme of S8Ge and 68Ga
although generators based on solvent extraction and volatilization have also been proposed. Both inorganic absorbers and synthetic resins have been evaluated as the chromatographic supports, with inorganic supports having the
advantage
of being rather resistant to radiation damage.The inorganic absorbers primarily include the hydrated metal oxides (e.g., AI203, SnO 2, Fe203). As discussed in Sect. 6.4, most metal oxides show a tendency to absorb Ge as well as Ga. In dilute acidic solutions or in the presence of a chelating ligand, however, the adsorption of Ga decreases much faster than that of Ge. Hence, under a narrow range of acidity and ligand concentration, Ga can be separated from Ge. Under optimum conditions, it is hoped that Ge is retained on the support irreversibly to the extent that less than 10"2% of Ge is co-eluted with Ga. Another important parameter that needs to be considered here is the solubility of metal oxide supports in aqueous
S, MIRZADEH, R. M. LAMBRECHT: RADIOCHEMISTRY OF GERMANIUM
solutions. In general, the solubility of metal oxides increases with the alkalinity of the solutions. Methods of oxide preparation also have significant effects on their solubilities.
A few extraction-based 68Ge--~68Ga generators have been proposed. In one of the first generators, Ga (not carrier-free) was extracted into acetylacetone (dissolved in cyclohexane) from a buffered solution.containing Ge. The Ga was then back-extracted into 0.1 M HCI. 245 In another procedure, 68Ge was extracted from HCI solution into CCi 4, whereas Ga remained almost entirely in HCI solution 246 (see Sect. 6.3). Erhardth et al. reported an extraction generator where 68Ga was complexed w i t h 8- hydroxyquinoline (oxine). 247
The only reported volatilization-based generator takes advantage of the substantial vapor pressure of the chlorogermanium compounds from strong aqueous HCI. 248 An azeotropic solution of HCI (6 M) containing 68Ga' and 68Ge in secular equilibrium was evaporated to dryness under a heat lamp, in a stream of N 2. During this step 68Ga was retained quantitatively by an evaporation dish; the fraction of 68Ge retained with Ga was <5x10 -4. Subsequently, the 68Ga was removed from the surface of the evaporation dish with 0.1 M HCI or 0.1 M NaCI. The 68Ge was recovered essentially quantitatively in a cold trap at -40~ An apparatus for cyclic operation is shown in Fig. 7.2.
The most widely used generator was proposed by Green and Tucker. 249 In this system, Ge is adsorbed on aluminum or zirconium oxides, and Ga is eluted with a neutral solution of 5 mM Na-EDTA. The initial Ga yield from this generator was -70%
but decreased considerably with time. In a comparative study, Karpeles 126 evaluated TEFLON
STOPCOCK 7
OIL BATH, -13ooc
-12 cm
LIQUID N 2
I
"•)--•'•"
COLDf ~ -- TRAP
Figure 7.2. Apparatus for cyclic operation of volatilization-based 6SGe--,S8Ga generator
S. MIRZADEH, R. M. LAMBRECHT: RADIOCHEMISTRY OF GERMANIUM
several generators which included an Ai203/EDTA system. Alternatively, carrier-free 68Ge was adsorbed on Sb20 5, and 68Ga was eluted with an oxalate solution at pH 5-11. 25o The generator in which gallium is obtained in the form of Ga complex is commercially available in the U.S. and Europe.
For the preparation of 68Ga radiopharmaceuticals other than 68Ga-EDTA, it is necessary to prepare 68Ga in ionic form. For this purpose, the 68Ga-EDTA complex (or any other complex) is usually destroyed with concentrated HCI after the addition of a carrier. The 68Ga is then separated in ionic form by ion exchange or extraction.
Because of the rather fast decay of 58Ga, the final yield is significantly reduced.
In a two-part study, Kopecky et al. 224'251 reported the adsorption behavior of carrier-free 68Ga and 68Ge on alumina, AI(OH)3 and Fe(OH)3. A part of this study is presented in Sect. 6.4. Based on this research, a generator was proposed from which the 68Ga could be eluted directly in an ionic form. Malyshev et al. 252 studied the feasibility of efuting ionic 68Ga with mineral acids from generators where Ge was adsorbed on hydrated ZrO 2, SnO2, and TiO 2. Subsequent studies 253 confirmed that the SIlO 2 was a superior support for germanium. In this system, Ga was eluted with 1 M__
HCI. Among the three systems (ZrO2/HNO 3, SiO2/HNO 3, and TiO2/dilute NaOH or Na3PO 4 buffer) which were studied by Neirinckx and Davis 254 for generating ionic 68Ga, only the silica gel/HNO 3 system was found to be suitable. Lewis and Camin 255 suggested eluting the Ga from an alumina generator with 0.1 M__ NaOH. Ambe 256 examined the adsorption of carrier-free 68Ge on a-Fe20 3 and found that 50-70% of Ga can be eluted with an HCI solution of pH 2.0.
The significant difference between the behavior of Ga and Ge from dilute hydrofluoric acid solutions on anion exchangers (Kd=27 and >4000, respectively) was the basis for a generator proposed by Neirinckx and Davis. 257 The reported breakthrough of 68Ge was >10 -4 for up to 600 elutions of the generator with a 65Ga yield of ~90%.
A germanium-specific synthetic resin was prepared and evaluated for 68Ge/68Ga generators. 258'259 This chelating resin was prepared by condensing 1,2,3-trihydroxy- benzene (pyrogallol) with formaldehyde.
OH
H O ~ D H
CH2
D
OH OH
J
rl
S. MIRZADEH, R. M. LAMBRECHT: RADIOCHEMISTRY OF GERMANIUM
The batch distribution coefficient (Kcl)* of carrier-free 68Ge for the resin from solutions of 0.9 M NaCI and dilute HCI (0.1-0.5 M__) is >-5x103, whereas, the K d for 68Ga is 50 for 0.9 M NaCI and 1.8-0.3 for dilute HCI. The yield of 68Ga from the generator was reproducible at 60% after 600 elutions, while the breakthrough of 68Ge remained at
<10 ppm per elution. The pyrogallol-formaldehyde resin was found to be rather resistant to dissociation from radiation. At a radiation dose of 3.8x108 rad/g, no evidence of physical or chemical change was observed. Schuhmacher and Maier-BOrst 259 independently synthesized the pyrogallol-formaldehyde resin for the same purpose.
They reported an average yield of 68Ga of 75% during a period of 250 days of study.
The Ge breakthrough was <0.5 ppm with no detectable radiolytic byproducts for a 10- mCi generator.
14 12
~
E 10 _J UJ
8 oo
6 .J ..J
<
0 4
_
o 0