The Generator Eluate

The Mo/ Tc generator is a closed system providing sterile Tc eluate on a daily basis. Generators are available from manufacturers with a wide range of Mo activities (2-43 GBq 54-1.162 mGi) sterile, evacuated vials are supplied with the generator, offering also variable elution volumes (5, 10, 15, and 20 ml). 

Sterile saline is used for elution of the generator. The eluate is a clear, colorless, isotonic solution of Tc(VII)-pertechnetate. 

The concentration of the Tc activity in the eluate ( Tc activity/volume) depends on the available Mo activity and the elution volume. With daily elution of the generator, high specific activity is assured. 

The following quality criteria are stated in the Ph. Eur. and should be evaluated for each generator  

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Albumin nanocolloid is less affected by the concentration of Al ion in the generator eluate than inorganic colloids. A reaction volume containing 1 pg AP ion per milliliter had no effect 2 pg/ml showed an increase in the particle diameter (80-100 nm) from 1-23% (Chia 1986 Haney 1971). 

While centrifuging the tubes, reconstitute one vial of HMPAO with 1.5 ml of Tc eluate containing 700-750 MBq (19-20 mCi) of Tc-pertechnetate (400-500 MBq/ ml, resp. 11-13 mCi/ml)). Gently invert the shielded vial for 10 sec to dissolve the lyophilisate. The generator eluate should not be more than 2 h old and the generator must have been eluted within the past 24 h. 

Presence of aluminum in the generator eluate and treatment with aluminum-containing drugs may result in colloid formation, with liver and spleen uptake and trapping of particles in lung capillaries (Zimmer and Pavel 1978). Colloid formation is also observed at elevated pH above 8.5 (Chaudhuri 1976). 

Sodium pertechnetate, Na Tc04 from the generator is the starting material for all radiopharmaceuticals based on 99mTc The generator eluate, Tc04, is introduced into... 

Cation exchange chromatography The key step in this procedure is the direct transfer of the initial 0.1 N HCl Ga eluate to a cation exchanger. Due to high distribution coefficients, Ga is quantitatively adsorbed on only about 50 mg of the resin directly from the generator eluate. This effect also occurs with higher concentrations of HCl, e.g., 0.6 N HCl, as used for SnOa-based Ge/ Ga generators. Low volumes of 0.4-1.0 mL of hydrochloric acid/acetone mixtures... 

The Mo/ Tc generator consists of an alumina column in which Mo (a fission- or reactor-produced radionuclide) is adsorbed as Mo-molybdate. Mo decays 87% to " Tc, and a Tc-pertechnetate solution is easily obtained by eluting the column with sterile sahne solution. Tc-radiopharmaceuticals are then synthesized by adding the generator eluate to one of the many commercially available radiopharmaceutical kits. Because the parent radionuclide decays to " Tc with a half-life of 66 h, the Mo/ Tc generator can be used daily for up to 1 week. 

The preparation of the pharmaceutical is achieved simply by injection of generator eluate into a vial containing ligand and reductant. Heating may be necessary, to ensure complete reaction. A portion of the vial contents is then injected into the patient for imaging. 

Figure 5. Breakthrough of Hg-195m in eluate of Au-195m generator. Notice large breakthrough in eluates 1 and 3 during the first 3 days of use of the generator.

The generator is eluted with 2 ml of 8N HCl. The eluate is evaporated on a hot plate in a stream of filtered nitrogen gas until dry. The Mn-52m is then redissolved in 3 ml of sodium acetate buffer (pH - 5.6). The solution is passed through a disposable 0.45 ym bacterial filter before injection to ensure sterility of the Mn-52m. These steps take less than 10 minutes. 

Breakthrough. Eluate radionuclidic purity is determined by Nal scintillation spectrometry on 50 ml of eluate. Samples must be held at least one hour before measurement to allow full decay of Rb-82. To improve sensitivity of measurement, the most prominent 511+514 keV peak is counted. Computations are based upon comparison with an aliquot of Sr-82+Sr-85 solution used to prepare the generator.. Data are expressed in units of yCi Sr-82/ml of eluate/ mCi Rb-82 at end of elution. 

At the end of four weeks of continued use, during which 4 liters of eluate were collected, samples were sterile and non-pyrogenic. Isotonicity was confirmed (NaCl = 8.94 .03 mg/ml) and neutrality maintained (pH = 6.27 0.16). No tin was detected in generator eluates by differential pulse polarography above a detection limit of 0.1 lig/ml. The radionuclidic identity of Rb-82 is easily confirmed by verification of its 76 sec half-life or through gamma spectrometry. 

Radionuclidic Purity Radionuclidic purity is defined as the fraction of the total radioactivity in the form of the desired radionuclide present in a radiopharmaceutical. Radionuclide impurities may arise from impurities in the target material or from fission of heavy elements in the reactor [2], In radionuclide generator systems, the appearance of the parent nuclide in the daughter nuclide product is a radionuclidic impurity. In a "Mo/"mTc generator, "Mo may be found in the "mTc eluate due to breakthrough of "Mo on the aluminum column. The presence of these extraneous radionuclides increases the radiation dose to the patient and may also obscure the scintigraphic image. 

The Tc complexes are conveniently prepared shortly before use, by addition of the Tc generator eluate to the contents of commercially available kits that contain the coordinating species to be labeled and often the reducing agent (usually Sn ). 

This aspect has led to the production of micro- and nanoelectrospray sources, where the chromatographic eluate flow is in the range 1-10 2 pL/min. A typical instrument setup for nano-ESI experiments is shown in Fig. 1.10. In this case, the supplementary gas flow for spray generation is no longer present and the spray formation is only due to the action of the electrical field. The sprayer capillary, with an internal... 

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