Evaluation of alternative rapid thin layer chromatography systems for quality control of technetium-99m radiopharmaceuticals.

Whatman 3MM™ and Tec-Control™ systems were evaluated as ITLC-SG alternatives for 99mTc-radiopharmaceuticals. They compare well in accuracy and reproducibility, and are faster and more convenient than ITLC-SG. Tec-Control™ radiochemical purity values for 99mTc-sestamibi were more conservative than ITLC-SG. Full solvent migration was not reproduced for 99mTc-tetrofosmin in Tec-Control™, and for this Whatman 3MM™ is preferred. Developing times were 10-15 min, 7-9 min and ~1min for ITLC-SG, Whatman 3MM™ and Tec-Control™, respectively. Overall, Tec-Control™ strips are preferred due to speed and ease of use.

Comparison of three cold kit reconstitution techniques for the reduction of hand radiation dose.

In the performance of conventional nuclear pharmacy work, personnel usually receive the highest hand radiation dose during reconstitution of 99Tcm-labelled radiopharmaceuticals. This study was conducted to compare the hand radiation doses incurred during the preparation of 99Tcm-labelled radiopharmaceuticals using three different reconstitution procedures: (1) the standard reconstitution method (i.e. withdrawing 99Tcm activity and normal saline [NS] into the same syringe before adding to the cold kit) (standard); (2) an alternative reconstitution procedure using two syringes to add normal saline separately before 99Tcm activity to the cold kit (NS/Tc); and (3) a standard reconstitution procedure using a robotic system (Amercare Syringe Fill Station, model NuMed SFS 3a, Amercare Ltd, Oxon, UK) (robot). Radiation doses were monitored by thermoluminescent dosimeters (Landauer Inc., Glenwood, IL, USA) on the base of the fourth finger (i.e. ring finger) of the non-dominant hand and on the mid-portion of the second finger (i.e. index finger) of the dominant hand. Three sets of ring badges were measured for each procedure, with 10 stimulated or real reconstitutions per set. Two different radiopharmaceutical kits were evaluated: 99Tcm-MDP, as it is the most frequently used radiopharmaceutical in the majority of nuclear medicine departments (all three reconstitution methods; i.e. standard, NS/Tc and robot), and 99Tcm-sestamibi, as it is not only reconstituted with the highest amount of radioactivity but is also the most frequently dispensed radiopharmaceutical in our laboratory (standard and robot). All kits were prepared from an elution vial containing a standardized amount of 99Tcm activity (i.e. 104.4 +/- 3.6 GBq). To each of the cold MDP and sestamibi kits, 20.7 +/- 1.2 GBq and 44.2 +/- 0.7 GBq of 99Tcm activity were added, respectively. Average accumulated radiation doses for 10 reconstitutions to the fingers (non-dominant/dominant) for the preparations of 99Tcm-MDP were as follows: 14.2 +/- 0.9 mSv/2.8 +/- 0.8 mSv (standard), 10.0 +/- 0.6 mSv/2.7 +/- 0.2 mSv (NS/Tc), and 0.6 +/- 0.1 mSv/1.3 +/- 0.1 mSv (robot). For 99Tcm-sestamibi, the average accumulated radiation doses for 10 reconstitutions to the fingers (non-dominant/dominant) were 6.7 +/- 0.7 mSv/4.6 +/- 0.5 mSv (standard) and 1.1 +/- 0.1 mSv/3.1 +/- 0.4 mSv (robot). When compared to the standard reconstitution method, our results show that the NS/Tc method slightly reduced radiation dose to the non-dominant hand, without any significant reduction for the dominant hand. However, the robot has proved to be the most effective method to considerably reduce radiation dose to both hands. A robotic system should be a useful ALARA (as low as reasonably achievable) tool to prepare other high-activity 99Tcm-labelled radiopharmaceuticals, as well as therapeutic and PET radiopharmaceuticals.

[Determination of radiochemical purity of 99mTc(Sn)-methylene diphosphonate using gel chromatography]. / Odredivanje radiohemijske cistoce 99mTc(Sn)-metilen difosfonata gel hromatografijom.

The paper presents results of determining radiochemical purity of the osteopathic ligand 99mTc(Sn)-methylene diphosphonate (99mTc(Sn)-MDP). Application possibilities of gel chromatography on Sephadex G 25M were investigated depending on concentrations of reagents and composition of the eluence (Ph = 4-6.5). Concentrations of the ligand were 6.3 x 10(-3) and 6.3 x 10(-1) mol/dm3 Na3 - methylene diphosphonate and of the reductant 4.2 x 10(-1) and 4.2 x 10(-5) mol/dm3 SnCl2. The ratio ligand/reductant remained constant. It was concluded that under the given experimental conditions results of analyses depend solely on the composition of the eluence. The complex partially decomposes if pure saline is used as the eluence. The best results are obtained if the eluence contained both ligand and reductant. According to the obtained results it can be recommended to use eluence with the same concentration of the reagents (excluding technetium), as in the labelled complex. Under this condition Sephadex can be applied in determining radiochemical purity of 99mTc(Sn)-methylene diphosphonate.

Biodistribution of anionic separated MDP complexes from different MDP preparations.

The biodistributions of different Tc-MDP complexes, separated from different MDP preparations by anionic exchange chromatography, were investigated. We included MDP preparations from one producer with both ascorbic and gentisic acid as stabilizing agent and one preparation with ascorbic acid from a second producer. Bone to soft tissue ratios in rats were compared for the different Tc-MDP complexes separated. It seems that the elution profile of the radiochromatogram may indicate the biodistribution of the preparation. Ascorbic acid and gentisic acid caused different elution profiles and the different complexes isolated were demonstrated to have different bone to muscle ratios.

99mTc bone scanning agents--V. Influence of experimental conditions on the labeling efficiency and gel chromatography of 99mTc(Sn)HMDP.

The preparation of 99mTc(Sn)HMDP was investigated as a function of pH, Sn(II) and ligand concentration. HMDP could be labeled efficiently from pH 2-9. The Sn(II) and the ligand concentrations had a beneficial influence. The composition of the radiopharmaceutical under various experimental conditions was studied by means of gel chromatography on Biogel P-4. Six different complexes were found. A preparation consisted of maximally three major complexes. The presence of a particular complex was mainly determined by pH and ligand concentration. The Sn(II) concentration had little influence.

99mTc bone scanning agents--III. Preparation and gel chromatography of 99mTc(Sn)MDP complexes.

The preparation of 99mTc(Sn)MDP was investigated as a function of pH, MDP concentration and Sn(II) concentration. The labeling efficiency was over 90% in the majority of the experiments and remained constant over the range pH 2-9. The MDP concentration had little effect, while the Sn(II) concentration had a significant positive influence. The complex formation appeared to be partly reversible. The formation of different complexes was investigated by means of gel chromatography under various experimental conditions. Altogether six complexes were found. At acid conditions two major complexes were found and at neutral pH one major complex. The presence or absence of a particular complex was mainly determined by the pH and by the MDP concentration. The Sn(II) concentration had very little effect. The results are compared with previous results of similar experiments with 99mTc(Sn)pyrophosphate.

Reversed-phase HPLC of 99mTc methylene diphosphonate bone imaging kits with quantification of pertechnetate.

Ion-pairing reversed-phase HPLC is used to separate a mixture of 99mTc methylene diphosphonate (MDP) complexes prepared by tin reduction of pertechnetate in the presence of ligand. Chromatographic conditions allow for the quantification of total pertechnetate concentration, as well as the determination of chemical purity of generator eluents from which 99mTc is derived. Both determinations can be made prior to actual labeling. Commercially available MDP kits from three manufacturers are evaluated. All three MDP kits, when labeled with 99mTc, produce multiple, chromatographically separable components. The formation of these Tc-MDP complexes is time dependent. The labeling procedure produces several products within the first 20 min, with up to fifteen complexes observed after 4 h. The results of this work demonstrate the presence of substantial chemical contamination in generator eluents.