Technetium-99m-tetrofosmin: retention of nitrogen atmosphere in kit vial as a cause of poor quality material

Abstract

Technetium-99m (99Tc(m))-tetrofosmin was prepared using four different reconstitution methods. The radiochemical purity (RCP) of these products was assessed 8 h later using thin layer chromatography (TLC). Material produced using the original method supplied by the manufacturer and using an newer method, which involves the use of a vent needle and the addition of air, had acceptable RCP (mean +/- SD 94.2 +/- 1.1% and 94.7 +/- 1.7%, respectively) and similar chromatograms. In addition, both products showed good clinical efficacy and exhibited normal biodistribution behaviour. Preparing 99Tc(m)-tetrofosmin using the two other methods, one using a high radioactive concentration and the other maintaining the nitrogen content of the kit vial, gave rise to chromatograms with reduced RCP (63.5 +/- 10.9% and 61.9 +/- 7.6%, respectively) and greater levels of impurities. Although neither of these last two preparations was used clinically, we suggest that reports of poor quality images may be the result of administration of materials similar to these. Results for the high radioactive concentration method were as expected and are consistent with the restrictions imposed by the manufacturer. However, results using the last method are surprising and would suggest that the production of good quality 99Tc(m)-tetrofosmin is dependent on the quantity of nitrogen in the kit vial. We believe that the amount of nitrogen removed from the kit vial during the process of reconstitution is critical. If too much nitrogen is present this will result in poor quality material. In practice it is conceivable that there could be occasions when insufficient nitrogen is removed when following the manufacturer's original guidance, thereby leading to low RCP material. To ensure adequate nitrogen is removed during reconstitution, adoption of the manufacturer's revised method, involving the deliberate introduction of air, is therefore appropriate.

Pitfalls and Limitations of SPECT, PET, and Therapeutic Radiopharmaceuticals

“…Venting the vial to allow air to enter immediately after the complex has formed prevents the subsequent formation of the alternative complex. 32 Preparation of 99m Tc mertiatide (MAG3) requires boiling to hydrolyze the protected benzoyl precursor and allow transchelation from 99m Tc tartrate, which forms rapidly when 99m Tc pertechnetate is added to the kit. It has been noted that saline ampoules exposed to light can adversely affect the formation of the desired complex; curiously, this appears to affect the formation of 99m Tc tartrate rather than the transchelation step.…”