Methylene blue-enhanced stability of (99mTc)HMPAO and simplified quality control — a comparative investigation

Abstract ( 99m Tc)HMPAO is a radiopharmaceutical used for SPECT imaging of regional cerebral perfusion and for labeling cellular blood elements. The addition of methylene blue enhanced the stability of lipophilic ( 99m Tc)HMPAO complex up to 3 h after reconstitution, 86.9±4.2% compared to 49.8±8.9% for the non-stabilised complex and persists over time (86.2±3.5% after 15 min compared to 78.2±4.0% after 3 h). The method widely used for estimation of radiochemical purity is a standard chromatographic procedure which is quite time-consuming taking about 30 min. Comparison of the more rapid and simple solvent extraction method with octanol, which needs only about 10 min to complete, showed a good correlation with the chromatographic method (84.4±4.4% compared to 89.1±4.3%). Using ethyl acetate as solvent instead of octanol gave a slightly higher extraction rate of the lipophilic complex (91.5±5.5% compared to 89.1±4.3%). Further, the ethyl acetate extraction method results in an overestimation, extracting partly secondary complex. It is confirmed, that the stability of the lipophilic ( 99m Tc)HMPAO complex can be increased with methylene blue. The octanol extraction method, using higher extraction volume (up to 3 ml), is recommended as a fast and efficient approach for the quality control in daily clinical routine.