technetium-tc-99m-exametazime and 2-5-dihydroxybenzoic-acid

The objective of this study was to increase the stability of 99Tcm-exametazime and to investigate the effects of relaxing the eluate restrictions imposed by the manufacturer. We added 1800 MBq freshly eluted pertechnetate to 0.5 ml aliquots of stannous-enhanced exametazime followed by the addition of 0.7 mg gentisic acid and 0.5 ml sterile absolute alcohol BP. The radiochemical purity as measured by thin-layer chromatography was maintained at over 80% (range 88-99%, n = 40) for up to 7 h after preparation. High-performance liquid chromatography confirmed that the primary complex was maintained at over 80% (ranges 89-92%) for up to 7 h. In a second series of studies using the first eluate from a newly delivered generator to prepare 99Tcm-exametazime, a radiochemical purity of more than 80% was achieved for up to 7 h (range 88-95%, n = 24). In a third series using a 3-hour-old generator eluate, a radiochemical purity of more than 80% (range 88-93%, n = 18) was achieved for up to 5 h (for logistic reasons, we were unable to continue readings beyond 5 h). These results suggest that the manufacturer's restrictions on the eluate may be relaxed. Clinical validation was performed in a blinded study of 21 patients using single photon emission tomography. Image quality was assessed on the basis of salivary activity, nasal activity and the overall (global) image quality. There was no significant difference between the images obtained using the stabilized exametazime and exametazime prepared without gentisic acid and ethanol (chi 2 = 2.85, P = 0.05). We conclude that stabilization of 99Tcm-exametazime can be achieved for up to 7 h by using gentisic acid and alcohol and that the eluate restrictions may be disregarded.

Topics: Butanones; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Costs and Cost Analysis; Drug Stability; Gentisates; Humans; Hydroxybenzoates; Indicators and Reagents; Nose; Radionuclide Imaging; Radiopharmaceuticals; Salivary Glands; Technetium Tc 99m Exametazime; Time Factors; United Kingdom

Leukocytes can be labelled with 99mTc using HMPAO and gentisic acid methods. We compared the two methods with respect to labelling efficiency on mixed leukocytes and isolated polymorphonuclear (PMN) and mononuclear (MN) cells, and the in vitro stability of the label. HMPAO produced approximately 70% labelling efficiency on mixed or PMN cells and the label was stable in saline or plasma. Labelling efficiency on MN was only 14% and was less stable. Gentisic acid produced a labelling efficiency of 52% on PMN and 35% on MN; both were stable in saline but less stable in plasma. In conclusion, HMPAO produces higher labelling efficiency and the label shows greater in vitro stability in plasma. However, gentisic acid is much less expensive to use, allows labelling of MN cells, and should result in more favourable microdosimetry. Preliminary clinical results suggest that gentisic acid is equivalent to HMPAO but has the advantage of being much cheaper.

Topics: Costs and Cost Analysis; Gentisates; Humans; Hydroxybenzoates; In Vitro Techniques; Isotope Labeling; Leukocytes; Leukocytes, Mononuclear; Neutrophils; Organotechnetium Compounds; Oximes; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Exametazime