Abstract
166
Introduction: 99mTc-labeled pyrophosphate (PYP) is routinely used at Mayo Clinic to differentiate types of cardiac amyloidosis [1]. During cardiac amyloidosis imaging, distribution of radiotracer uptake indicating presence of free 99mTc-pertechnetate in the given dose has been observed. Development of free pertechnetate in dispensed doses has been attributed to radiolytic decomposition or oxidation, air contamination, storage in plastic syringes, and storage temperature [2]. The kit formulation of PYP contains nitrogen as atmosphere which should help to prevent decomposition of the 99mTc PYP. However, once 99mTc PYP is drawn into syringes as unit doses and stored, exposure to oxygen increases which may decrease stability. Our study examined various storage conditions of 99mTc PYP to address effects of oxygen and its impact on stability over time.
Methods: Twelve PYP kits were prepared, including six kits by Curium and six kits by Sun Pharma. Two doses from each kit were drawn into syringes while intentionally introducing air to all drawn doses. Two kits and their doses from each manufacturer were prepared and stored at room temperature as a control; two kits and their doses from each manufacturer were prepared and stored under refrigeration (2-8°C). 2.0 mg in 0.15 mL of ascorbic acid were added to the remaining kits from each manufacturer and the kits and doses were stored at room temperature. Radiochemical purity quality control testing was performed on the kits immediately after preparation and the kits and doses at two-, four-, six-, and eight-hour intervals using acetone solvent and Whatman 31 ET chromatography paper.
Results: All 99mTc PYP stored in kits containing nitrogen atmosphere remained stable over time. Dose stability in syringes at 6 hours (BUD for PYP doses) for both manufacturers had an average of 99.9% bound for ascorbic acid, 98.6% bound in the refrigerator, and 84.8% bound for the control. Average disassociation under refrigeration was 1.2% and no significant change was observed in ascorbic acid doses. Control doses showed an average disassociation of 15%.
Conclusions: The research conducted indicates that if doses are drawn far in advance of the time of use, either to be stored on site or shipped to other facilities, either refrigeration of the doses or the addition of ascorbic acid to kits before dose preparation may help ensure the binding of 99mTc to PYP remains stable. Nitrogen atmosphere in the kits likely accounts for their stability regardless of storage conditions. Ascorbic acid is an antioxidant and reduces the number of free radicals in PYP doses, allowing 99mTc to stay bound to PYP [3]. Refrigeration appears to be similarly effective without the need to alter pharmaceutical chemistry.