Preparation of 99mTc radiopharmaceuticals: the effect on radiochemical purity of using sodium chloride injection from plastic ampoules that have been exposed to light.

OBJECTIVE: To determine whether radiochemical purity is affected when 99mTc radiopharmaceuticals are prepared using sodium chloride injection from plastic ampoules that have been exposed to light. METHODS: Sodium chloride injection from plastic ampoules that were either exposed to light for 7 days or protected from light was used in the preparation of nine common 99mTc radiopharmaceuticals: albumin nanocolloid, exametazime, macrosalb, mebrofenin, medronate, pentetate, sestamibi, succimer and tetrofosmin. Five different batches of ampoules (exposed and unexposed) were used for each radiopharmaceutical. Radiochemical purity was measured by established analytical methods (thin-layer chromatography, liquid chromatography and nuclepore filtration) as specified in the European Pharmacopoeia or by the manufacturer. Analysis was performed within 1 h of preparation and at the products' expiries. RESULTS: The radiochemical purity of each 99mTc radiopharmaceutical was satisfactory when unexposed sodium chloride injection was used in its preparation. There was a significant difference between exposed and unexposed results (P < 0.05) for 99mTc exametazime (69.0 ± 9.3% vs. 88.6 ± 0.8%), 99mTc albumin nanocolloid (94.3 ± 1.1% vs. 98.8 ± 0.4%) and 99mTc macrosalb (84.0 ± 4.1% vs. 98.0 ± 2.2%) after preparation. Unsatisfactory radiochemical purity was the result of 99mTc pertechnetate impurity. The radiochemical purities of 99mTc albumin nanocolloid and 99mTc macrosalb increased over time and were satisfactory at their expiries. CONCLUSION: When 99mTc albumin nanocolloid, 99mTc macrosalb and 99mTc exametazime are prepared using sodium chloride injection from plastic ampoules that have been exposed to light, radiochemical purity is adversely affected. The other 99mTc radiopharmaceuticals tested are unaffected.

Preparation of 99m Tc-MAG3: the effect on radiochemical purity of using sodium chloride injection from plastic ampoules that have been exposed to light.

OBJECTIVE: To determine the circumstances under which sodium chloride injection (SCI) that has been exposed to fluorescent light then used to prepare 99m Tc-MAG3 causes low radiochemical purity (RCP). METHODS: Two brands of SCI in plastic ampoules (Braun and Steri-Amp) and one in glass vials (Drytec) were exposed to light for up to 7 days then used to prepare 99m Tc-MAG3. RCP was measured by liquid chromatography. To study the effect on the labelling reaction, the reconstituted MAG3 kit was analysed before and after boiling and the formation of the 99m Tc-tartrate intermediate was investigated. Exposed water from plastic ampoules was analysed by mass spectrometry. RESULTS: After no exposure, each brand resulted in high RCP 99m Tc-MAG3 (>94%). Drytec SCI produced high RCP throughout (96.7 +/- 0.3%, n=5, 7 days). The RCP produced by Steri-Amp and Braun fell to 85.2 +/- 5.2% and 93.5 +/- 1.6% after exposure for 2 and 4 days, respectively. The chromatogram before boiling contained peaks corresponding to 99m Tc-tartrate and 99m Tc-pertechnetate. After boiling with unexposed SCI, these were minimal and a 99m Tc-MAG3 peak dominated. After boiling with exposed SCI, 99m Tc-pertechnetate and 99m Tc-MAG3 peaks were present. Measurements on tartrate showed a high level of 99m Tc-tartrate before and after boiling with unexposed SCI but a high level of 99m Tc-pertechnetate after boiling with exposed SCI. Mass spectrometry showed that compounds leach into the solution upon exposure to light. CONCLUSION: Preparing 99m Tc-MAG3 using SCI from plastic ampoules that have been exposed to light causes reduced RCP. Exposure of plastic ampoules to light causes leaching of many compounds into the solution. An unknown leached compound destabilizes the 99m Tc-tartrate intermediate complex.

Preparation of 99mTc-MAG3: radiochemical purity is affected by the residence time of sodium chloride injection in a three-part syringe.

BACKGROUND: Routine technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) radiochemical purity measurements have revealed occasional unacceptably low values. Preliminary investigations suggested a causal link with the residence time of sodium chloride injection in the syringe used to reconstitute the MAG3 kit. OBJECTIVES: To investigate the cause of this phenomenon, determine how it can be avoided and establish whether it occurs with other 99mTc radiopharmaceuticals. METHODS: 99mTc-MAG3 was prepared by drawing sodium chloride injection into a lubricated, three-part, 10 ml Plastipak syringe and using it to reconstitute a MAG3 kit immediately or after a 15 min incubation period. The radiochemical purity was measured by high-performance liquid chromatography. The experiment was repeated using lubricant-free, two-part, Norm-Ject syringes and lubricated, two-part, Monoject syringes (15 min incubation only). To investigate the influence of Plastipak's rubber components on the radiochemical purity, samples were prepared using sodium chloride injection that had been incubated with lubricated or lubricant-free rubber plunger ends. Similar experiments were performed to determine the effect of Plastipak on 99mTc-exametazime, 99mTc-sestamibi and 99mTc-tetrofosmin. RESULTS: The radiochemical purities of 99mTc-MAG3 prepared with sodium chloride injection incubated for 0 and 15 min in Plastipak syringes were 96.4+/-0.5% and 89.4+/-5.5%, respectively. The difference was significant (P<0.05, n=10). With Norm-Ject syringes, the radiochemical purities were 96.5+/-0.5% and 96.6+/-0.5%, respectively. The difference was not significant (P>0.05, n=10). With Monoject syringes, the radiochemical purity was 96.6+/-0.4% (n=10). 99mTc-MAG3 prepared using sodium chloride injection treated with lubricated and unlubricated syringe rubber plunger ends had radiochemical purities of 85.3+/-6.6% and 82.1+/-6.5% (n=5), respectively. The radiochemical purities of other 99mTc radiopharmaceuticals prepared using sodium chloride injection incubated for 0 or 15 min in Plastipak syringes were as follows: 99mTc-exametazime, 95.3+/-0.6% and 94.5+/-1.8%; 99mTc-sestamibi, 98.0+/-0.6% and 97.7+/-0.6%; 99mTc-tetrofosmin, 96.5+/-0.2% and 97.0+/-0.4%. None of the differences was significant (P>0.05, n=5). CONCLUSIONS: A lipophilic impurity, originating from the rubber plunger of a three-part Plastipak syringe, is formed in 99mTc-MAG3 when the sodium chloride injection used to reconstitute the kit is in the syringe for a prolonged time. The effect is eliminated by using a two-part syringe or by injecting the sodium chloride injection into the kit immediately. The phenomenon does not occur with 99mTc-exametazime, 99mTc-sestamibi or 99mTc-tetrofosmin.