Adsorption of ^99mTc-Radiopharmaceuticals onto Injection Vials and Syringes

MATERIALS AND METHODS

All kits were products of the Kit Production Group of PINSTECH. Most of the precursors for these kits are purchased from commercial suppliers, whereas diisopropyl iminodiacetic acid, exametazime, mercaptoacetyltriglycine, and sestamibi are synthesized and characterized locally. ^99mTc was obtained from a locally produced fission-based PAKGEN ⁹⁹Mo/^99mTc generator (PINSTECH). All chemicals were of analytic reagent grade and purchased from E. Merck. Ascending paper chromatography was performed using Whatman paper (no. 1 or 3), and instant thin-layer chromatography silica gel strips were obtained from Gelman Sciences. The distribution of radioactivity on chromatographic strips was measured using a 2π scanner (Berthold), or the strips were cut into 1-cm segments and counted in a γ-counter. The activity of the ^99mTc was measured using a dose calibrator (Capintec). The disposable plastic syringes were the products of 3 different commercial manufacturers (Becton Dickinson Worldwide, Inc. [syringe A]; Safti syringes, Zafra International, Ltd., in collaboration with Boin Medica Co., Ltd. [syringe B]; and Shandong Qiaopai Group Co., Ltd. [syringe C]), and the injection vials and rubber stoppers were purchased from SCHOTT Glass Malaysia and Helvoet Pharma, respectively. All 3 types of syringes were 2.5 mL.

To study the rate of adsorption of ^99mTc-radiopharmaceuticals onto vials, we prepared all radiopharmaceuticals using standard labeling techniques (7–9). The vial containing lyophilized material was reconstituted with 3 mL of freshly eluted Na^99mTcO₄. All preparations were stored at room temperature (∼22°C). At 0.25, 0.5, 1, 3, and 5 h after reconstitution, the following procedure was adopted to measure the degree of radioactivity adhesion in vials. The vial was weighed, and the ^99mTc activity was measured using a dose calibrator. A 1-mL sample of the solution in the vial was withdrawn into a syringe. The vial was reweighed, and the activity remaining in the vial was measured. The sample was reinjected into the vial. From the original weight and activity of the solution in the vial, the initial activity per gram was calculated. From the weight and activity remaining in the vial after withdrawal of the sample, the activity per gram of sample was calculated. From the difference between the initial activity per gram and the activity per gram of sample, the percentage of ^99mTc adsorbed onto the vial was calculated. All experiments were performed on 3 separate occasions.

To study the adsorption of ^99mTc-radiopharmaceuticals onto the disposable plastic syringes, we kept all preparations in the syringe for 15 min and measured the activity before and after emptying the syringe. The needle and plunger of the syringe were separated, and activity in the needle and plunger was also measured. All experiments were performed on 3 separate occasions.

Radioactivity on the rubber stopper was determined just after reconstitution of the kit. The activity in the sealed vial was measured using a dose calibrator. The rubber stopper was then carefully removed and blotted dry, the activity on the stopper was measured, and the percentage of activity was calculated.

RESULTS

The ingredients of different freeze-dried kits are given in Table 1. Table 1 also gives the pH value at which labeling efficiency is maximal. The labeling efficiency of all radiopharmaceuticals used during these studies was more than 95%. Table 2 presents the percentage adhesion activity of ^99mTc-radiopharmaceuticals on vials and rubber stoppers. The activity on rubber stoppers was measured just after reconstitution of the kit. In most cases, the activity of ^99mTc on rubber stoppers was less than 1%. The maximum activity, approximately 1%, was found for sestamibi, mercaptoacetyltriglycine, and dimercaptosuccinic acid (DMSA) (V)—radiopharmaceuticals for which a boiling or shaking step was used for labeling.

The adsorption of ^99mTc onto vials increased gradually with storage time. Adsorption was minimal at the initial stages, whereas retention was maximal after 5 h. After 15 min, retention was less than 1%, except in vials of sestamibi, mercaptoacetyltriglycine, dextran, ciprofloxacin, and DMSA (III and V). After 5 h of storage time, nearly 5% adsorption of activity was observed for vials of sestamibi, mercaptoacetyltriglycine, dextran, ciprofloxacin, and DMSA (III and V). These findings indicate that total retention of radioactivity on vials and stoppers is insignificant in our setting.

Mean values for the percentage of radioactivity remaining in the 3 types of syringes and their parts are presented in Table 3. The percentage of activity left on a syringe and parts was calculated using the following formula: residual activity (%) = (residual activity/initial activity) × 100. Retention of activity on needles ranged from 1% to 2% for all preparations studied. Plungers did not retain any significant radioactivity; in most cases, retention was less than 0.5%. The maximum retention of radioactivity on plastic syringe bodies was more than 3% for sestamibi, DMSA, dextran, pyrophosphate, and phytate. However, it cannot be concluded that one brand of syringe showed less retention of radioactivity than the others for all study radiopharmaceuticals.

DISCUSSION

For the last 2 decades, the Kit Production Group at PINSTECH has been manufacturing and supplying freeze-dried kits for the preparation of ^99mTc-radiopharmaceuticals to more than 20 hospitals practicing nuclear medicine in different cities of Pakistan. During that time, no incidents of loss of activity on vials or syringes have been reported by the end users. In contrast, adsorption of ¹³¹I (oral solution of sodium iodide [¹³¹I] in carbonate buffer) on rubber stoppers has been reported a few times. Investigations of the adsorption of ¹³¹I on rubber stoppers are in progress and may be the subject of another publication.

It would be reasonable to expect manufacturers of freeze-dried kits for ^99mTc-radiopharmaceuticals to investigate the compatibility of their products with vials and rubber stoppers. It is also important that hospital radiopharmacies check for compatibility between syringes and radiopharmaceuticals. The use of an inappropriate syringe may reduce the administered radioactivity to a patient, leading to poor-quality images.

CONCLUSION

Freeze-dried kits produced at our institute show insignificant adhesion of radioactivity on the vial, rubber stopper, plastic syringe, needle, and plunger after labeling with ^99mTc. Because the time of use after reconstitution affects adsorption of radioactivity onto syringes, needles, and vials, users should reconstitute the preparation soon before administration to the patient. Determining the compatibility of radiopharmaceuticals with these objects is an integral part of quality assurance programs.