Validation of an Ergonomic Method of Withdrawing ^99mTc-Radiopharmaceuticals

Visual Examination and Physicochemical Controls

The system was tested with the following solutions: ^99mTc-pertechnetate eluate, ^99mTc-hydroxymethylene diphosphonate (^99mTc-HMDP) (Osteocis; IBA Molecular), ^99mTc-albumin nanocolloid (Nanocoll; GE Healthcare), and ^99mTc-human serum albumin (^99mTc-HSA) (Vasculocis; IBA Molecular).

^99mTc-sodium pertechnetate was eluted from a Drytec ⁹⁹Mo/^99mTc generator (GE Healthcare). The ^99mTc-radiopharmaceuticals were prepared following the manufacturer’s instructions. The studied system was introduced into vials before the content for first quality control test was withdrawn (baseline). The stability study was performed for 7 h for ^99mTc-eluate (n = 5), ^99mTc-HMDP (n = 5), and ^99mTc-HSA (n = 5) and for 4 h for ^99mTc-albumin nanocolloid (n = 5). Luer slip connector syringes with a capacity of 1 mL (Plastipak) were used for sampling. Vials were stored at room temperature throughout the study. Organoleptic specifications detailed in the product-characteristic summary were checked by a visual examination. pH was determined by pH indicator strips (MColorpHast; Merck Millipore).

Radiochemical purity was tested by instant thin-layer chromatography. For ^99mTc-pertechnetate eluate, ^99mTc-HSA (4), and ^99mTc-albumin nanocolloid (5), the method required Whatman 31ET strips (Clerad; Biodex) and acetone as solvent (GPR Rectapur; VWR). Concerning ^99mTc-HMDP, the radiochemical purity was determined by a 2-strip procedure (5): instant thin-layer chromatography–silica gel strips and distilled water as solvent were used to determine the percentage of reduced or hydrolyzed ^99mTc, and Whatman 31ET strip and acetone as solvent were used to evaluate the percentage of free pertechnetate.

After migration of the solvent, paper strips were scanned with a sodium iodine crystal detector on a MiniGITA Star (Elysia Raytest). Chromatograms were recorded and analyzed with GINA-Star thin-layer chromatography (version 5.8).

Visual Examination of IN-Stopper Connector

The IN-Stopper membrane was examined for integrity and for the absence of small cores or plugs.

Sterility Test

The sterility tests were performed on 3 different days by 3 different operators. The rubber cap of the growth medium vial was cleansed with a chlorhexidine-sterilized pad before being punctured by the system. Each day, 10 syringes per operator (total, 30) were prepared with the spinal needle and IN-Stopper up to 7 h after the introduction of the system into the growth medium vial. Syringes were withdrawn at regular time intervals. Each 2.5-mL Luer slip connector syringe was prepared following the same protocol to simulate volume readjustment: IN-Stopper connector cleaned with chlorhexidine-sterilized pad; 1.5 mL of broth withdrawn into syringe; needle removed and then inserted; 1 mL withdrawn into growth medium vial; needle removed and then inserted; 0.5 mL of broth withdrawn into syringe (final volume, 1 mL); needle disassembled and then assembled with 0.22-nm Perifix filter (B. Braun); hood air withdrawn; and filter disassembled and then assembling with a cap (Vygon).

The growth medium vials were stored at room temperature during the study.

Experimental conditions were validated by a positive control and a negative control. The positive control syringes were inoculated with Staphylococcus aureus and Aspergillus brasiliensis growth. Sterile water was used for the negative control. A positive transport sample and a negative transport sample were also prepared in syringes to validate transport conditions.

Each day, syringes were collected by Bioclin Laboratory. Microbiologic cultures were performed by Bioclin Laboratory according to the European Pharmacopoeia, 8th edition (6). Samples (spinal needle and IN-Stopper tests, positive control, negative control, positive transport sample, negative transport sample) were divided into 2 equal parts and directly inoculated onto 2 different media. Fluid thioglycolate medium and soybean casein digest broth were incubated at 30°C–35°C and at 20°C–25°C, respectively, for 14 d, with the exception of the positive control, which was incubated for 5 d.

Fingertip Radiation Exposure and Contamination

A fingertip radiation dosimeter, Nuclear Educational Dosimeter (Unfors Instruments), was attached to the distal medial aspect of the index finger and covered with a pair of latex examination gloves. Tests were performed on the right index finger and then on the left index finger of each operator.

Dosimetry was measured and compared for 3 operators for both procedures: a routine process involving disinfection of the vial cap followed by reversal withdrawal of one syringe, and a spinal needle/obturator process consisting of insertion of the system into the vial followed by disinfection of the obturator and withdrawal of one syringe. The vials used for the tests were filled with ^99mTc-pertechnetate eluate. Vials were measured using a dose calibrator, CRC 25R (Capintec), to calculate the received dose per megabecquerel for each hand.

Spillage and radioactive contamination were also studied. A contamination detector, LB 124 (Berthold), was used to measure radioactivity on shielded hood, gloves, vials, and syringe shields. Areas that registered more than twice the previously determined background level were considered contaminated.