A better method of quality control for 99mTc-tetrofosmin

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Quality Control
• Analytical Chemistry

Background:

• The standard quality control (QC) for technetium-99m-tetrofosmin requires time-consuming, meticulous techniques for accurate radiochemical purity (RCP) assessment.
• Existing alternative methods have limited validation, often only with pertechnetate, which may not reflect actual impurities in (99m)Tc-tetrofosmin preparations.
• Accurate RCP is crucial for ensuring the efficacy and safety of radiopharmaceuticals in diagnostic imaging.

Purpose of the Study:

• To develop and validate a convenient, accurate, and rapid new method for assessing the radiochemical purity of (99m)Tc-tetrofosmin using silica cartridges.
• To compare the performance of the novel silica cartridge method against the traditional package insert technique and instant thin-layer chromatography (ITLC).

Main Methods:

• A novel quality control method utilizing silica cartridges with a 70:30 methanol:water solvent system was developed.
• The method was validated against various technetium-99m radiopharmaceuticals, including sodium pertechnetate ((99m)TcO(4)), (99m)Tc-glucoheptonate, (99m)Tc-sulfur colloid, and low-purity (99m)Tc-tetrofosmin.
• Validation involved comparing results with the package insert method and ITLC across multiple nuclear pharmacies, assessing factors like sample volume and flow rate.

Main Results:

• The silica cartridge method demonstrated robustness, unaffected by sample volumes (25-100 µL), unlike ITLC.
• A critical flow rate of ≤5 mL/min was identified for the silica cartridge method, which exhibited significantly lower variability (SD and variance) compared to ITLC.
• The silica cartridge method showed near-perfect correlation (R=0.99) with the gold standard package insert technique, achieving 100% sensitivity, accuracy, and specificity in identifying batches with <90% RCP.

Conclusions:

• The developed silica cartridge method is a superior alternative for (99m)Tc-tetrofosmin radiochemical purity testing, scoring 90.2 compared to 65.8 for ITLC based on established criteria.
• The study demonstrated that common validation impurities like free (99m)TcO(4) are not the significant radiochemical impurities in (99m)Tc-tetrofosmin, invalidating prior alternative methods.
• This new method is fast, convenient, accurate, safe, and economical, though precise control of flow rate is essential for optimal performance.