Applying Quality by Design Principles in the Development and Preparation of a New Radiopharmaceutical: Technetium-99m-Imatinib Mesylate.

The clinical impact and accessibility of Tc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. In this study, Technetium-99m-imatinib mesylate ([Tc]Tc) was developed and prepared as a new radiopharmaceutical for breast cancer diagnosis. The effect of critical process parameters on the product quality and stability of [Tc]Tc was investigated using the quality by design concept of the ICH Q8 (Pharmaceutical Development) guideline. [Tc]Tc was subjected to in vitro cell binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. The optimal radiolabeling procedure with 1 mg of IMT, 500 μg of stannous chloride, 0.1 mg of ascorbic acid, and Ci Tc radioactivity was obtained for [Tc]Tc. The pH of the reaction mixture was adjusted to 10 and allowed to react for 15 min at room temperature. The radiochemical purity of [Tc]Tc was found to be higher than 90% at room temperature up to 6 h. Chromatography analysis revealed >85% [Tc]Tc complex formation with promising stability in saline, cell medium, and serum up to 6 h. The radiolabeled complex showed a higher cell-binding ratio to MCF-7 cells (88.90% ± 3.12) than HaCaT cells (45.64 ± 4.72) when compared to Tc. Our findings show that the developed preparation method for [Tc]Tc falls well within the proven acceptable ranges. Applying quality by design (QbD) principles is feasible and worthwhile for the preparation of [Tc]Tc. In conclusion, radiochemical purity, stability, and in vitro cell binding evaluation of the [Tc]Tc complex indicate that the agent can be utilized for imaging of breast cancer cells.