Gündoğdu, EvrenDemir, Emine SelinÖzgenç, EmreYeğen, GizemAksu, Buket2021-05-152021-05-1520202470-1343https://doi.org/10.1021/acsomega.9b04327https://hdl.handle.net/20.500.12939/223Aksu, Buket/0000-0001-7555-0603; gundogdu, evren/0000-0003-2111-101X; Yegen, Gizem/0000-0003-0427-8918The clinical impact and accessibility of Tc-99m 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-99m]TcIMT) 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-99m]TcIMT was investigated using the quality by design concept of the ICH Q8 (Pharmaceutical Development) guideline. [Tc-99m]TcIMT 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 mu g of stannous chloride, 0.1 mg of ascorbic acid, and (1m)Ci Tc-99m radioactivity was obtained for [Tc-99m]TcIMT. 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-99m]TcIMT was found to be higher than 90% at room temperature up to 6 h. Chromatography analysis revealed >85% [Tc-99m]Tc1MT 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-99m. Our findings show that the developed preparation method for [Tc-99m]TcIMT falls well within the proven acceptable ranges. Applying quality by design (QbD) principles is feasible and worthwhile for the preparation of [Tc-99m]TcIMT. In conclusion, radiochemical purity, stability, and in vitro cell binding evaluation of the [Tc-99m]TCIMT complex indicate that the agent can be utilized for imaging of breast cancer cells.eninfo:eu-repo/semantics/openAccessDevelopmentTechnetium-99m-Imatinib MesylateRadiopharmaceuticalArticle10.1021/acsomega.9b0432751052975305322018182-s2.0-85081547090Q1WOS:000520853400064Q2