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

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dc.contributor.authorGundogdu, Evren
dc.contributor.authorDemir, Emine Selin
dc.contributor.authorOzgenc, Emre
dc.contributor.authorYegen, Gizem
dc.contributor.authorAksu, Buket
dc.date.accessioned2020-12-01T12:02:00Z
dc.date.available2020-12-01T12:02:00Z
dc.date.issued2020
dc.departmentEge Üniversitesien_US
dc.description.abstractThe 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.en_US
dc.description.sponsorshipT.R. Prime Ministry State Planning Organization FoundationTurkiye Cumhuriyeti Kalkinma Bakanligi [09/DPT/001]; COST (European Cooperation in Science and Technology) ActionEuropean Cooperation in Science and Technology (COST) [CA17104]en_US
dc.description.sponsorshipThe authors would like to thank the T.R. Prime Ministry State Planning Organization Foundation (project number: 09/DPT/001). the authors would like to thank the COST (European Cooperation in Science and Technology) Action (project number: CA17104). the authors would like to acknowledge the support of Ege University Nuclear Medicine Department in obtaining the <SUP>99m</SUP>Tc radionuclide.en_US
dc.identifier.doi10.1021/acsomega.9b04327en_US
dc.identifier.endpage5305en_US
dc.identifier.issn2470-1343
dc.identifier.issue10en_US
dc.identifier.scopus2-s2.0-85081547090en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage5297en_US
dc.identifier.urihttps://doi.org/10.1021/acsomega.9b04327
dc.identifier.urihttps://hdl.handle.net/11454/62572
dc.identifier.volume5en_US
dc.identifier.wosWOS:000520853400064en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Chemical Socen_US
dc.relation.ispartofAcs Omegaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleApplying Quality by Design Principles in the Development and Preparation of a New Radiopharmaceutical: Technetium-99m-Imatinib Mesylateen_US
dc.typeArticleen_US

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