Radiolabeling and in vitro evaluation of a new 5‐fluorouracil derivative with cell culture studies

• Published in: Journal of labelled compounds & radiopharmaceuticals 2019-11, Vol.62 (13), p.874-884
• Main Authors: Ilem‐Ozdemir, Derya, Atlihan‐Gundogdu, Evren, Ekinci, Meliha, Halay, Erkan, Ay, Kadir, Karayildirim, Tamer, Asikoglu, Makbule
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; 5‐fluorouracil derivative; Binding; Breast cancer; Breast carcinoma; cell binding; Cell culture; Control stability; Cytotoxicity; Fluorouracil - chemistry; Fluorouracil - metabolism; Fluorouracil - toxicity; Humans; Hydrogen-Ion Concentration; Isotope Labeling; MCF-7 Cells; Quality control; Radiochemical analysis; Radiochemistry; radiolabeled compound; Radiolabelling; Room temperature; Stability analysis; Technetium - chemistry; technetium‐99m; Thin layer chromatography; Toxicity; Tracers
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3804

The clinical impact and accessibility of 99mTc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5‐Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5‐Fluorouracil was synthesized as (1‐[{1′‐(1′′‐deoxy‐2′′,3′′:4′′,5′′‐di‐O‐isopropylidene‐β‐D‐fructopyranose‐1′′‐yl)‐1′H‐1′,2′, 3′‐triazol‐4′‐yl}methyl]‐5‐fluorouracil) (E) and radiolabeled with 99mTc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell‐binding studies to determine healthy and cancer cell affinity using HaCaT and MCF‐7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF‐5 cells. The radiochemical purity of the [99mTc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF‐7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 μM and 20.7 ± 2.77 μM for MCF‐7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99mTc has selective for breast cancer cells. In this study, we propose that radiolabeled compound of 5‐FU derivative bearing pyranose sugar and nucleobase groups could be beneficial for increasing ‘MFC‐7/HaCaT cellular uptake ratios' and aim to radiolabel compound E with 99mTc and show cellular binding capacity for different types of cells by using in vitro cell cultures studies.