Munir Miftakul, Forentin Alfian Mahardika, Febrian Muhammad Basit, Fakih Taufik Muhammad, Utomo Rohmad Yudi, Aries Arni, Lestari Wening, Meiyanto Edy, Muchtaridi Muchtaridi, Septisetyani Endah Puji, Astirin Okid Parama, Syaifudin Mukh
Research Center for Radioisotope, Radiopharmaceutical and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency (BRIN), Building 71, Kawasan Puspiptek, Setu, Tangerang Selatan, Banten, 15310, Indonesia; School of Biomedical Sciences, Faculty of Health Medicine and Behavioural Sciences, the University of Queensland, Australia.
Research Center for Radioisotope, Radiopharmaceutical and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency (BRIN), Building 71, Kawasan Puspiptek, Setu, Tangerang Selatan, Banten, 15310, Indonesia.
Appl Radiat Isot. 2025 Nov;225:111977. doi: 10.1016/j.apradiso.2025.111977. Epub 2025 Jun 9.
Hesperidin, a citrus flavonoid, has been investigated for its potential health benefits, including anticancer. However, the study of hesperidin as a theranostic agent and its cancer cellular uptake is still lacking. Therefore, in this research, we developed radiolabeling methods of hesperidin with Iodine-131 (I) for radiotracing and investigating its potential theranostic application. Here, we showed that the radiochemical purity of [I]I-hesperidin prepared with chloramine-T in methanol or DMSO, iodogen, and iodobeads as a catalyst were 97.75, 79.08, 78.13, and 49.91 %, respectively. The LogP and plasma protein-binding after 24 h of [I]I-hesperidin prepared by chloramine-T in methanol were 0.54 ± 0.02 and 51.01 %, respectively. It was also stable in PBS for up to two days (RCP>90 %). The cellular uptake assay demonstrated the high and rapid uptake of [I]I- hesperidin in A549 cells (92.03 % in 30 min), relatively low uptake in MCF-7 (21.30 % in 1 h), and deficient uptake in MDA-MB-231 (3.64 %). Interaction and binding energies of [I]I-hesperidin-b toward EGFR, HER2, ERα, and ERβ, were -169.910; -131.574; -152.623, and -184.844 kJ/mol, respectively. Considering that the cellular uptake was the highest in A549 cells among the tested cells, the cellular uptake may be related to both EGFR and HER2 receptors. In addition, the interaction and binding energy of [I]I-hesperidin-b toward AKT1 was -150.939 kJ/mol, indicating the potential [I]I-hesperidin-b intervention in EGFR/HER2 signaling. Our data suggest that [I]I-hesperidin-b is a potential radiopharmaceutical, especially for lung cancers with EGFR and HER2 expression. However, further studies are still needed to evaluate the uptake mechanism of [I]I-hesperidin at the molecular level. Hopefully, [I]I-hesperidin will provide an opportunity to investigate the biodistribution, pharmacokinetics, and its potential as a targeted therapeutic-diagnostic agent supported with beta decay for cancer cell eradication.
橙皮苷是一种柑橘类黄酮，人们已对其潜在的健康益处进行了研究，包括抗癌作用。然而，关于橙皮苷作为一种诊疗剂及其在癌细胞中的摄取情况的研究仍很缺乏。因此，在本研究中，我们开发了用碘 - 131（I）对橙皮苷进行放射性标记的方法，用于放射性追踪并研究其潜在的诊疗应用。在此，我们表明，以氯胺 - T为催化剂，在甲醇或二甲基亚砜中、使用碘代甘氨酸和碘珠制备的[I]I - 橙皮苷的放射化学纯度分别为97.75%、79.08%、78.13%和49.91%。用氯胺 - T在甲醇中制备的[I]I - 橙皮苷在24小时后的LogP和血浆蛋白结合率分别为0.54±0.02和51.01%。它在磷酸盐缓冲盐溶液（PBS）中也能稳定长达两天（放射化学纯度>90%）。细胞摄取试验表明，[I]I - 橙皮苷在A549细胞中摄取迅速且量高（30分钟内为92.03%），在MCF - 7细胞中摄取相对较低（1小时内为21.30%），而在MDA - MB - 231细胞中摄取不足（3.64%）。[I]I - 橙皮苷 - b与表皮生长因子受体（EGFR）、人表皮生长因子受体2（HER2）、雌激素受体α（ERα）和雌激素受体β（ERβ）的相互作用和结合能分别为 - 169.910、 - 131.�74、 - 152.623和 - 184.844 kJ/mol。鉴于在测试细胞中A549细胞的摄取量最高，细胞摄取可能与EGFR和HER2受体都有关。此外，[I]I - 橙皮苷 - b与蛋白激酶B1（AKT1）的相互作用和结合能为 - 150.939 kJ/mol，表明[I]I - 橙皮苷 - b可能对EGFR/HER2信号传导有干预作用。我们的数据表明，[I]I - 橙皮苷 - b是一种潜在的放射性药物，尤其适用于表达EGFR和HER2的肺癌。然而，仍需要进一步研究以在分子水平评估[I]I - 橙皮苷的摄取机制。有望地，[I]I - 橙皮苷将提供一个机会，用于研究其生物分布、药代动力学以及作为一种通过β衰变支持的用于根除癌细胞的靶向治疗诊断剂其具有的潜力。
