New hybrid radio-fluorescent probes [131I]-BPF-01 and [131I]-BPF-02 for visualisation of cancer cells: Synthesis and preliminary in vitro and ex vivo evaluations
Hendris Wongso,
Ahmad Kurniawan,
Alfian M. Forentin,
Veronika Y. Susilo,
Yanuar Setiadi,
Isa Mahendra,
Muhamad B. Febrian,
Aziiz M. Rosdianto,
Iwan Setiawan,
Hanna Goenawan,
Susianti Susianti,
Unang Supratman,
Eva M. Widyasari,
Teguh H.A. Wibawa,
Maula E. Sriyani,
Iim Halimah,
Ronny Lesmana
Affiliations
Hendris Wongso
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia; Research Collaboration Center for Theranostic Radiopharmaceuticals, National Research and Innovation Agency, Jl. Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia; Corresponding author. Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia.
Ahmad Kurniawan
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Alfian M. Forentin
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Veronika Y. Susilo
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Yanuar Setiadi
Research Center for Environmental and Clean Technology, Research Organization for Life Sciences and Environment, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Isa Mahendra
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia; Research Collaboration Center for Theranostic Radiopharmaceuticals, National Research and Innovation Agency, Jl. Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia
Muhamad B. Febrian
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Aziiz M. Rosdianto
Department of Biomedical Science, Physiology Division, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; Laboratory of Sciences, Graduate School, Universitas Padjadjaran, Bandung, Indonesia
Iwan Setiawan
Department of Biomedical Science, Physiology Division, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; Laboratory of Sciences, Graduate School, Universitas Padjadjaran, Bandung, Indonesia
Hanna Goenawan
Department of Biomedical Science, Physiology Division, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; Laboratory of Sciences, Graduate School, Universitas Padjadjaran, Bandung, Indonesia
Susianti Susianti
Central Laboratory, Universitas Padjadjaran, Jatinangor 45363, Indonesia
Unang Supratman
Central Laboratory, Universitas Padjadjaran, Jatinangor 45363, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor 45363, Indonesia
Eva M. Widyasari
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Teguh H.A. Wibawa
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Maula E. Sriyani
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Iim Halimah
Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia
Ronny Lesmana
Department of Biomedical Science, Physiology Division, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; Laboratory of Sciences, Graduate School, Universitas Padjadjaran, Bandung, Indonesia; Corresponding author. Department of Biomedical Science, Physiology Division, Faculty of Medicine, Universitas Padjadjaran, Jatinangor 45363, Indonesia.
We synthesised and biologically evaluated two new hybrid probes [131I]BPF-01 and [131I]BPF-02 which were built from three structural entities: benzothiazole-phenyl, fluorescein isothiocyanate (FITC), and iodine-131. These probes were designed for potential applications in assisting surgical procedures of solid cancers. The cytotoxicity study demonstrated that fluorescent probes BPF-01 (31.23 μg/mL) and BPF-02 (250 μg/mL) were relatively not toxic to normal immortalized human keratinocytes (HaCaT) cells, as indicated by the percentage of cell survival above 50 %. Furthermore, both probes displayed low to moderate anticancer activity against the breast cancer cells (MDA-MB-231) and prostate cancer cells (LNCaP and DU-145). The probe BPF-01 apparently showed an accumulation in the tumour tissues, as suggested by ex vivo fluorescence examinations. In addition, the cellular uptake study suggests that hybrid probe [131I]-BPF-01 was potentially accumulated in the MCF-7 cell line with the highest uptake of 16.11 ± 1.52 % after 2 h of incubation, approximately 50-fold higher than the accumulation of iodine-131 (control). The magnetic bead assay suggests that [131I]-BPF-02 and [131I]-BPF-02 showed a promising capability to interact with translocator protein 18 kDa (TSPO). Moreover, the computational data showed that the binding scores for ligands 7–8, BPF-01 and BPF-02, and [131I]-BPF-01 and [131I]-BPF-02 in the TSPO were considerably high. Accordingly, fluorescent probes BPF-01 and BPF-02, and hybrid probes [131I]BPF-01 and [131I]BPF-02 can be further developed for targeting cancer cells during intraoperative tumour surgery.