Radioiodinated bis-(α-mangostin)-cobalt (II) ([131I]I-AM-Co): Radiolabelling, in vitro and in vivo evaluation for breast cancer radiopharmaceutical

Context: The development of radiopharmaceuticals derived from natural compounds has been extensively studied, particularly for cancer treatment. α-Mangostin is a molecule claimed to be toxic to cancer cells, and its derivative, an organometallic compound, has been synthesized successfully, namely bis-(α-mangostin)-cobalt(II) or AM-Co. The AM-Co structure shows promise as a radiopharmaceutical candidate, especially when labelled with radioactive iodine. Aims: To optimise the radiolabelling conditions of AM-Co with iodine-131 and assess its internalization profile in breast cancer cell lines, as well as biodistribution and pharmacokinetic profile using in vivo approaches. Methods: The radiolabelling of [131I]I-AM-Co was carried out by electrophilic aromatic substitution, with CATas the oxidising agent at low temperatures for synthesis. Internalization studies of [131I]I-AM-Co were conducted in MCF-7 cell lines. Additionally, the biodistribution and pharmacokinetic profiles were assessed by administering 0.37–1.11 MBq of [131I]I-AM-Co (i.v. route) in normal mice and rats. Results: The [131I]I-AM-Co was successfully synthesized with radiopharmaceutical purity of 99.12 ± 0.18% and internalized into MCF-7 cell lines greater than 46% after one hour of incubation. In addition, [131I]I-AM-Co demonstrates 11 times slower diffusion from blood into organs compared with iodine -131, with t½ α was 0.33 ± 0.17 hour. Interestingly, based on AUC data, it reveals that systemic exposure of [131I]I-AM-Co exhibits increasing five times than iodine-131. However, the highest accumulation of [131I]I-AM-Co was still found in the thyroid gland. Conclusions: The [131I]I-AM-Co can be synthesized, achieving a radiochemical purity of over 90%. In addition, the [131I]I-AM-Co compound greatly enhances cellular uptake and plasma concentration compared to iodine-131, which exhibits rapid clearance.