Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of [131I]Iodine-α-Mangostin for Breast Cancer Diagnosis and Therapy.

The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.

Future Prospective of Radiopharmaceuticals from Natural Compounds Using Iodine Radioisotopes as Theranostic Agents.

Natural compounds provide precursors with various pharmacological activities and play an important role in discovering new chemical entities, including radiopharmaceuticals. In the development of new radiopharmaceuticals, iodine radioisotopes are widely used and interact with complex compounds including natural products. However, the development of radiopharmaceuticals from natural compounds with iodine radioisotopes has not been widely explored. This review summarizes the development of radiopharmaceuticals from natural compounds using iodine radioisotopes in the last 10 years, as well as discusses the challenges and strategies to improve future discovery of radiopharmaceuticals from natural resources. Literature research was conducted via PubMed, from which 32 research articles related to the development of natural compounds labeled with iodine radioisotopes were reported. From the literature, the challenges in developing radiopharmaceuticals from natural compounds were the purity and biodistribution. Despite the challenges, the development of radiopharmaceuticals from natural compounds is a golden opportunity for nuclear medicine advancement.

General toxicity studies of alpha mangostin from Garcinia mangostana: A systematic review.

Alpha mangostin (AM), the main xanthone derivative contained in mangosteen pericarp (Garcinia mangostana/GM), has many pharmacological activities such as antioxidant, antiproliferation, antiinflammatory, and anticancer. Several general toxicity studies of AM have been previously reported to assess the safety profile of AM. Toxicity studies were carried out by various methods such as on test animals, interventions, and various routes of administration, but the test results have not been well documented. Our study aimed to systematically summarizes research on the safety profile of GM containing AM through general toxicity tests to get the LD50 and NOAEL values, and so, can be used as a database related to AM toxicity profiles. This could facilitate other researchers in determining further development of GM-or-AM-based products. Pubmed, Google scholar, ScienceDirect, and EBSCO were chosen to collect the articles while ARRIVE 2.0 was used to evaluate the quality and risk-of-bias of the in vivo toxicity studies included in this systematic review. A total of 20 articles met the eligibility criteria and were reviewed to predict the LD50 and NOAEL of AM. The results showed that the LD50 of AM is between >15.480 mg/kgBW to ≤6000 mg/kgBW while the NOAEL value is between <100 and ≤2000 mg/kgBW.

The purity identification and radiolabeling of α-mangostin with technetium-99m.

Alpha-mangostin (AM) is a natural compound that has the greatest activity in breast cancer. Radiolabeling AM with technetium-99 m (Tc-99m) has a function as breast cancer radiotracer. This study is aimed to identify the purity of Tc-99m-labeled AM. The identification method was conducted by a validated radio-high-performance liquid chromatography (HPLC) to confirm the chemical purity of the compound when the thin layer of chromatography and paper chromatography were used to find out the radiochemical purity (RCP). The validated radio-HPLC method obtained was C18 column with methanol:water (90:10) as the mobile phase and ultraviolet (243 nm) tandem radioactive detector (Gabi Star). The result showed that the RCP was 70.6% ± 2.87%. The analytical method met the validation criteria according to ICH Q2 (R1); thus, it could be applied in the identification. Unfortunately, the 99mTc-AM identification using radio-HPLC showed that the expected complex was not yet formed perfectly because of chemical impurities.