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.

Translocator Protein 18 kDa (TSPO): A Promising Molecular Target for Image-Guided Surgery of Solid Cancers.

The translocator protein 18-kDa (TSPO) is a mitochondrial membrane protein that is previously identified as the peripheral benzodiazepine receptor (PBR). Furthermore, it plays a significant role in a diverse range of biochemical processes, including steroidogenesis, mitochondrial cholesterol transport, cell survival and death, cell proliferation, and carcinogenesis. Several investigations also reported its roles in various types of cancers, including colorectal, brain, breast, prostate, and lung cancers, as well as melanoma. According to a previous study, the expression of TSPO was upregulated in cancer cells, which corresponds to an aggressive phenotype and/or poor prognosis. Consequently, the potential for crafting diagnostic and prognostic tools with a focus on TSPO holds great potential. In this context, several radioligands designed to target this protein have been identified, and some of the candidates have advanced to clinical trials. In recent years, the use of hybrid probes with radioactive and fluorescence molecules for image-guided surgery has exhibited promising results in animal and human studies. This indicates that the approach can serve as a valuable surgical navigator during cancer surgery. The current hybrid probes are built from various molecular platforms, including small molecules, nanoparticles, and antibodies. Although several TSPO-targeted imaging probes have been developed, their development for image-guided surgery of cancers is still limited. Therefore, this review aims to highlight recent findings on the involvement of TSPO in carcinogenesis, as well as provide a new perspective on the potential application of TSPO-targeted hybrid probes for image-guided surgery.

Method development, validation, and impurity measurement of ß-estradiol from radiolabeled [131I]ß-estradiol using radio-high-performance liquid chromatography for radioligand of saturation binding assay.

ß-estradiol is an estrogen steroid hormone and acts as an estrogen receptor agonist. Radiolabeled ß-estradiol is widely used as a radioligand for binding assays. In this present study, the synthesis of [131I]ß-estradiol has been successfully carried out. Accordingly, the measurement of the radiochemical purity (RCP) value and the presence of chemical impurities are needed. To validate the method for identifying the RCP and chemical impurities from [131I]ß-estradiol using high-performance liquid chromatography (HPLC). The synthesis of [131I]ß-estradiol was accomplished by a radioiodination reaction, and the RCP was determined by radio-HPLC. The method for ß-estradiol measurement was validated by reversed-phase HPLC radio-analytical employing ultraviolet-visible (UV-Vis) and radioactive detector. The method for radio-HPLC analysis was validated and established using a C-18 column and MeCN: H2O (55:45 v/v) as the mobile phase. The following conditions were applied: a flow rate of 1.2 mL/min, isocratic, and a UV-Vis detector at 280 nm. The RCP of [131I]ß-estradiol measured by thin-layer chromatography and radio-HPLC was 99.27% ± 1.25% and 95.75% ± 2.41%, respectively. The validation parameters were appropriate and met the requirements for acceptance. HPLC analysis was able to identify the presence of unlabeled estradiol (24.51%-27.29%) in the mixture of [131I]ß-estradiol. As a result, purification using preparative HPLC or other methods will be required in future studies.

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2-A Candidate for Passive Immunization against COVID-19.

The coronavirus disease 2019 (COVID-19) has become a substantial threat to the international health sector and the global economy. As of 26 December 2021, the number of mortalities resulting from COVID-19 exceeded 5.3 million worldwide. The absence of an effective non-vaccine treatment has prompted the quest for prophylactic agents that can be used to combat COVID-19. This study presents the feasibility of chicken egg yolk antibody (IgY) anti-receptor-binding domain (RBD) spike SARS-CoV-2 as a strong candidate to neutralize the virus for application in passive immunization. For the purpose of preclinical studies, we radiolabeled IgY anti-RBD spike SARS-CoV-2 with radionuclide iodine-131. This allowed us to evaluate several biological characteristics of IgY in vitro, in vivo, and ex vivo. The preclinical data suggest that IgY anti-RBD spike SARS-CoV-2 could specifically bind to the SARS-CoV-2 antigens; however, little uptake was observed in normal cells (MRC-5) (<2%). Furthermore, the ex vivo biodistribution study revealed that IgY predominantly accumulated in the trachea of normal mice compared to other organs. We also found that IgY possessed a good safety profile when used as an intranasal agent. Taken together, we propose that IgY anti-RBD spike SARS-CoV-2 has the potential for application in passive immunization against COVID-19.

Synthesis, stability, and cellular uptake of 131I-estradiol against MCF7 and T-47D human cell lines as a radioligand for binding assay.

Estradiol is a steroid hormone that works as an agonist estrogen receptor (ER). This compound is widely used as a ligand and bind specifically to the ERα. Radioligand binding assay is an in vitro method for drug development from natural products by synthesizing estradiol through radiolabeling using the radioiodination method. Synthesis of 131I-estradiol was perfomed by direct method using chloramine T as an oxidizer and by indirect labeling using 131I-histamine. The purity of chemical was determined by thin-layer chromatography and paper electrophoresis, as well as its stability for 30 days of storage in refrigerator, freezer and room temperature. The cellular uptake test of the radioligands from both methods was carried out with MCF7 and T-47D cell lines at 60 min. The results exhibited that 131I-estradiol was succesfully obtained with radiochemical purity greater than 95% and more stable in the refrigerator until 21 days than freezer and room temperature. 131I-estradiol and 131I-his-estradiol were internalized higher in T-47D cells than MCF7 cells (44.34 ± 5.93% vs. 17.27 ± 1.71% and 45.34 ± 6.42% vs. 4.92 ± 1.59%, respectively). Furthermore, the radioligands can be used to binding assay in determining the agonist or antagonist to ER of new drugs development.