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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.

Prostate-specific membrane antigen (PSMA) represents a promising target for PSMA-overexpressing diseases, especially prostate cancer-a common type of cancer among men worldwide. In response to the challenges in tackling prostate cancers, several promising PSMA inhibitors from a variety of molecular scaffolds (e.g., phosphorous-, thiol-, and urea-based molecules) have been developed. In addition, PSMA inhibitors bearing macrocyclic chelators have attracted interest due to their favorable pharmacokinetic properties. Recently, conjugating a small PSMA molecule inhibitor-bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator, as exemplified by [177Lu]Lu-PSMA-617 could serve as a molecular imaging probe and targeted radioligand therapy (TRT) of metastatic castration resistant prostate cancer (mCRPC). Hence, studies related to mCRPC have drawn global attention. In this review, the recent development of PSMA ligand-617-labeled with 177Lu for the management of mCRPC is presented. Its molecular mechanism of action, safety, efficacy, and future direction are also described.

Abstract The archipelagic country of Indonesia is populated by the densest marine biodiversity in the world which has created strong global interest and is valued by both Indigenous and European settlements for different purposes. Nearly 1000 chemicals have been extracted and identified. In this review, a systematic data curation was employed to collate bioprospecting related manuscripts providing a comprehensive directory based on publications from 1988 to 2022. Findings with significant pharmacological activities are further discussed through a scoping data collection. This review discusses macroorganisms (Sponges, Ascidian, Gorgonians, Algae, Mangrove) and microorganism (Bacteria and Fungi) and highlights significant discoveries, including a potent microtubule stabilizer laulimalide from Hyattella sp., a prospective doxorubicin complement papuamine alkaloid from Neopetrosia cf exigua, potent antiplasmodial manzamine A from Acanthostrongylophora ingens, the highly potent anti trypanosomal manadoperoxide B from Plakortis cfr. Simplex, mRNA translation disrupter hippuristanol from Briareum sp, and the anti-HIV-1 (+)-8-hydroxymanzamine A isolated from Acanthostrongylophora sp. Further, some potent antibacterial extracts were also found from a limited biomass of bacteria cultures. Although there are currently no examples of commercial drugs from the Indonesian marine environment, this review shows the molecular diversity present and with the known understudied biodiversity, reveals great promise for future studies and outcomes. Graphical Abstract

β-estradiol is an estrogen steroid hormone and acts as an estrogen receptor agonist. Radiolabeled β-estradiol is widely used as a radioligand for binding assays. In this present study, the synthesis of [131I]β-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]β-estradiol using high-performance liquid chromatography (HPLC). The synthesis of [131I]β-estradiol was accomplished by a radioiodination reaction, and the RCP was determined by radio-HPLC. The method for β-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]β-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]β-estradiol. As a result, purification using preparative HPLC or other methods will be required in future studies.

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.

Natural products provide a bountiful supply of pharmacologically relevant precursors for the development of various drug-related molecules, including radiopharmaceuticals. However, current knowledge regarding the importance of natural products in developing new radiopharmaceuticals remains limited. To date, several radionuclides, including gallium-68, technetium-99m, fluorine-18, iodine-131, and iodine-125, have been extensively studied for the synthesis of diagnostic and therapeutic radiopharmaceuticals. The availability of various radiolabeling methods allows the incorporation of these radionuclides into bioactive molecules in a practical and efficient manner. Of the radiolabeling methods, direct radioiodination, radiometal complexation, and halogenation are generally suitable for natural products owing to their simplicity and robustness. This review highlights the pharmacological benefits of curcumin and its analogs, flavonoids, and marine peptides in treating human pathologies and provides a perspective on the potential use of these bioactive compounds as molecular templates for the design and development of new radiopharmaceuticals. Additionally, this review provides insights into the current strategies for labeling natural products with various radionuclides using either direct or indirect methods.

Cancer is the second-highest mortality rate disease worldwide, and it has been estimated that cancer will increase by up to 20 million cases yearly by 2030. There are various options of treatment for cancer, including surgery, radiotherapy, and chemotherapy. All of these options have damaging adverse effects that can reduce the patient’s quality of life. Cancer itself arises from a series of mutations in normal cells that generate the ability to divide uncontrollably. This cell mutation can happen as a result of DNA damage induced by the high concentration of ROS in normal cells. High levels of reactive oxygen species (ROS) can cause oxidative stress, which can initiate cancer cell proliferation. On the other hand, the cytotoxic effect from elevated ROS levels can be utilized as anticancer therapy. Some bioactive compounds from natural foods such as fruit, vegetables, herbs, honey, and many more have been identified as a promising source of natural antioxidants that can prevent oxidative stress by regulating the level of ROS in the body. In this review, we have highlighted and discussed the benefits of various natural antioxidant compounds from natural foods that can regulate reactive oxygen species through various pathways.

Bovine colostrum (BC) is the initial milk produced by cows after giving birth. It has been used to treat human diseases, such as infections, inflammations, and cancers. Accumulating evidence suggests that bovine lactoferrin and bovine antibodies seem to be the most important bioactive constituents in BC. Thus, BC has also been reviewed for its potential to deliver short-term protection against coronavirus disease 2019 (COVID-19). In addition, it can potentially be explored as a precursor for peptide-based radiopharmaceuticals. To date, several bioactive peptides have been isolated from BC, including casocidin-1, casecidin 15 and 17, isracidin, caseicin A, B, and C. Like other peptides, bioactive peptides derived from BC could be used as a valuable precursor for radiopharmaceuticals either for diagnosis or therapy purposes. This review provides bovine colostrum’s biological activities and a perspective on the potential use of peptides from BC for developing radiopharmaceuticals in nuclear medicine.

Neuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future. Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRRT Neuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future. Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRRT

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) (

Cancer is a serious health burden on global societies. The discovery and development of new anti-cancer therapies remains a challenging objective. Although it has been shown that lichen secondary metabolites may be potent sources for new anti-cancer agents, the Indonesian- grown folious lichens, Physcia millegrana, Parmelia dilatata and Parmeila aurulenta, have not yet been explored. In this study exhaustive preparative high-performance liquid chromatography was employed to isolate the lichen constituents with spectroscopic and spectrometric protocols identifying nine depsides 9–17, including the new methyl 4-formyl-2,3-dihydroxy-6-methylbenzoate 13. The cytotoxicity of the depsides towards cancer cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results indicated lowest toxicity of the depsides towards human A549 lung cancer cells. Importantly, the di-depsides (11, 12 and 17) showed greatest toxicity, indicating that these structures are biologically more active than the mono-depsides against the HepG2 liver cancer, A549 lung cancer and HL-60 leukemia cell lines.