Preparation and in vitro investigation of prostate-specific membrane antigen targeted lycopene loaded niosomes on prostate cancer cells.

In this study, it's aimed to develop prostate-specific membrane antigen (PSMA) targeted niosomes with a multifunctional theranostic approach. With this aim, PSMA-targeted niosomes were synthesized by a thin-film hydration method followed by bath sonication. Drug-loaded niosomes (Lyc-ICG-Nio) were coated with DSPE-PEG-COOH (Lyc-ICG-Nio-PEG) and subsequently anti-PSMA antibody conjugated to niosomes (Lyc-ICG-Nio-PSMA) with amide bond formation. Dynamic light scattering (DLS) analysis showed that the hydrodynamic diameter of Lyc-ICG-Nio-PSMA was approximately 285 nm and it was found with transmission electron microscopy (TEM) that the niosome formulation was spherical. Encapsulation efficiency was 45% and %65 upon dual encapsulation of ICG and lycopene. The results of fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrated that PEG coating and antibody coupling were successfully done. In vitro studies showed that cell viability decreased when lycopene was entrapped into niosomes applied while the total apoptotic cell population rose slightly. When Lyc-ICG-Nio-PSMA was applied to cells, decreased cell viability and enhanced apoptotic effect were seen compared to those for Lyc-ICG-Nio. In conclusion, it was demonstrated that targeted niosomes displayed improved cellular association and decreased cell viability on PSMA + cells.

A dual-modal PET/near infrared fluorescent nanotag for long-term immune cell tracking.

Adoptive cell transfer of targeted chimeric antigen receptor (CAR) T cells has emerged as a highly promising cancer therapy. The pharmacodynamic action or CAR T cells is closely related to their pharmacokinetic profile; because of this as well as the risk of non-specific action, it is important to monitor their biodistribution and fate following infusion. To this end, we developed a dual-modal PET/near infrared fluorescent (NIRF) nanoparticle-based imaging agent for non-genomic labeling of human CAR T cells. Since the PET/NIRF nanoparticles did not affect cell viability or cytotoxic functionality and enabled long-term whole-body CAR T cell tracking using PET and NIRF in an ovarian peritoneal carcinomatosis model, this platform is a viable imaging technology to be applied in other cancer models.

Radioiodination of Pimonidazole as a Novel Theranostic Hypoxia Probe.

BACKGROUND: Tumors are defined as abnormal tissue masses, and one of the most important factors leading to the growth of these abnormal tissue masses is Vascular Endothelial Growth Factor, which stimulates angiogenesis by releasing cells under hypoxic conditions. Hypoxia has a vital role in cancer therapy, thus it is important to monitor hypoxia. The hypoxia marker Pimonidazole (PIM) is a candidate biomarker of cancer aggressiveness. OBJECTIVE: The study aimed to perform radioiodination of PIM with Iodine-131 (131I) to join a theranostic approach. For this purpose, PIM was derived as PIM-TOS to be able to be radioiodinated. METHODS: PIM was derived via a tosylation reaction. Derivatization product (PIM-TOS) was radioiodinated by using iodogen method and was analyzed by High-Performance Liquid Chromatography and Liquid chromatography-mass spectrometry. Thin layer radiochromatography was utilized for its quality control studies. RESULTS: PIM was derived successfully after the tosylation reaction. The radioiodination yield of PIM-TOS was over 85%. CONCLUSION: In the current study, radioiodination potential of PIM with 131I, as a potential theranostic hypoxia agent was investigated. Further experimental studies should be performed for developing a novel hypoxia probe including theranostics approaches.

Examination of the Association Between 3,4-Divanillyltetrahydrofuran Lignan (Urtica dioica Origin) and Prostate Cancer Cells by 131I Radiolabeling.

Background: Prostate cancer is the most common type of cancer for men in many countries. One of the various prostate cancer therapy methods is hormone therapy, and explaining the association between androgen hormones and prostate cancer is a critical role for successful prostate cancer treatment. Materials and Methods: In the current study, the behavior of 3,4-divanillyltetrahydrofuran (DTH) was examined against prostate cancer cells, which have androgen sensitivity differences [LNCaP (+), PC3 (-)]. For this aim, DTH was obtained by extraction of Urtica dioica roots. The molecular structure of isolated compound was confirmed as DTH by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy analyses. To evaluate the association of androgen sensitivity, DTH was radiolabeled with 131I, and cell uptake assay was performed by using 131I-radiolabeled DTH. Also, cytotoxicity (WST-1) assay of DTH was performed against LNCaP and PC3 cells to determinate the toxic effects of DTH on different androgen mechanisms. Results: The results of assays on cells have shown that DTH lignan behaves different like being more toxic to LNCaP cells than PC3 cells, depending on androgen sensitivity. Conclusion: The results may contribute both the research topics of phytolignan prostate cancer and androgen-sensitive prostate cancer.

An in-vivo pilot study into the effects of FDG-mNP in cancer in mice.

PURPOSE: Previously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice. MATERIALS AND METHODS: FDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points. RESULTS: In prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months. CONCLUSION: Intravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.

In Vitro Incorporation of Radioiodinated Eugenol on Adenocarcinoma Cell Lines (Caco2, MCF7, and PC3).

Recently, the synthesis of radiolabeled plant origin compounds has been increased due to their high uptake on some cancer cell lines. Eugenol (EUG), a phenolic natural compound in the essential oils of different spices such as Syzygium aromaticum (clove), Pimenta racemosa (bay leaves), and Cinnamomum verum (cinnamon leaf), has been exploited for various medicinal applications. EUG has antiviral, antioxidant, and anti-inflammatory functions and several anticancer properties. The objective of this article is to synthesize radioiodinated (131I) EUG and investigate its effect on Caco2, MCF7, and PC3 adenocarcinoma cell lines. It is observed that radioiodinated EUG would have potential on therapy and imaging due to its notable uptakes in studied cells.

In Vitro/In Vivo Evaluation of Radiolabeled [(99m)Tc(CO)3](+)-Hydroxyurea and Fluorescein Isothiocyanate-Hydroxyurea.

The aim of current study is to examine hydroxyurea (HU), which is an antineoplastic drug used for the treatment of leukemia, sickle-cell disease, HIV, psoriasis, thrombocythemia, and various neoplastic diseases in two aspects. The active ingredient hydroxyurea was obtained by purification of the capsule form drug, commercially named as HYDREA. Then, [(99m)Tc(CO)3](+)core radiolabeling with HU was performed as first aspect. Quality control studies of (99m)Tc(CO)3-HU complex were performed by thin-layer radiochromatography and high-performance liquid radiochromatography methods. The results demonstrated that the radiolabeling yield was quite high (98.43% ± 2.29%). Also, (99m)Tc(CO)3-HU complex has good stability during the 24-hour period. Biological behavior of (99m)Tc(CO)3-HU complex is evaluated by biodistribution studies on Wistar Albino rats. Fluorescein isothiocyanate (FITC) labeling of HU was performed as second aspect. Fluorometric evaluation of binding efficacy and fluorescence imaging studies on MCF7 and Hela cell lines were carried out. It was thought that the knowledge achieved in this study would contribute to using (99m)Tc(CO)3-HU complex as an imaging agent, which inhibits the DNA synthesis selectively, by inhibiting ribonucleotide reductase enzyme. It was observed that FITC-HU has noteworthy incorporation on both cell lines.

Investigation of therapeutic efficiency of bleomycin and bleomycin-glucuronide labeled with (131)I on the cancer cell lines.

The aim of this study is to determine the incorporations of radiolabeled bleomycin ((131)I-BLM) and bleomycin-glucuronide ((131)I-BLMGLU) on PC-3 (human prostate carcinoma cell line), Caco-2 (human colon adenocarcinoma cell line), Hutu-80 (Human Duodenum adenocarcinoma cell line), and A549 (Human lung adenocarcinoma epithelial cell line) cancerous cell lines. For this purpose, BLM and BLMGLU enyzmatically synthesized were labeled with (131)I, quality control studies were done and the incorporation yields of (131)I-BLM and (131)I-BLMGLU on these cell lines were measured. Quality-control studies showed that the radiolabeling yields were obtained as 95% and 90% for (131)I-BLM and (131)I-BLMGLU, respectively. Also, as a result of the cell culture studies, it was found that (131)I-BLM and (131)I-BLMGLU had higher incorporation on PC-3 cells than that of other cell lines. In addition to this, it was reported that the incorporation yield of (131)I-BLMGLU was higher than that (131)I-BLM. At the end of the study, cytotoxicities of BLM and BLMGLU on PC-3 cancerous cell line were inspected and fluorescent images of BLM and BLMGLU were taken on PC-3 cells by using fluorescein isothiocyanate. In conclusion, cell culture studies demonstrated that the incorporation values of (131)I-BLMGLU on the four cell lines were about five to six times higher than (131)I-BLM. Radiolabeled glucuronide derivatives can be used in cancer therapy and tumor imaging, depending on the properties of radioiodine for the ß-glucuronidase-rich tissues because glucuronidation leads to rapid and higher incorporation on adenocarcinoma cells.

Radiolabeling of methanol extracts of yarrow (Achillea millefolium l) in rats.

PURPOSE: Current study is focused on extraction with methanol, purification, labeling with (131)I using iodogen method of the yarrow plant and investigating in vivo biological activity using biodistribution and imaging studies on healthy animal models. The aim of the study is to contribute plant extracts to discover new drugs in the diagnosis and treatment of several diseases. METHODS: Nine female and nine male healthy Wistar albino rats, which were approximately 100-150 g in weight, were used for biodistribution studies. For imaging studies four healthy male Balb-C mice were used. Quality control studies were done utilizing thin layer radio chromatography (TLRC) and high performance liquid chromatography (HPLC) methods. For biodistribution studies, (131)I radiolabeled Peak 7 ((131)I-Peak 7) was sterilized and injected into the tail veil of rats and imaging studies were obtained using Kodak FX PRO in vivo Imaging System. RESULTS: The radiolabeling yield of each purified the bioactive extracts of the yarrow plant, seven peaks was between 79 and 92%. The highest radiolabeling yield was calculated for (131)I radiolabeled seventh peak ((131)I-Peak 7) (92.78 ± 5.04, n=5). For this reason the biodistribution and imaging studies were done for (131)I-Peak 7. That's why; these studies with Peak 7 were carried out. CONCLUSION: Peak 7 was radiolabeled with (131)I in high yield for using imaging and therapeutic studies in nuclear medical applications.

Radiolabeling of methanol extracts of yarrow (Achillea millefolium l) in rats / Radiomarcação do extrato metanólico de yarrow (Achillea millefolium l) em ratos

PURPOSE: Current study is focused on extraction with methanol, purification, labeling with 131I using iodogen method of the yarrow plant and investigating in vivo biological activity using biodistribution and imaging studies on healthy animal models. The aim of the study is to contribute plant extracts to discover new drugs in the diagnosis and treatment of several diseases. METHODS: Nine female and nine male healthy Wistar albino rats, which were approximately 100-150 g in weight, were used for biodistribution studies. For imaging studies four healthy male Balb-C mice were used. Quality control studies were done utilizing thin layer radio chromatography (TLRC) and high performance liquid chromatography (HPLC) methods. For biodistribution studies, 131I radiolabeled Peak 7 (131I-Peak 7) was sterilized and injected into the tail veil of rats and imaging studies were obtained using Kodak FX PRO in vivo Imaging System. RESULTS: The radiolabeling yield of each purified the bioactive extracts of the yarrow plant, seven peaks was between 79 and 92%. The highest radiolabeling yield was calculated for 131I radiolabeled seventh peak (131I-Peak 7) (92.78±5.04, n=5). For this reason the biodistribution and imaging studies were done for 131I-Peak 7. That's why; these studies with Peak 7 were carried out. CONCLUSION: Peak 7 was radiolabeled with 131I in high yield for using imaging and therapeutic studies in nuclear medical applications.

OBJETIVO: O atual estudo tem por objetivo a extração com metanol, purificação, marcação com I131 usando o método direto de marcação da planta Achillea, para investigar in vivo a atividade biológica usando biodistribuição e estudos de imagem em modelos animais saudáveis. O objetivo do estudo é contribuir com extratos de plantas para descobrir novas drogas para o diagnóstico e tratamento de várias doenças. MÉTODOS: Nove fêmeas e nove machos ratos Wistar albino saudáveis, com aproximadamente 100 a 150g de peso foram usados para estudos de biodistribuição. Para estudos de imagem, quatro camundongos Balb-C machos e saudáveis foram usados. Estudos de controle de qualidade foram realizados usando métodos de cromatografia de camada fina e cromatografia líquida de alta performance. Para estudos de biodistribuição, pico 5 radiografado com I131 (I131-Peak 7) foi esterilizado e injetado na veia da cauda dos ratos e estudos de imagem foram obtidos usando Sistema de Imagem Kodak FX PRO in vivo. RESULTADOS: O retorno radiomarcado de cada extrato bioativo purificado da planta Achillea sete picos estavam entre 79 e 92%. O retorno com maior marcação foi calculado para I131 sétimo pico (I131-Peak 7) (92,78±5,04, n=5). Por esta razão os estudos de biodistribuição e de imagem foram feitos para I131-Peak 7. CONCLUSÃO: Peak 7 foi radiomarcado com I131 em alto retorno para uso em estudos terapêuticos e de imagens nas aplicações médicas nucleares.

L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake.

OBJECTIVE: In this study, we aimed to investigate the cytoprotective effect of L-carnitine against cisplatin-induced nephrotoxicity and to compare its efficacy with that of amifostin by quantitative renal Tc 99m DMSA uptake. MATERIAL AND METHODS: Male Wistar rats were randomly divided into six groups of six animals each. 1) Control (saline; 5 ml/kg intraperitoneally); 2) L-carnitine (CAR; 300 mg/kg intraperitoneally); 3) Amifostine (AMI; 200 mg /kg intraperitoneally); 4) Cisplatin (CIS;7 mg/kg intraperitoneally); 5) Cisplatin plus L-carnitine (CIS + CAR); 6) Cisplatin plus amifostine (CIS + AMI). L-carnitine and amifostine were injected 30 minutes before cisplatin in Group 5 and 6. Tc 99m DMSA, 7.4 MBq/0.2 ml, was injected through the tail vein 72 hours after the drug administration. Rats were killed and kidneys removed by dissection 2 hours after the injection of the radiopharmaceutical. The percentage of the injected dose per gram of kidney tissue (%ID/g) was calculated. Renal function was monitored by measuring BUN and plasma levels of creatinine. Lipid peroxidation and glutathione content were determined by measuring malondialdehyde (MDA) and reduced glutathione (GSH) in kidney tissue homogenates. RESULTS: Tc 99m DMSA uptake per gram tissue of the kidney as %ID/g was 29.54±4.72, 29.86 ± 7.47 and 26.37 ± 4.54 in the control, CAR and AMI groups respectively. %ID/g was the lowest of all the groups, 11.60±3.59 (p<0.01), in the cisplatin group. Carnitine or amifostine administration 30 minutes before cisplatin injection resulted a significant increase in %ID/g, 21.28±7.73 and 18.97±3.24 respectively, compared to those of cisplatin-treated rats (p<0.002). A marked increase in plasma BUN and creatinine indicating nephrotoxicity and acute renal failure was observed in the cisplatin-treated group. MDA and GSH levels were concordant with cisplatin-induced oxidative stress in the kidney tissue. CONCLUSION: The results showed that L-carnitine significantly attenuates the cisplatin-induced nephrotoxicity as amifostin. CONFLICT OF INTEREST: None declared.

Preparation of (99m)Tc labeled vitamin C (ascorbic acid) and biodistribution in rats.

The aim of this study was to label ascorbic acid with (99m)Tc and to investigate its radiopharmaceutical potential in rats. Ascorbic acid was labeled with (99m)Tc using the stannous chloride method. The radiochemical purity of [(99m)Tc]ascorbic acid ((99m)Tc-AA) was determined by RTLC, paper electrophoresis, and RHPLC methods. The labeling yield was found to be 93+/-5.0%. The maximum labeling yield of (99m)Tc-AA was determined at pH 5 and 25 degrees C. The biodistribution studies related to (99m)Tc-AA were done in male albino Wistar rats. (99m)Tc-AA, which has a specific activity of 13.02 GBq/mmol, was administered into the tail vein of the rats. The rats were sacrificed at 15, 30, 60, and 120 min after the injection by heart puncture under ether anaesthesia. The organs were weighed after removal. Their activities were counted using a Cd(Te) detector equipped with a RAD 501 count system. The %ID/g (% of injected dose per gram of tissue weight) in each organ and in blood was calculated. Maximum uptake of (99m)Tc-AA was observed in prostate and kidneys at the 60th min. (99m)Tc-AA may be a promising radiopharmaceutical for the imaging of prostate and kidneys.