Effects of Fluorodeoxyglucose Conjugated and Unconjugated Iron Oxide Magnetic Nanoparticles on Macrophages: a Pilot Study

Abstract The effects of fluorodeoxyglucose conjugated iron oxide magnetic nanoparticles (FDGMNP) on macrophages are presented using a yeast substrate. Iron oxide magnetic nanoparticles (MNP) were synthesized by partially reducing FeCl3, then conjugated with (3-aminopropyl) triethoxysilane (APTES) after silication with tetraethyl orthosilicate. Silanated MMP nanoparticles were combined with fluorodeoxyglucose (FDG). Fluorodeoxyglucose iron oxide magnetic nanoparticles (FDGMNP) and its unconjugated control (MNP) were added (1mL) to the cells from the murine macrophage-like, Abelson murine leukemia virus transformed cell line RAW 264.7 (American Type Culture Collection number TIB-71) cell culture wells at different concentrations from 90-3.6 μg/mL. Cells were placed on the magnet plate for 30 min before incubating at 37°C, 5% CO2 overnight. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium) assay was performed to measure cell viability. Our results demonstrate that iron based nanoparticles can be linked to macrophages (elements of the immune system that attack bacteria) without the function of the macrophages being affected, ie no detrimental effects to the macrophages were evident in these experiments. We conclude that neither FDGMNP nor MNP had a detrimental effect on macrophage function.

Effect of rosemary (Rosmarinus officinalis) extract on the biodistribution of 99mTc sulphur colloid and on the radiolabeled blood constituents

With this study we evaluated the effects of the herb rosemary (Rosmarinus officinalis L. Lamiaceae) extract on the labeling of blood constituents with technetium-99m (99mTc) labeled sulphur colloid and on the biodistribution of 99mTc-Sulphur Colloid in Wistar albino rats. For this purpose, two groups of animals (male wistar rats, 130-140 g) were treated (1 mL) with a rosemary extract (750 mg/kg body wt.,n=9) and water (control, n=9) separately by gavage for five days. 99mTc-Sulphur Colloid was administrated by intravenous injection; organs/tissues were withdrawn and weighted. Blood was centrifuged, plasma and blood cells were isolated. The radioactivity was counted to calculate the percentage of activity per gram for each organ/tissue and percentage of activity in blood cells and plasma. A significant increase (p<0.05) in the uptake of 99mTc-Sulphur Colloid in the liver after the treatment with rosemary extract was observed. These results indicate that the substances or metabolites of the rosemary extract would change the biodistribution of99mTc-Sulphur Colloid.

Anti toxic effect of broccoli extract on stannous dichloride toxicity / Efeito antitóxico do extrato de brócolis na toxicidade do dicloreto de estanho

PURPOSE: Since Technetium-99m (99mTc) has favorable physical and chemical characteristics, it is widely used radioisotope in Nuclear Medicine. However, stannous dichloride (SnCl2) has been widely used as a reducing agent in labeling procedure of pharmaceutical with radionuclide, it has been realized that SnCl2 have genotoxic and cytotoxic effects on biological systems. In previous studies, it has been shown that some herbal extract can reduce genotoxic and cytotoxic effects of SnCl2. In the present study, it is aimed to evaluate the effect of the broccoli extract on the survival of E. coli ATCC 25922 strain against to toxic effects of SnCl2. METHODS: Broccoli was extracted with methanol extraction. HPLC and TLC analysis of broccoli extract were performed. Then antitoxicity and dose response assays were performed on bacterial strain. RESULTS: The broccoli extract had dose dependent protective effect against SnCl2 toxic effect on E. coli. CONCLUSIONS: The consumption of broccoli may alter the stannous dichloride toxicity. Broccoli extract may use as a new protective strategies against the toxic effect of SnCl2 on patients who were taken 99mTc radiopharmaceuticals.

OBJETIVO: Em face de suas características físico-químicas, o Tecnécio-99m (99mTc) é um radiofármaco amplamente utilizado na Medicina Nuclear. Todavia, o dicloreto de estanho (SnCl2) tem sido largamente aplicado como um agente redutor no procedimento farmacêutico de marcação com radionuclídeos. Constatou-se que o SnCl2 apresenta efeitos genotóxicos e citotóxicos nos sistemas biológicos. Em estudos prévios, foi demonstrado que alguns extratos de ervas podem reduzir tais efeitos. O estudo atual objetivou avaliar os efeitos do extrato de brócolis na sobrevida da cepa E. coli ATCC 25922, exposta ao efeito tóxico do SnCl2. MÉTODOS: O extrato de brócolis foi obtido mediante extração com metanol. Analises com HPLC e TLC foram efetuadas. Avaliou-se a antitoxicidade e realizou-se um ensaio dose-resposta para uma cepa de bactérias. RESULTADOS: O extrato de brócolis mostrou um efeito protetor dose dependente para os efeitos tóxicos do SnCl2 sobre a E. coli. CONCLUSÕES: O consumo de brócolis pode alterar a toxicidade do dicloreto de estanho. O extrato de brócolis pode ser utilizado como uma nova estratégia para proteção de pacientes contra os efeitos tóxicos do SnCl2, nos quais foi administrado o radiofármaco Tecnécio-99m.

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.

Effect of a plant origin drug on the biodistribution of 99mTc-DTPA in Wistar albino rats

In recent years all over the world, medicinal plants are used quite a lot but side effects of biological and chemical contents and radiopharmaceutical interactions for each consumer in question aren't entirely well-known. The studies of plant origin drug interaction with radiopharmaceuticals are highly relevant and desired. One of them is passiflora syrup (Passiflora incarnata L., Passifloraceae) which is widely used for depression, insomnia, anxiety and menopause period. The aim of current study is to evaluate possible effects of passiflora syrup on the biodistribution of 99mTc-DTPA and its blood cells uptake. DTPA was labeled with 99mTc radionuclide. Biodistribution studies were performed on male Wistar albino rats which were treated via oral feeding-gavage-method with either passiflora syrup or 0.9 % NaCl as control group for ten days. Blood samples were obtained by cardiac blood withdrawal from the rats and they were radiolabeled. The biodistribution results showed that the passiflora syrup decreased the uptake of 99mTc-DTPA in kidneys and in blood cells. 99mTc-DTPA being used widely as a kidney diagnostic agent in nuclear medicine seems to be interacting with orally taken passiflora. Passiflora syrup may modify the uptake of 99mTc-DTPA by kidney. The knowledge of this negative effect may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in nuclear medicine.

Effects of broccoli extract on biodistribution and labeling blood components with 99mTc-GH / Efeitos do extrato de brócolis na biodistribuição e marcação dos componentes do sangue com 99mTc-GH

PURPOSE: People consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate (99mTc-GH) and radiolabeling of blood components. METHODS: GH was labeled with 99mTc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl2 and 99m Tc. RESULTS: Radiochemical yield of 99mTc-GH is 98.46±1.48 percent (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups. CONCLUSIONS: Although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine.

OBJETIVO: As pessoas consomem verduras sem o conhecimento dos efeitos colaterais dos conteúdos biológicos e químicos e interações entre os medicamentos radiofarmacêuticos e os extratos vegetais. Para este fim, o estudo atual é focado sobre os efeitos do extrato de brócolis na biodistribuição do fármaco glucoheptonato (99mTc-GH) e da marcação de componentes do sangue. MÉTODOS: GH foi marcado com 99mTc. Estudos de controle de qualidade foram feitos utilizando o método do TLC. Os estudos de biodistribuição foram realizados em ratos machos que foram tratados por gavagem com um extrato de brócolis ou SF como grupo controle para 15 dias. Amostras de sangue foram retiradas do coração de ratos. Marcação de constituintes sanguíneos realizados incubação com SnCl2 GH e 99mTc. RESULTADOS: Radioquímica rendimento de 99mTc-GH é 98,46 ± 1,48 por cento (n = 8). Os estudos de biodistribuição mostraram que de acordo com o controle, o grupo tratado com brócolis tem aproximadamente 10 vezes menor absorção no rim. O percentual do ratio de radioatividade dos componentes do sangue é encontrado para ser igual nos dois grupos. CONCLUSÕES: Embora não haja nenhum efeito considerável sobre a marcação dos componentes do sangue há uma mudança notável na biodistribuição especialmente nos rins. O conhecimento desta mudança na captação de rim pode contribuir para reduzir o risco de erro diagnóstico e/ou a repetição dos exames de Medicina Nuclear.

In Vivo investigation of radiolabeled Bevacizumab in healthy rat tissues

In this study, BevMab was conjugated with the bifunctional chelating agent [diethylenetriamine pentaacetic acid (DTPA)] and the product (BevMab-DTPA) was labeled with 99mTc using stannous chloride reducing method. The quality control studies of radiolabeled compound (99mTc-BevMab-DTPA) were done with Thin Layer Radio Chromatography (TLRC) and High Performance Liquid Radio Chromatography (HPLRC) methods ( percent 95 <) to confirm the labeling efficiency. High radiochemical yield [98.07 percent ± 2.17 (n = 13)] was obtained by TLRC method. Biodistribution studies of 99mTc labeled BevMab-DTPA was run on healthy female and male Albino Wistar rats. The distribution figures demonstrated that the radiolabeled compound was eliminated through the kidneys and accumulated in urinary bladder. The values of the BevMab-DTPA uptakes were similar in heart, blood, liver and spleen in both sexes.

Imaging and therapy with radionuclide labeled magnetic nanoparticles

Magnetic nanoparticles offer exciting new opportunities including the improvement of the quality of magnetic resonance imaging (MRI), hyperthermic treatment for malignant cells, site-specific drug delivery and also the recent research interest of manipulating cell membranes. The biological applications of these nanomaterials require these nanoparticles to have high magnetization values, size smaller than 20 nm, narrow particle size distribution and a special surface coating for both avoiding toxicity and allowing the coupling of biomolecules. In this review, we focus on the feasibility of radionuclide labeled magnetic nanoparticles, as drug carriers, and summarize recent advances in this field.

Nanopartículas magnéticas oferecem novas oportunidades interessantes, incuindo a melhora da qualidade da imagem de ressonância magnética (MRI), no tratamento hipertérmico para células malignas, na administração de medicamentos sítio-específicos e também no recente interesse da manipulação de membranas celulares. As aplicações biológicas desses nanomateriais requer que essas nanopartículas tenham valores altos de magnetização, tamanho menor que 20 nm, partículas de dimensão de distribuição restrita e um revestimento especial de superfície para evitar a toxicidade e permitir o acoplamento de biomoléculas. Nessa revisão, focalizamos na viabilidade de nanopartículas magnéticas marcadas com radionuclídeos, como transportadoras de medicamentos, e resumimos os recentes avanços nesse campo.

Targeted tumor radiotherapy

Targeted tumor radiotherapy is selectively delivery of curative doses of radiation to malignant sites. The aim of the targeted tumor radiotherapy is to use the radionuclides which have high LET particle emissions conjugated to appropriate carrier molecules. The radionuclides are selectively collected by tumor cells, depositing lethal doses to tumor cells while no admission occur to normal cells. In theory, targeted radiotherapy has several advantages over conventional radiotherapy since it allows a high radiation dose to be administered without causing normal tissue toxicity, although there are some limitations in the availability of appropriate targeting agents and in the calculations of administered doses. Therefore, for routine clinical applications more progress is still needed. In this article, the potential use of targeted tumor radiotherapy is briefly reviewed. More general aspects and considerations, such as potential radionuclides, mechanisms of tumor targeting was also outlined