New 99mTc-Labeled Digitoxigenin Derivative for Cancer Cell Identification

In recent years, cardiac glycosides (CGs) have been investigated as potential antiviral and anticancer drugs. Digitoxigenin (DIG) and other CGs have been shown to bind and inhibit Na+/K+-adenosinetriphosphatase (ATPase). Tumor cells show a higher expression rate of the Na+/K+-ATPase protein or a stronger affinity towards the binding of CGs and are therefore more prone to CGs than non-tumor cells. Cancer imaging techniques using radiotracers targeted at specific receptors have yielded successful results. Technetium-99m (99mTc) is one of the radionuclides of choice to radiolabel pharmaceuticals because of its favorable physical and chemical properties along with reasonable costs. Herein, we describe a new Na+/K+-ATPase targeting radiotracer consisting of digitoxigenin and diethylenetriaminepentaacetic acid (DTPA), a bifunctional chelating ligand used to prepare 99mTc-labeled complexes, and its evaluation as an imaging probe. We report the synthesis and characterization of the radiolabeled compound including stability tests, blood clearance, and biodistribution in healthy mice. Additionally, we investigated the binding of the compound to A549 human non-small-cell lung cancer cells and the inhibition of the Na+/K+-ATPase by the labeled compound in vitro. The 99mTc-labeled DTPA–digitoxigenin (99mTc-DTPA–DIG) compound displayed high stability in vitro and in vivo, a fast renal excretion, and a specific binding towards A549 cancer cells in comparison to non-tumor cells. Therefore, 99mTc-DTPA–DIG could potentially be used for non-invasive visualization of tumor lesions by means of scintigraphic imaging

New 99mTc-labeled digitoxigenin derivative for cancer cell identification

In recent years, cardiac glycosides (CGs) have been investigated as potential antiviral and anticancer drugs. Digitoxigenin (DIG) and other CGs have been shown to bind and inhibit Na+ /K+ -adenosinetriphosphatase (ATPase). Tumor cells show a higher expression rate of the Na+ /K+ - ATPase protein or a stronger affinity towards the binding of CGs and are therefore more prone to CGs than non-tumor cells. Cancer imaging techniques using radiotracers targeted at specific receptors have yielded successful results. Technetium99m (99mTc) is one of the radionuclides of choice to radiolabel pharmaceuticals because of its favorable physical and chemical properties along with reasonable costs. Herein, we describe a new Na+ /K+ -ATPase targeting radiotracer consisting of digitoxigenin and diethylenetriaminepentaacetic acid (DTPA), a bifunctional chelating ligand used to prepare 99mTc-labeled complexes, and its evaluation as an imaging probe. We report the synthesis and characterization of the radiolabeled compound including stability tests, blood clearance, and biodistribution in healthy mice. Additionally, we investigated the binding of the compound to A549 human non-small-cell lung cancer cells and the inhibition of the Na+ /K+ - ATPase by the labeled compound in vitro. The 99mTc-labeled DTPA−digitoxigenin (99mTc-DTPA−DIG) compound displayed high stability in vitro and in vivo, a fast renal excretion, and a specific binding towards A549 cancer cells in comparison to nontumor cells. Therefore, 99mTc-DTPA−DIG could potentially be used for non-invasive visualization of tumor lesions by means of scintigraphic imaging

Diagnóstico diferencial da Síndrome de Takotsubo e infarto agudo do miocárdio: uma revisão sistemática: Differential diagnosis of Takotsubo Syndrome and acute myocardial infarction: a systematic review

A cardiomiopatia de Takotsubo e o infarto agudo do miocárdio compartilham apresentação clínica e risco de morte semelhantes, embora uma das diferenças mais importantes seja a ausência de doença coronariana obstrutiva na cardiomiopatia de Takotsubo. Neste estudo, tem-se como objetivo analisar a literatura disponível avaliando o diagnóstico diferencial entre pacientes com CTT em comparação com pacientes com infarto agudo do miocárdio. Para isso, foi realizada uma revisão sistemática, utilizando-se a Pubmed e a Medline como base de dados. A partir da análise dos estudos e interpretação de suas principais descobertas, concluiu-se que para pacientes com CTT, outras condições e comorbidades, em vez de apenas dislipidemia e/ou outros fatores de risco estabelecidos, sejam responsáveis por um risco de morte comparável ao de IAM. No entanto, as conclusões desse estudo têm várias limitaçõe

Toxicological Issues Faced after Liposomes Administration

Nanoparticles are defined as structures in nanometric range-often smaller than 100 nm [1-4]. These particles can be made of sundry materials, the most common being metals, metal oxides, silicates,&nbsp; polymers, carbon, lipids and biomolecules. In addition, they can assume different shapes such as spheres, cylinders, platelets, tubes, etc. The study of these structures in living organisms, for diagnosis, monitoring physical and pathologic processes, therapy and control of biological systems is known as nanomedicine [1]. The study and development of these nanoparticles, mainly lipid carriers, has gained great notoriety for many uses, especially due to their potential as cytotoxic drugs carriers. Over the years, many lipid nanosystems have been developed and applied for different purposes. Liposomes are one of the most studied nanocarrier since Bangham and colleagues [5] reported their preparation in 1965. Afterwards, several kinds of enclosed phospholipid bilayer structures, formed by single bilayers, were described. In this scenario, Gregory Gregoriadis established a new concept that liposomes could entrap drugs, being promising drug delivery systems [6]. Moreover, other researchers showed that liposomes could change the in vivo distribution of entrapped drugs leading to better pharmacokinetics compared to free drugs [7-9]. As a result, these systems may have some advantages, such as the improvement of physicochemical characteristics of the drugs, the delivery to a specific site and controlled release of these molecules. These factors lead to a positive impact on the safety profile. Currently, there are over ten liposomal formulations approved for human use, apart from many preparations in advanced stage of clinical study [8].</p

Radiolabeling of cidofovir with technetium-99m and biodistribution studies

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug

Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects and deaths. In this work, a novel pH-sensitive liposomal formulation capable of co-encapsulating DOX and SIM at different molar ratios was investigated for its potential in breast tumor treatment. Studies on physicochemical characterization of the liposomal formulations were carried out. The cytotoxic effects of DOX, SIM, and their combinations at different molar ratios (1:1; 1:2 and 2:1), free or co-encapsulated into pH-sensitive liposomes, were evaluated against three human breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3). Experimental protocols included cell viability, combination index, nuclear morphological changes, and migration capacity. The formulations showed a mean diameter of less than 200 nm, with a polydispersity index lower than 0.3. The encapsulation content was ~100% and ~70% for DOX and SIM, respectively. A more pronounced inhibitory effect on breast cancer cell lines was observed at a DOX:SIM molar ratio of 2:1 in both free and encapsulated drugs. Furthermore, the 2:1 ratio showed synergistic combination rates for all concentrations of cell inhibition analyzed (50, 75, and 90%). The results demonstrated the promising potential of the co-encapsulated liposome for breast tumor treatment

Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects and deaths. In this work, a novel pH-sensitive liposomal formulation capable of co-encapsulating DOX and SIM at different molar ratios was investigated for its potential in breast tumor treatment. Studies on physicochemical characterization of the liposomal formulations were carried out. The cytotoxic effects of DOX, SIM, and their combinations at different molar ratios (1:1; 1:2 and 2:1), free or co-encapsulated into pH-sensitive liposomes, were evaluated against three human breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3). Experimental protocols included cell viability, combination index, nuclear morphological changes, and migration capacity. The formulations showed a mean diameter of less than 200 nm, with a polydispersity index lower than 0.3. The encapsulation content was ~100% and ~70% for DOX and SIM, respectively. A more pronounced inhibitory effect on breast cancer cell lines was observed at a DOX:SIM molar ratio of 2:1 in both free and encapsulated drugs. Furthermore, the 2:1 ratio showed synergistic combination rates for all concentrations of cell inhibition analyzed (50, 75, and 90%). The results demonstrated the promising potential of the co-encapsulated liposome for breast tumor treatment