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Seo D.,Institute of Energy and Nuclear Research | Faintuch B.L.,Institute of Energy and Nuclear Research | Aparecida de Oliveira E.,University of Sao Paulo | Faintuch J.,Hospital das Clinicas
Nuclear Medicine and Biology | Year: 2017

Introduction Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed. Methods GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO. Biodistribution and ex-vivo planar imaging were documented. Results Radiolabeling yield was in the range of 97% and both agents were hydrophilic. Fasting Blood Glucose (FBG) was 79.2 ± 8.2 mg/dl in C, 590.4 ± 23.3 mg/dl in ADC, 234.3 ± 66.7 mg/dl in DIO, and 96.6 ± 9.3 in DRO (p = 0.010). Biodistribution confirmed predominantly urinary excretion. DIO mice exhibited depressed uptake in liver and pancreas, for both radiomarkers, in the range of ADC. DRO only partially restored such values. 99mTc-HYNIC-βAla-Exendin-4 demonstrated better results than GLP-1-βAla-HYNIC-99mTc. Conclusions 1) Diet-induced obesity remarkably depressed beta cell uptake; 2) Restriction of obesity failed to normalize uptake, despite robust improvement of FBG; 3) HYNIC-βAla-Exendin-4 was the most useful marker; 4) Further studies are recommended in obesity and dieting, including bariatric surgery. © 2017 Elsevier Inc.

Faintuch B.L.,Institute of Energy and Nuclear Research | Seo D.,Institute of Energy and Nuclear Research | de Oliveira E.A.,Institute of Energy and Nuclear Research | Targino R.C.,Butantan Institute | Moro A.M.,Butantan Institute
Current Radiopharmaceuticals | Year: 2017

Background and Objective: Radiotracer diagnosis of insulinoma, can be done using somatostatin or glucagon-like peptide 1 (GLP-1). Performance of GLP-1 antagonists tends to be better than of agonists. Methods: We investigated the uptake of the antagonist exendin (9-39), radiolabeled with technetium- 99m. Two different sites of the biomolecule were selected for chelator attachment. Results: HYNIC-βAla chelator attached to serine (C- terminus) of exendin, was associated with higher tumor uptake than to aspartate (N- terminus). Conclusion: The chelator position in the biomolecule influenced receptor uptake. © 2017 Bentham Science Publishers.

PubMed | Federal University of São Paulo, Institute of Energy and Nuclear Research and University of Sao Paulo
Type: Journal Article | Journal: Medical mycology | Year: 2014

Paracoccidioidomycosis (PCM) is a chronic granulomatous disease that is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. It is endemic in some countries of Latin America and can cause a high-burden fungal infection with significant morbidity and mortality. The peptide P10, which demonstrates immune protection against experimental PCM, was radiolabeled with a radioisotope and evaluated in vivo. The radiolabeling was conducted to trace the pharmacokinetics of the molecule in principal organs and tissues. This was achieved with high radiochemical purity. Biodistribution and scintigraphic imaging showed fast blood clearance that was mainly renal; however, hepatobiliar excretion was also, with marked uptake in cervical lymph nodes. This profile may be useful for the development of a prophylactic drug or vaccine for patients exposed to PCM.

PubMed | Butantan Institute, Institute of Energy and Nuclear Research, University of Sao Paulo and Hospital Sirio Libanes
Type: Journal Article | Journal: Amino acids | Year: 2016

Gliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with (99m)Tc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.

PubMed | University of the Republic of Uruguay, University of the Free State, University of Würzburg, Service Hospitalier Frederic Joliot and 10 more.
Type: | Journal: Zeitschrift fur medizinische Physik | Year: 2016

Accurate quantitation of activity provides the basis for internal dosimetry of targeted radionuclide therapies. This study investigated quantitative imaging capabilities at sites with a variety of experience and equipment and assessed levels of errors in activity quantitation in Single-Photon Emission Computed Tomography (SPECT) and planar imaging. Participants from 9 countries took part in a comparison in which planar, SPECT and SPECT with X ray computed tomography (SPECT-CT) imaging were used to quantify activities of four epoxy-filled cylinders containing

Faintuch B.L.,Institute of Energy and Nuclear Research | Oliveira E.A.,Institute of Energy and Nuclear Research | Targino R.C.,Butantan Institute | Moro A.M.,Butantan Institute
Applied Radiation and Isotopes | Year: 2014

The asparagine-glycine-arginine (NGR) peptide sequence found by phage display, was radiolabeled with technetium-99. m and tested in different tumor models. Similar uptake occurred with ovarian and lung tumor cells. Biodistribution of the radiotracer revealed predominant renal excretion with more substantial uptake in animals bearing ovarian tumor cells. In contrast imaging studies indicated better visualization for lung tumor. NGR peptide was characterized as a promising diagnostic candidate, particularly for lung cancer. Improvements are envisaged using NGR combined with RGD as a heterodimer molecule. © 2014 Elsevier Ltd.

Zen H.A.,Institute of Energy and Nuclear Research | Ribeiro G.,Institute of Energy and Nuclear Research | Geraldes A.N.,Institute of Energy and Nuclear Research | Souza C.P.,Institute of Energy and Nuclear Research | And 2 more authors.
Radiation Physics and Chemistry | Year: 2013

In this study the ETFE film with 125. μm of thickness was placed inside a nylon bag and filled with either acetylene, nitrogen or oxygen. Following the procedure, the samples were irradiated at 5, 10 and 20. kGy. The physical and chemical properties of the modified and pristine films were evaluated by rheological and thermal analyses (TG and DSC), X-ray diffraction (XRD) and infrared spectroscopy (IR-ATR). In rheological analysis the storage modulus (G') indicates opposite profiles when the atmospheres (acetylene and oxygen) are evaluated according to the absorbed dose. For the samples submitted to radiation under oxygen atmosphere it is possible to observe the degradation process with the low levels of the storage modulus. The changes in the degree of crystallinity were verified in all modified samples when compared to the pristine polymer and this behavior was confirmed by DSC analysis. A decrease in the intensity of crystalline peak by X-ray diffraction was observed. © 2012 Elsevier Ltd.

Scagliusi S.R.,Institute of Energy and Nuclear Research | Cardoso E.C.L.,Institute of Energy and Nuclear Research | Parra D.F.,Institute of Energy and Nuclear Research | Lima L.F.C.P.,Institute of Energy and Nuclear Research | Lugao A.B.,Institute of Energy and Nuclear Research
Radiation Physics and Chemistry | Year: 2013

The major effect of high energy photon, such as gamma rays, in organic polymers is the generation of free radicals, causing changes in electrical, optical and mechanical properties. This work aims to the study of a controlled degradation of a chlorobutyl rubber compound after irradiation at: 25, 100 and 200. kGy doses. Effects of irradiation on a rubber compound were investigated via DMA (Dynamic Mechanical Analysis) tests using the so-called Payne effect, which is directly related to the dynamic properties of the vulcanized rubber. The test begins in a low strain excitation upwards to a maximum programmed strain, and then downwards to a minimum strain at room temperature. The dependency of the material related to the strain amplitude is illustrated by Payne effect. Material behavior presents a non linear evolution on both modulus and Tan when increasing the strain (Payne effect). A difference on G' and tangent δ values at low strain can be observed between the sweeping ways up and down. The difference between new and irradiated material at 25. kGy dose material is not very significant. Nevertheless, the chain scission for higher irradiation doses (≥25. kGy) is verified, as observed by Payne effect. Another interest in strain sweep is to facilitate the detection of strong breaking in materials linkage at high strain amplitude as illustrated by Mullins effect. © 2012 Elsevier Ltd.

Oliveira E.A.,Institute of Energy and Nuclear Research | Faintuch B.L.,Institute of Energy and Nuclear Research
Nuclear Medicine and Biology | Year: 2015

Introduction: Aiming to develop a novel 99mTc-labeled imaging agent, for angiogenesis and tumor receptors, two peptides obtained from phage display library, namely GX1 and the heterodimer RGD-GX1, were synthesized in a cyclic conformation. They were radiolabeled with 99mTc, employing the HYNIC chelator, for radiochemical evaluation and biological properties. Methods: Radiolabeling, radiochemical control, plasma protein binding, and partition coefficient were assessed for both radioconjugates. Biodistribution in healthy Balb/c mice was carried out, in order to evaluate the biological behaviour of the radiocomplexes. Results: The conjugates displayed a rather similar pharmacokinetic profile. They were prepared with high radiochemical purity (>96%), and both were hydrophilic (log P of -2.25 and -2.51 respectively). Preferential renal excretion was observed. Kidney uptake (42.31±5.35 %ID/g) for 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)], 1h post-injection was about three times higher than the uptake of 99mTc-HYNIC-PEG4-c(GX1) (11.92±4.77%ID/g). Total blood, bone and muscle values revealed a slightly slower clearance for the RGD-GX1 radiocomplex. Conclusion: The high radiochemical purity achieved, and the similar in vivo profile observed for both radioconjugates, make them potential candidates for radiopharmaceuticals for tumor imaging. Further investigations of binding affinity, and uptake of GX1 and RGD-GX1 peptides in tumor models, are warranted. © 2014 Elsevier Inc.

Scagliusi S.R.,Institute of Energy and Nuclear Research | Cardoso E.C.L.,Institute of Energy and Nuclear Research | Lugao A.B.,Institute of Energy and Nuclear Research
Radiation Physics and Chemistry | Year: 2012

Butyl rubber (IIR) is an isobutylene/isoprene copolymer and is provided with good properties including low permeability to gases, good thermal stability and high resistance to oxygen and ozone action, among others. It is well known that the major effect of ionizing radiations on butyl rubber is chain scission accompanied with a significant reduction in molar mass. This work aimed to study the effects of gamma radiation on the properties of butyl rubbers vulcanized by three different curing systems, such as, the ones based on sulfur, sulfur donor and phenolic resin to identify which curing system is the most stable under irradiation. The butyl rubber vulcanized by three different systems was gamma irradiated with doses of 25. kGy, 50. kGy, 100. kGy, 150. kGy and 200. kGy. Irradiated and non-irradiated samples were characterized by the following techniques: tensile, elongation and hardness. It was observed that doses higher than 150. kGy practically destroy the assessed properties for all butyl compounds, irrespective of the vulcanization system used; however compounds cured with phenolic resin showed a decrease in properties proportional to the dose. © 2012 Elsevier Ltd.

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