Institute of Energetic and Nuclear Research

São Paulo, Brazil

Institute of Energetic and Nuclear Research

São Paulo, Brazil
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Oliveira E.A.,Institute of Energetic and Nuclear Research | Faintuch B.L.,Institute of Energetic and Nuclear Research | Nunez E.G.F.,Institute of Energetic and Nuclear Research | Maria Moro A.,Butantan Institute | And 2 more authors.
Melanoma Research | Year: 2012

Early and reliable diagnosis of melanoma, a skin tumor with a poor prognosis, is extremely important. Phage display peptide libraries are a convenient screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was to evaluate two technetium-99m tracers for angiogenesis detection in a melanoma model, using cyclic pegylated pentapeptide with RGD and NGR motifs conjugated with the bifunctional chelator mercaptoacetyltriglycine (MAG 3). The conjugated peptides (10 μl of a μg/μl solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was carried out by instant thin-layer chromatography and confirmed by high-performance liquid chromatography. The partition coefficient was determined and internalization assays were performed in two melanoma cell lines (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was carried out in healthy animals at different time points and also in tumor-bearing mice, 120 min post injection. Blocking studies were also conducted by coinjection of cold peptides. The conjugates displayed a rather similar pharmacokinetic profile. They were radiolabeled with high radiochemical purity (>97%) and both were hydrophilic with preferential renal excretion. Yet, tumor uptake was higher for human than for murine melanoma cells, especially for [ 99mTc]-MAG 3-PEG 8-c(RGDyk) (7.85±2.34%injected dose/g 120 min post injection). The performance of [ 99nTc]-MAG 3-PEG 8-c(RGDyk) was better than the NGR tracer with regard to human melanoma uptake. In this sense, it should be considered for future radiotracer studies of tumor diagnosis. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Galante A.M.S.,Institute of Energetic and Nuclear Research | Galante O.L.,Av. Torres de Oliveira | Camposa L.L.,Institute of Energetic and Nuclear Research
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2010

Changes induced by radiation in the UV-vis and Infrared absorbance spectra of fluoropolymer films were investigated. Samples (3 × 1 cm 2) of commercially available fluoropolymers, tetrafluoropolymer homopolymer (PTFE-Tecnofluor/DuPont) and its copolymers with hexafluoropropylene (FEP 1000 C-DuPont) and perfluoroalkoxy (PFA 500 CLP-Dupont) were irradiated with 60Co gamma radiation in free air at electronic equilibrium conditions with absorbed doses between 1 and 150kGy. Studies of environmental condition effects, such as temperature and light, pre- and post-irradiation stability and dose range useful response were carried out. Fluoropolymers are very stable when exposed to different ambient conditions; the dosimetric wavelength is characteristic for each type of fluoropolymer and a linear correlation was found between gamma radiation dose and optical response. © 2009 Elsevier B.V.


Teodoro R.,Institute of Energetic and Nuclear Research | Faintuch B.L.,Institute of Energetic and Nuclear Research | Nunez E.G.F.,Institute of Energetic and Nuclear Research | Queiroz R.G.,Institute of Energetic and Nuclear Research
Nuclear Medicine and Biology | Year: 2011

Introduction: Several strategies on the development of radiopharmaceuticals have been employed. Bifunctional chelators seem to be a promising approach since high radiochemical yields as well as good in vitro and in vivo stability have been achieved. To date, neurotensin analogs have been radiolabeled using the 99mTc-carbonyl approach and none was described employing the bifunctional chelating agent technique. Aim: The purpose of this study was to evaluate the radiochemical and biological behaviour of NT(8-13) analogue radiolabeled with 99mTc, using HYNIC and NHS-S-acetyl-MAG3 as chelator agents. Methods: Radiolabeling, in vitro stability toward cysteine and glutathione, partition coefficient and plasma protein binding were assessed for both radioconjugates. Biodistribution in healthy Swiss mice were carried out in order to evaluate the biological behaviour of the radiocomplexes. Results: Radiochemical yields were higher than 97% and no apparent instability toward transchelant agents was observed for both radioconjugates. A higher lipophilic character was observed for the radioconjugate labeled via MAG3. The chelators seem to have no effect on the percentage of the radioconjugate bound to plasma proteins. A similar biological pattern was observed for both radioconjugates. Total blood, bone and muscle values revealed a slightly slower clearance for the radiocomplex labeled via MAG3. Moreover, a remarkable liver and intestinal uptake was observed for the radiocomplex labeled via MAG3 even at the later time points studied. Conclusion: The high radiochemical yields achieved and the similar in vivo pattern found for both radioconjugates make them potential candidates for imaging tumors using nuclear medicine techniques. © 2011 Elsevier Inc.


Nunez E.G.F.,Institute of Energetic and Nuclear Research | de Oliveira E.A.,Institute of Energetic and Nuclear Research | da Silva N.G.,Institute of Energetic and Nuclear Research | de Oliveira Filho R.S.,Federal University of São Paulo
Nuclear Medicine and Biology | Year: 2012

Introduction: The aim of this work was to quantify the effects of injection volume at different technetium-99m specific radiotracer doses on its lymphatic movement in animal model. Procedures: Effects of injection volume (50, 100 μl) at different doses (0.05, 0.135, 0.22 nmol) on popliteal node (PN) detection were studied in rats. The radiotracer under study was 99mTechnetium-cysteine-mannose-dextran conjugate (30 kDa). Results: At 0.05 nmol dose, higher PN uptake was observed at 50 μl injection volume (2.6 fold increase). Conversely, at 0.135 nmol dose, an increase of radiotracer retention in PN was achieved at 100 μl volume, 78% higher than 50 μl. However, at 0.22 nmol dose, the injection volume changes did not influence on the PN uptake. Considering as suitable radiotracer performance: high PN uptake and extraction, better combinations were 0.05 nmol/50 μl, 0.135 nmol/100 μl, 0.22/50 μl. Conclusion: Suitable performances could be reached by proper combinations of dose, injection volume and concentration for a specific radiotracer used in sentinel lymph node detection. © 2012.


Nunez E.G.F.,Institute of Energetic and Nuclear Research | Teodoro R.,Institute of Energetic and Nuclear Research | Wiecek D.P.,Institute of Energetic and Nuclear Research | Da Silva N.G.,Institute of Energetic and Nuclear Research | And 2 more authors.
Acta Radiologica | Year: 2011

Background: Biological performance of radiotracers for sentinel node detection analyzed in the light of molecular design and dimension is not widely available. Purpose: To evaluate the effect of dextran molecular size and the presence of tissue-binding units (mannose) within the model of 99mTc-carbonyl conjugate for sentinel lymph node detection. Material and Methods: Four dextran conjugates with and without mannose in the chemical backbone were included. All polymers were radiolabeled using the precursor [99mTc(OH2)3(CO)3]+. Radiolabeling conditions targeted the best radiochemical purity and specific activity for each radiopharmaceutical, and partition coefficients were also defined. Lymphoscintigraphy and ex-vivo biodistribution in popliteal lymph node, liver and kidneys were performed in Wistar rats. The effects of molecular weight and mannose presence were assessed by a two-level factorial design. Results: Radiochemical purity was indirectly related to molecular weight and presence of mannose in the polymer structure. All products were able to detect popliteal lymph node, however, uptake was strongly influenced by use of mannose (4-fold higher). Excretion was similarly modulated by differences in molecular weight. Mannose-enhanced lymph node uptake and higher molecule size in the range under study benefitted lymphoscintigraphic performance. Conclusion: Screening of radiopharmaceuticals for lymphoscintigraphy might improve with attention to the mentioned physico-chemical features of the molecule.


PubMed | Institute of Energetic and Nuclear Research
Type: Journal Article | Journal: Acta radiologica (Stockholm, Sweden : 1987) | Year: 2011

Biological performance of radiotracers for sentinel node detection analyzed in the light of molecular design and dimension is not widely available.To evaluate the effect of dextran molecular size and the presence of tissue-binding units (mannose) within the model of (99m)Tc-carbonyl conjugate for sentinel lymph node detection.Four dextran conjugates with and without mannose in the chemical backbone were included. All polymers were radiolabeled using the precursor [(99m)Tc(OH(2))(3)(CO)(3)](+). Radiolabeling conditions targeted the best radiochemical purity and specific activity for each radiopharmaceutical, and partition coefficients were also defined. Lymphoscintigraphy and ex-vivo biodistribution in popliteal lymph node, liver and kidneys were performed in Wistar rats. The effects of molecular weight and mannose presence were assessed by a two-level factorial design.Radiochemical purity was indirectly related to molecular weight and presence of mannose in the polymer structure. All products were able to detect popliteal lymph node, however, uptake was strongly influenced by use of mannose (4-fold higher). Excretion was similarly modulated by differences in molecular weight. Mannose-enhanced lymph node uptake and higher molecule size in the range under study benefitted lymphoscintigraphic performance.Screening of radiopharmaceuticals for lymphoscintigraphy might improve with attention to the mentioned physico-chemical features of the molecule.


PubMed | Institute of Energetic and Nuclear Research
Type: Journal Article | Journal: Melanoma research | Year: 2012

Early and reliable diagnosis of melanoma, a skin tumor with a poor prognosis, is extremely important. Phage display peptide libraries are a convenient screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was to evaluate two technetium-99m tracers for angiogenesis detection in a melanoma model, using cyclic pegylated pentapeptide with RGD and NGR motifs conjugated with the bifunctional chelator mercaptoacetyltriglycine (MAG(3)). The conjugated peptides (10 l of a g/l solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was carried out by instant thin-layer chromatography and confirmed by high-performance liquid chromatography. The partition coefficient was determined and internalization assays were performed in two melanoma cell lines (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was carried out in healthy animals at different time points and also in tumor-bearing mice, 120 min post injection. Blocking studies were also conducted by coinjection of cold peptides. The conjugates displayed a rather similar pharmacokinetic profile. They were radiolabeled with high radiochemical purity (>97%) and both were hydrophilic with preferential renal excretion. Yet, tumor uptake was higher for human than for murine melanoma cells, especially for [(99m)Tc]-MAG(3)-PEG(8)-c(RGDyk) (7.852.34%injected dose/g 120 min post injection). The performance of [(99m)Tc]-MAG(3)-PEG(8)-c(RGDyk) was better than the NGR tracer with regard to human melanoma uptake. In this sense, it should be considered for future radiotracer studies of tumor diagnosis.


PubMed | Institute of Energetic and Nuclear Research
Type: Evaluation Studies | Journal: Nuclear medicine and biology | Year: 2012

The aim of this work was to quantify the effects of injection volume at different technetium-99m specific radiotracer doses on its lymphatic movement in animal model.Effects of injection volume (50, 100 l) at different doses (0.05, 0.135, 0.22 nmol) on popliteal node (PN) detection were studied in rats. The radiotracer under study was (99m)Technetium-cysteine-mannose-dextran conjugate (30 kDa).At 0.05 nmol dose, higher PN uptake was observed at 50 l injection volume (2.6 fold increase). Conversely, at 0.135 nmol dose, an increase of radiotracer retention in PN was achieved at 100 l volume, 78% higher than 50 l. However, at 0.22 nmol dose, the injection volume changes did not influence on the PN uptake. Considering as suitable radiotracer performance: high PN uptake and extraction, better combinations were 0.05 nmol/50 l, 0.135 nmol/100 l, 0.22/50 l.Suitable performances could be reached by proper combinations of dose, injection volume and concentration for a specific radiotracer used in sentinel lymph node detection.


PubMed | Institute of Energetic and Nuclear Research
Type: Journal Article | Journal: Nuclear medicine and biology | Year: 2011

Several strategies on the development of radiopharmaceuticals have been employed. Bifunctional chelators seem to be a promising approach since high radiochemical yields as well as good in vitro and in vivo stability have been achieved. To date, neurotensin analogs have been radiolabeled using the (99m)Tc-carbonyl approach and none was described employing the bifunctional chelating agent technique.The purpose of this study was to evaluate the radiochemical and biological behaviour of NT(8-13) analogue radiolabeled with (99m)Tc, using HYNIC and NHS-S-acetyl-MAG(3) as chelator agents.Radiolabeling, in vitro stability toward cysteine and glutathione, partition coefficient and plasma protein binding were assessed for both radioconjugates. Biodistribution in healthy Swiss mice were carried out in order to evaluate the biological behaviour of the radiocomplexes.Radiochemical yields were higher than 97% and no apparent instability toward transchelant agents was observed for both radioconjugates. A higher lipophilic character was observed for the radioconjugate labeled via MAG(3). The chelators seem to have no effect on the percentage of the radioconjugate bound to plasma proteins. A similar biological pattern was observed for both radioconjugates. Total blood, bone and muscle values revealed a slightly slower clearance for the radiocomplex labeled via MAG(3). Moreover, a remarkable liver and intestinal uptake was observed for the radiocomplex labeled via MAG(3) even at the later time points studied.The high radiochemical yields achieved and the similar in vivo pattern found for both radioconjugates make them potential candidates for imaging tumors using nuclear medicine techniques.


PubMed | Institute of Energetic and Nuclear Research
Type: Journal Article | Journal: Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine | Year: 2011

The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/g.

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