Rodrigo Teodoro | Helmholtz-Zentrum Dresden Rossendorf (original) (raw)
Papers by Rodrigo Teodoro
Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 14... more Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 148.9 TA2 10.4 nM 77 nM 7.4 TA3 11.4 nM 318 nM 27.9 TA4 7.3 nM 913 nM 125.1 TA5 3.0 nM > 1000 nM > 300 Radioligand Labelling yield Radiochemical yield Specific activity [ 18 F]TA3 72.5 ± 6.4% 48.7 ± 8.5% 60.4 ± 11.6 GBq/µmol [ 18 F]TA4 41.5 ± 9.6% 25.4 ± 3.9% 77.1 ± 23.8 GBq/µmol [ 18 F]TA5 65.3 ± 2.1% 44.8 ± 5.7% 21.4 ± 4.2 GBq/µmol Radioligand RP-HPLC (recovery of activity: 65 -85%) MLC (samples directly injected) [ 18 F]TA3 Plasma: 8%; Brain: 50% Plasma: 5%; Brain: 29% [ 18 F]TA4 Plasma: 6%; Brain: n. d. Plasma: 5%; Brain: 4%
Precipitation of 99 Mo by α-benzoin oxime (α-Bz) is a standard precipitation method for molybdenu... more Precipitation of 99 Mo by α-benzoin oxime (α-Bz) is a standard precipitation method for molybdenum due the high selectivity of this agent. Nowadays, statistical analysis tools have been employed in analytical systems to prove its efficiency and feasibility. IPEN has a project aiming the production of 99 Mo by the fission of 235 U route. The processing uses as the first step the precipitation of 99 Mo with α-Bz. This precipitation step involves many key reaction parameters. The aim of this work is based on the development of the already known acidic route to produce 99 Mo as well as the optimization of the reactional parameters applying statistical tools. In order to simulate 99 Mo precipitation, the study was conducted in acidic media using HNO 3 , αBz as precipitant agent and NaOH /1%H 2 O 2 as dissolver solution. Then, a Mo carrier, KMnO 4 solutions and 99 Mo tracer were added to the reaction flask. The reactional parameters (α-Bz/Mo ratio, Mo carrier, reaction time and temperatur...
Introduction: Apoptosis or programmed cell death is an active, energy-dependent mechanism for eli... more Introduction: Apoptosis or programmed cell death is an active, energy-dependent mechanism for elimination of cells that have been injured, infected, or immunologically recognized as harmful or superfluous. Apoptosis may be used in diagnosis of malignant tumors as it often occurs in hypoxic zones adjoining areas of necrosis, and it is endpoint of most forms of anticancer therapy. The N-terminal sequence of Annexin V, consisting of 13 amino acids (Anx13), is considered a useful marker in this context because of interaction with other molecules such as phosphatidyl-serine, the compound expressed on the surface of the apoptotic cells. Aim: The scope of this study was the labeling of Anx13 fragment with the derivatization of it for nitrido and tricarbonyl technetium approach, and their biological evaluation. Methods: For nitrido technetium labeling, a readily-available lyophilized kit (Schering CIS Bio International) was used. Na 99m TcO4 was added to this kit as well absolute ethanol. T...
Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 14... more Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 148.9 TA2 10.4 nM 77 nM 7.4 TA3 11.4 nM 318 nM 27.9 TA4 7.3 nM 913 nM 125.1 TA5 3.0 nM > 1000 nM > 300 Radioligand Labelling yield Radiochemical yield Specific activity [ 18 F]TA3 72.5 ± 6.4% 48.7 ± 8.5% 60.4 ± 11.6 GBq/µmol [ 18 F]TA4 41.5 ± 9.6% 25.4 ± 3.9% 77.1 ± 23.8 GBq/µmol [ 18 F]TA5 65.3 ± 2.1% 44.8 ± 5.7% 21.4 ± 4.2 GBq/µmol Radioligand RP-HPLC (recovery of activity: 65 -85%) MLC (samples directly injected) [ 18 F]TA3 Plasma: 8%; Brain: 50% Plasma: 5%; Brain: 29% [ 18 F]TA4 Plasma: 6%; Brain: n. d. Plasma: 5%; Brain: 4%
Molecules, 2015
Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions tha... more Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions that are affected by neurological disorders and in certain tumors. Development of a specific PDE2A radioligand would enable molecular imaging of the PDE2A protein via positron emission tomography (PET). Herein we report on the syntheses of three novel fluoroalkylated triazine derivatives (TA2-4) and on the evaluation of their effect on the enzymatic activity of human PDE2A. The most potent PDE2A inhibitors were 18 F-radiolabelled ([ 18 F]TA3 and [ 18 F]TA4) and investigated regarding their potential as PET radioligands for imaging of PDE2A in mouse brain. In vitro autoradiography on rat brain displayed region-specific distribution of [ 18 F]TA3 and [ 18 F]TA4, which is consistent with the expression pattern of PDE2A protein. Metabolism studies of both [ 18 F]TA3 and [ 18 F]TA4 in mice showed a significant accumulation of two major radiometabolites of each radioligand in brain as investigated by micellar radio-chromatography. Small-animal PET/MR studies in OPEN ACCESS mice using [ 18 F]TA3 revealed a constantly increasing uptake of activity in the non-target region cerebellum, which may be caused by the accumulation of brain penetrating radiometabolites. Hence, [ 18 F]TA3 and [ 18 F]TA4 are exclusively suitable for in vitro investigation of PDE2A. Nevertheless, further structural modification of these promising radioligands might result in metabolically stable derivatives.
Acta cirúrgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia, 2011
Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amin... more Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of ⁹⁹(m)Tc-HYNIC-ß-Ala-RGD. ⁹⁹(m)Tc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies. The highest ratio between ischemia and control was achieved at the 7th day (2.62 ± 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 ± 0.23. Scintigraphic image confirmed dif...
Revista Brasileira de Ciências Farmacêuticas, 2008
... v. 6, p. 15-21. [ Links ]. KOTHARI, KK; RAGHURAMAN, K.; PILLARSETTY, NK; HOFFMAN, TJ; OWEN, N... more ... v. 6, p. 15-21. [ Links ]. KOTHARI, KK; RAGHURAMAN, K.; PILLARSETTY, NK; HOFFMAN, TJ; OWEN, NK; KATTI, KV VOLKERT, WA Syntheses, in vitro and in vivo characterization of a 99m Tc-(I)-tricarbonyl-benzylamino-dihydroxymethyl phosphine (NP 2 ) chelate. Appl. Radiat. ...
Acta Radiologica, 2011
Biological performance of radiotracers for sentinel node detection analyzed in the light of molec... more 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.
Nuclear Medicine and Biology, 2011
Introduction: Several strategies on the development of radiopharmaceuticals have been employed. B... more 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 99m Tc-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 99m Tc, using HYNIC and NHS-S-acetyl-MAG 3 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 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. 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.
![Research paper thumbnail of A high-yield automated radiosynthesis of the alpha-7 nicotinic receptor radioligand [(18)F]NS10743](https://attachments.academia-assets.com/43491953/thumbnails/1.jpg)
](Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, Jan 8, 2014
Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity... more Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity ( 499%) and specific activities (5717 17 GBq/mmol, EOS) were achieved. Successful HPLC separation of the [ 18 F]NS10743 from its respective nitro precursor was implemented.
Organic and medicinal chemistry letters, 2013
The level of expression of cannabinoid receptor type 2 (CB2R) in healthy and diseased brain has n... more The level of expression of cannabinoid receptor type 2 (CB2R) in healthy and diseased brain has not been fully elucidated. Therefore, there is a growing interest to assess the regional expression of CB2R in the brain. Positron emission tomography (PET) is an imaging technique, which allows quantitative monitoring of very low amounts of radiolabelled compounds in living organisms at high temporal and spatial resolution and, thus, has been widely used as a diagnostic tool in nuclear medicine. Here, we report on the radiofluorination of N-aryl-oxadiazolyl-propionamides at two different positions in the lead structure and on the biological evaluation of the potential of the two tracers [18F]1 and [18F]2 as CB2 receptor PET imaging agents. High binding affinity and specificity towards CB2 receptors of the lead structure remained unaffected by the structural changes such as the insertion of the aliphatic and aromatic fluorine in the selected labelling sites of 1 and 2. Aliphatic and aroma...
![Research paper thumbnail of A high-yield automated radiosynthesis of the alpha-7 nicotinic receptor radioligand [(18)F]NS10743](https://attachments.academia-assets.com/45844620/thumbnails/1.jpg)
](Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, Jan 8, 2014
Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity... more Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity ( 499%) and specific activities (5717 17 GBq/mmol, EOS) were achieved. Successful HPLC separation of the [ 18 F]NS10743 from its respective nitro precursor was implemented.
Clinics, 2011
OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusin... more OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment.
Nuclear Medicine and Biology, 2011
Introduction: Several strategies on the development of radiopharmaceuticals have been employed. B... more 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 99m Tc-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 99m Tc, using HYNIC and NHS-S-acetyl-MAG 3 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 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. 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.
Nuclear Medicine and Biology, 2009
Introduction: Particle size of colloids employed for sentinel lymph node (LN) detection is not we... more Introduction: Particle size of colloids employed for sentinel lymph node (LN) detection is not well studied. This investigation aimed to correlate particle size and distribution of different products with LN uptake. Methods: All agents (colloidal tin, dextran, phytate and colloidal rhenium sulfide) were labeled with 99m Tc according to manufacturer's instructions. Sizing of particles was carried out on electron micrographs using Image Tool for Windows (Version 2.0). Biodistribution studies in main excretion organs as well as in popliteal LN were performed in male Wistar rats [30 and 90 min post injection (p.i.)]. The injected dose was 0.1 ml (37 MBq) in the footpad of the left posterior limb. Dynamic images (0-15 min p.i.) as well as static ones (30 and 90 min) were acquired in gamma camera. Results: Popliteal LN was clearly reached by all products. Nevertheless, particle size remarkably influenced node uptake. Colloidal rhenium sulfide, with the smallest diameter (5.1×10 -3 ±3.9×10 -3 μm), permitted the best result [2.72±0.64 percent injected dose (%ID) at 90 min]. Phytate displayed small particles (b15 μm) with favorable uptake (1.02±0.14%ID). Dextran (21.4±12.8 μm) and colloidal tin (39.0±8.3 μm) were less effective (0.55±0.14 and 0.06±0.03%ID respectively). Particle distribution also tended to influence results. When asymmetric, it was associated with biphasic uptake which increased over time; conversely, symmetric distribution (colloidal tin) was consistent with a constant pattern. Conclusion: The results are suggesting that particle size and symmetry may interfere with LN radiopharmaceutical uptake.
Applied Radiation and Isotopes, 2011
The objective of this study was the development of a statistical approach for radiolabeling optim... more 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/mg. Crown
Nuclear Medicine and Biology, 2008
Introduction: Radionuclide imaging can be a useful tool for the diagnosis of prostate cancer. Bom... more Introduction: Radionuclide imaging can be a useful tool for the diagnosis of prostate cancer. Bombesin (BBN) is a molecule with high affinity for gastrin releasing peptide (GRP) receptors which are over-expressed in that tumor. This report compares 99m Tc-HYNIC-βAla-BBN (7-14)NH2 [ 99m Tc-HYNIC-BBN] and 99m Tc≡N(PNP6)-Cys-βAla-BBN(7-14)NH2 [ 99m TcN(PNP6)-Cys-BBN] with regard to labeling procedures as well as in vitro and in vivo evaluation (biodistribution and scintigraphic imaging). Methods: Peptide synthesis was performed in an automated peptide synthesizer. HYNIC-BBN was radiolabeled with pertechnetate using tricine and ethylenediamine diacetic acid (EDDA) as coligands. Cys-BBN was radiolabeled in a two-step procedure with the preparation of the precursor 99m Tc-Nitrido first and then introducing diphosphine (PNP6). Radiochemical evaluation of conjugates, as well as studies of stability, transchelation toward cysteine, and partition coefficient were done. Biological studies included internalization, biodistribution in healthy animals and in animals bearing PC3 cancer cells with acquisition of images from the tumor-bearing animals. Results: Both complexes showed a high radiochemical yield along with good stability. Biodistribution studies pointed out strong renal excretion for the former complex due to its hydrophilic profile and marked hepatobiliary excretion for the latter, corresponding to observed lipophilicity. Tumor uptake was higher for 99m Tc-HYNIC-BBN and the same occurred with internalization findings, which exceeded those of 99m TcN(PNP6)-BBN. Blocking studies in mice bearing PC-3 tumor cells revealed significantly reduced pancreas and tumor uptake, demonstrating receptor specificity of the conjugates. Conclusion: The best radiotracer was 99m Tc-HYNIC-BBN on the basis of high radiochemical yield, fast radiolabeling procedure without need for a purification step, and more consistent tumor uptake.
Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 14... more Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 148.9 TA2 10.4 nM 77 nM 7.4 TA3 11.4 nM 318 nM 27.9 TA4 7.3 nM 913 nM 125.1 TA5 3.0 nM > 1000 nM > 300 Radioligand Labelling yield Radiochemical yield Specific activity [ 18 F]TA3 72.5 ± 6.4% 48.7 ± 8.5% 60.4 ± 11.6 GBq/µmol [ 18 F]TA4 41.5 ± 9.6% 25.4 ± 3.9% 77.1 ± 23.8 GBq/µmol [ 18 F]TA5 65.3 ± 2.1% 44.8 ± 5.7% 21.4 ± 4.2 GBq/µmol Radioligand RP-HPLC (recovery of activity: 65 -85%) MLC (samples directly injected) [ 18 F]TA3 Plasma: 8%; Brain: 50% Plasma: 5%; Brain: 29% [ 18 F]TA4 Plasma: 6%; Brain: n. d. Plasma: 5%; Brain: 4%
Precipitation of 99 Mo by α-benzoin oxime (α-Bz) is a standard precipitation method for molybdenu... more Precipitation of 99 Mo by α-benzoin oxime (α-Bz) is a standard precipitation method for molybdenum due the high selectivity of this agent. Nowadays, statistical analysis tools have been employed in analytical systems to prove its efficiency and feasibility. IPEN has a project aiming the production of 99 Mo by the fission of 235 U route. The processing uses as the first step the precipitation of 99 Mo with α-Bz. This precipitation step involves many key reaction parameters. The aim of this work is based on the development of the already known acidic route to produce 99 Mo as well as the optimization of the reactional parameters applying statistical tools. In order to simulate 99 Mo precipitation, the study was conducted in acidic media using HNO 3 , αBz as precipitant agent and NaOH /1%H 2 O 2 as dissolver solution. Then, a Mo carrier, KMnO 4 solutions and 99 Mo tracer were added to the reaction flask. The reactional parameters (α-Bz/Mo ratio, Mo carrier, reaction time and temperatur...
Introduction: Apoptosis or programmed cell death is an active, energy-dependent mechanism for eli... more Introduction: Apoptosis or programmed cell death is an active, energy-dependent mechanism for elimination of cells that have been injured, infected, or immunologically recognized as harmful or superfluous. Apoptosis may be used in diagnosis of malignant tumors as it often occurs in hypoxic zones adjoining areas of necrosis, and it is endpoint of most forms of anticancer therapy. The N-terminal sequence of Annexin V, consisting of 13 amino acids (Anx13), is considered a useful marker in this context because of interaction with other molecules such as phosphatidyl-serine, the compound expressed on the surface of the apoptotic cells. Aim: The scope of this study was the labeling of Anx13 fragment with the derivatization of it for nitrido and tricarbonyl technetium approach, and their biological evaluation. Methods: For nitrido technetium labeling, a readily-available lyophilized kit (Schering CIS Bio International) was used. Na 99m TcO4 was added to this kit as well absolute ethanol. T...
Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 14... more Enzyme assay) Ligand IC 50 PDE2A IC 50 PDE10A Selectivity ratio PDE10A/PDE2A TA1 4.5 nM 670 nM 148.9 TA2 10.4 nM 77 nM 7.4 TA3 11.4 nM 318 nM 27.9 TA4 7.3 nM 913 nM 125.1 TA5 3.0 nM > 1000 nM > 300 Radioligand Labelling yield Radiochemical yield Specific activity [ 18 F]TA3 72.5 ± 6.4% 48.7 ± 8.5% 60.4 ± 11.6 GBq/µmol [ 18 F]TA4 41.5 ± 9.6% 25.4 ± 3.9% 77.1 ± 23.8 GBq/µmol [ 18 F]TA5 65.3 ± 2.1% 44.8 ± 5.7% 21.4 ± 4.2 GBq/µmol Radioligand RP-HPLC (recovery of activity: 65 -85%) MLC (samples directly injected) [ 18 F]TA3 Plasma: 8%; Brain: 50% Plasma: 5%; Brain: 29% [ 18 F]TA4 Plasma: 6%; Brain: n. d. Plasma: 5%; Brain: 4%
Molecules, 2015
Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions tha... more Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions that are affected by neurological disorders and in certain tumors. Development of a specific PDE2A radioligand would enable molecular imaging of the PDE2A protein via positron emission tomography (PET). Herein we report on the syntheses of three novel fluoroalkylated triazine derivatives (TA2-4) and on the evaluation of their effect on the enzymatic activity of human PDE2A. The most potent PDE2A inhibitors were 18 F-radiolabelled ([ 18 F]TA3 and [ 18 F]TA4) and investigated regarding their potential as PET radioligands for imaging of PDE2A in mouse brain. In vitro autoradiography on rat brain displayed region-specific distribution of [ 18 F]TA3 and [ 18 F]TA4, which is consistent with the expression pattern of PDE2A protein. Metabolism studies of both [ 18 F]TA3 and [ 18 F]TA4 in mice showed a significant accumulation of two major radiometabolites of each radioligand in brain as investigated by micellar radio-chromatography. Small-animal PET/MR studies in OPEN ACCESS mice using [ 18 F]TA3 revealed a constantly increasing uptake of activity in the non-target region cerebellum, which may be caused by the accumulation of brain penetrating radiometabolites. Hence, [ 18 F]TA3 and [ 18 F]TA4 are exclusively suitable for in vitro investigation of PDE2A. Nevertheless, further structural modification of these promising radioligands might result in metabolically stable derivatives.
Acta cirúrgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia, 2011
Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amin... more Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of ⁹⁹(m)Tc-HYNIC-ß-Ala-RGD. ⁹⁹(m)Tc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies. The highest ratio between ischemia and control was achieved at the 7th day (2.62 ± 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 ± 0.23. Scintigraphic image confirmed dif...
Revista Brasileira de Ciências Farmacêuticas, 2008
... v. 6, p. 15-21. [ Links ]. KOTHARI, KK; RAGHURAMAN, K.; PILLARSETTY, NK; HOFFMAN, TJ; OWEN, N... more ... v. 6, p. 15-21. [ Links ]. KOTHARI, KK; RAGHURAMAN, K.; PILLARSETTY, NK; HOFFMAN, TJ; OWEN, NK; KATTI, KV VOLKERT, WA Syntheses, in vitro and in vivo characterization of a 99m Tc-(I)-tricarbonyl-benzylamino-dihydroxymethyl phosphine (NP 2 ) chelate. Appl. Radiat. ...
Acta Radiologica, 2011
Biological performance of radiotracers for sentinel node detection analyzed in the light of molec... more 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.
Nuclear Medicine and Biology, 2011
Introduction: Several strategies on the development of radiopharmaceuticals have been employed. B... more 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 99m Tc-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 99m Tc, using HYNIC and NHS-S-acetyl-MAG 3 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 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. 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.
Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, Jan 8, 2014
Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity... more Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity ( 499%) and specific activities (5717 17 GBq/mmol, EOS) were achieved. Successful HPLC separation of the [ 18 F]NS10743 from its respective nitro precursor was implemented.
Organic and medicinal chemistry letters, 2013
The level of expression of cannabinoid receptor type 2 (CB2R) in healthy and diseased brain has n... more The level of expression of cannabinoid receptor type 2 (CB2R) in healthy and diseased brain has not been fully elucidated. Therefore, there is a growing interest to assess the regional expression of CB2R in the brain. Positron emission tomography (PET) is an imaging technique, which allows quantitative monitoring of very low amounts of radiolabelled compounds in living organisms at high temporal and spatial resolution and, thus, has been widely used as a diagnostic tool in nuclear medicine. Here, we report on the radiofluorination of N-aryl-oxadiazolyl-propionamides at two different positions in the lead structure and on the biological evaluation of the potential of the two tracers [18F]1 and [18F]2 as CB2 receptor PET imaging agents. High binding affinity and specificity towards CB2 receptors of the lead structure remained unaffected by the structural changes such as the insertion of the aliphatic and aromatic fluorine in the selected labelling sites of 1 and 2. Aliphatic and aroma...
Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, Jan 8, 2014
Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity... more Development of a high-yield automated radiosynthesis of [ 18 F]NS10743. High radiochemical purity ( 499%) and specific activities (5717 17 GBq/mmol, EOS) were achieved. Successful HPLC separation of the [ 18 F]NS10743 from its respective nitro precursor was implemented.
Clinics, 2011
OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusin... more OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment.
Nuclear Medicine and Biology, 2011
Introduction: Several strategies on the development of radiopharmaceuticals have been employed. B... more 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 99m Tc-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 99m Tc, using HYNIC and NHS-S-acetyl-MAG 3 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 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. 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.
Nuclear Medicine and Biology, 2009
Introduction: Particle size of colloids employed for sentinel lymph node (LN) detection is not we... more Introduction: Particle size of colloids employed for sentinel lymph node (LN) detection is not well studied. This investigation aimed to correlate particle size and distribution of different products with LN uptake. Methods: All agents (colloidal tin, dextran, phytate and colloidal rhenium sulfide) were labeled with 99m Tc according to manufacturer's instructions. Sizing of particles was carried out on electron micrographs using Image Tool for Windows (Version 2.0). Biodistribution studies in main excretion organs as well as in popliteal LN were performed in male Wistar rats [30 and 90 min post injection (p.i.)]. The injected dose was 0.1 ml (37 MBq) in the footpad of the left posterior limb. Dynamic images (0-15 min p.i.) as well as static ones (30 and 90 min) were acquired in gamma camera. Results: Popliteal LN was clearly reached by all products. Nevertheless, particle size remarkably influenced node uptake. Colloidal rhenium sulfide, with the smallest diameter (5.1×10 -3 ±3.9×10 -3 μm), permitted the best result [2.72±0.64 percent injected dose (%ID) at 90 min]. Phytate displayed small particles (b15 μm) with favorable uptake (1.02±0.14%ID). Dextran (21.4±12.8 μm) and colloidal tin (39.0±8.3 μm) were less effective (0.55±0.14 and 0.06±0.03%ID respectively). Particle distribution also tended to influence results. When asymmetric, it was associated with biphasic uptake which increased over time; conversely, symmetric distribution (colloidal tin) was consistent with a constant pattern. Conclusion: The results are suggesting that particle size and symmetry may interfere with LN radiopharmaceutical uptake.
Applied Radiation and Isotopes, 2011
The objective of this study was the development of a statistical approach for radiolabeling optim... more 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/mg. Crown
Nuclear Medicine and Biology, 2008
Introduction: Radionuclide imaging can be a useful tool for the diagnosis of prostate cancer. Bom... more Introduction: Radionuclide imaging can be a useful tool for the diagnosis of prostate cancer. Bombesin (BBN) is a molecule with high affinity for gastrin releasing peptide (GRP) receptors which are over-expressed in that tumor. This report compares 99m Tc-HYNIC-βAla-BBN (7-14)NH2 [ 99m Tc-HYNIC-BBN] and 99m Tc≡N(PNP6)-Cys-βAla-BBN(7-14)NH2 [ 99m TcN(PNP6)-Cys-BBN] with regard to labeling procedures as well as in vitro and in vivo evaluation (biodistribution and scintigraphic imaging). Methods: Peptide synthesis was performed in an automated peptide synthesizer. HYNIC-BBN was radiolabeled with pertechnetate using tricine and ethylenediamine diacetic acid (EDDA) as coligands. Cys-BBN was radiolabeled in a two-step procedure with the preparation of the precursor 99m Tc-Nitrido first and then introducing diphosphine (PNP6). Radiochemical evaluation of conjugates, as well as studies of stability, transchelation toward cysteine, and partition coefficient were done. Biological studies included internalization, biodistribution in healthy animals and in animals bearing PC3 cancer cells with acquisition of images from the tumor-bearing animals. Results: Both complexes showed a high radiochemical yield along with good stability. Biodistribution studies pointed out strong renal excretion for the former complex due to its hydrophilic profile and marked hepatobiliary excretion for the latter, corresponding to observed lipophilicity. Tumor uptake was higher for 99m Tc-HYNIC-BBN and the same occurred with internalization findings, which exceeded those of 99m TcN(PNP6)-BBN. Blocking studies in mice bearing PC-3 tumor cells revealed significantly reduced pancreas and tumor uptake, demonstrating receptor specificity of the conjugates. Conclusion: The best radiotracer was 99m Tc-HYNIC-BBN on the basis of high radiochemical yield, fast radiolabeling procedure without need for a purification step, and more consistent tumor uptake.