Revista Portuguesa de Pneumologia (English Edition), 2009
Resumo A drenagem linfática pulmonar profunda (DLPP) desempenha um papel importante na remoção de... more Resumo A drenagem linfática pulmonar profunda (DLPP) desempenha um papel importante na remoção de materiais estranhos, constituindo os macrófagos alveolares a primeira linha de defesa fagocitária, dada a grande afinidade para microrganismos patogénicos. Os Bacillus subtilis são saprófitas do tracto respiratório humano com ampla utilização em investigação e em biotecnologia.
Cells stem cells (CSCs) have been identified in several types of malignancies and referred as the... more Cells stem cells (CSCs) have been identified in several types of malignancies and referred as the responsible for driving tumor growth and resistance to chemotherapy. Previous studies have identified CSCs in a human osteosarcoma cell line that is relatively resistant to doxorubicin. We aimed to identify the mechanisms underlying this resistant phenotype and to assess the functional alterations occurring during
Advances in Experimental Medicine and Biology, 1997
The use of the patch-clamp technique has made possible the characterization of the glucose sensit... more The use of the patch-clamp technique has made possible the characterization of the glucose sensitivity of a number of cation channels present in the β-cell membrane. One of these channels, the ATP-dependent K+ (KATP) channel, is specifically blocked by intracellular ATP and appears to play an essential role in the coupling of glucose metabolism to membrane depolarization and, hence, to Ca2+ influx and to the initiation of insulin release[1]. The available data indicate that the activity of the KATP channel is almost fully suppressed at 6 mM glucose, ie. a concentration which brings the membrane potential to a level just below the threshold for the appearance of electrical activity. At glucose concentrations above 7 mM the β-cell displays a pattern of bursting electrical activity which is remarkably sensitive to the hexose concentration, with the silent unexcited period (“silent phase”) being progressively reduced and the depolarized active phase (“active phase”) becoming progressively elongated as the size of the glucose stimulus increases[2]. We conclude that, while the glucose-mediated reduction in the activity of the KATP channels is indeed essential for the glucose-evoked initial depolarization of the β-cell, the modulation of bursting electrical activity by the hexose in the range 7–20 mM is apparently accounted for, at least in part, by a channel distinct from the KATP channel. The present account aims at providing evidence to support this hypothesis.
European Heart Journal - Cardiovascular Imaging, 2021
Type of funding sources: None. Calcification plays a major role in coronary atherogenesis. Positr... more Type of funding sources: None. Calcification plays a major role in coronary atherogenesis. Positron emission tomography (PET) imaging with fluorine-18 sodium fluoride (Na[18F]F) is able to detect microcalcification and is associated with cardiovascular (CV) risk factors. Thoracic fat volume (TFV) and epicardial adipose tissue (EAT) are associated with atherosclerosis, pro-inflammatory state, and CV events. We aimed to evaluate the association between Na[18F]F uptake and cardiac fat variables. Cardiac Na[18F]F uptake was assessed as global molecular calcification score (GMCS): the sum of the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. TFV was assessed in computed tomography (CT) using automated software to sum the voxels consisting of fat (threshold of -190 to -30 Hounsfield units) between the bifurcation of pulmonary artery and the e...
Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing ... more Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, ...
18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis. It is know that its upta... more 18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis. It is know that its uptake is related with microcalcification. The purpose of this study is to assess the relationship between 18F-NaF uptake by the aortic valve and by the main arterial vessels and cardiovascular risk. Twenty-five hypertensive patients without known cardiovascular disease or aortic stenosis underwent PET-CT with 18F-NaF. Cardiovascular risk was assessed through the ASCVD risk calculator. The patients had a mean age of 64.0±8.6 years and 56% were males. The mean ASCVD risk was of 28.8±19.0 (IQR: 10–48.5). The uptake of 18F-NaF assessed through the corrected uptake per lesion (CUL = max SUV – mean blood-pool SUV) was of 0.49±0.14 (IQR: 0.44–0.57) and the mean uptake in the aortic, coronary and carotid territories was of 0.66±0.21 (IQR: 0.53 - 0.76).The patients were classified according to the ASCVD: Group A: patients with a risk above the 50thpercentile of the ASCVD risk distribution (50thperce...
The purpose of this study was to evaluate 18F-FDG activity in the right atrium in a group of pati... more The purpose of this study was to evaluate 18F-FDG activity in the right atrium in a group of patients with ischemic cardiomyopathy, scheduled for viability assessment. 41 patients were evaluated according to the viability protocol with 18F-FDG. 39 men and 2 women were included with a mean age of 65.1 ± 9.6 years. The activity in the right atrium (RA) wall was corrected for blood-pool activity registered in the lumen of the RA. The tracer activity was compared with echocardiography parameters: LVEF; RA area; tricuspid annular plane systolic excursion (TAPSE) and RA area. Left ventricular ejection fraction (LVEF) was of 33.9 ± 10.0, the TAPSE was of 17.2 ± 4.2 and RA area 15.4 ± 4.9. The corrected 18F-FDG activity in RA wall was of 1.3 ± 0.5. No correlation was seen between RA activity and LVEF: r = 0.12, p = 0.45. RA activity was related with the TAPSE: r = 0.42, p = 0.008 and the RA area: r = 0.47, p = 0.006. It seems that right atrium 18F-FDG activity is related with right ventricle function and enlargement of the right atrium. Further studies should be performed in order to confirm these results and validate 18F-FDG activity in the right atrium as an image marker of right heart overload.
Background/Introduction:Abnormal myocardial perfusion at rest can be due to scar or hibernating m... more Background/Introduction:Abnormal myocardial perfusion at rest can be due to scar or hibernating myocardium. Hibernating myocardium is metabolically active and its recognition in patients with severe coronary artery disease and left ventricle dysfunction, who may benefit from aggressive management, is of the utmost importance. Myocardial viability, with technetium agents, may be suggested by the severity of the perfusion defects. On the other hand, cardiac [18F]FDG PET/CT is the gold standard for myocardial viability assessment. Purpose:To compare myocardial viability assessed by [99mTc]Tc-Tetrafosmin SPECT and [13N]Ammonia/[18F]FDG PET/CT. Methods:All patients submitted to rest [13N]Ammonia/[18F]FDG PET/CT and rest [99mTc]Tc-Tetrafosmin SPECT/CT in our center were selected. All studies were evaluated according to a semi-quantitative visual scale. Uptake in each individual segment was scored from 0 to 4, 0 denoting normal perfusion or metabolism, and 4 total absence. All [99mTc]Tc-Tetrafosmin SPECT/CT perfusion defects with uptake inferior to 55% of peak activity were classifiedas nonviable, and those with uptake equal or greater than 55% were considered viable. For PET/CT, the perfusion and metabolic studies were compared and a viability score was calculated. Viability extent percentages were calculated for both methods. Statistical analysis was performed using SPSS. Results:A total of 51 rest [13N]Ammonia/[18F]FDG PET/CT for viability assessment were performed, however only 22 patients had also been submitted to [99mTc]Tc-Tetrafosmin SPECT/CT during the selected time period (1 woman; 21 men; average age:64.9 ± 7.8 years). A difference was found in the extent of myocardial viability identified by rest [13N]Ammonia/[18F]FDG PET/CT and [99mTc]Tc-Tetrafosmin SPECT/CT, with median higher percentages for the former (25.9 ± 18.9% vs 15.8 ± 9.3%, respectively). However, probably due to the small sample size, a statistically significant difference was not found (paired samples T-test, p = 0.055), Conclusion(s):[99mTc]Tc-Tetrafosmin SPECT/CT underestimated the extent of viability when compared to [18F]FDG PET/CT PET/CT, the accepted gold standard, however a statistically significant difference was not found, most likely due to the small sample size.
Background and objective: 18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis... more Background and objective: 18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis. It is know that its uptake is related with microcalcification. The purpose of this study is to assess the relationship between 18F-NaF uptake by the aortic valve, aortic valve calcium score and cardiovascular risk. Methods and Results: Twenty-five hypertensive patients without known cardiovascular disease or aortic stenosis underwent PET-CT with 18F-NaF. Cardiovascular risk was assessed through the ASCVD risk calculator. The patients had a mean age of 64.0± 8.6 years and 56% were males. The mean ASCVD risk was of 28.8 ±19.0 (IQR: 10-48.5). The aortic valve calcium score (AoV score) was of 53.2 ± 164.4(IQR: 0-29.8), the uptake of 18F-NaF assessed through the corrected uptake per lesion (CUL = max SUV-mean blood-pool SUV) was of 0.49 ± 0.14 (IQR: 0.44-0.57). The patients were classified according to the ASCVD: Group A: patients with a risk above the 50thpercentile of the ASCVD risk distribution (50thpercentile = 25: 12 patients) and Group B: patients with a risk under or equal to the 50thpercentile of the ASCVD risk distribution, 13 patients. The uptake of 18F-NaF and the aortic valve calcium score were evaluated in both groups: A vs B: CUL = 0.57 ± 0.09 vs0. 42 ± 0.14, p = 0.005; AoV score= 102.4 ± 231.7 vs7.8 ± 13.2, p = 0.15. Conclusion: In this study microcalcification, evaluated through 18F-NaF uptake, was related with cardiovascular risk as was reported with vulnerable atherosclerotic plaques reinforcing the importance of cardiovascular risk prevention in aortic valve degeneration. Although the score of calcium seems to be higher in higher cardiovascular risk patients, no significant difference was found in this study.
The purpose of this study was to evaluate 18F-FDG activity in the atria in a group of patients wi... more The purpose of this study was to evaluate 18F-FDG activity in the atria in a group of patients with ischemic cardiomyopathy, scheduled for viability assessment and find clinical variables related with this finding.
Following our previous work on the production of radiometals, such as 64Cu and 68Ga, through the ... more Following our previous work on the production of radiometals, such as 64Cu and 68Ga, through the irradiation of liquid targets using a medical cyclotron, we describe in this paper a technique to produce 61Cu through the irradiation of natural zinc using a liquid target.
This work describes the production of two clinically relevant metal radioisotopes [Formula: see t... more This work describes the production of two clinically relevant metal radioisotopes [Formula: see text] and [Formula: see text] with a medical cyclotron by the irradiation of liquid targets. New results are presented for the implementation of this methodology in a fully automated system, using commercially available equipment. Liquid target solutions containing enriched [Formula: see text] and [Formula: see text] were loaded, bombarded and transferred to synthesis modules where a purified solution containing the desired radiometal is obtained and can then be used to further radiolabeling within only one hour after End-Of-Bombardment (EOB). Typical production runs using enriched material lead to the production of 5 GBq and 6 GBq (0.14 MBq/([Formula: see text]Ah ⋅ mg) and 1.5 MBq/([Formula: see text]Ah ⋅ mg)) of [Formula: see text] and [Formula: see text]; although the technique can be used to obtain up to 25 GBq and 40 GBq, respectively, by simply scaling up the amount of the enriched ...
A fully automated system for the production of 68Ga based on commercially available cyclotron liq... more A fully automated system for the production of 68Ga based on commercially available cyclotron liquid target and synthesis modules is described. A solution containing enriched 68Zn dissolved in a nitric solution is irradiated in a Cyclone 18/9 IBA cyclotron leading to the production of up to about 25 GBq of 68Ga. The irradiated solution is transferred to a Synthera synthesis module in which 68Ga is separated and purified with a yield superior to 85 % and where further labelling is achieved with yields no inferior to 70 %. The developed and implemented method presents an improved approach for the production of 68Ga-radiopharmaceuticals suitable for human use, in a process that takes less than 2 hours. This technique represents an economically viable alternative to 68Ge/68Ga generators with improved characteristics.
2015 IEEE 4th Portuguese Meeting on Bioengineering (ENBENG), 2015
Positron Emission Tomography (PET) is a powerful functional imaging technique targeted for in viv... more Positron Emission Tomography (PET) is a powerful functional imaging technique targeted for in vivo quantification and localization of physiological and pathophysiological functions. The possibility to develop a vast number of diseases in transgenic and knockout mice, and the chance to follow the onset of the diseases and the evolution of the treatment efficacy in an individual basis, made PET the third preferred preclinical imaging technique (20%) in research and development of new drug therapies [1]. Two features are mandatory in a preclinical PET system: a high Full Width at Half Maximum (FWHM) Spatial Resolution (SR), comprised between 0.40 and 0.27 mm for mice, so as to achieve the same level of detail of current state-of-the art PET scanners for humans [2], and a sensitivity as high as possible, to allow to differentiate and quantify a subtle signal in the presence of significant background counts [3]. Commercially available state-of-the-art preclinical PET systems make use of detectors based on segmented inorganic scintillation crystals coupled to photodetectors [2]. To reduce the complexity and cost, light multiplexing is used to decode the position of interaction of annihilation photons [3]. This scheme poses some limitations to the sensitivity and SR attained by preclinical PET systems, due to, among other problems, the difficulty of measuring efficiently the Depth-Of-Interaction [3]. The best reported values for the sensitivity and SR of current commercially available preclinical PET systems, are of, respectively, ~10% and ~1 mm FWHM [2]. Timing Resistive Plate Chambers (RPCs) are gaseous detectors with resistive parallel plate electrodes (made of glass) separated by small (~300 μm thick) and precise amplification gaps filled with an appropriate gas mixture. For the detection of photons, these are first converted into electrons in the resistive plates in an electronic cascade process. Some of the originated electrons will eventually escape to the amplification gap, where they will be accelerated by a uniform electric field, leading to a Townsend avalanche, which induces a current in a set of signal pickup strips. These low cost detectors have an excellent time resolution of 300 ps FWHM for 511 keV photon pairs, an excellent intrinsic SR, the readout being in almost full 3D mode. Recently, we developed a first fully functional prototype of a preclinical RPC-PET scanner for mice, which revealed a SR of 0.4 mm FWHM after image reconstruction by a Maximum Likelihood Expectation Maximization type algorithm. Preliminary tests with mice, preformed at the Institute of Nuclear Sciences Applied to Health (ICNAS - Instituto de Ciências Nucleares Aplicada às Saúde) of the University of Coimbra, shown the capability of the system to clearly identify the very small brain structures of mice, as well as the heart walls. The results obtained thus far are very promising, revealing unprecedented SR.
Ideal reaction conditions were found to promote the "cold" monomethylation of 5,10,15,2... more Ideal reaction conditions were found to promote the "cold" monomethylation of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin with CH 3 I , at minute time scale, in the presence of base. The photophysical characterization, cellular uptake and dark cytotoxicity of the resulting monomethylated porphyrin were appraised. Moreover, the syntheses of the corresponding labeled porphyrin, using short-lived carbon-11, prepared in the automated radiolabeling system were efficiently performed. The purification of the labeled product was achieved via preparative HPLC with high radiochemical purity and specific radioactivity. Preliminary studies on the biodistribution of 5,10,15-tris(3-hydroxyphenyl)-20-(3-[11C]methoxyphenyl)porphyrin carried out in a BALB/C normal mouse, using PET imaging, showed that the liver is the main pathway for excretion.
Revista Portuguesa de Pneumologia (English Edition), 2009
Resumo A drenagem linfática pulmonar profunda (DLPP) desempenha um papel importante na remoção de... more Resumo A drenagem linfática pulmonar profunda (DLPP) desempenha um papel importante na remoção de materiais estranhos, constituindo os macrófagos alveolares a primeira linha de defesa fagocitária, dada a grande afinidade para microrganismos patogénicos. Os Bacillus subtilis são saprófitas do tracto respiratório humano com ampla utilização em investigação e em biotecnologia.
Cells stem cells (CSCs) have been identified in several types of malignancies and referred as the... more Cells stem cells (CSCs) have been identified in several types of malignancies and referred as the responsible for driving tumor growth and resistance to chemotherapy. Previous studies have identified CSCs in a human osteosarcoma cell line that is relatively resistant to doxorubicin. We aimed to identify the mechanisms underlying this resistant phenotype and to assess the functional alterations occurring during
Advances in Experimental Medicine and Biology, 1997
The use of the patch-clamp technique has made possible the characterization of the glucose sensit... more The use of the patch-clamp technique has made possible the characterization of the glucose sensitivity of a number of cation channels present in the β-cell membrane. One of these channels, the ATP-dependent K+ (KATP) channel, is specifically blocked by intracellular ATP and appears to play an essential role in the coupling of glucose metabolism to membrane depolarization and, hence, to Ca2+ influx and to the initiation of insulin release[1]. The available data indicate that the activity of the KATP channel is almost fully suppressed at 6 mM glucose, ie. a concentration which brings the membrane potential to a level just below the threshold for the appearance of electrical activity. At glucose concentrations above 7 mM the β-cell displays a pattern of bursting electrical activity which is remarkably sensitive to the hexose concentration, with the silent unexcited period (“silent phase”) being progressively reduced and the depolarized active phase (“active phase”) becoming progressively elongated as the size of the glucose stimulus increases[2]. We conclude that, while the glucose-mediated reduction in the activity of the KATP channels is indeed essential for the glucose-evoked initial depolarization of the β-cell, the modulation of bursting electrical activity by the hexose in the range 7–20 mM is apparently accounted for, at least in part, by a channel distinct from the KATP channel. The present account aims at providing evidence to support this hypothesis.
European Heart Journal - Cardiovascular Imaging, 2021
Type of funding sources: None. Calcification plays a major role in coronary atherogenesis. Positr... more Type of funding sources: None. Calcification plays a major role in coronary atherogenesis. Positron emission tomography (PET) imaging with fluorine-18 sodium fluoride (Na[18F]F) is able to detect microcalcification and is associated with cardiovascular (CV) risk factors. Thoracic fat volume (TFV) and epicardial adipose tissue (EAT) are associated with atherosclerosis, pro-inflammatory state, and CV events. We aimed to evaluate the association between Na[18F]F uptake and cardiac fat variables. Cardiac Na[18F]F uptake was assessed as global molecular calcification score (GMCS): the sum of the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. TFV was assessed in computed tomography (CT) using automated software to sum the voxels consisting of fat (threshold of -190 to -30 Hounsfield units) between the bifurcation of pulmonary artery and the e...
Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing ... more Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, ...
18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis. It is know that its upta... more 18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis. It is know that its uptake is related with microcalcification. The purpose of this study is to assess the relationship between 18F-NaF uptake by the aortic valve and by the main arterial vessels and cardiovascular risk. Twenty-five hypertensive patients without known cardiovascular disease or aortic stenosis underwent PET-CT with 18F-NaF. Cardiovascular risk was assessed through the ASCVD risk calculator. The patients had a mean age of 64.0±8.6 years and 56% were males. The mean ASCVD risk was of 28.8±19.0 (IQR: 10–48.5). The uptake of 18F-NaF assessed through the corrected uptake per lesion (CUL = max SUV – mean blood-pool SUV) was of 0.49±0.14 (IQR: 0.44–0.57) and the mean uptake in the aortic, coronary and carotid territories was of 0.66±0.21 (IQR: 0.53 - 0.76).The patients were classified according to the ASCVD: Group A: patients with a risk above the 50thpercentile of the ASCVD risk distribution (50thperce...
The purpose of this study was to evaluate 18F-FDG activity in the right atrium in a group of pati... more The purpose of this study was to evaluate 18F-FDG activity in the right atrium in a group of patients with ischemic cardiomyopathy, scheduled for viability assessment. 41 patients were evaluated according to the viability protocol with 18F-FDG. 39 men and 2 women were included with a mean age of 65.1 ± 9.6 years. The activity in the right atrium (RA) wall was corrected for blood-pool activity registered in the lumen of the RA. The tracer activity was compared with echocardiography parameters: LVEF; RA area; tricuspid annular plane systolic excursion (TAPSE) and RA area. Left ventricular ejection fraction (LVEF) was of 33.9 ± 10.0, the TAPSE was of 17.2 ± 4.2 and RA area 15.4 ± 4.9. The corrected 18F-FDG activity in RA wall was of 1.3 ± 0.5. No correlation was seen between RA activity and LVEF: r = 0.12, p = 0.45. RA activity was related with the TAPSE: r = 0.42, p = 0.008 and the RA area: r = 0.47, p = 0.006. It seems that right atrium 18F-FDG activity is related with right ventricle function and enlargement of the right atrium. Further studies should be performed in order to confirm these results and validate 18F-FDG activity in the right atrium as an image marker of right heart overload.
Background/Introduction:Abnormal myocardial perfusion at rest can be due to scar or hibernating m... more Background/Introduction:Abnormal myocardial perfusion at rest can be due to scar or hibernating myocardium. Hibernating myocardium is metabolically active and its recognition in patients with severe coronary artery disease and left ventricle dysfunction, who may benefit from aggressive management, is of the utmost importance. Myocardial viability, with technetium agents, may be suggested by the severity of the perfusion defects. On the other hand, cardiac [18F]FDG PET/CT is the gold standard for myocardial viability assessment. Purpose:To compare myocardial viability assessed by [99mTc]Tc-Tetrafosmin SPECT and [13N]Ammonia/[18F]FDG PET/CT. Methods:All patients submitted to rest [13N]Ammonia/[18F]FDG PET/CT and rest [99mTc]Tc-Tetrafosmin SPECT/CT in our center were selected. All studies were evaluated according to a semi-quantitative visual scale. Uptake in each individual segment was scored from 0 to 4, 0 denoting normal perfusion or metabolism, and 4 total absence. All [99mTc]Tc-Tetrafosmin SPECT/CT perfusion defects with uptake inferior to 55% of peak activity were classifiedas nonviable, and those with uptake equal or greater than 55% were considered viable. For PET/CT, the perfusion and metabolic studies were compared and a viability score was calculated. Viability extent percentages were calculated for both methods. Statistical analysis was performed using SPSS. Results:A total of 51 rest [13N]Ammonia/[18F]FDG PET/CT for viability assessment were performed, however only 22 patients had also been submitted to [99mTc]Tc-Tetrafosmin SPECT/CT during the selected time period (1 woman; 21 men; average age:64.9 ± 7.8 years). A difference was found in the extent of myocardial viability identified by rest [13N]Ammonia/[18F]FDG PET/CT and [99mTc]Tc-Tetrafosmin SPECT/CT, with median higher percentages for the former (25.9 ± 18.9% vs 15.8 ± 9.3%, respectively). However, probably due to the small sample size, a statistically significant difference was not found (paired samples T-test, p = 0.055), Conclusion(s):[99mTc]Tc-Tetrafosmin SPECT/CT underestimated the extent of viability when compared to [18F]FDG PET/CT PET/CT, the accepted gold standard, however a statistically significant difference was not found, most likely due to the small sample size.
Background and objective: 18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis... more Background and objective: 18F-sodium fluoride (18F-NaF) has been used to evaluate aortic stenosis. It is know that its uptake is related with microcalcification. The purpose of this study is to assess the relationship between 18F-NaF uptake by the aortic valve, aortic valve calcium score and cardiovascular risk. Methods and Results: Twenty-five hypertensive patients without known cardiovascular disease or aortic stenosis underwent PET-CT with 18F-NaF. Cardiovascular risk was assessed through the ASCVD risk calculator. The patients had a mean age of 64.0± 8.6 years and 56% were males. The mean ASCVD risk was of 28.8 ±19.0 (IQR: 10-48.5). The aortic valve calcium score (AoV score) was of 53.2 ± 164.4(IQR: 0-29.8), the uptake of 18F-NaF assessed through the corrected uptake per lesion (CUL = max SUV-mean blood-pool SUV) was of 0.49 ± 0.14 (IQR: 0.44-0.57). The patients were classified according to the ASCVD: Group A: patients with a risk above the 50thpercentile of the ASCVD risk distribution (50thpercentile = 25: 12 patients) and Group B: patients with a risk under or equal to the 50thpercentile of the ASCVD risk distribution, 13 patients. The uptake of 18F-NaF and the aortic valve calcium score were evaluated in both groups: A vs B: CUL = 0.57 ± 0.09 vs0. 42 ± 0.14, p = 0.005; AoV score= 102.4 ± 231.7 vs7.8 ± 13.2, p = 0.15. Conclusion: In this study microcalcification, evaluated through 18F-NaF uptake, was related with cardiovascular risk as was reported with vulnerable atherosclerotic plaques reinforcing the importance of cardiovascular risk prevention in aortic valve degeneration. Although the score of calcium seems to be higher in higher cardiovascular risk patients, no significant difference was found in this study.
The purpose of this study was to evaluate 18F-FDG activity in the atria in a group of patients wi... more The purpose of this study was to evaluate 18F-FDG activity in the atria in a group of patients with ischemic cardiomyopathy, scheduled for viability assessment and find clinical variables related with this finding.
Following our previous work on the production of radiometals, such as 64Cu and 68Ga, through the ... more Following our previous work on the production of radiometals, such as 64Cu and 68Ga, through the irradiation of liquid targets using a medical cyclotron, we describe in this paper a technique to produce 61Cu through the irradiation of natural zinc using a liquid target.
This work describes the production of two clinically relevant metal radioisotopes [Formula: see t... more This work describes the production of two clinically relevant metal radioisotopes [Formula: see text] and [Formula: see text] with a medical cyclotron by the irradiation of liquid targets. New results are presented for the implementation of this methodology in a fully automated system, using commercially available equipment. Liquid target solutions containing enriched [Formula: see text] and [Formula: see text] were loaded, bombarded and transferred to synthesis modules where a purified solution containing the desired radiometal is obtained and can then be used to further radiolabeling within only one hour after End-Of-Bombardment (EOB). Typical production runs using enriched material lead to the production of 5 GBq and 6 GBq (0.14 MBq/([Formula: see text]Ah ⋅ mg) and 1.5 MBq/([Formula: see text]Ah ⋅ mg)) of [Formula: see text] and [Formula: see text]; although the technique can be used to obtain up to 25 GBq and 40 GBq, respectively, by simply scaling up the amount of the enriched ...
A fully automated system for the production of 68Ga based on commercially available cyclotron liq... more A fully automated system for the production of 68Ga based on commercially available cyclotron liquid target and synthesis modules is described. A solution containing enriched 68Zn dissolved in a nitric solution is irradiated in a Cyclone 18/9 IBA cyclotron leading to the production of up to about 25 GBq of 68Ga. The irradiated solution is transferred to a Synthera synthesis module in which 68Ga is separated and purified with a yield superior to 85 % and where further labelling is achieved with yields no inferior to 70 %. The developed and implemented method presents an improved approach for the production of 68Ga-radiopharmaceuticals suitable for human use, in a process that takes less than 2 hours. This technique represents an economically viable alternative to 68Ge/68Ga generators with improved characteristics.
2015 IEEE 4th Portuguese Meeting on Bioengineering (ENBENG), 2015
Positron Emission Tomography (PET) is a powerful functional imaging technique targeted for in viv... more Positron Emission Tomography (PET) is a powerful functional imaging technique targeted for in vivo quantification and localization of physiological and pathophysiological functions. The possibility to develop a vast number of diseases in transgenic and knockout mice, and the chance to follow the onset of the diseases and the evolution of the treatment efficacy in an individual basis, made PET the third preferred preclinical imaging technique (20%) in research and development of new drug therapies [1]. Two features are mandatory in a preclinical PET system: a high Full Width at Half Maximum (FWHM) Spatial Resolution (SR), comprised between 0.40 and 0.27 mm for mice, so as to achieve the same level of detail of current state-of-the art PET scanners for humans [2], and a sensitivity as high as possible, to allow to differentiate and quantify a subtle signal in the presence of significant background counts [3]. Commercially available state-of-the-art preclinical PET systems make use of detectors based on segmented inorganic scintillation crystals coupled to photodetectors [2]. To reduce the complexity and cost, light multiplexing is used to decode the position of interaction of annihilation photons [3]. This scheme poses some limitations to the sensitivity and SR attained by preclinical PET systems, due to, among other problems, the difficulty of measuring efficiently the Depth-Of-Interaction [3]. The best reported values for the sensitivity and SR of current commercially available preclinical PET systems, are of, respectively, ~10% and ~1 mm FWHM [2]. Timing Resistive Plate Chambers (RPCs) are gaseous detectors with resistive parallel plate electrodes (made of glass) separated by small (~300 μm thick) and precise amplification gaps filled with an appropriate gas mixture. For the detection of photons, these are first converted into electrons in the resistive plates in an electronic cascade process. Some of the originated electrons will eventually escape to the amplification gap, where they will be accelerated by a uniform electric field, leading to a Townsend avalanche, which induces a current in a set of signal pickup strips. These low cost detectors have an excellent time resolution of 300 ps FWHM for 511 keV photon pairs, an excellent intrinsic SR, the readout being in almost full 3D mode. Recently, we developed a first fully functional prototype of a preclinical RPC-PET scanner for mice, which revealed a SR of 0.4 mm FWHM after image reconstruction by a Maximum Likelihood Expectation Maximization type algorithm. Preliminary tests with mice, preformed at the Institute of Nuclear Sciences Applied to Health (ICNAS - Instituto de Ciências Nucleares Aplicada às Saúde) of the University of Coimbra, shown the capability of the system to clearly identify the very small brain structures of mice, as well as the heart walls. The results obtained thus far are very promising, revealing unprecedented SR.
Ideal reaction conditions were found to promote the "cold" monomethylation of 5,10,15,2... more Ideal reaction conditions were found to promote the "cold" monomethylation of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin with CH 3 I , at minute time scale, in the presence of base. The photophysical characterization, cellular uptake and dark cytotoxicity of the resulting monomethylated porphyrin were appraised. Moreover, the syntheses of the corresponding labeled porphyrin, using short-lived carbon-11, prepared in the automated radiolabeling system were efficiently performed. The purification of the labeled product was achieved via preparative HPLC with high radiochemical purity and specific radioactivity. Preliminary studies on the biodistribution of 5,10,15-tris(3-hydroxyphenyl)-20-(3-[11C]methoxyphenyl)porphyrin carried out in a BALB/C normal mouse, using PET imaging, showed that the liver is the main pathway for excretion.
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Papers by A J Abrunhosa