Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 27, 2016
The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistanc... more The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([(11)C]AEPH) derivative for positron emission tomography (PET), as a novel probe to better understand the activity and the function of Pgp in vivo. The synthetic procedure and the quality control of the selected lead compound, [(11)C]AEPH-1, were set up and optimized. The biodistribution and the dynamic extraction in target organs of [(11)C]AEPH-1 were studied in vivo by PET in healthy rats at baseline and after pre-treatment with a Pgp inhibitor (tariquidar). In vivo dynamic imaging was consistent with the results of ex vivo extraction on explanted organs. An adequate stability for in vivo studies, as well as a high activity of [(11)C]AEPH-1 in intestine and barrier tissues, has been demonstrated. Results of the bl...
A2B adenosine receptors (ARs) are commonly defined as &am... more A2B adenosine receptors (ARs) are commonly defined as "danger" sensors because they are triggered during cell injury when the endogenous molecule, adenosine, increases rapidly. These receptors, together with the other receptor subtypes (A1, A2A and A3), exert a wide variety of immunomodulating and (cyto)protective effects, thus representing a pivotal therapeutic target for different pathologies including diabetes, tumors, cardiovascular diseases, pulmonary fibrosis and others. The limited availability of potent and selective ligands for A2B ARs has prevented this receptor to emerge both as therapeutic and diagnostic target. Recently, a new class of potent A2B ARs antagonists was developed featuring the triazinobenzimidazole scaffold. Starting from this chemotype, we synthesized a new radiotracer, [(11)C]-4 (1-[(11)C]methyl-3-phenyl triazino[4,3-a]benzimidazol-4(1H)-one), and investigated the pharmacokinetics of this compound in vivo to define its potential use in the imaging of A2B AR with positron emission tomography. [(11)C]-4 showed a very high chemical and blood stability. Results of in vivo and ex vivo experiments underlined the ability of this molecule to bind the A2B AR and correlated with the A2B AR protein and gene expression data. Although further studies are necessary, these data suggest that [(11)C]-4 may represent a good lead compound for the development of novel selective and potent A2B AR radiotracers, and a new option for the clinical investigation of several pathophysiological processes and chronic diseases.
ABSTRACT Il rapporto tra numero di neutroni (N) e numero di protoni (Z) determina la stabilità di... more ABSTRACT Il rapporto tra numero di neutroni (N) e numero di protoni (Z) determina la stabilità di un nuclide: per gli elementi leggeri la condizione di stabilità è in generale raggiunta quando il numero di neutroni è uguale o appena superiore a quello dei protoni (N = Z o N = Z+1). I nuclidi che hanno un numero di neutroni inferiore rispetto a quello di protoni (N/Z
Scandinavian Journal of Clinical & Laboratory Investigation, 1997
We amplified and sequenced the rearranged immunoglobulin heavy chain VDJ genomic unit in B-leukem... more We amplified and sequenced the rearranged immunoglobulin heavy chain VDJ genomic unit in B-leukemias and used it as a clone-specific marker for the molecular monitoring of the patients during and after therapeutic treatment. The method described is patient-specific rather than disorder-specific, more sensitive and less time-consuming than other conventional techniques for the detection of minimal residual disease. We propose reproducible and quick procedures, from DNA extraction to Southern blotting, that can be easily performed in any clinical laboratory and also applied to other kinds of investigation.
The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) ima... more The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. 11C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 27, 2016
The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistanc... more The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([(11)C]AEPH) derivative for positron emission tomography (PET), as a novel probe to better understand the activity and the function of Pgp in vivo. The synthetic procedure and the quality control of the selected lead compound, [(11)C]AEPH-1, were set up and optimized. The biodistribution and the dynamic extraction in target organs of [(11)C]AEPH-1 were studied in vivo by PET in healthy rats at baseline and after pre-treatment with a Pgp inhibitor (tariquidar). In vivo dynamic imaging was consistent with the results of ex vivo extraction on explanted organs. An adequate stability for in vivo studies, as well as a high activity of [(11)C]AEPH-1 in intestine and barrier tissues, has been demonstrated. Results of the bl...
A2B adenosine receptors (ARs) are commonly defined as &am... more A2B adenosine receptors (ARs) are commonly defined as "danger" sensors because they are triggered during cell injury when the endogenous molecule, adenosine, increases rapidly. These receptors, together with the other receptor subtypes (A1, A2A and A3), exert a wide variety of immunomodulating and (cyto)protective effects, thus representing a pivotal therapeutic target for different pathologies including diabetes, tumors, cardiovascular diseases, pulmonary fibrosis and others. The limited availability of potent and selective ligands for A2B ARs has prevented this receptor to emerge both as therapeutic and diagnostic target. Recently, a new class of potent A2B ARs antagonists was developed featuring the triazinobenzimidazole scaffold. Starting from this chemotype, we synthesized a new radiotracer, [(11)C]-4 (1-[(11)C]methyl-3-phenyl triazino[4,3-a]benzimidazol-4(1H)-one), and investigated the pharmacokinetics of this compound in vivo to define its potential use in the imaging of A2B AR with positron emission tomography. [(11)C]-4 showed a very high chemical and blood stability. Results of in vivo and ex vivo experiments underlined the ability of this molecule to bind the A2B AR and correlated with the A2B AR protein and gene expression data. Although further studies are necessary, these data suggest that [(11)C]-4 may represent a good lead compound for the development of novel selective and potent A2B AR radiotracers, and a new option for the clinical investigation of several pathophysiological processes and chronic diseases.
ABSTRACT The last decade has seen extraordinary growth in the clinical use of Positron Emission T... more ABSTRACT The last decade has seen extraordinary growth in the clinical use of Positron Emission Tomography (PET), an in vivo molecular imaging modality widely used in oncology that requires the use of radiopharmaceuticals labeled with short-lived radionuclides. These medicinal products have found widespread application in Nuclear Medicine departments equipped with PET scanners. Due to the great increase in radiopharmaceutical demand, their production has been centralized and moved to industrial manufacturing sites in which Good Manufacturing Practice (GMP) principles and guidelines for medicinal products are to be applied. The production of PET radiopharmaceuticals features particular aspects such as the use of the lot before the completion of all tests, the multiplicity of batches produced per single day and the absence of product stock due to radionuclide short half-life. In this context, the application of quality principles to all stages of the process and the implementation of a quality management system (QMS) are of primary importance. This paper reports on the development of a QMS applied to a GMP manufacturing site of an in vivo PET diagnostic product, and on how its application can describe the performance of the site. Data were collected over a 6-year period (2008-2013) and demonstrate the ability of Key Performance Indicators, strictly related to the structure and organization of the QMS, and quality tools (data analysis, internal audit, etc.) to monitor process performance in terms of effectiveness, efficacy and stability.
Abstract: Co(II), Ni(II), and Cu(II) complexes with a tetradentate nitrogen donor [N4] macrocycli... more Abstract: Co(II), Ni(II), and Cu(II) complexes with a tetradentate nitrogen donor [N4] macrocyclic ligand, viz. 6,15-dimethyl-8,17diphenyl-7,16-dihyd-rodibenzo[b,i][1.4.8.11]tetraazacyclotetradecine , were synthesized. Their struc-tures were determined based on elemental analyses, ...
The N, N-diethylcarbamato derivative of zirconium (IV), Zr (O2CNEt2) 4 has been studied by X-ray ... more The N, N-diethylcarbamato derivative of zirconium (IV), Zr (O2CNEt2) 4 has been studied by X-ray crystallography. Crystal data: C20H40Na4O8Zr, monoclinic, space group C2/c, a= 14.057 (1), b= 12.168 (1), c= 16.746 (2) Å, β= 108.071 (4)°, Z= 4, Dc= 1.356, F (000)= ...
The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron... more The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that (18)F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose-boronophenylalanine (BPA). Therefore, FET-PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 27, 2016
The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistanc... more The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([(11)C]AEPH) derivative for positron emission tomography (PET), as a novel probe to better understand the activity and the function of Pgp in vivo. The synthetic procedure and the quality control of the selected lead compound, [(11)C]AEPH-1, were set up and optimized. The biodistribution and the dynamic extraction in target organs of [(11)C]AEPH-1 were studied in vivo by PET in healthy rats at baseline and after pre-treatment with a Pgp inhibitor (tariquidar). In vivo dynamic imaging was consistent with the results of ex vivo extraction on explanted organs. An adequate stability for in vivo studies, as well as a high activity of [(11)C]AEPH-1 in intestine and barrier tissues, has been demonstrated. Results of the bl...
A2B adenosine receptors (ARs) are commonly defined as &am... more A2B adenosine receptors (ARs) are commonly defined as "danger" sensors because they are triggered during cell injury when the endogenous molecule, adenosine, increases rapidly. These receptors, together with the other receptor subtypes (A1, A2A and A3), exert a wide variety of immunomodulating and (cyto)protective effects, thus representing a pivotal therapeutic target for different pathologies including diabetes, tumors, cardiovascular diseases, pulmonary fibrosis and others. The limited availability of potent and selective ligands for A2B ARs has prevented this receptor to emerge both as therapeutic and diagnostic target. Recently, a new class of potent A2B ARs antagonists was developed featuring the triazinobenzimidazole scaffold. Starting from this chemotype, we synthesized a new radiotracer, [(11)C]-4 (1-[(11)C]methyl-3-phenyl triazino[4,3-a]benzimidazol-4(1H)-one), and investigated the pharmacokinetics of this compound in vivo to define its potential use in the imaging of A2B AR with positron emission tomography. [(11)C]-4 showed a very high chemical and blood stability. Results of in vivo and ex vivo experiments underlined the ability of this molecule to bind the A2B AR and correlated with the A2B AR protein and gene expression data. Although further studies are necessary, these data suggest that [(11)C]-4 may represent a good lead compound for the development of novel selective and potent A2B AR radiotracers, and a new option for the clinical investigation of several pathophysiological processes and chronic diseases.
ABSTRACT Il rapporto tra numero di neutroni (N) e numero di protoni (Z) determina la stabilità di... more ABSTRACT Il rapporto tra numero di neutroni (N) e numero di protoni (Z) determina la stabilità di un nuclide: per gli elementi leggeri la condizione di stabilità è in generale raggiunta quando il numero di neutroni è uguale o appena superiore a quello dei protoni (N = Z o N = Z+1). I nuclidi che hanno un numero di neutroni inferiore rispetto a quello di protoni (N/Z
Scandinavian Journal of Clinical & Laboratory Investigation, 1997
We amplified and sequenced the rearranged immunoglobulin heavy chain VDJ genomic unit in B-leukem... more We amplified and sequenced the rearranged immunoglobulin heavy chain VDJ genomic unit in B-leukemias and used it as a clone-specific marker for the molecular monitoring of the patients during and after therapeutic treatment. The method described is patient-specific rather than disorder-specific, more sensitive and less time-consuming than other conventional techniques for the detection of minimal residual disease. We propose reproducible and quick procedures, from DNA extraction to Southern blotting, that can be easily performed in any clinical laboratory and also applied to other kinds of investigation.
The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) ima... more The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. 11C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 27, 2016
The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistanc... more The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([(11)C]AEPH) derivative for positron emission tomography (PET), as a novel probe to better understand the activity and the function of Pgp in vivo. The synthetic procedure and the quality control of the selected lead compound, [(11)C]AEPH-1, were set up and optimized. The biodistribution and the dynamic extraction in target organs of [(11)C]AEPH-1 were studied in vivo by PET in healthy rats at baseline and after pre-treatment with a Pgp inhibitor (tariquidar). In vivo dynamic imaging was consistent with the results of ex vivo extraction on explanted organs. An adequate stability for in vivo studies, as well as a high activity of [(11)C]AEPH-1 in intestine and barrier tissues, has been demonstrated. Results of the bl...
A2B adenosine receptors (ARs) are commonly defined as &am... more A2B adenosine receptors (ARs) are commonly defined as "danger" sensors because they are triggered during cell injury when the endogenous molecule, adenosine, increases rapidly. These receptors, together with the other receptor subtypes (A1, A2A and A3), exert a wide variety of immunomodulating and (cyto)protective effects, thus representing a pivotal therapeutic target for different pathologies including diabetes, tumors, cardiovascular diseases, pulmonary fibrosis and others. The limited availability of potent and selective ligands for A2B ARs has prevented this receptor to emerge both as therapeutic and diagnostic target. Recently, a new class of potent A2B ARs antagonists was developed featuring the triazinobenzimidazole scaffold. Starting from this chemotype, we synthesized a new radiotracer, [(11)C]-4 (1-[(11)C]methyl-3-phenyl triazino[4,3-a]benzimidazol-4(1H)-one), and investigated the pharmacokinetics of this compound in vivo to define its potential use in the imaging of A2B AR with positron emission tomography. [(11)C]-4 showed a very high chemical and blood stability. Results of in vivo and ex vivo experiments underlined the ability of this molecule to bind the A2B AR and correlated with the A2B AR protein and gene expression data. Although further studies are necessary, these data suggest that [(11)C]-4 may represent a good lead compound for the development of novel selective and potent A2B AR radiotracers, and a new option for the clinical investigation of several pathophysiological processes and chronic diseases.
ABSTRACT The last decade has seen extraordinary growth in the clinical use of Positron Emission T... more ABSTRACT The last decade has seen extraordinary growth in the clinical use of Positron Emission Tomography (PET), an in vivo molecular imaging modality widely used in oncology that requires the use of radiopharmaceuticals labeled with short-lived radionuclides. These medicinal products have found widespread application in Nuclear Medicine departments equipped with PET scanners. Due to the great increase in radiopharmaceutical demand, their production has been centralized and moved to industrial manufacturing sites in which Good Manufacturing Practice (GMP) principles and guidelines for medicinal products are to be applied. The production of PET radiopharmaceuticals features particular aspects such as the use of the lot before the completion of all tests, the multiplicity of batches produced per single day and the absence of product stock due to radionuclide short half-life. In this context, the application of quality principles to all stages of the process and the implementation of a quality management system (QMS) are of primary importance. This paper reports on the development of a QMS applied to a GMP manufacturing site of an in vivo PET diagnostic product, and on how its application can describe the performance of the site. Data were collected over a 6-year period (2008-2013) and demonstrate the ability of Key Performance Indicators, strictly related to the structure and organization of the QMS, and quality tools (data analysis, internal audit, etc.) to monitor process performance in terms of effectiveness, efficacy and stability.
Abstract: Co(II), Ni(II), and Cu(II) complexes with a tetradentate nitrogen donor [N4] macrocycli... more Abstract: Co(II), Ni(II), and Cu(II) complexes with a tetradentate nitrogen donor [N4] macrocyclic ligand, viz. 6,15-dimethyl-8,17diphenyl-7,16-dihyd-rodibenzo[b,i][1.4.8.11]tetraazacyclotetradecine , were synthesized. Their struc-tures were determined based on elemental analyses, ...
The N, N-diethylcarbamato derivative of zirconium (IV), Zr (O2CNEt2) 4 has been studied by X-ray ... more The N, N-diethylcarbamato derivative of zirconium (IV), Zr (O2CNEt2) 4 has been studied by X-ray crystallography. Crystal data: C20H40Na4O8Zr, monoclinic, space group C2/c, a= 14.057 (1), b= 12.168 (1), c= 16.746 (2) Å, β= 108.071 (4)°, Z= 4, Dc= 1.356, F (000)= ...
The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron... more The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that (18)F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose-boronophenylalanine (BPA). Therefore, FET-PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT.
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Papers by Debora Petroni