Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of super(18)F-Fluoroacetate ( super(18)F-FACE) in Non-human Primates
Introduction: To facilitate the clinical translation of super(18)F-fluoroacetate ( super(18)F-FACE), the pharmacokinetics, biodistribution, radiolabeled metabolites, radiation dosimetry, and pharmacological safety of diagnostic doses of super(18)F-FACE were determined in non-human primates. Methods:...
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| Veröffentlicht in: | Molecular imaging and biology 2012-04, Vol.14 (2), p.213-224 |
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| creator | Nishii, Ryuichi Tong, William Wendt, Richard Soghomonyan, Suren Mukhopadhyay, Uday Balatoni, Julius Mawlawi, Osama Bidaut, Luc Tinkey, Peggy Borne, Agatha Alauddin, Mian Gonzalez-Lepera, Carlos Yang, Bijun Gelovani, Juri G |
| description | Introduction: To facilitate the clinical translation of super(18)F-fluoroacetate ( super(18)F-FACE), the pharmacokinetics, biodistribution, radiolabeled metabolites, radiation dosimetry, and pharmacological safety of diagnostic doses of super(18)F-FACE were determined in non-human primates. Methods: super(18)F-FACE was synthesized using a custom-built automated synthesis module. Six rhesus monkeys (three of each sex) were injected intravenously with super(18)F-FACE (165.4 plus or minus 28.5 MBq), followed by dynamic positron emission tomography (PET) imaging of the thoracoabdominal area during 0-30 min post-injection and static whole-body PET imaging at 40, 100, and 170 min. Serial blood samples and a urine sample were obtained from each animal to determine the time course of super(18)F-FACE and its radiolabeled metabolites. Electrocardiograms and hematology analyses were obtained to evaluate the acute and delayed toxicity of diagnostic dosages of super(18)F-FACE. The time-integrated activity coefficients for individual source organs and the whole body after administration of super(18)F-FACE were obtained using quantitative analyses of dynamic and static PET images and were extrapolated to humans. Results: The blood clearance of super(18)F-FACE exhibited bi-exponential kinetics with half-times of 4 and 250 min for the fast and slow phases, respectively. A rapid accumulation of super(18)F-FACE-derived radioactivity was observed in the liver and kidneys, followed by clearance of the radioactivity into the intestine and the urinary bladder. Radio-HPLC analyses of blood and urine samples demonstrated that super(18)F-fluoride was the only detectable radiolabeled metabolite at the level of less than 9% of total radioactivity in blood at 180 min after the super(18)F-FACE injection. The uptake of free super(18)F-fluoride in the bones was insignificant during the course of the imaging studies. No significant changes in ECG, CBC, liver enzymes, or renal function were observed. The estimated effective dose for an adult human is 3.90-7.81 mSv from the administration of 185-370 MBq of super(18)F-FACE. Conclusions: The effective dose and individual organ radiation absorbed doses from administration of a diagnostic dosage of super(18)F-FACE are acceptable. From a pharmacologic perspective, diagnostic dosages of super(18)F-FACE are non-toxic in primates and, therefore, could be safely administered to human patients for PET imaging. |
| doi_str_mv | 10.1007/s11307-011-0485-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_968167635</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>968167635</sourcerecordid><originalsourceid>FETCH-proquest_miscellaneous_9681676353</originalsourceid><addsrcrecordid>eNqNjM1KAzEURoMoWH8ewF12tjDRZGIz41JrBzdKke5LOpPaq0luzc2AfRJf1xHcuHP1HfgOh7ELJa-UlNU1KaVlJaRSQt7UU6EP2EjVRopSyvJw4Kk2QhldHrMTojcpVaVKPWJfi61Nwbb4DtFlaKngTy7bNXqgUPB7wA4oJ1j3GTAW_MV2YH-QPyBBcDntC25jx5f4CS16fN1z3HDqdy6NVT1pRON7TGjboZodH_-57mbzCYfInzGKbR9s5IsEYfDojB1trCd3_run7LKZL2ePYpfwo3eUVwGodd7b6LCn1a2plamMnur_m9_mZWEw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>968167635</pqid></control><display><type>article</type><title>Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of super(18)F-Fluoroacetate ( super(18)F-FACE) in Non-human Primates</title><source>Springer Nature - Complete Springer Journals</source><creator>Nishii, Ryuichi ; Tong, William ; Wendt, Richard ; Soghomonyan, Suren ; Mukhopadhyay, Uday ; Balatoni, Julius ; Mawlawi, Osama ; Bidaut, Luc ; Tinkey, Peggy ; Borne, Agatha ; Alauddin, Mian ; Gonzalez-Lepera, Carlos ; Yang, Bijun ; Gelovani, Juri G</creator><creatorcontrib>Nishii, Ryuichi ; Tong, William ; Wendt, Richard ; Soghomonyan, Suren ; Mukhopadhyay, Uday ; Balatoni, Julius ; Mawlawi, Osama ; Bidaut, Luc ; Tinkey, Peggy ; Borne, Agatha ; Alauddin, Mian ; Gonzalez-Lepera, Carlos ; Yang, Bijun ; Gelovani, Juri G</creatorcontrib><description>Introduction: To facilitate the clinical translation of super(18)F-fluoroacetate ( super(18)F-FACE), the pharmacokinetics, biodistribution, radiolabeled metabolites, radiation dosimetry, and pharmacological safety of diagnostic doses of super(18)F-FACE were determined in non-human primates. Methods: super(18)F-FACE was synthesized using a custom-built automated synthesis module. Six rhesus monkeys (three of each sex) were injected intravenously with super(18)F-FACE (165.4 plus or minus 28.5 MBq), followed by dynamic positron emission tomography (PET) imaging of the thoracoabdominal area during 0-30 min post-injection and static whole-body PET imaging at 40, 100, and 170 min. Serial blood samples and a urine sample were obtained from each animal to determine the time course of super(18)F-FACE and its radiolabeled metabolites. Electrocardiograms and hematology analyses were obtained to evaluate the acute and delayed toxicity of diagnostic dosages of super(18)F-FACE. The time-integrated activity coefficients for individual source organs and the whole body after administration of super(18)F-FACE were obtained using quantitative analyses of dynamic and static PET images and were extrapolated to humans. Results: The blood clearance of super(18)F-FACE exhibited bi-exponential kinetics with half-times of 4 and 250 min for the fast and slow phases, respectively. A rapid accumulation of super(18)F-FACE-derived radioactivity was observed in the liver and kidneys, followed by clearance of the radioactivity into the intestine and the urinary bladder. Radio-HPLC analyses of blood and urine samples demonstrated that super(18)F-fluoride was the only detectable radiolabeled metabolite at the level of less than 9% of total radioactivity in blood at 180 min after the super(18)F-FACE injection. The uptake of free super(18)F-fluoride in the bones was insignificant during the course of the imaging studies. No significant changes in ECG, CBC, liver enzymes, or renal function were observed. The estimated effective dose for an adult human is 3.90-7.81 mSv from the administration of 185-370 MBq of super(18)F-FACE. Conclusions: The effective dose and individual organ radiation absorbed doses from administration of a diagnostic dosage of super(18)F-FACE are acceptable. From a pharmacologic perspective, diagnostic dosages of super(18)F-FACE are non-toxic in primates and, therefore, could be safely administered to human patients for PET imaging.</description><identifier>ISSN: 1536-1632</identifier><identifier>EISSN: 1860-2002</identifier><identifier>DOI: 10.1007/s11307-011-0485-3</identifier><language>eng</language><subject>Bone imaging ; Dose-response effects ; Dosimetry ; EKG ; Enzymes ; Intestine ; Kinetics ; Liver ; Macaca mulatta ; Metabolites ; Organs ; Pharmacokinetics ; Positron emission tomography ; Primates ; Radiation ; Radioactivity ; Renal function ; Sex ; Toxicity ; Translation ; Urinary bladder ; Urine</subject><ispartof>Molecular imaging and biology, 2012-04, Vol.14 (2), p.213-224</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></links><search><creatorcontrib>Nishii, Ryuichi</creatorcontrib><creatorcontrib>Tong, William</creatorcontrib><creatorcontrib>Wendt, Richard</creatorcontrib><creatorcontrib>Soghomonyan, Suren</creatorcontrib><creatorcontrib>Mukhopadhyay, Uday</creatorcontrib><creatorcontrib>Balatoni, Julius</creatorcontrib><creatorcontrib>Mawlawi, Osama</creatorcontrib><creatorcontrib>Bidaut, Luc</creatorcontrib><creatorcontrib>Tinkey, Peggy</creatorcontrib><creatorcontrib>Borne, Agatha</creatorcontrib><creatorcontrib>Alauddin, Mian</creatorcontrib><creatorcontrib>Gonzalez-Lepera, Carlos</creatorcontrib><creatorcontrib>Yang, Bijun</creatorcontrib><creatorcontrib>Gelovani, Juri G</creatorcontrib><title>Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of super(18)F-Fluoroacetate ( super(18)F-FACE) in Non-human Primates</title><title>Molecular imaging and biology</title><description>Introduction: To facilitate the clinical translation of super(18)F-fluoroacetate ( super(18)F-FACE), the pharmacokinetics, biodistribution, radiolabeled metabolites, radiation dosimetry, and pharmacological safety of diagnostic doses of super(18)F-FACE were determined in non-human primates. Methods: super(18)F-FACE was synthesized using a custom-built automated synthesis module. Six rhesus monkeys (three of each sex) were injected intravenously with super(18)F-FACE (165.4 plus or minus 28.5 MBq), followed by dynamic positron emission tomography (PET) imaging of the thoracoabdominal area during 0-30 min post-injection and static whole-body PET imaging at 40, 100, and 170 min. Serial blood samples and a urine sample were obtained from each animal to determine the time course of super(18)F-FACE and its radiolabeled metabolites. Electrocardiograms and hematology analyses were obtained to evaluate the acute and delayed toxicity of diagnostic dosages of super(18)F-FACE. The time-integrated activity coefficients for individual source organs and the whole body after administration of super(18)F-FACE were obtained using quantitative analyses of dynamic and static PET images and were extrapolated to humans. Results: The blood clearance of super(18)F-FACE exhibited bi-exponential kinetics with half-times of 4 and 250 min for the fast and slow phases, respectively. A rapid accumulation of super(18)F-FACE-derived radioactivity was observed in the liver and kidneys, followed by clearance of the radioactivity into the intestine and the urinary bladder. Radio-HPLC analyses of blood and urine samples demonstrated that super(18)F-fluoride was the only detectable radiolabeled metabolite at the level of less than 9% of total radioactivity in blood at 180 min after the super(18)F-FACE injection. The uptake of free super(18)F-fluoride in the bones was insignificant during the course of the imaging studies. No significant changes in ECG, CBC, liver enzymes, or renal function were observed. The estimated effective dose for an adult human is 3.90-7.81 mSv from the administration of 185-370 MBq of super(18)F-FACE. Conclusions: The effective dose and individual organ radiation absorbed doses from administration of a diagnostic dosage of super(18)F-FACE are acceptable. From a pharmacologic perspective, diagnostic dosages of super(18)F-FACE are non-toxic in primates and, therefore, could be safely administered to human patients for PET imaging.</description><subject>Bone imaging</subject><subject>Dose-response effects</subject><subject>Dosimetry</subject><subject>EKG</subject><subject>Enzymes</subject><subject>Intestine</subject><subject>Kinetics</subject><subject>Liver</subject><subject>Macaca mulatta</subject><subject>Metabolites</subject><subject>Organs</subject><subject>Pharmacokinetics</subject><subject>Positron emission tomography</subject><subject>Primates</subject><subject>Radiation</subject><subject>Radioactivity</subject><subject>Renal function</subject><subject>Sex</subject><subject>Toxicity</subject><subject>Translation</subject><subject>Urinary bladder</subject><subject>Urine</subject><issn>1536-1632</issn><issn>1860-2002</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNjM1KAzEURoMoWH8ewF12tjDRZGIz41JrBzdKke5LOpPaq0luzc2AfRJf1xHcuHP1HfgOh7ELJa-UlNU1KaVlJaRSQt7UU6EP2EjVRopSyvJw4Kk2QhldHrMTojcpVaVKPWJfi61Nwbb4DtFlaKngTy7bNXqgUPB7wA4oJ1j3GTAW_MV2YH-QPyBBcDntC25jx5f4CS16fN1z3HDqdy6NVT1pRON7TGjboZodH_-57mbzCYfInzGKbR9s5IsEYfDojB1trCd3_run7LKZL2ePYpfwo3eUVwGodd7b6LCn1a2plamMnur_m9_mZWEw</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Nishii, Ryuichi</creator><creator>Tong, William</creator><creator>Wendt, Richard</creator><creator>Soghomonyan, Suren</creator><creator>Mukhopadhyay, Uday</creator><creator>Balatoni, Julius</creator><creator>Mawlawi, Osama</creator><creator>Bidaut, Luc</creator><creator>Tinkey, Peggy</creator><creator>Borne, Agatha</creator><creator>Alauddin, Mian</creator><creator>Gonzalez-Lepera, Carlos</creator><creator>Yang, Bijun</creator><creator>Gelovani, Juri G</creator><scope>7QO</scope><scope>7ST</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>SOI</scope></search><sort><creationdate>20120401</creationdate><title>Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of super(18)F-Fluoroacetate ( super(18)F-FACE) in Non-human Primates</title><author>Nishii, Ryuichi ; Tong, William ; Wendt, Richard ; Soghomonyan, Suren ; Mukhopadhyay, Uday ; Balatoni, Julius ; Mawlawi, Osama ; Bidaut, Luc ; Tinkey, Peggy ; Borne, Agatha ; Alauddin, Mian ; Gonzalez-Lepera, Carlos ; Yang, Bijun ; Gelovani, Juri G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_9681676353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Bone imaging</topic><topic>Dose-response effects</topic><topic>Dosimetry</topic><topic>EKG</topic><topic>Enzymes</topic><topic>Intestine</topic><topic>Kinetics</topic><topic>Liver</topic><topic>Macaca mulatta</topic><topic>Metabolites</topic><topic>Organs</topic><topic>Pharmacokinetics</topic><topic>Positron emission tomography</topic><topic>Primates</topic><topic>Radiation</topic><topic>Radioactivity</topic><topic>Renal function</topic><topic>Sex</topic><topic>Toxicity</topic><topic>Translation</topic><topic>Urinary bladder</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishii, Ryuichi</creatorcontrib><creatorcontrib>Tong, William</creatorcontrib><creatorcontrib>Wendt, Richard</creatorcontrib><creatorcontrib>Soghomonyan, Suren</creatorcontrib><creatorcontrib>Mukhopadhyay, Uday</creatorcontrib><creatorcontrib>Balatoni, Julius</creatorcontrib><creatorcontrib>Mawlawi, Osama</creatorcontrib><creatorcontrib>Bidaut, Luc</creatorcontrib><creatorcontrib>Tinkey, Peggy</creatorcontrib><creatorcontrib>Borne, Agatha</creatorcontrib><creatorcontrib>Alauddin, Mian</creatorcontrib><creatorcontrib>Gonzalez-Lepera, Carlos</creatorcontrib><creatorcontrib>Yang, Bijun</creatorcontrib><creatorcontrib>Gelovani, Juri G</creatorcontrib><collection>Biotechnology Research Abstracts</collection><collection>Environment Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environment Abstracts</collection><jtitle>Molecular imaging and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishii, Ryuichi</au><au>Tong, William</au><au>Wendt, Richard</au><au>Soghomonyan, Suren</au><au>Mukhopadhyay, Uday</au><au>Balatoni, Julius</au><au>Mawlawi, Osama</au><au>Bidaut, Luc</au><au>Tinkey, Peggy</au><au>Borne, Agatha</au><au>Alauddin, Mian</au><au>Gonzalez-Lepera, Carlos</au><au>Yang, Bijun</au><au>Gelovani, Juri G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of super(18)F-Fluoroacetate ( super(18)F-FACE) in Non-human Primates</atitle><jtitle>Molecular imaging and biology</jtitle><date>2012-04-01</date><risdate>2012</risdate><volume>14</volume><issue>2</issue><spage>213</spage><epage>224</epage><pages>213-224</pages><issn>1536-1632</issn><eissn>1860-2002</eissn><abstract>Introduction: To facilitate the clinical translation of super(18)F-fluoroacetate ( super(18)F-FACE), the pharmacokinetics, biodistribution, radiolabeled metabolites, radiation dosimetry, and pharmacological safety of diagnostic doses of super(18)F-FACE were determined in non-human primates. Methods: super(18)F-FACE was synthesized using a custom-built automated synthesis module. Six rhesus monkeys (three of each sex) were injected intravenously with super(18)F-FACE (165.4 plus or minus 28.5 MBq), followed by dynamic positron emission tomography (PET) imaging of the thoracoabdominal area during 0-30 min post-injection and static whole-body PET imaging at 40, 100, and 170 min. Serial blood samples and a urine sample were obtained from each animal to determine the time course of super(18)F-FACE and its radiolabeled metabolites. Electrocardiograms and hematology analyses were obtained to evaluate the acute and delayed toxicity of diagnostic dosages of super(18)F-FACE. The time-integrated activity coefficients for individual source organs and the whole body after administration of super(18)F-FACE were obtained using quantitative analyses of dynamic and static PET images and were extrapolated to humans. Results: The blood clearance of super(18)F-FACE exhibited bi-exponential kinetics with half-times of 4 and 250 min for the fast and slow phases, respectively. A rapid accumulation of super(18)F-FACE-derived radioactivity was observed in the liver and kidneys, followed by clearance of the radioactivity into the intestine and the urinary bladder. Radio-HPLC analyses of blood and urine samples demonstrated that super(18)F-fluoride was the only detectable radiolabeled metabolite at the level of less than 9% of total radioactivity in blood at 180 min after the super(18)F-FACE injection. The uptake of free super(18)F-fluoride in the bones was insignificant during the course of the imaging studies. No significant changes in ECG, CBC, liver enzymes, or renal function were observed. The estimated effective dose for an adult human is 3.90-7.81 mSv from the administration of 185-370 MBq of super(18)F-FACE. Conclusions: The effective dose and individual organ radiation absorbed doses from administration of a diagnostic dosage of super(18)F-FACE are acceptable. From a pharmacologic perspective, diagnostic dosages of super(18)F-FACE are non-toxic in primates and, therefore, could be safely administered to human patients for PET imaging.</abstract><doi>10.1007/s11307-011-0485-3</doi></addata></record> |
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| subjects | Bone imaging Dose-response effects Dosimetry EKG Enzymes Intestine Kinetics Liver Macaca mulatta Metabolites Organs Pharmacokinetics Positron emission tomography Primates Radiation Radioactivity Renal function Sex Toxicity Translation Urinary bladder Urine |
| title | Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of super(18)F-Fluoroacetate ( super(18)F-FACE) in Non-human Primates |
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