4‑[18F]Fluoro‑m‑hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography
4-[18F]Fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG, [18F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [18F]1 was developed in which the intermediate 4-[1...
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| Veröffentlicht in: | Journal of medicinal chemistry 2013-09, Vol.56 (18), p.7312-7323 |
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| creator | Jang, Keun Sam Jung, Yong-Woon Gu, Guie Koeppe, Robert A Sherman, Phillip S Quesada, Carole A Raffel, David M |
| description | 4-[18F]Fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG, [18F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [18F]1 was developed in which the intermediate 4-[18F]fluoro-m-tyramine ([18F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [18F]fluorination. In PET imaging studies in rhesus macaque monkeys, [18F]1 demonstrated high quality cardiac images with low uptake in lungs and the liver. Compartmental modeling of [18F]1 kinetics provided net uptake rate constants K i (mL/min/g wet), and Patlak graphical analysis of [18F]1 kinetics provided Patlak slopes K p (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [18F]1 can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET. |
| doi_str_mv | 10.1021/jm400770g |
| format | Article |
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An automated synthesis of [18F]1 was developed in which the intermediate 4-[18F]fluoro-m-tyramine ([18F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [18F]fluorination. In PET imaging studies in rhesus macaque monkeys, [18F]1 demonstrated high quality cardiac images with low uptake in lungs and the liver. Compartmental modeling of [18F]1 kinetics provided net uptake rate constants K i (mL/min/g wet), and Patlak graphical analysis of [18F]1 kinetics provided Patlak slopes K p (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [18F]1 can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm400770g</identifier><identifier>PMID: 23965035</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Adrenal Glands - metabolism ; Animals ; Biological Transport ; Female ; Fluorine Radioisotopes ; Guanidines - chemistry ; Guanidines - metabolism ; Guanidines - pharmacokinetics ; Haplorhini ; Heart - innervation ; Humans ; Male ; Phenethylamines - chemistry ; Phenethylamines - metabolism ; Phenethylamines - pharmacokinetics ; Positron-Emission Tomography - methods ; Radiation Dosage ; Radiochemistry ; Radiopharmaceuticals - chemistry ; Radiopharmaceuticals - metabolism ; Radiopharmaceuticals - pharmacokinetics ; Rats ; Sympathetic Nervous System - diagnostic imaging</subject><ispartof>Journal of medicinal chemistry, 2013-09, Vol.56 (18), p.7312-7323</ispartof><rights>Copyright © 2013 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a405t-c43af58b451e1db41cc47a2a7640b8bab95fa29ecd57711be531fe731151ea3e3</citedby><cites>FETCH-LOGICAL-a405t-c43af58b451e1db41cc47a2a7640b8bab95fa29ecd57711be531fe731151ea3e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm400770g$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm400770g$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23965035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jang, Keun Sam</creatorcontrib><creatorcontrib>Jung, Yong-Woon</creatorcontrib><creatorcontrib>Gu, Guie</creatorcontrib><creatorcontrib>Koeppe, Robert A</creatorcontrib><creatorcontrib>Sherman, Phillip S</creatorcontrib><creatorcontrib>Quesada, Carole A</creatorcontrib><creatorcontrib>Raffel, David M</creatorcontrib><title>4‑[18F]Fluoro‑m‑hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>4-[18F]Fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG, [18F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [18F]1 was developed in which the intermediate 4-[18F]fluoro-m-tyramine ([18F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [18F]fluorination. In PET imaging studies in rhesus macaque monkeys, [18F]1 demonstrated high quality cardiac images with low uptake in lungs and the liver. Compartmental modeling of [18F]1 kinetics provided net uptake rate constants K i (mL/min/g wet), and Patlak graphical analysis of [18F]1 kinetics provided Patlak slopes K p (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [18F]1 can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET.</description><subject>Adrenal Glands - metabolism</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Female</subject><subject>Fluorine Radioisotopes</subject><subject>Guanidines - chemistry</subject><subject>Guanidines - metabolism</subject><subject>Guanidines - pharmacokinetics</subject><subject>Haplorhini</subject><subject>Heart - innervation</subject><subject>Humans</subject><subject>Male</subject><subject>Phenethylamines - chemistry</subject><subject>Phenethylamines - metabolism</subject><subject>Phenethylamines - pharmacokinetics</subject><subject>Positron-Emission Tomography - methods</subject><subject>Radiation Dosage</subject><subject>Radiochemistry</subject><subject>Radiopharmaceuticals - chemistry</subject><subject>Radiopharmaceuticals - metabolism</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Rats</subject><subject>Sympathetic Nervous System - diagnostic imaging</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1u1DAUhS0EokNhwQsgb1iwCPh3MsMCqRo6gFTxU8oKoejGuUk8SuzITgrZ9RX6DLwZT4KrKSOQWFi2db9zrnQOIY85e86Z4C92vWIsz1lzhyy4FixTK6bukgVjQmRiKeQReRDjjjEmuZD3yZGQ66VmUi_IT_Xr6vorX22_bbvJB59-fTrtXAX_Yx5adDi2c9dM4GxlHb6kJ_QcKuuHFkIPBqfRGuho7QP9lKDR1rN1DT3HxnqXBhsIlQVDP8_9AGOLCafvMVwifY0u2nGm3-3Y0o8-vYN39LS3MSYpvfC9bwIM7fyQ3Kuhi_jo9j4mX7anF5u32dmHN-82J2cZKKbHzCgJtV6VSnPkVam4MSoHAflSsXJVQrnWNYg1mkrnOeclaslrzCXnSQAS5TF5tfcdprLHyqAbA3TFEGwPYS482OLfibNt0fjLQqXMU6LJ4NnewAQfY8D6oOWsuGmqODSV2Cd_LzuQf6pJwNM9ACYWOz-FlGb8j9FvrbGjiA</recordid><startdate>20130926</startdate><enddate>20130926</enddate><creator>Jang, Keun Sam</creator><creator>Jung, Yong-Woon</creator><creator>Gu, Guie</creator><creator>Koeppe, Robert A</creator><creator>Sherman, Phillip S</creator><creator>Quesada, Carole A</creator><creator>Raffel, David M</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20130926</creationdate><title>4‑[18F]Fluoro‑m‑hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography</title><author>Jang, Keun Sam ; Jung, Yong-Woon ; Gu, Guie ; Koeppe, Robert A ; Sherman, Phillip S ; Quesada, Carole A ; Raffel, David M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a405t-c43af58b451e1db41cc47a2a7640b8bab95fa29ecd57711be531fe731151ea3e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adrenal Glands - metabolism</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Female</topic><topic>Fluorine Radioisotopes</topic><topic>Guanidines - chemistry</topic><topic>Guanidines - metabolism</topic><topic>Guanidines - pharmacokinetics</topic><topic>Haplorhini</topic><topic>Heart - innervation</topic><topic>Humans</topic><topic>Male</topic><topic>Phenethylamines - chemistry</topic><topic>Phenethylamines - metabolism</topic><topic>Phenethylamines - pharmacokinetics</topic><topic>Positron-Emission Tomography - methods</topic><topic>Radiation Dosage</topic><topic>Radiochemistry</topic><topic>Radiopharmaceuticals - chemistry</topic><topic>Radiopharmaceuticals - metabolism</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>Rats</topic><topic>Sympathetic Nervous System - diagnostic imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jang, Keun Sam</creatorcontrib><creatorcontrib>Jung, Yong-Woon</creatorcontrib><creatorcontrib>Gu, Guie</creatorcontrib><creatorcontrib>Koeppe, Robert A</creatorcontrib><creatorcontrib>Sherman, Phillip S</creatorcontrib><creatorcontrib>Quesada, Carole A</creatorcontrib><creatorcontrib>Raffel, David M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jang, Keun Sam</au><au>Jung, Yong-Woon</au><au>Gu, Guie</au><au>Koeppe, Robert A</au><au>Sherman, Phillip S</au><au>Quesada, Carole A</au><au>Raffel, David M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>4‑[18F]Fluoro‑m‑hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2013-09-26</date><risdate>2013</risdate><volume>56</volume><issue>18</issue><spage>7312</spage><epage>7323</epage><pages>7312-7323</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>4-[18F]Fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG, [18F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [18F]1 was developed in which the intermediate 4-[18F]fluoro-m-tyramine ([18F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [18F]fluorination. In PET imaging studies in rhesus macaque monkeys, [18F]1 demonstrated high quality cardiac images with low uptake in lungs and the liver. Compartmental modeling of [18F]1 kinetics provided net uptake rate constants K i (mL/min/g wet), and Patlak graphical analysis of [18F]1 kinetics provided Patlak slopes K p (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [18F]1 can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>23965035</pmid><doi>10.1021/jm400770g</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Adrenal Glands - metabolism Animals Biological Transport Female Fluorine Radioisotopes Guanidines - chemistry Guanidines - metabolism Guanidines - pharmacokinetics Haplorhini Heart - innervation Humans Male Phenethylamines - chemistry Phenethylamines - metabolism Phenethylamines - pharmacokinetics Positron-Emission Tomography - methods Radiation Dosage Radiochemistry Radiopharmaceuticals - chemistry Radiopharmaceuticals - metabolism Radiopharmaceuticals - pharmacokinetics Rats Sympathetic Nervous System - diagnostic imaging |
| title | 4‑[18F]Fluoro‑m‑hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography |
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