Radiosynthesis and biodistribution of the S-[ 18F]fluoroethyl analog of McN5652
[ 11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of 11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[ 18F]fluoroethyl...
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| Veröffentlicht in: | Nuclear medicine and biology 1996-05, Vol.23 (4), p.407-412 |
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| creator | Suehiro, Makiko Greenberg, Joel H. Shiue, Chyng-Yann Gonzalez, Carlos Dembowski, Barry Reivich, Martin |
| description | [
11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of
11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[
18F]fluoroethyl analog of McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([
18F]fluoroethylthio)-phenyl]pyrrolo-[2,1-a]-isoquinoline) ([
18F]FEMcN) and evaluated as a PET radiotracer for imaging serotonin uptake sites. The radiosynthesis was performed via a one-pot, two-step procedure. In the first step, 1-bromo-2-[
18F]fluoroethane was prepared from 2-bromoethyl triflate and K
18F/Kryptofix 2.2.2. in THF at room temperature. The second step, the S-fluoroalkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2[
18F] fluoroethane, by adding the normethyl McN5652 to the reaction vial, which was warmed at 45 °C for 1 min. The fluoroalkylation reaction proceeded quickly, giving [
18F]FEMcN in an average overall radiochemical yield of 13 ± 7%. The specific activity was 1593 ± 625 mCi/μmol.
Ex vivo autoradiographic studies revealed that [
18F]FEMcN accumulated into regions with high densities of 5-HT uptake sites such as hypothalamus, substantia nigra, and raphe nuclei. With blockade by nitroquipazine, a selective and highly potent 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, suggesting that this radiotracer binds specifically to 5-HT uptake sites. The regional distribution of [
18F]FEMcN at 60 min postinjection correlated with the distribution of [
11C]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT uptake blocker agreed with the distribution of the number of 5-HT uptake sites measured
in vitro. Thus, 5-HT uptake sites were visualized
in vivo with [
18F]FEMcN. However, comparison with the
in vivo behavior of [
11C]McN5652 indicated less favorable properties of [
18F]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood-brain barrier penetration and lower target-to-nontarget ratios. |
| doi_str_mv | 10.1016/0969-8051(96)00013-3 |
| format | Article |
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11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of
11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[
18F]fluoroethyl analog of McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([
18F]fluoroethylthio)-phenyl]pyrrolo-[2,1-a]-isoquinoline) ([
18F]FEMcN) and evaluated as a PET radiotracer for imaging serotonin uptake sites. The radiosynthesis was performed via a one-pot, two-step procedure. In the first step, 1-bromo-2-[
18F]fluoroethane was prepared from 2-bromoethyl triflate and K
18F/Kryptofix 2.2.2. in THF at room temperature. The second step, the S-fluoroalkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2[
18F] fluoroethane, by adding the normethyl McN5652 to the reaction vial, which was warmed at 45 °C for 1 min. The fluoroalkylation reaction proceeded quickly, giving [
18F]FEMcN in an average overall radiochemical yield of 13 ± 7%. The specific activity was 1593 ± 625 mCi/μmol.
Ex vivo autoradiographic studies revealed that [
18F]FEMcN accumulated into regions with high densities of 5-HT uptake sites such as hypothalamus, substantia nigra, and raphe nuclei. With blockade by nitroquipazine, a selective and highly potent 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, suggesting that this radiotracer binds specifically to 5-HT uptake sites. The regional distribution of [
18F]FEMcN at 60 min postinjection correlated with the distribution of [
11C]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT uptake blocker agreed with the distribution of the number of 5-HT uptake sites measured
in vitro. Thus, 5-HT uptake sites were visualized
in vivo with [
18F]FEMcN. However, comparison with the
in vivo behavior of [
11C]McN5652 indicated less favorable properties of [
18F]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood-brain barrier penetration and lower target-to-nontarget ratios.</description><identifier>ISSN: 0969-8051</identifier><identifier>EISSN: 1872-9614</identifier><identifier>DOI: 10.1016/0969-8051(96)00013-3</identifier><identifier>PMID: 8832694</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Analog ; Animals ; Autoradiography ; Biodistribution ; Biological and medical sciences ; Brain - diagnostic imaging ; Brain - metabolism ; Contrast media. Radiopharmaceuticals ; Fluorine Radioisotopes - chemistry ; Hydrocarbons, Fluorinated - chemical synthesis ; Hydrocarbons, Fluorinated - pharmacokinetics ; Isotope Labeling - methods ; Medical sciences ; Mice ; Pharmacology. Drug treatments ; Pyrroles - chemical synthesis ; Pyrroles - pharmacokinetics ; Quinolines - chemical synthesis ; Quinolines - pharmacokinetics ; Radiosynthesis ; S-[ 18F]Fluoroethyl ; Tissue Distribution ; Tomography, Emission-Computed</subject><ispartof>Nuclear medicine and biology, 1996-05, Vol.23 (4), p.407-412</ispartof><rights>1996</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3473-c479839792c6cbd1e0e29d60e997ba5565612d95666648705b39cf923b3ab2a93</citedby><cites>FETCH-LOGICAL-c3473-c479839792c6cbd1e0e29d60e997ba5565612d95666648705b39cf923b3ab2a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0969-8051(96)00013-3$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3168134$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8832694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suehiro, Makiko</creatorcontrib><creatorcontrib>Greenberg, Joel H.</creatorcontrib><creatorcontrib>Shiue, Chyng-Yann</creatorcontrib><creatorcontrib>Gonzalez, Carlos</creatorcontrib><creatorcontrib>Dembowski, Barry</creatorcontrib><creatorcontrib>Reivich, Martin</creatorcontrib><title>Radiosynthesis and biodistribution of the S-[ 18F]fluoroethyl analog of McN5652</title><title>Nuclear medicine and biology</title><addtitle>Nucl Med Biol</addtitle><description>[
11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of
11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[
18F]fluoroethyl analog of McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([
18F]fluoroethylthio)-phenyl]pyrrolo-[2,1-a]-isoquinoline) ([
18F]FEMcN) and evaluated as a PET radiotracer for imaging serotonin uptake sites. The radiosynthesis was performed via a one-pot, two-step procedure. In the first step, 1-bromo-2-[
18F]fluoroethane was prepared from 2-bromoethyl triflate and K
18F/Kryptofix 2.2.2. in THF at room temperature. The second step, the S-fluoroalkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2[
18F] fluoroethane, by adding the normethyl McN5652 to the reaction vial, which was warmed at 45 °C for 1 min. The fluoroalkylation reaction proceeded quickly, giving [
18F]FEMcN in an average overall radiochemical yield of 13 ± 7%. The specific activity was 1593 ± 625 mCi/μmol.
Ex vivo autoradiographic studies revealed that [
18F]FEMcN accumulated into regions with high densities of 5-HT uptake sites such as hypothalamus, substantia nigra, and raphe nuclei. With blockade by nitroquipazine, a selective and highly potent 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, suggesting that this radiotracer binds specifically to 5-HT uptake sites. The regional distribution of [
18F]FEMcN at 60 min postinjection correlated with the distribution of [
11C]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT uptake blocker agreed with the distribution of the number of 5-HT uptake sites measured
in vitro. Thus, 5-HT uptake sites were visualized
in vivo with [
18F]FEMcN. However, comparison with the
in vivo behavior of [
11C]McN5652 indicated less favorable properties of [
18F]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood-brain barrier penetration and lower target-to-nontarget ratios.</description><subject>Analog</subject><subject>Animals</subject><subject>Autoradiography</subject><subject>Biodistribution</subject><subject>Biological and medical sciences</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Contrast media. Radiopharmaceuticals</subject><subject>Fluorine Radioisotopes - chemistry</subject><subject>Hydrocarbons, Fluorinated - chemical synthesis</subject><subject>Hydrocarbons, Fluorinated - pharmacokinetics</subject><subject>Isotope Labeling - methods</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrroles - chemical synthesis</subject><subject>Pyrroles - pharmacokinetics</subject><subject>Quinolines - chemical synthesis</subject><subject>Quinolines - pharmacokinetics</subject><subject>Radiosynthesis</subject><subject>S-[ 18F]Fluoroethyl</subject><subject>Tissue Distribution</subject><subject>Tomography, Emission-Computed</subject><issn>0969-8051</issn><issn>1872-9614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1LwzAUhoMoc07_gUIvRPSimjRtPm4EGU6F6cCPK5GQJqlGumYmrbB_b8rKLj034fA-5yU8ABwjeIkgIleQE54yWKBzTi4ghAineAeMEaNZygnKd8F4i-yDgxC-I0NyBEdgxBjOCM_HYPEstXVh3bRfJtiQyEYnpXXahtbbsmutaxJXJTFNXtL3BLHZR1V3zjvTfq3riMvaffbEo3oqSJEdgr1K1sEcDe8EvM1uX6f36Xxx9zC9macK5xSnKqecYU55pogqNTLQZFwTaDinpSxiE0GZ5gWJkzMKixJzVfEMl1iWmeR4As42vSvvfjoTWrG0QZm6lo1xXRCUYUoL0oP5BlTeheBNJVbeLqVfCwRF71H0kkQvSfC49B4FjmcnQ39XLo3eHg3iYn465DIoWVdeNsqGLYYRYQj32PUGM9HFrzVeBGVNo4y23qhWaGf__8cfzcmL_A</recordid><startdate>199605</startdate><enddate>199605</enddate><creator>Suehiro, Makiko</creator><creator>Greenberg, Joel H.</creator><creator>Shiue, Chyng-Yann</creator><creator>Gonzalez, Carlos</creator><creator>Dembowski, Barry</creator><creator>Reivich, Martin</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>199605</creationdate><title>Radiosynthesis and biodistribution of the S-[ 18F]fluoroethyl analog of McN5652</title><author>Suehiro, Makiko ; Greenberg, Joel H. ; Shiue, Chyng-Yann ; Gonzalez, Carlos ; Dembowski, Barry ; Reivich, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3473-c479839792c6cbd1e0e29d60e997ba5565612d95666648705b39cf923b3ab2a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Analog</topic><topic>Animals</topic><topic>Autoradiography</topic><topic>Biodistribution</topic><topic>Biological and medical sciences</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Contrast media. Radiopharmaceuticals</topic><topic>Fluorine Radioisotopes - chemistry</topic><topic>Hydrocarbons, Fluorinated - chemical synthesis</topic><topic>Hydrocarbons, Fluorinated - pharmacokinetics</topic><topic>Isotope Labeling - methods</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrroles - chemical synthesis</topic><topic>Pyrroles - pharmacokinetics</topic><topic>Quinolines - chemical synthesis</topic><topic>Quinolines - pharmacokinetics</topic><topic>Radiosynthesis</topic><topic>S-[ 18F]Fluoroethyl</topic><topic>Tissue Distribution</topic><topic>Tomography, Emission-Computed</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Suehiro, Makiko</creatorcontrib><creatorcontrib>Greenberg, Joel H.</creatorcontrib><creatorcontrib>Shiue, Chyng-Yann</creatorcontrib><creatorcontrib>Gonzalez, Carlos</creatorcontrib><creatorcontrib>Dembowski, Barry</creatorcontrib><creatorcontrib>Reivich, Martin</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nuclear medicine and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suehiro, Makiko</au><au>Greenberg, Joel H.</au><au>Shiue, Chyng-Yann</au><au>Gonzalez, Carlos</au><au>Dembowski, Barry</au><au>Reivich, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Radiosynthesis and biodistribution of the S-[ 18F]fluoroethyl analog of McN5652</atitle><jtitle>Nuclear medicine and biology</jtitle><addtitle>Nucl Med Biol</addtitle><date>1996-05</date><risdate>1996</risdate><volume>23</volume><issue>4</issue><spage>407</spage><epage>412</epage><pages>407-412</pages><issn>0969-8051</issn><eissn>1872-9614</eissn><abstract>[
11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of
11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[
18F]fluoroethyl analog of McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([
18F]fluoroethylthio)-phenyl]pyrrolo-[2,1-a]-isoquinoline) ([
18F]FEMcN) and evaluated as a PET radiotracer for imaging serotonin uptake sites. The radiosynthesis was performed via a one-pot, two-step procedure. In the first step, 1-bromo-2-[
18F]fluoroethane was prepared from 2-bromoethyl triflate and K
18F/Kryptofix 2.2.2. in THF at room temperature. The second step, the S-fluoroalkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2[
18F] fluoroethane, by adding the normethyl McN5652 to the reaction vial, which was warmed at 45 °C for 1 min. The fluoroalkylation reaction proceeded quickly, giving [
18F]FEMcN in an average overall radiochemical yield of 13 ± 7%. The specific activity was 1593 ± 625 mCi/μmol.
Ex vivo autoradiographic studies revealed that [
18F]FEMcN accumulated into regions with high densities of 5-HT uptake sites such as hypothalamus, substantia nigra, and raphe nuclei. With blockade by nitroquipazine, a selective and highly potent 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, suggesting that this radiotracer binds specifically to 5-HT uptake sites. The regional distribution of [
18F]FEMcN at 60 min postinjection correlated with the distribution of [
11C]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT uptake blocker agreed with the distribution of the number of 5-HT uptake sites measured
in vitro. Thus, 5-HT uptake sites were visualized
in vivo with [
18F]FEMcN. However, comparison with the
in vivo behavior of [
11C]McN5652 indicated less favorable properties of [
18F]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood-brain barrier penetration and lower target-to-nontarget ratios.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>8832694</pmid><doi>10.1016/0969-8051(96)00013-3</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-8051 |
| ispartof | Nuclear medicine and biology, 1996-05, Vol.23 (4), p.407-412 |
| issn | 0969-8051 1872-9614 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_78377569 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Analog Animals Autoradiography Biodistribution Biological and medical sciences Brain - diagnostic imaging Brain - metabolism Contrast media. Radiopharmaceuticals Fluorine Radioisotopes - chemistry Hydrocarbons, Fluorinated - chemical synthesis Hydrocarbons, Fluorinated - pharmacokinetics Isotope Labeling - methods Medical sciences Mice Pharmacology. Drug treatments Pyrroles - chemical synthesis Pyrroles - pharmacokinetics Quinolines - chemical synthesis Quinolines - pharmacokinetics Radiosynthesis S-[ 18F]Fluoroethyl Tissue Distribution Tomography, Emission-Computed |
| title | Radiosynthesis and biodistribution of the S-[ 18F]fluoroethyl analog of McN5652 |
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