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Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys
Purpose 4-[ 18 F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken. Methods Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected...
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| Published in: | European journal of nuclear medicine and molecular imaging 2010-03, Vol.37 (3), p.545-555 |
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| container_end_page | 555 |
| container_issue | 3 |
| container_start_page | 545 |
| container_title | European journal of nuclear medicine and molecular imaging |
| container_volume | 37 |
| creator | Huang, Ya-Yao Ma, Kuo-Hsing Tseng, Ta-Wei Chou, Ta-Kai Ng, Hanna Mirsalis, Jon C. Fu, Ying-Kai Chu, Tieh-Chi Huang, Wen-Sheng Shiue, Chyng-Yann |
| description | Purpose
4-[
18
F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken.
Methods
Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 μg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 μg/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[
18
F]-ADAM (182±8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time–activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software.
Results
In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 μGy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 μSv/MBq, respectively.
Conclusion
Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[
18
F]-ADAM is safe for use in human PET imaging studies. |
| doi_str_mv | 10.1007/s00259-009-1281-z |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_214653272</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1967484291</sourcerecordid><originalsourceid>FETCH-LOGICAL-c370t-537e4eadab320baed2872d14420c8dcdb068856a3cfd793f8e682b6a566b66593</originalsourceid><addsrcrecordid>eNp1kM1OAyEURonR-P8AbgxxLXphZhhY1mrVpMaNrowhzMAo1Q4VmMR264s7tY2uXF1yOd-5yYfQEYUzClCeRwBWSAIgCWWCksUG2qWcSlKCkJu_7xJ20F6MEwAqmJDbaIdKwUBmsIu-Lpw3Lqbgqi45357i5D9d7dIc69bgoI3Tyz02PrqpTWGOY-qMsxH7BqdXi6MNPvnWtTgF3caZD8mGn6B_dy9LSU6eqBg9k8Hl4A73XNAp_tinvn2z83iAthr9Hu3heu6jx9HVw_CGjO-vb4eDMamzEhIpstLmVhtdZQwqbQ0TJTM0zxnUwtSmAi5EwXVWN6aUWSMsF6ziuuC84ryQ2T46WXlnwX90NiY18V1o-5OK0ZwXGStZD9EVVAcfY7CNmgU31WGuKKhl62rVuupbV8vW1aLPHK_FXTW15i-xrrkH2AqI_Vf7YsPf5f-t3-mlj4A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>214653272</pqid></control><display><type>article</type><title>Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys</title><source>Springer Nature</source><creator>Huang, Ya-Yao ; Ma, Kuo-Hsing ; Tseng, Ta-Wei ; Chou, Ta-Kai ; Ng, Hanna ; Mirsalis, Jon C. ; Fu, Ying-Kai ; Chu, Tieh-Chi ; Huang, Wen-Sheng ; Shiue, Chyng-Yann</creator><creatorcontrib>Huang, Ya-Yao ; Ma, Kuo-Hsing ; Tseng, Ta-Wei ; Chou, Ta-Kai ; Ng, Hanna ; Mirsalis, Jon C. ; Fu, Ying-Kai ; Chu, Tieh-Chi ; Huang, Wen-Sheng ; Shiue, Chyng-Yann</creatorcontrib><description>Purpose
4-[
18
F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken.
Methods
Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 μg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 μg/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[
18
F]-ADAM (182±8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time–activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software.
Results
In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 μGy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 μSv/MBq, respectively.
Conclusion
Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[
18
F]-ADAM is safe for use in human PET imaging studies.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-009-1281-z</identifier><identifier>PMID: 19820930</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adult ; Animals ; Benzylamines - chemistry ; Benzylamines - metabolism ; Benzylamines - pharmacokinetics ; Benzylamines - toxicity ; Cardiology ; Dosimetry ; Female ; Fluorine Radioisotopes - chemistry ; Haplorhini ; Humans ; Imaging ; Male ; Medical imaging ; Medicine ; Medicine & Public Health ; Nuclear Medicine ; Oncology ; Original Article ; Orthopedics ; Radiation Dosage ; Radiation therapy ; Radioligand Assay ; Radiology ; Radiometry ; Rats ; Serotonin ; Serotonin Plasma Membrane Transport Proteins - metabolism ; Tissue Distribution ; Toxicity</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2010-03, Vol.37 (3), p.545-555</ispartof><rights>Springer-Verlag 2009</rights><rights>Springer-Verlag 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c370t-537e4eadab320baed2872d14420c8dcdb068856a3cfd793f8e682b6a566b66593</citedby><cites>FETCH-LOGICAL-c370t-537e4eadab320baed2872d14420c8dcdb068856a3cfd793f8e682b6a566b66593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19820930$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Ya-Yao</creatorcontrib><creatorcontrib>Ma, Kuo-Hsing</creatorcontrib><creatorcontrib>Tseng, Ta-Wei</creatorcontrib><creatorcontrib>Chou, Ta-Kai</creatorcontrib><creatorcontrib>Ng, Hanna</creatorcontrib><creatorcontrib>Mirsalis, Jon C.</creatorcontrib><creatorcontrib>Fu, Ying-Kai</creatorcontrib><creatorcontrib>Chu, Tieh-Chi</creatorcontrib><creatorcontrib>Huang, Wen-Sheng</creatorcontrib><creatorcontrib>Shiue, Chyng-Yann</creatorcontrib><title>Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Purpose
4-[
18
F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken.
Methods
Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 μg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 μg/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[
18
F]-ADAM (182±8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time–activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software.
Results
In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 μGy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 μSv/MBq, respectively.
Conclusion
Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[
18
F]-ADAM is safe for use in human PET imaging studies.</description><subject>Adult</subject><subject>Animals</subject><subject>Benzylamines - chemistry</subject><subject>Benzylamines - metabolism</subject><subject>Benzylamines - pharmacokinetics</subject><subject>Benzylamines - toxicity</subject><subject>Cardiology</subject><subject>Dosimetry</subject><subject>Female</subject><subject>Fluorine Radioisotopes - chemistry</subject><subject>Haplorhini</subject><subject>Humans</subject><subject>Imaging</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Nuclear Medicine</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Radiation Dosage</subject><subject>Radiation therapy</subject><subject>Radioligand Assay</subject><subject>Radiology</subject><subject>Radiometry</subject><subject>Rats</subject><subject>Serotonin</subject><subject>Serotonin Plasma Membrane Transport Proteins - metabolism</subject><subject>Tissue Distribution</subject><subject>Toxicity</subject><issn>1619-7070</issn><issn>1619-7089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp1kM1OAyEURonR-P8AbgxxLXphZhhY1mrVpMaNrowhzMAo1Q4VmMR264s7tY2uXF1yOd-5yYfQEYUzClCeRwBWSAIgCWWCksUG2qWcSlKCkJu_7xJ20F6MEwAqmJDbaIdKwUBmsIu-Lpw3Lqbgqi45357i5D9d7dIc69bgoI3Tyz02PrqpTWGOY-qMsxH7BqdXi6MNPvnWtTgF3caZD8mGn6B_dy9LSU6eqBg9k8Hl4A73XNAp_tinvn2z83iAthr9Hu3heu6jx9HVw_CGjO-vb4eDMamzEhIpstLmVhtdZQwqbQ0TJTM0zxnUwtSmAi5EwXVWN6aUWSMsF6ziuuC84ryQ2T46WXlnwX90NiY18V1o-5OK0ZwXGStZD9EVVAcfY7CNmgU31WGuKKhl62rVuupbV8vW1aLPHK_FXTW15i-xrrkH2AqI_Vf7YsPf5f-t3-mlj4A</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Huang, Ya-Yao</creator><creator>Ma, Kuo-Hsing</creator><creator>Tseng, Ta-Wei</creator><creator>Chou, Ta-Kai</creator><creator>Ng, Hanna</creator><creator>Mirsalis, Jon C.</creator><creator>Fu, Ying-Kai</creator><creator>Chu, Tieh-Chi</creator><creator>Huang, Wen-Sheng</creator><creator>Shiue, Chyng-Yann</creator><general>Springer-Verlag</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20100301</creationdate><title>Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys</title><author>Huang, Ya-Yao ; Ma, Kuo-Hsing ; Tseng, Ta-Wei ; Chou, Ta-Kai ; Ng, Hanna ; Mirsalis, Jon C. ; Fu, Ying-Kai ; Chu, Tieh-Chi ; Huang, Wen-Sheng ; Shiue, Chyng-Yann</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-537e4eadab320baed2872d14420c8dcdb068856a3cfd793f8e682b6a566b66593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Benzylamines - chemistry</topic><topic>Benzylamines - metabolism</topic><topic>Benzylamines - pharmacokinetics</topic><topic>Benzylamines - toxicity</topic><topic>Cardiology</topic><topic>Dosimetry</topic><topic>Female</topic><topic>Fluorine Radioisotopes - chemistry</topic><topic>Haplorhini</topic><topic>Humans</topic><topic>Imaging</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Nuclear Medicine</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Radiation Dosage</topic><topic>Radiation therapy</topic><topic>Radioligand Assay</topic><topic>Radiology</topic><topic>Radiometry</topic><topic>Rats</topic><topic>Serotonin</topic><topic>Serotonin Plasma Membrane Transport Proteins - metabolism</topic><topic>Tissue Distribution</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Ya-Yao</creatorcontrib><creatorcontrib>Ma, Kuo-Hsing</creatorcontrib><creatorcontrib>Tseng, Ta-Wei</creatorcontrib><creatorcontrib>Chou, Ta-Kai</creatorcontrib><creatorcontrib>Ng, Hanna</creatorcontrib><creatorcontrib>Mirsalis, Jon C.</creatorcontrib><creatorcontrib>Fu, Ying-Kai</creatorcontrib><creatorcontrib>Chu, Tieh-Chi</creatorcontrib><creatorcontrib>Huang, Wen-Sheng</creatorcontrib><creatorcontrib>Shiue, Chyng-Yann</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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4-[
18
F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken.
Methods
Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 μg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 μg/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[
18
F]-ADAM (182±8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time–activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software.
Results
In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 μGy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 μSv/MBq, respectively.
Conclusion
Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[
18
F]-ADAM is safe for use in human PET imaging studies.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>19820930</pmid><doi>10.1007/s00259-009-1281-z</doi><tpages>11</tpages></addata></record> |
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| identifier | ISSN: 1619-7070 |
| ispartof | European journal of nuclear medicine and molecular imaging, 2010-03, Vol.37 (3), p.545-555 |
| issn | 1619-7070 1619-7089 |
| language | eng |
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| source | Springer Nature |
| subjects | Adult Animals Benzylamines - chemistry Benzylamines - metabolism Benzylamines - pharmacokinetics Benzylamines - toxicity Cardiology Dosimetry Female Fluorine Radioisotopes - chemistry Haplorhini Humans Imaging Male Medical imaging Medicine Medicine & Public Health Nuclear Medicine Oncology Original Article Orthopedics Radiation Dosage Radiation therapy Radioligand Assay Radiology Radiometry Rats Serotonin Serotonin Plasma Membrane Transport Proteins - metabolism Tissue Distribution Toxicity |
| title | Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys |
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