Lung clearance of inhaled aerosol of Tc‐99m‐methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender
Summary Tc‐99m‐methoxyisobutyl isonitrile (Tc‐99m‐MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc‐99m‐MIBI clearance has previously b...
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| Veröffentlicht in: | Clinical physiology and functional imaging 2019-07, Vol.39 (4), p.236-239 |
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| creator | Mohan, Hosahalli K. Livieratos, Lefteris Peters, A. Michael |
| description | Summary
Tc‐99m‐methoxyisobutyl isonitrile (Tc‐99m‐MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc‐99m‐MIBI clearance has previously been shown to be delayed in cigarette smokers. The aim of the current study was to determine whether smoking correlates with bronchopulmonary MRP1 expression, to confirm that Tc‐99m‐MIBI disappearance rate from the lungs following inhalation is delayed in smokers, and to determine the effects of gender and age on disappearance rate. Participants underwent dynamic imaging for 40 min over the lungs following inhalation of Tc‐99m‐MIBI using a double‐headed gamma camera. The half‐time of clearance was obtained from geometric mean of anterior and posterior counts and averaged between the two lungs. Paraffin‐embedded tissue obtained from healthy lung during surgery in 13 patients was graded immunohistochemically for MRP1 as negative (0), weak (1), moderate (2) or strong (3). In 4 non‐smokers, grading was 1 in three and 0 in one. In 9 smokers, in contrast, expression was graded 2–3 in 8 and 1 in one (P |
| doi_str_mv | 10.1111/cpf.12562 |
| format | Article |
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Tc‐99m‐methoxyisobutyl isonitrile (Tc‐99m‐MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc‐99m‐MIBI clearance has previously been shown to be delayed in cigarette smokers. The aim of the current study was to determine whether smoking correlates with bronchopulmonary MRP1 expression, to confirm that Tc‐99m‐MIBI disappearance rate from the lungs following inhalation is delayed in smokers, and to determine the effects of gender and age on disappearance rate. Participants underwent dynamic imaging for 40 min over the lungs following inhalation of Tc‐99m‐MIBI using a double‐headed gamma camera. The half‐time of clearance was obtained from geometric mean of anterior and posterior counts and averaged between the two lungs. Paraffin‐embedded tissue obtained from healthy lung during surgery in 13 patients was graded immunohistochemically for MRP1 as negative (0), weak (1), moderate (2) or strong (3). In 4 non‐smokers, grading was 1 in three and 0 in one. In 9 smokers, in contrast, expression was graded 2–3 in 8 and 1 in one (P<0·02). Mean clearance half‐time in smokers (142 ± 29 min; n = 17) was longer than in non‐smokers (91 ± 14 min; n = 18; P<0·0001). In non‐smokers, half‐times were not significantly different between men (96 ± 16; n = 6) min and women (88 ± 12 min; P = 0·2). Combining genders into one group, half‐time correlated with participant age (P = 0·0005). We conclude that smoking upregulates MRP1 and delays clearance of inhaled Tc‐99m‐MIBI. There is no significant gender difference in non‐smokers but ageing is associated with longer clearance half‐times.</description><identifier>ISSN: 1475-0961</identifier><identifier>EISSN: 1475-097X</identifier><identifier>DOI: 10.1111/cpf.12562</identifier><identifier>PMID: 30649835</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Adult ; Aerosols ; Age ; Age Factors ; Aging ; Cigarette smoking ; Cigarette Smoking - adverse effects ; Cigarette Smoking - metabolism ; Cigarette Smoking - physiopathology ; Correlation analysis ; Female ; Gender ; Half-Life ; Humans ; Inhalation ; Inhalation Exposure ; Lung - diagnostic imaging ; Lung - metabolism ; Lung - physiopathology ; Lungs ; Male ; Metabolic Clearance Rate ; Middle Aged ; Multidrug resistance ; multidrug resistance protein 1 ; Multidrug Resistance-Associated Proteins - metabolism ; Multidrug resistant organisms ; Non-Smokers ; Organotechnetium Compounds - administration & dosage ; Organotechnetium Compounds - pharmacokinetics ; Paraffin ; Paraffins ; Predictive Value of Tests ; Radionuclide Imaging ; Radiopharmaceuticals - administration & dosage ; Radiopharmaceuticals - pharmacokinetics ; Respiration ; Sex Factors ; Smokers ; Smoking ; Surgery ; Tc‐99m‐MIBI ; Young Adult</subject><ispartof>Clinical physiology and functional imaging, 2019-07, Vol.39 (4), p.236-239</ispartof><rights>2019 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd</rights><rights>2019 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2019 Scandinavian Society of Clinical Physiology and Nuclear Medicine</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-3bf6b16090a970224f0e1b944bccfe05f096d3d0fc6059302c082509a21cab8b3</citedby><cites>FETCH-LOGICAL-c3532-3bf6b16090a970224f0e1b944bccfe05f096d3d0fc6059302c082509a21cab8b3</cites><orcidid>0000-0002-4623-3614</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcpf.12562$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcpf.12562$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30649835$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohan, Hosahalli K.</creatorcontrib><creatorcontrib>Livieratos, Lefteris</creatorcontrib><creatorcontrib>Peters, A. Michael</creatorcontrib><title>Lung clearance of inhaled aerosol of Tc‐99m‐methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender</title><title>Clinical physiology and functional imaging</title><addtitle>Clin Physiol Funct Imaging</addtitle><description>Summary
Tc‐99m‐methoxyisobutyl isonitrile (Tc‐99m‐MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc‐99m‐MIBI clearance has previously been shown to be delayed in cigarette smokers. The aim of the current study was to determine whether smoking correlates with bronchopulmonary MRP1 expression, to confirm that Tc‐99m‐MIBI disappearance rate from the lungs following inhalation is delayed in smokers, and to determine the effects of gender and age on disappearance rate. Participants underwent dynamic imaging for 40 min over the lungs following inhalation of Tc‐99m‐MIBI using a double‐headed gamma camera. The half‐time of clearance was obtained from geometric mean of anterior and posterior counts and averaged between the two lungs. Paraffin‐embedded tissue obtained from healthy lung during surgery in 13 patients was graded immunohistochemically for MRP1 as negative (0), weak (1), moderate (2) or strong (3). In 4 non‐smokers, grading was 1 in three and 0 in one. In 9 smokers, in contrast, expression was graded 2–3 in 8 and 1 in one (P<0·02). Mean clearance half‐time in smokers (142 ± 29 min; n = 17) was longer than in non‐smokers (91 ± 14 min; n = 18; P<0·0001). In non‐smokers, half‐times were not significantly different between men (96 ± 16; n = 6) min and women (88 ± 12 min; P = 0·2). Combining genders into one group, half‐time correlated with participant age (P = 0·0005). We conclude that smoking upregulates MRP1 and delays clearance of inhaled Tc‐99m‐MIBI. There is no significant gender difference in non‐smokers but ageing is associated with longer clearance half‐times.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aerosols</subject><subject>Age</subject><subject>Age Factors</subject><subject>Aging</subject><subject>Cigarette smoking</subject><subject>Cigarette Smoking - adverse effects</subject><subject>Cigarette Smoking - metabolism</subject><subject>Cigarette Smoking - physiopathology</subject><subject>Correlation analysis</subject><subject>Female</subject><subject>Gender</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Inhalation</subject><subject>Inhalation Exposure</subject><subject>Lung - diagnostic imaging</subject><subject>Lung - metabolism</subject><subject>Lung - physiopathology</subject><subject>Lungs</subject><subject>Male</subject><subject>Metabolic Clearance Rate</subject><subject>Middle Aged</subject><subject>Multidrug resistance</subject><subject>multidrug resistance protein 1</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Multidrug resistant organisms</subject><subject>Non-Smokers</subject><subject>Organotechnetium Compounds - administration & dosage</subject><subject>Organotechnetium Compounds - pharmacokinetics</subject><subject>Paraffin</subject><subject>Paraffins</subject><subject>Predictive Value of Tests</subject><subject>Radionuclide Imaging</subject><subject>Radiopharmaceuticals - administration & dosage</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Respiration</subject><subject>Sex Factors</subject><subject>Smokers</subject><subject>Smoking</subject><subject>Surgery</subject><subject>Tc‐99m‐MIBI</subject><subject>Young Adult</subject><issn>1475-0961</issn><issn>1475-097X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUtqHDEQhkVIiB_JIhcwgmxiyNh6tLpH3oXBTgIDycKB7IRaXeqRrZbGUjf27HwEn9EniSbjeGFILaqK4uOnqn6EPlByQkucmrU9oUzU7BXap1UjZkQ2v18_9zXdQwc5XxFCG141b9EeJ3Ul51zso_vlFHpsPOikgwEcLXZhpT10WEOKOfrt6NI83j9IOZQ8wLiKdxuXYzuNG49LE9yYnIcznMDr0cWQV26d8a0bV9i4XicYR8B5iNcu9J-x7gHr0OEeQgfpHXpjtc_w_qkeol8X55eLb7Plj6_fF1-WM8MFZzPe2rqlNZFEy4YwVlkCtJVV1RpjgQhbzux4R6ypiZCcMEPmTBCpGTW6nbf8EH3a6a5TvJkgj2pw2YD3OkCcsmK0kRXhlM4L-vEFehWnFMp2ijHOa1GLaksd7yhT3pQTWLVObtBpoyhRW1tUsUX9taWwR0-KUztA90z-86EApzvgtjxy838ltfh5sZP8A0IUmVg</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Mohan, Hosahalli K.</creator><creator>Livieratos, Lefteris</creator><creator>Peters, A. Michael</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7TS</scope><scope>7U5</scope><scope>8FD</scope><scope>K9.</scope><scope>L7M</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4623-3614</orcidid></search><sort><creationdate>201907</creationdate><title>Lung clearance of inhaled aerosol of Tc‐99m‐methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender</title><author>Mohan, Hosahalli K. ; Livieratos, Lefteris ; Peters, A. Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-3bf6b16090a970224f0e1b944bccfe05f096d3d0fc6059302c082509a21cab8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aerosols</topic><topic>Age</topic><topic>Age Factors</topic><topic>Aging</topic><topic>Cigarette smoking</topic><topic>Cigarette Smoking - adverse effects</topic><topic>Cigarette Smoking - metabolism</topic><topic>Cigarette Smoking - physiopathology</topic><topic>Correlation analysis</topic><topic>Female</topic><topic>Gender</topic><topic>Half-Life</topic><topic>Humans</topic><topic>Inhalation</topic><topic>Inhalation Exposure</topic><topic>Lung - diagnostic imaging</topic><topic>Lung - metabolism</topic><topic>Lung - physiopathology</topic><topic>Lungs</topic><topic>Male</topic><topic>Metabolic Clearance Rate</topic><topic>Middle Aged</topic><topic>Multidrug resistance</topic><topic>multidrug resistance protein 1</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Multidrug resistant organisms</topic><topic>Non-Smokers</topic><topic>Organotechnetium Compounds - administration & dosage</topic><topic>Organotechnetium Compounds - pharmacokinetics</topic><topic>Paraffin</topic><topic>Paraffins</topic><topic>Predictive Value of Tests</topic><topic>Radionuclide Imaging</topic><topic>Radiopharmaceuticals - administration & dosage</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>Respiration</topic><topic>Sex Factors</topic><topic>Smokers</topic><topic>Smoking</topic><topic>Surgery</topic><topic>Tc‐99m‐MIBI</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mohan, Hosahalli K.</creatorcontrib><creatorcontrib>Livieratos, Lefteris</creatorcontrib><creatorcontrib>Peters, A. Michael</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical physiology and functional imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mohan, Hosahalli K.</au><au>Livieratos, Lefteris</au><au>Peters, A. Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lung clearance of inhaled aerosol of Tc‐99m‐methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender</atitle><jtitle>Clinical physiology and functional imaging</jtitle><addtitle>Clin Physiol Funct Imaging</addtitle><date>2019-07</date><risdate>2019</risdate><volume>39</volume><issue>4</issue><spage>236</spage><epage>239</epage><pages>236-239</pages><issn>1475-0961</issn><eissn>1475-097X</eissn><abstract>Summary
Tc‐99m‐methoxyisobutyl isonitrile (Tc‐99m‐MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc‐99m‐MIBI clearance has previously been shown to be delayed in cigarette smokers. The aim of the current study was to determine whether smoking correlates with bronchopulmonary MRP1 expression, to confirm that Tc‐99m‐MIBI disappearance rate from the lungs following inhalation is delayed in smokers, and to determine the effects of gender and age on disappearance rate. Participants underwent dynamic imaging for 40 min over the lungs following inhalation of Tc‐99m‐MIBI using a double‐headed gamma camera. The half‐time of clearance was obtained from geometric mean of anterior and posterior counts and averaged between the two lungs. Paraffin‐embedded tissue obtained from healthy lung during surgery in 13 patients was graded immunohistochemically for MRP1 as negative (0), weak (1), moderate (2) or strong (3). In 4 non‐smokers, grading was 1 in three and 0 in one. In 9 smokers, in contrast, expression was graded 2–3 in 8 and 1 in one (P<0·02). Mean clearance half‐time in smokers (142 ± 29 min; n = 17) was longer than in non‐smokers (91 ± 14 min; n = 18; P<0·0001). In non‐smokers, half‐times were not significantly different between men (96 ± 16; n = 6) min and women (88 ± 12 min; P = 0·2). Combining genders into one group, half‐time correlated with participant age (P = 0·0005). We conclude that smoking upregulates MRP1 and delays clearance of inhaled Tc‐99m‐MIBI. There is no significant gender difference in non‐smokers but ageing is associated with longer clearance half‐times.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30649835</pmid><doi>10.1111/cpf.12562</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-4623-3614</orcidid></addata></record> |
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| subjects | Adolescent Adult Aerosols Age Age Factors Aging Cigarette smoking Cigarette Smoking - adverse effects Cigarette Smoking - metabolism Cigarette Smoking - physiopathology Correlation analysis Female Gender Half-Life Humans Inhalation Inhalation Exposure Lung - diagnostic imaging Lung - metabolism Lung - physiopathology Lungs Male Metabolic Clearance Rate Middle Aged Multidrug resistance multidrug resistance protein 1 Multidrug Resistance-Associated Proteins - metabolism Multidrug resistant organisms Non-Smokers Organotechnetium Compounds - administration & dosage Organotechnetium Compounds - pharmacokinetics Paraffin Paraffins Predictive Value of Tests Radionuclide Imaging Radiopharmaceuticals - administration & dosage Radiopharmaceuticals - pharmacokinetics Respiration Sex Factors Smokers Smoking Surgery Tc‐99m‐MIBI Young Adult |
| title | Lung clearance of inhaled aerosol of Tc‐99m‐methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender |
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