Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes
Purpose Previous studies demonstrated the utility of [ 18 F]fluoropropyl-(+)-dihydrotetrabenazine ([ 18 F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mel...
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| Veröffentlicht in: | Molecular imaging and biology 2018-10, Vol.20 (5), p.835-845 |
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| creator | Naganawa, Mika Lim, Keunpoong Nabulsi, Nabeel B. Lin, Shu-fei Labaree, David Ropchan, Jim Herold, Kevan C. Huang, Yiyun Harris, Paul Ichise, Masanori Cline, Gary W. Carson, Richard E. |
| description | Purpose
Previous studies demonstrated the utility of [
18
F]fluoropropyl-(+)-dihydrotetrabenazine ([
18
F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [
18
F]FP-(+)-DTBZ with the inactive enantiomer, [
18
F]FP-(−)-DTBZ. This was the first human study of [
18
F]FP-(−)-DTBZ.
Procedures
Six HCs and four T1DM patients were scanned on separate days after injection of [
18
F]FP-(+)-DTBZ or [
18
F]FP-(−)-DTBZ. Distribution volumes (
V
T
) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake (
V
ND
) or reference SUV were applied: (1) use of [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming
V
ND
is uniform across organs; (2) use of [
18
F]FP-(−)-DTBZ pancreatic
V
T
as
V
ND
, assuming that
V
ND
is uniform between enantiomers in the pancreas; and (3) use of a scaled [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in
V
T
(or SUV), binding potential (
BP
ND
), or SUV ratio (SUVR) were estimated using these three methods.
Results
[
18
F]FP-(−)-DTBZ
V
T
values were different among organs, and
V
T
(+) and
V
T
(−) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate
V
ND
(or reference SUV) gave the highest non-displaceable uptake and the largest HC
vs.
T1DM group differences. Significant group differences were also observed in
V
T
(or SUV) with method 1 using spleen. SUV was affected by differences in the input function between groups and between enantiomers.
Conclusions
Non-displaceable uptake was different among organs and between enantiomers. Use of scaled spleen
V
T
values for
V
ND
is a suitable method for quantification of VMAT2 in the pancreas. |
| doi_str_mv | 10.1007/s11307-018-1170-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6533199</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2007422236</sourcerecordid><originalsourceid>FETCH-LOGICAL-c514t-875c9791ff7f226360aafe3db9dea6bf86a8281d7746789b3aa40a5974f07ac03</originalsourceid><addsrcrecordid>eNp1kdtuEzEQhlcIREvhAbhBlrjhZosPGx9ukNI2aSsVEYnABQhZs15v4mjjTe3doDwGb4y3W8pB4soezf9_M6M_y14SfEowFm8jIQyLHBOZEyJwzh9lx0RynFOM6eP0nzCeE87oUfYsxg3GRBDKnmZHVBVcFrg4zn7M9tD00LnWo7ZGC_Am2FQa9Pn9dEnRmfOV8yv03XVrNDWd21sEvkLXHsZi5sEn99aGOAC-Ejn_Nl_kF8uzL8h5dGWh6dYH9LEvN9Z08c68SAOsT8UddXnYWUTQhYPSdjY-z57U0ET74v49yT7NZ8vzq_zmw-X1-fQmNxNSdLkUE6OEInUtako54xigtqwqVWWBl7XkIKkklRAFF1KVDKDAMFGiqLEAg9lJ9m7k7vpyayuTFgrQ6F1wWwgH3YLTf3e8W-tVu9d8whhRKgHe3ANCe9vb2Omti8Y2DXjb9lGnEERBKWU8SV__I920ffDpvEHFlWRSkaQio8qENsZg64dlCNZD4HoMXKfA9RC4Hsiv_rziwfEr4SSgoyCmll_Z8Hv0_6k_Afqqtew</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2006983891</pqid></control><display><type>article</type><title>Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes</title><source>MEDLINE</source><source>Springer journals</source><creator>Naganawa, Mika ; Lim, Keunpoong ; Nabulsi, Nabeel B. ; Lin, Shu-fei ; Labaree, David ; Ropchan, Jim ; Herold, Kevan C. ; Huang, Yiyun ; Harris, Paul ; Ichise, Masanori ; Cline, Gary W. ; Carson, Richard E.</creator><creatorcontrib>Naganawa, Mika ; Lim, Keunpoong ; Nabulsi, Nabeel B. ; Lin, Shu-fei ; Labaree, David ; Ropchan, Jim ; Herold, Kevan C. ; Huang, Yiyun ; Harris, Paul ; Ichise, Masanori ; Cline, Gary W. ; Carson, Richard E.</creatorcontrib><description>Purpose
Previous studies demonstrated the utility of [
18
F]fluoropropyl-(+)-dihydrotetrabenazine ([
18
F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [
18
F]FP-(+)-DTBZ with the inactive enantiomer, [
18
F]FP-(−)-DTBZ. This was the first human study of [
18
F]FP-(−)-DTBZ.
Procedures
Six HCs and four T1DM patients were scanned on separate days after injection of [
18
F]FP-(+)-DTBZ or [
18
F]FP-(−)-DTBZ. Distribution volumes (
V
T
) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake (
V
ND
) or reference SUV were applied: (1) use of [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming
V
ND
is uniform across organs; (2) use of [
18
F]FP-(−)-DTBZ pancreatic
V
T
as
V
ND
, assuming that
V
ND
is uniform between enantiomers in the pancreas; and (3) use of a scaled [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in
V
T
(or SUV), binding potential (
BP
ND
), or SUV ratio (SUVR) were estimated using these three methods.
Results
[
18
F]FP-(−)-DTBZ
V
T
values were different among organs, and
V
T
(+) and
V
T
(−) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate
V
ND
(or reference SUV) gave the highest non-displaceable uptake and the largest HC
vs.
T1DM group differences. Significant group differences were also observed in
V
T
(or SUV) with method 1 using spleen. SUV was affected by differences in the input function between groups and between enantiomers.
Conclusions
Non-displaceable uptake was different among organs and between enantiomers. Use of scaled spleen
V
T
values for
V
ND
is a suitable method for quantification of VMAT2 in the pancreas.</description><identifier>ISSN: 1536-1632</identifier><identifier>EISSN: 1860-2002</identifier><identifier>DOI: 10.1007/s11307-018-1170-6</identifier><identifier>PMID: 29468404</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adult ; Beta cells ; Binding ; Case-Control Studies ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - diagnostic imaging ; Diabetes Mellitus, Type 1 - metabolism ; Displacement ; Enantiomers ; Female ; Fluorine isotopes ; Fluorine Radioisotopes - blood ; Fluorine Radioisotopes - chemistry ; Fluorine Radioisotopes - pharmacokinetics ; Humans ; Imaging ; Injections ; Male ; Medicine ; Medicine & Public Health ; Organs ; Pancreas ; Patients ; Positron emission ; Positron emission tomography ; Radiology ; Renal cortex ; Research Article ; Spleen ; Stereoisomerism ; Tetrabenazine - analogs & derivatives ; Tetrabenazine - blood ; Tetrabenazine - chemistry ; Tetrabenazine - pharmacokinetics ; Tomography ; Vesicular Monoamine Transport Proteins - metabolism ; Vesicular monoamine transporter 2 ; Young Adult</subject><ispartof>Molecular imaging and biology, 2018-10, Vol.20 (5), p.835-845</ispartof><rights>World Molecular Imaging Society 2018</rights><rights>Molecular Imaging and Biology is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-875c9791ff7f226360aafe3db9dea6bf86a8281d7746789b3aa40a5974f07ac03</citedby><cites>FETCH-LOGICAL-c514t-875c9791ff7f226360aafe3db9dea6bf86a8281d7746789b3aa40a5974f07ac03</cites><orcidid>0000-0002-4408-2621</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11307-018-1170-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11307-018-1170-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,315,781,785,886,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29468404$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naganawa, Mika</creatorcontrib><creatorcontrib>Lim, Keunpoong</creatorcontrib><creatorcontrib>Nabulsi, Nabeel B.</creatorcontrib><creatorcontrib>Lin, Shu-fei</creatorcontrib><creatorcontrib>Labaree, David</creatorcontrib><creatorcontrib>Ropchan, Jim</creatorcontrib><creatorcontrib>Herold, Kevan C.</creatorcontrib><creatorcontrib>Huang, Yiyun</creatorcontrib><creatorcontrib>Harris, Paul</creatorcontrib><creatorcontrib>Ichise, Masanori</creatorcontrib><creatorcontrib>Cline, Gary W.</creatorcontrib><creatorcontrib>Carson, Richard E.</creatorcontrib><title>Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes</title><title>Molecular imaging and biology</title><addtitle>Mol Imaging Biol</addtitle><addtitle>Mol Imaging Biol</addtitle><description>Purpose
Previous studies demonstrated the utility of [
18
F]fluoropropyl-(+)-dihydrotetrabenazine ([
18
F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [
18
F]FP-(+)-DTBZ with the inactive enantiomer, [
18
F]FP-(−)-DTBZ. This was the first human study of [
18
F]FP-(−)-DTBZ.
Procedures
Six HCs and four T1DM patients were scanned on separate days after injection of [
18
F]FP-(+)-DTBZ or [
18
F]FP-(−)-DTBZ. Distribution volumes (
V
T
) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake (
V
ND
) or reference SUV were applied: (1) use of [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming
V
ND
is uniform across organs; (2) use of [
18
F]FP-(−)-DTBZ pancreatic
V
T
as
V
ND
, assuming that
V
ND
is uniform between enantiomers in the pancreas; and (3) use of a scaled [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in
V
T
(or SUV), binding potential (
BP
ND
), or SUV ratio (SUVR) were estimated using these three methods.
Results
[
18
F]FP-(−)-DTBZ
V
T
values were different among organs, and
V
T
(+) and
V
T
(−) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate
V
ND
(or reference SUV) gave the highest non-displaceable uptake and the largest HC
vs.
T1DM group differences. Significant group differences were also observed in
V
T
(or SUV) with method 1 using spleen. SUV was affected by differences in the input function between groups and between enantiomers.
Conclusions
Non-displaceable uptake was different among organs and between enantiomers. Use of scaled spleen
V
T
values for
V
ND
is a suitable method for quantification of VMAT2 in the pancreas.</description><subject>Adult</subject><subject>Beta cells</subject><subject>Binding</subject><subject>Case-Control Studies</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes Mellitus, Type 1 - blood</subject><subject>Diabetes Mellitus, Type 1 - diagnostic imaging</subject><subject>Diabetes Mellitus, Type 1 - metabolism</subject><subject>Displacement</subject><subject>Enantiomers</subject><subject>Female</subject><subject>Fluorine isotopes</subject><subject>Fluorine Radioisotopes - blood</subject><subject>Fluorine Radioisotopes - chemistry</subject><subject>Fluorine Radioisotopes - pharmacokinetics</subject><subject>Humans</subject><subject>Imaging</subject><subject>Injections</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Organs</subject><subject>Pancreas</subject><subject>Patients</subject><subject>Positron emission</subject><subject>Positron emission tomography</subject><subject>Radiology</subject><subject>Renal cortex</subject><subject>Research Article</subject><subject>Spleen</subject><subject>Stereoisomerism</subject><subject>Tetrabenazine - analogs & derivatives</subject><subject>Tetrabenazine - blood</subject><subject>Tetrabenazine - chemistry</subject><subject>Tetrabenazine - pharmacokinetics</subject><subject>Tomography</subject><subject>Vesicular Monoamine Transport Proteins - metabolism</subject><subject>Vesicular monoamine transporter 2</subject><subject>Young Adult</subject><issn>1536-1632</issn><issn>1860-2002</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kdtuEzEQhlcIREvhAbhBlrjhZosPGx9ukNI2aSsVEYnABQhZs15v4mjjTe3doDwGb4y3W8pB4soezf9_M6M_y14SfEowFm8jIQyLHBOZEyJwzh9lx0RynFOM6eP0nzCeE87oUfYsxg3GRBDKnmZHVBVcFrg4zn7M9tD00LnWo7ZGC_Am2FQa9Pn9dEnRmfOV8yv03XVrNDWd21sEvkLXHsZi5sEn99aGOAC-Ejn_Nl_kF8uzL8h5dGWh6dYH9LEvN9Z08c68SAOsT8UddXnYWUTQhYPSdjY-z57U0ET74v49yT7NZ8vzq_zmw-X1-fQmNxNSdLkUE6OEInUtako54xigtqwqVWWBl7XkIKkklRAFF1KVDKDAMFGiqLEAg9lJ9m7k7vpyayuTFgrQ6F1wWwgH3YLTf3e8W-tVu9d8whhRKgHe3ANCe9vb2Omti8Y2DXjb9lGnEERBKWU8SV__I920ffDpvEHFlWRSkaQio8qENsZg64dlCNZD4HoMXKfA9RC4Hsiv_rziwfEr4SSgoyCmll_Z8Hv0_6k_Afqqtew</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Naganawa, Mika</creator><creator>Lim, Keunpoong</creator><creator>Nabulsi, Nabeel B.</creator><creator>Lin, Shu-fei</creator><creator>Labaree, David</creator><creator>Ropchan, Jim</creator><creator>Herold, Kevan C.</creator><creator>Huang, Yiyun</creator><creator>Harris, Paul</creator><creator>Ichise, Masanori</creator><creator>Cline, Gary W.</creator><creator>Carson, Richard E.</creator><general>Springer International Publishing</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>7QO</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4408-2621</orcidid></search><sort><creationdate>20181001</creationdate><title>Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes</title><author>Naganawa, Mika ; Lim, Keunpoong ; Nabulsi, Nabeel B. ; Lin, Shu-fei ; Labaree, David ; Ropchan, Jim ; Herold, Kevan C. ; Huang, Yiyun ; Harris, Paul ; Ichise, Masanori ; Cline, Gary W. ; Carson, Richard E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-875c9791ff7f226360aafe3db9dea6bf86a8281d7746789b3aa40a5974f07ac03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Beta cells</topic><topic>Binding</topic><topic>Case-Control Studies</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes Mellitus, Type 1 - blood</topic><topic>Diabetes Mellitus, Type 1 - diagnostic imaging</topic><topic>Diabetes Mellitus, Type 1 - metabolism</topic><topic>Displacement</topic><topic>Enantiomers</topic><topic>Female</topic><topic>Fluorine isotopes</topic><topic>Fluorine Radioisotopes - blood</topic><topic>Fluorine Radioisotopes - chemistry</topic><topic>Fluorine Radioisotopes - pharmacokinetics</topic><topic>Humans</topic><topic>Imaging</topic><topic>Injections</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Organs</topic><topic>Pancreas</topic><topic>Patients</topic><topic>Positron emission</topic><topic>Positron emission tomography</topic><topic>Radiology</topic><topic>Renal cortex</topic><topic>Research Article</topic><topic>Spleen</topic><topic>Stereoisomerism</topic><topic>Tetrabenazine - analogs & derivatives</topic><topic>Tetrabenazine - blood</topic><topic>Tetrabenazine - chemistry</topic><topic>Tetrabenazine - pharmacokinetics</topic><topic>Tomography</topic><topic>Vesicular Monoamine Transport Proteins - metabolism</topic><topic>Vesicular monoamine transporter 2</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naganawa, Mika</creatorcontrib><creatorcontrib>Lim, Keunpoong</creatorcontrib><creatorcontrib>Nabulsi, Nabeel B.</creatorcontrib><creatorcontrib>Lin, Shu-fei</creatorcontrib><creatorcontrib>Labaree, David</creatorcontrib><creatorcontrib>Ropchan, Jim</creatorcontrib><creatorcontrib>Herold, Kevan C.</creatorcontrib><creatorcontrib>Huang, Yiyun</creatorcontrib><creatorcontrib>Harris, Paul</creatorcontrib><creatorcontrib>Ichise, Masanori</creatorcontrib><creatorcontrib>Cline, Gary W.</creatorcontrib><creatorcontrib>Carson, Richard E.</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>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular imaging and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naganawa, Mika</au><au>Lim, Keunpoong</au><au>Nabulsi, Nabeel B.</au><au>Lin, Shu-fei</au><au>Labaree, David</au><au>Ropchan, Jim</au><au>Herold, Kevan C.</au><au>Huang, Yiyun</au><au>Harris, Paul</au><au>Ichise, Masanori</au><au>Cline, Gary W.</au><au>Carson, Richard E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes</atitle><jtitle>Molecular imaging and biology</jtitle><stitle>Mol Imaging Biol</stitle><addtitle>Mol Imaging Biol</addtitle><date>2018-10-01</date><risdate>2018</risdate><volume>20</volume><issue>5</issue><spage>835</spage><epage>845</epage><pages>835-845</pages><issn>1536-1632</issn><eissn>1860-2002</eissn><abstract>Purpose
Previous studies demonstrated the utility of [
18
F]fluoropropyl-(+)-dihydrotetrabenazine ([
18
F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [
18
F]FP-(+)-DTBZ with the inactive enantiomer, [
18
F]FP-(−)-DTBZ. This was the first human study of [
18
F]FP-(−)-DTBZ.
Procedures
Six HCs and four T1DM patients were scanned on separate days after injection of [
18
F]FP-(+)-DTBZ or [
18
F]FP-(−)-DTBZ. Distribution volumes (
V
T
) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake (
V
ND
) or reference SUV were applied: (1) use of [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming
V
ND
is uniform across organs; (2) use of [
18
F]FP-(−)-DTBZ pancreatic
V
T
as
V
ND
, assuming that
V
ND
is uniform between enantiomers in the pancreas; and (3) use of a scaled [
18
F]FP-(+)-DTBZ reference
V
T
as
V
ND
, assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in
V
T
(or SUV), binding potential (
BP
ND
), or SUV ratio (SUVR) were estimated using these three methods.
Results
[
18
F]FP-(−)-DTBZ
V
T
values were different among organs, and
V
T
(+) and
V
T
(−) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate
V
ND
(or reference SUV) gave the highest non-displaceable uptake and the largest HC
vs.
T1DM group differences. Significant group differences were also observed in
V
T
(or SUV) with method 1 using spleen. SUV was affected by differences in the input function between groups and between enantiomers.
Conclusions
Non-displaceable uptake was different among organs and between enantiomers. Use of scaled spleen
V
T
values for
V
ND
is a suitable method for quantification of VMAT2 in the pancreas.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>29468404</pmid><doi>10.1007/s11307-018-1170-6</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-4408-2621</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1536-1632 |
| ispartof | Molecular imaging and biology, 2018-10, Vol.20 (5), p.835-845 |
| issn | 1536-1632 1860-2002 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6533199 |
| source | MEDLINE; Springer journals |
| subjects | Adult Beta cells Binding Case-Control Studies Diabetes Diabetes mellitus Diabetes mellitus (insulin dependent) Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 1 - diagnostic imaging Diabetes Mellitus, Type 1 - metabolism Displacement Enantiomers Female Fluorine isotopes Fluorine Radioisotopes - blood Fluorine Radioisotopes - chemistry Fluorine Radioisotopes - pharmacokinetics Humans Imaging Injections Male Medicine Medicine & Public Health Organs Pancreas Patients Positron emission Positron emission tomography Radiology Renal cortex Research Article Spleen Stereoisomerism Tetrabenazine - analogs & derivatives Tetrabenazine - blood Tetrabenazine - chemistry Tetrabenazine - pharmacokinetics Tomography Vesicular Monoamine Transport Proteins - metabolism Vesicular monoamine transporter 2 Young Adult |
| title | Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T17%3A55%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20Pancreatic%20VMAT2%20Binding%20with%20Active%20and%20Inactive%20Enantiomers%20of%20%5B18F%5DFP-DTBZ%20in%20Healthy%20Subjects%20and%20Patients%20with%20Type%201%20Diabetes&rft.jtitle=Molecular%20imaging%20and%20biology&rft.au=Naganawa,%20Mika&rft.date=2018-10-01&rft.volume=20&rft.issue=5&rft.spage=835&rft.epage=845&rft.pages=835-845&rft.issn=1536-1632&rft.eissn=1860-2002&rft_id=info:doi/10.1007/s11307-018-1170-6&rft_dat=%3Cproquest_pubme%3E2007422236%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2006983891&rft_id=info:pmid/29468404&rfr_iscdi=true |