Abstract
Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [11C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radio-HPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [11C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40.6 ± 16.8 years). After analysis by Logan plot using 23 metabolite-corrected arterial samples, total distribution volume (VT) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake (VND) as 1.40 mL · cm−3, which generated a specific-to-nondisplaceable ratio (BPND) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. VT increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, VT did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [11C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.
Original language | English (US) |
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Journal | Journal of Cerebral Blood Flow and Metabolism |
DOIs | |
State | Accepted/In press - Jan 1 2018 |
Externally published | Yes |
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Keywords
- distribution volume
- high-affinity binder
- mixed-affinity binder
- Translocator protein
- [C]PBR28
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Cite this
Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects. / Paul, Soumen; Gallagher, Evan; Liow, Jeih San; Mabins, Sanche; Henry, Katharine; Zoghbi, Sami S.; Gunn, Roger N.; Kreisl, William C.; Richards, Erica; Zanotti-Fregonara, Paolo; Morse, Cheryl L.; Hong, Jinsoo; Kowalski, Aneta; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro.
In: Journal of Cerebral Blood Flow and Metabolism, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects
AU - Paul, Soumen
AU - Gallagher, Evan
AU - Liow, Jeih San
AU - Mabins, Sanche
AU - Henry, Katharine
AU - Zoghbi, Sami S.
AU - Gunn, Roger N.
AU - Kreisl, William C.
AU - Richards, Erica
AU - Zanotti-Fregonara, Paolo
AU - Morse, Cheryl L.
AU - Hong, Jinsoo
AU - Kowalski, Aneta
AU - Pike, Victor W.
AU - Innis, Robert B.
AU - Fujita, Masahiro
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [11C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radio-HPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [11C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40.6 ± 16.8 years). After analysis by Logan plot using 23 metabolite-corrected arterial samples, total distribution volume (VT) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake (VND) as 1.40 mL · cm−3, which generated a specific-to-nondisplaceable ratio (BPND) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. VT increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, VT did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [11C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.
AB - Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [11C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radio-HPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [11C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40.6 ± 16.8 years). After analysis by Logan plot using 23 metabolite-corrected arterial samples, total distribution volume (VT) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake (VND) as 1.40 mL · cm−3, which generated a specific-to-nondisplaceable ratio (BPND) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. VT increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, VT did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [11C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.
KW - distribution volume
KW - high-affinity binder
KW - mixed-affinity binder
KW - Translocator protein
KW - [C]PBR28
UR - http://www.scopus.com/inward/record.url?scp=85047434340&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047434340&partnerID=8YFLogxK
U2 - 10.1177/0271678X18771250
DO - 10.1177/0271678X18771250
M3 - Article
C2 - 29749279
AN - SCOPUS:85047434340
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
ER -