Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects

Soumen Paul, Evan Gallagher, Jeih San Liow, Sanche Mabins, Katharine Henry, Sami S. Zoghbi, Roger N. Gunn, William C. Kreisl, Erica Richards, Paolo Zanotti-Fregonara, Cheryl L. Morse, Jinsoo Hong, Aneta Kowalski, Victor W. Pike, Robert B. Innis, Masahiro Fujita

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalJournal of Cerebral Blood Flow and Metabolism
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Healthy Volunteers
Databases
Radio
Brain
High Pressure Liquid Chromatography
Proteins
Body Mass Index
Obesity
(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine

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 journalArticle

Paul, S, Gallagher, E, Liow, JS, Mabins, S, Henry, K, Zoghbi, SS, Gunn, RN, Kreisl, WC, Richards, E, Zanotti-Fregonara, P, Morse, CL, Hong, J, Kowalski, A, Pike, VW, Innis, RB & Fujita, M 2018, 'Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects', Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X18771250
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. / Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects. In: Journal of Cerebral Blood Flow and Metabolism. 2018.
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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.",
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AU - Henry, Katharine

AU - Zoghbi, Sami S.

AU - Gunn, Roger N.

AU - Kreisl, William C.

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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

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