Merck
  • Home
  • Search Results
  • Determination of [(11)C]PBR28 binding potential in vivo: a first human TSPO blocking study.

Determination of [(11)C]PBR28 binding potential in vivo: a first human TSPO blocking study.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2014-03-20)
David R Owen, Qi Guo, Nicola J Kalk, Alessandro Colasanti, Dimitra Kalogiannopoulou, Rahul Dimber, Yvonne L Lewis, Vincenzo Libri, Julien Barletta, Joaquim Ramada-Magalhaes, Aruloly Kamalakaran, David J Nutt, Jan Passchier, Paul M Matthews, Roger N Gunn, Eugenii A Rabiner
ABSTRACT

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [(11)C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (VND), and hence estimate the BPND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [(11)C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, VND was estimated via the occupancy plot. Values of BPND for all subjects were calculated using this VND estimate. Total volume of distribution (VT) of MABs (2.94±0.31) was lower than VT of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a VND estimate of 1.98 (1.69, 2.26). Based on these VND estimates, BPND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [(11)C]PBR28 VND and hence BPND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating VND for TSPO targeting radioligands.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethanol, purum, secunda spirit, denaturated with 2% 2-butanone and 0.5% 4-methyl-2-pentanone, S15, ~96% (based on denaturant-free substance)
Sigma-Aldrich
Ethanol, tested according to Ph. Eur.
Supelco
Ethanol, standard for GC
Sigma-Aldrich
Ethanol, for residue analysis
Sigma-Aldrich
Ethanol, purum, absolute ethanol, denaturated with 4.8% isopropanol, A15 IPA1, ≥99.8% (based on denaturant-free substance)
Sigma-Aldrich
Ethanol, purum, fine spirit, denaturated with 2% 2-butanone, F25 MEK1, ~96% (based on denaturant-free substance)
Sigma-Aldrich
Ethanol, purum, fine spirit, denaturated with 4.8% methanol, F25 METHYL1, ~96% (based on denaturant-free substance)
Sigma-Aldrich
Ethanol, purum, absolute ethanol, denaturated with 2% 2-butanone, A15 MEK1, ≥99.8% (based on denaturant-free substance)
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, meets USP testing specifications
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS reagent, meets USP testing specifications, Excise Tax-free, Permit for use required
Sigma-Aldrich
Ethanol, BioUltra, for molecular biology, ≥99.8%, (absolute alcohol, without additive, A15 o1)
Supelco
Dehydrated Alcohol, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Ethanol solution, certified reference material, 2000 μg/mL in methanol
USP
Dehydrated Alcohol, United States Pharmacopeia (USP) Reference Standard