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Comparative Study
. 2011 Feb;38(2):352-7.
doi: 10.1007/s00259-010-1622-y. Epub 2010 Nov 18.

Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography

Leah P Dickstein  1 , Sami S Zoghbi, Yota Fujimura, Masao Imaizumi, Yi Zhang, Victor W Pike, Robert B Innis, Masahiro Fujita
Affiliations
Comparative Study

Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography

Leah P Dickstein et al. Eur J Nucl Med Mol Imaging. 2011 Feb.

Abstract

Purpose: Translocator protein (TSPO) is a promising biomarker for neuroinflammation. We developed two new PET ligands, (18)F-PBR06 and (11)C-PBR28, to image TSPOs. Although our prior studies suggest that either of the two ligands could be used to quantify TSPOs in human brain, the studies were done in different sets of subjects. In this study, we directly compared (18)F-PBR06 and (11)C-PBR28 in eight human subjects to determine (1) whether either ligand provides more precise measurements of TSPOs and (2) whether the higher in vitro affinity of PBR06 compared to PBR28 led to higher in vivo binding of (18)F-PBR06 compared to (11)C-PBR28.

Methods: In vivo binding was calculated as total distribution volume (V(T)), using an unconstrained two-tissue compartment model. V(T) was corrected for plasma free fraction (f (P)) to measure ligand binding based on free ligand concentration in brain.

Results: Both ligands measured V(T) with similar precision, as evidenced by similarly good identifiability. However, V(T) for both radioligands increased with increasing lengths of data acquisition, consistent with the accumulation of radiometabolites in brain. Despite its higher lipophilicity and higher in vitro affinity, V(T)/f(P) of (18)F-PBR06 was similar to that of (11)C-PBR28.

Conclusion: Both (18)F-PBR06 and (11)C-PBR28 are similar in terms of precision, sensitivity to accumulation of radiometabolites, and magnitude of in vivo binding. Thus, selection between the two radioligands will be primarily determined by the logistical impact of the different half-lives of the two radionuclides (110 vs 20 min).

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Conflict of interest statement

Conflicts of interest None.

Figures

Fig. 1
Fig. 1
Chemical structures of 18F-PBR06 and 11C-PBR28
Fig. 2
Fig. 2
Concentration and percentage composition of unchanged total (= free+protein-bound) radioligand and percentage composition of radiometabolites in plasma after injection. a Concentrations of total 18F-PBR06 and 11C-PBR28 are decay-corrected SUV. Error bars representing SD begin at 20 min after injection for clarity. b Percentage of total plasma activity representing unchanged radioligand (○, ●) and radiometabolites (△, ▲) of 18F-PBR06 (open symbols) and 11C-PBR28 (closed symbols). Values are means of eight subjects
Fig. 3
Fig. 3
Concentration of radioactivity in frontal cortex after injection of 18F-PBR06 or 11C-PBR28. Values are mean (symbols) and SD (error bars) of decay-corrected SUV values from eight subjects
Fig. 4
Fig. 4
VT values of 18F-PBR06 (○) and 11C-PBR28 (●) as a function of scan duration. Values are means from eight subjects across ten brain regions
Fig. 5
Fig. 5
Correlation between VT/fP of 18F-PBR06 and 11C-PBR28. Each symbol (●) represents the mean of eight subjects in a single brain region. Pearson’s r=0.92 (p<0.0005). The best-fit linear regression line (solid line) had a slope of 1.37
See this image and copyright information in PMC

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