Quantitative Analysis for Estimating Binding Potential of the Peripheral Benzodiazepine Receptor with [¹¹C]DAA1106

Abstract

[ 11 C]DAA1106 is a potent and selective ligand for the peripheral benzodiazepine receptor (PBR) with high affinity. It has been reported that the density of PBR is related to brain damage, so a reliable tracer method for the evaluation of PBR would be of use. We evaluated a quantification method of [ 11 C]DAA1106 binding in simulated data and human brain data. In the simulation study, the reliability of parameters estimated from the nonlinear least-squares (NLS) method, graphical analysis (GA), and multilinear analysis (MA) was evaluated. In GA, variation of the estimated distribution volume (DV) was small. However, DV was underestimated as noise increased. In MA, bias was smaller, and variation of the estimated DV was larger than in GA. In NLS, although variation was larger than in GA, it was small enough in regions of interest analysis, and not only DV but also binding potential (BP), determined from the k 3 /k 4 without any constraint, could be estimated. The variation of BP estimated with NLS became larger as k 3 or k 4 became smaller. In human studies with normal volunteers, regions of interest were drawn on several brain regions, BP was calculated by NLS, and DV was also estimated by NLS, GA, and MA. As a result, DVs estimated with each method were well correlated. However, there was no correlation between BP with NLS and DV with NLS, GA, and MA, because of the variation of K 1 /k 2 between individuals. In conclusion, BP is estimated most reliably by NLS with the two-tissue compartment model.

Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation

“…Among this class of ligands, [ 11 C]DAA1106 and [ 18 F] FEDAA1106 have been studied in monkeys and demonstrate high brain uptake and high ratios of specific to nonspecific binding Zhang et al, 2004). Studies in human with these ligands show high brain uptake, but displacement studies have not been performed to measure definitively the percentage of specific binding in human brain (Fujimura et al, 2006;Ikoma et al, 2007). Furthermore, [ 11 C]DAA1106 has been directly compared with [ 11 C](R)-PK11195 in rats under baseline conditions and after inflammation had been induced with neurotoxins (Venneti et al, 2007a;Venneti et al, 2007b).…”

Brain and whole-body imaging in nonhuman primates of [11C]PBR28, a promising PET radioligand for peripheral benzodiazepine receptors

“…Among this class of ligands, [ 11 C]DAA1106 and [ 18 F]FEDAA1106 ( Fig. 1) have successfully imaged PBRs in human and nonhuman primates with high brain uptake and a high percentage of specific binding (Fujimura et al, 2006;Ikoma et al, 2007;Maeda et al, 2004;Zhang et al, 2003). We also synthesized aryloxyanilide-based PET ligands that have high affinity and selectivity for PBRs: [ 11 C]PBR01, [ 18 F]PBR06, and [ 11 C]PBR28 ( Fig.…”

11C-AC-5216: A Novel PET Ligand for Peripheral Benzodiazepine Receptors in the Primate Brain

“…In vivo studies demonstrated that they had higher uptake and more specific binding in rodent and primate brains than 11 C-PK11195 (20)(21)(22). Now, 11 C-DAA1106 and 18 F-FEDAA1106 are being used to investigate PBR in the human brain at our facility to elucidate the relationship between PBR and brain diseases (25,26). Subsequently, 11 C-PBR28, an analog of 11 C-DAA1106, was developed to localize and quantify upregulated PBR associated with cerebral ischemia in rats (27).…”