[11C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brain

Zhang, Ming‐Rong; Kida, Takayo; Noguchi, Junko; Furutsuka, Kenji; Maeda, Jun; Suhara, Tetsuya; Suzuki, Kazutoshi

doi:10.1016/s0969-8051(03)00016-7

Cited by 142 publications

(134 citation statements)

References 23 publications

Supporting

Mentioning

129

Contrasting

Order By: Relevance

“…It has also been reported that [ 11 C]DAA1106 binding was inhibited by unlabeled DAA1106 and PK11195 in monkey brain and that the [ 11 C]DAA1106 binding corresponded to specific binding (Maeda et al, 2004). Moreover, the radiolabeled metabolite of [ 11 C]DAA1106 was more polar than [ 11 C]DAA1106, and was shown not to cross the BBB in mice (Zhang et al, 2003). The application of [ 11 C]DAA1106 can be useful in the diagnosis of neurodegenerative disorders and in the investigation of the mechanism of glia-neuron interactions.…”

Section: Introductionmentioning

confidence: 88%

See 1 more Smart Citation

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

Ikoma¹,

Yasuno²,

Ito³

et al. 2007

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

[ 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.

show abstract

Section: Introductionmentioning

confidence: 88%

“…After adding CH 3 CN/H 2 O (6/4, 500 mL), the radioactive mixture was applied to a semipreparative high-performance liquid chromatograph (HPLC) column (Zhang et al, 2003). The radioactive fraction corresponding to [ 11 C]DAA1106 was collected in a sterile flask.…”

Section: Human Study Analysismentioning

confidence: 99%

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

Ikoma¹,

Yasuno²,

Ito³

et al. 2007

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, several other compounds have been evaluated: [ 11 65 Maeda et al, 66 Zhang et al, 67,68 and Fujimara et al 69 have extensively described [ 11 C]DAA1106 and fluorinated derivatives in ex vivo binding experiments on rat brain sections and biodistribution studies in mice. PET imaging has also been performed in normal monkeys or healthy patients, but so far no published data from in vivo experiments using DAA1106 and derivatives in disease states have been published.…”

Section: New Pbr Ligands For Pet Studies Of Microglial Activationmentioning

confidence: 99%

Positron Emission Tomography Imaging of Neuroinflammation

et al. 2007

View full text Add to dashboard Cite

In the diseased brain, upon activation microglia express binding sites for synthetic ligands designed to recognize the 18-kDa translocator protein TP-18, which is part of the so-called peripheral benzodiazepine receptor complex. PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide], the prototype synthetic ligand, has been widely used for the functional characterization of TP-18. Its cellular source in activated microglia has been established using high-resolution, single-cell autoradiography with the R-enantiomer [3H](R)-PK11195. Radiolabeled [11C](R)-PK11195 has been used to image active brain disease with positron emission tomography. Consistent with experimental and postmortem observations of a characteristically distributed pattern of microglia activation in areas of focal pathology, as well as in anterograde and retrograde projection areas, the in vivo regional [11C](R)-PK11195 signal is found in active focal lesions and over time also along the affected neural tracts and their respective cortical and subcortical projection areas. Thus, a profile of active disease emerges that matches some of the typical distribution patterns known from structural neuroimaging techniques, but additionally shows involvement of brain regions linked through neural pathways. In the context of cell-based in vivo neuropathology, the image data are thus best interpreted in the context of the emerging cellular understanding of brain disease or damage, rather than the definitions of clinical diagnosis. One important observation, borne out by experiment, is the long latency with which activated microglia or increased PK11195 retention appear to gradually emerge and remain in distal areas secondarily affected by disease, supporting speculations that the presence of activated microglia is an important corollary of brain plasticity

show abstract

“…These radioligands have 4 to 18 times greater affinity for PBRs than PK 11195 and have higher levels of brain uptake (Zhang et al, 2003). 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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

Self Cite

View full text Add to dashboard Cite

The peripheral benzodiazepine receptor (PBR) is upregulated on activated microglia and macrophages and thereby is a useful biomarker of inflammation. We developed a novel PET radioligand, [ 11 C]PBR28, that was able to image and quantify PBRs in healthy monkeys and in a rat model of stroke. The objective of this study was to evaluate the ability of [ 11 C]PBR28 to quantify PBRs in brain of healthy human subjects. Twelve subjects had PET scans of 120 to 180 min duration as well as serial sampling of arterial plasma to measure the concentration of unchanged parent radioligand. One-and two-tissue compartmental analyses were performed. To obtain stable estimates of distribution volume, which is a summation of B max /K D and nondisplaceable activity, 90 min of brain imaging was required. Distribution volumes in human were only ∼5% of those in monkey. This comparatively low amount of receptor binding required a two-rather than a one-compartment model, suggesting that nonspecific binding was a sizeable percentage compared to specific binding. The time-activity curves in two of the twelve subjects appeared as if they had no PBR binding -i.e., rapid peak of uptake and fast washout from brain. The cause(s) of these unusual findings are unknown, but both subjects were also found to lack binding to PBRs in peripheral organs such as lung and kidney. In conclusion, with the exception of those subjects who appeared to have no PBR binding, [ 11 C]PBR28 is a promising ligand to quantify PBRs and localize inflammation associated with increased densities of PBRs.

show abstract

[11C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brain

Cited by 142 publications

References 23 publications

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

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

Positron Emission Tomography Imaging of Neuroinflammation

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

Contact Info

Product

Resources

About

[11C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brain

Cited by 142 publications

References 23 publications

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

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

Positron Emission Tomography Imaging of Neuroinflammation

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

Contact Info

Product

Resources

About

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

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