Iodinated tracers for imaging amyloid plaques in the brain

Kung, Hank F.; Kung, Mei‐Ping; Zhuang, Zhi Ping; Hou, Catherine; Lee, Chi-Wan; Plößl, Karl; Zhuang, Bing; Skovronsky, Daniel; Lee, Virginia M.‐Y.; Trojanowski, John Q.

doi:10.1016/j.mibio.2003.09.003

Cited by 38 publications

(22 citation statements)

References 25 publications

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“…After removal of solvents by rotary evaporation (G40-C), the product was redissolved in anhydrous CH 3 CN, distributed into 5-mL vials (2 mg each), and evaporated again. The vials containing the precursor material were further dried under high vacuum at room temperature overnight, sealed, and stored over Drierite at j80-C. 18 F nuclear reaction using a RDS-112 cyclotron, was transferred to a reaction vessel containing Kryptofix 2.2.2. (10 mg) and K 2 CO 3 (1.0 mg) in CH 3 CN/water (25:1 v/v; 1 mL).…”

Section: Radiolabeling Methodsmentioning

confidence: 99%

High-Yield, Automated Radiosynthesis of 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) Ready for Animal or Human Administration

et al. 2006

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The biomarker 2-(1-{6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([(18)F]FDDNP) is used as a positron emission tomography (PET) imaging probe for Alzheimer's disease and other neurodegenerative diseases. A high-yield and fully automated synthesis of [(18)F]FDDNP--along with the synthesis and characterization of non-radioactive FDDNP, a fluorescent probe derived from 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP)--are reported. Radiofluorination of the tosyloxy precursor 2-{[6-(2,2-dicyano-1-methylvinyl)-2-naphthyl](methyl)amino}ethyl-4-methylbenzenesulfonate (DDNPTs) with K(18)F/Kryptofix 2.2.2. yielded chemically (>99%) and radiochemically (>99%) pure [(18)F]FDDNP in high radiochemical yields (40-60%; n> 120), with specific activities ranging from 4 to 8 Ci/mumol at the end of synthesis (90 minutes). Both remote, semiautomated and automated synthesis procedures are described. Either approach provides a reliable method for production of large quantities (110-170 mCi from 500 mCi of [(18)F]fluoride) of [(18)F]FDDNP allowing for multiple PET experiments in the same day or for distribution of the tracer from a single cyclotron facility to PET imaging centers at various geographical distances.

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Section: Radiolabeling Methodsmentioning

confidence: 99%

High-Yield, Automated Radiosynthesis of 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) Ready for Animal or Human Administration

et al. 2006

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“…The binding properties of the ligands to A␤ fibrils have all been characterized by using essentially identical filter binding assays employing either narrow ranges of radioligand to determine K d values (10, 13) or a single fixed low concentration of radioligand and varying concentrations of cold competitor (7,18). The former assay format will only generally detect very high affinity binding as lower affinity interactions dissociate during the filter washing step, whereas the latter format is a site-specific assay and will not be sensitive to novel ligandbinding sites.…”

Section: -[4-(methylamino)phenyl]benzothiazole and 2-(4-dimethylaminomentioning

confidence: 99%

Evidence for the Presence of Three Distinct Binding Sites for the Thioflavin T Class of Alzheimer's Disease PET Imaging Agents on β-Amyloid Peptide Fibrils

Lockhart

Liang

Judd

et al. 2005

Journal of Biological Chemistry

209

278

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“…Another amyloid-imaging agent, SB-13, was also applied in a human PET study and exhibited binding properties similar to those of PIB (21). Several iodinated agents, 6-iodo-2-(49-dimethylamino-) phenyl-imidazo[1,2-a]-pyridine (IMPY) and I-stilbene, have also been explored for use as SPECT probes (22). Although validation remains necessary to determine whether retention of these agents in the neocortex truly reflects the level of amyloid deposition, such findings suggest the potential usefulness of this technique for early diagnosis of AD.…”

Section: Voxel-by-voxel Analysis Of 11 C-bf-227 Pet Imagesmentioning

confidence: 99%

2-(2-[2-Dimethylaminothiazol-5-yl]Ethenyl)-6- (2-[Fluoro]Ethoxy)Benzoxazole: A Novel PET Agent for In Vivo Detection of Dense Amyloid Plaques in Alzheimer's Disease Patients

Kudo¹,

Okamura²,

Furumoto³

et al. 2007

Journal of Nuclear Medicine

225

139

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Extensive deposition of dense amyloid fibrils is a characteristic neuropathologic hallmark in Alzheimer's disease (AD). Noninvasive detection of these molecules is potentially useful for early and precise detection of patients with AD. This study reports a novel compound, 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227), for in vivo detection of dense amyloid deposits using PET. Methods: The binding affinity of BF-227 to amyloid-b (Ab) fibrils was calculated. The binding property of BF-227 to amyloid plaques was evaluated by neuropathologic staining of AD brain sections. Brain uptake and in vivo binding of BF-227 to Ab deposits were also evaluated using mice. For clinical evaluation of 11 C-BF-227 as a PET probe, 11 normal (healthy) subjects and 10 patients with AD participated in this study. Dynamic PET images were obtained for 60 min after administration of 11 C-BF-227. The regional standardized uptake value (SUV) and the ratio of regional to cerebellar SUV were calculated as an index of 11 C-BF-227 retention. The regional tracer distribution in AD patients was statistically compared with that of aged normal subjects on a voxel-by-voxel basis. Results: BF-227 displayed high binding affinity to synthetic Ab1-42 fibrils (K i [inhibition constant], 4.3 6 1.5 nM). Neuropathologic staining has demonstrated preferential binding of this agent to dense amyloid deposits in AD brain. Moreover, a biodistribution study of this agent revealed excellent brain uptake and specific labeling of amyloid deposits in transgenic mice. The present clinical PET study using 11 C-BF-227 demonstrated the retention of this tracer in cerebral cortices of AD patients but not in those of normal subjects. All AD patients were clearly distinguishable from normal individuals using the temporal SUV ratio. Voxel-by-voxel analysis of PET images revealed that cortical BF-227 retention in AD patients is distributed primarily to the posterior association area of the brain and corresponded well with the preferred site for neuritic plaque depositions containing dense Ab fibrils. Conclusion: These findings suggest that BF-227 is a promising PET probe for in vivo detection of dense amyloid deposits in AD patients.

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Iodinated tracers for imaging amyloid plaques in the brain

Cited by 38 publications

References 25 publications

High-Yield, Automated Radiosynthesis of 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) Ready for Animal or Human Administration

High-Yield, Automated Radiosynthesis of 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) Ready for Animal or Human Administration

Evidence for the Presence of Three Distinct Binding Sites for the Thioflavin T Class of Alzheimer's Disease PET Imaging Agents on β-Amyloid Peptide Fibrils

2-(2-[2-Dimethylaminothiazol-5-yl]Ethenyl)-6- (2-[Fluoro]Ethoxy)Benzoxazole: A Novel PET Agent for In Vivo Detection of Dense Amyloid Plaques in Alzheimer's Disease Patients

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