BODIPY-Based Molecular Probe for Imaging of Cerebral β-Amyloid Plaques

Ono, Masahiro; Watanabe, Hiroyuki; Kimura, Hiroyuki; Saji, Hideo

doi:10.1021/cn3000058

Cited by 146 publications

(123 citation statements)

References 55 publications

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“…Fluorescence molecular imaging is appealing for small animal studies because of its low cost, easy operation, and stable imaging probes. In the past decade, the development of fluorescent imaging probes for AD has been actively pursued, and several probes showed capacity for imaging Aβs (37)(38)(39)(40)(41)(42)(43)(44)(45) and Tau tangles (64) in mice. Nonetheless, none has been used to monitor the effectiveness of drug therapy.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

Zhang

Tian

Zhang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

199

180

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Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to monitoring therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied successfully to monitoring therapy for Alzheimer's disease (AD). Although several NIRF probes for detecting amyloid beta (Aβ) species of AD have been reported, none of these probes has been used to monitor changes of Aβs during therapy. In this article, we demonstrated that CRANAD-3, a curcumin analog, is capable of detecting both soluble and insoluble Aβ species. In vivo imaging showed that the NIRF signal of CRANAD-3 from 4-mo-old transgenic AD (APP/PS1) mice was 2.29-fold higher than that from age-matched wild-type mice, indicating that CRANAD-3 is capable of detecting early molecular pathology. To verify the feasibility of CRANAD-3 for monitoring therapy, we first used the fast Aβ-lowering drug LY2811376, a well-characterized beta-amyloid cleaving enzyme-1 inhibitor, to treat APP/PS1 mice. Imaging data suggested that CRANAD-3 could monitor the decrease in Aβs after drug treatment. To validate the imaging capacity of CRANAD-3 further, we used it to monitor the therapeutic effect of CRANAD-17, a curcumin analog for inhibition of Aβ cross-linking. The imaging data indicated that the fluorescence signal in the CRANAD-17-treated group was significantly lower than that in the control group, and the result correlated with ELISA analysis of brain extraction and Aβ plaque counting. It was the first time, to our knowledge, that NIRF was used to monitor AD therapy, and we believe that our imaging technology has the potential to have a high impact on AD drug development.Alzheimer's | amyloid | imaging | fluorescence | curcumin

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Section: Discussionmentioning

confidence: 99%

“…Several NIRF probes for insoluble Aβs have been reported (37)(38)(39)(40)(41)(42)(43)(44)(45). It has been almost 10 y since the first report of NIRF imaging of Aβs by Hintersteiner et al in 2005 (41).…”

mentioning

confidence: 99%

Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

Zhang

Tian

Zhang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

199

180

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“…28 bound to Aβ aggregates with a high affinity (K d =44.1 nmol/L) and clearly stained Aβ plaques in the brains of transgenic mice. Moreover, 28 possesses ideal metabolic kinetics in vivo and could clearly differentiate between 25-month-old wild-type and Tg2576 mice at 1 h post-injection ex vivo [80] . The same group also developed derivatives of 28, BAP-2 (29), BAP-3 (30), BAP-4 (31), and BAP-5 (32), which contain most of the advantageous features of 28 but a better maximal emission wavelength, up to 700 nm.…”

Section: Bodipy-derived Probesmentioning

confidence: 99%

Advances in development of fluorescent probes for detecting amyloid-β aggregates

Ren

Tang

et al. 2016

Acta Pharmacol Sin

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With accumulating evidence suggesting that amyloid-β (Aβ) deposition is a good diagnostic biomarker for Alzheimer's disease (AD), the discovery of active Aβ probes has become an active area of research. Among the existing imaging methods, optical imaging targeting Aβ aggregates (fibrils or oligomers), especially using near-infrared (NIR) fluorescent probes, is increasingly recognized as a promising approach for the early diagnosis of AD due to its real time detection, low cost, lack of radioactive exposure and high-resolution. In the past decade, a variety of fluorescent probes have been developed and tested for efficiency in vitro, and several probes have shown efficacy in AD transgenic mice. This review classifies these representative probes based on their chemical structures and functional modes (dominant solvent-dependent mode and a novel solvent-independent mode). Moreover, the pharmaceutical characteristics of these representative probes are summarized and discussed. This review provides important perspectives for the future development of novel NIR Aβ diagnostic probes.

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“…13,14 Next, saturation assays were carried out to quantify the binding affinity of PT-1 to aggregated b-amyloid fibrils according to conventional methods. 17,22,24,26 The amyloid plaques in AD brains are mainly composed of aggregated Ab 1-42 fibrils, so that Ab 1-42 aggregates were used for in vitro binding assays. PT-1 binds to Ab 1-42 aggregates with a binding affinity K d of 54.3 nM, which is much higher than that of the reported amyloid-specific fluorescence probe AOI987 (K d = 220 nM), and is close to that of CRANAD-2 (K d = 38.9 nM) and NIR-2c (K d = 26.9 nM).…”

Section: Introductionmentioning

confidence: 99%

“…12,13,15 At present, there are limited fluorescence probes for b-amyloid fibrils compared to PET probes. 13,[16][17][18][19][20][21][22][23][24][25] Although most of the optical imaging systems are so far limited to animal studies, several new technologies are poised to enter clinical trials. Thus, strategies for noninvasive optical imaging of cerebral b-amyloid fibrils with novel imaging agents are still worth pursuing.…”

mentioning

confidence: 99%

A pyrane based fluorescence probe for noninvasive prediction of cerebral β-amyloid fibrils

Cheng

Zhu

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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BODIPY-Based Molecular Probe for Imaging of Cerebral β-Amyloid Plaques

Cited by 146 publications

References 55 publications

Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

Advances in development of fluorescent probes for detecting amyloid-β aggregates

A pyrane based fluorescence probe for noninvasive prediction of cerebral β-amyloid fibrils

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