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Am J Nucl Med Mol Imaging 2013;3(2):102-117
Original Article
Alzheimer’s disease imaging with a novel Tau targeted near infrared ratiometric
probe
Hye-Yeong Kim, Urmi Sengupta, Pin Shao, Marcos J Guerrero-Muñoz, Rakez Kayed, Mingfeng Bai
Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15219, USA; Departments of
Neurology and Neuroscience & Cell Biology, George and Cynthia Mitchell Center for Neurodegenerative Diseases, University of
Texas Medical Branch, Gal-veston, Texas 77555-1045, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Received January 15, 2013; Accepted February 11, 2013; Epub March 8, 2013; Published March 18, 2013
Abstract: Neurofibrillary tangles (NFTs) have long been recognized as one of the pathological hallmarks in Alzheimer’s disease
(AD). Recent studies, however, showed that soluble aggregated Tau species, especially hyperphosphorylated Tau oligomers, which
are formed at early stage of AD prior to the formation of NFT, disrupted neural system integration. Unfortunately, little is known about
Tau aggregates, and few Tau targeted imaging probe has been reported. Successful development of new imaging methods that can
visualize early stages of Tau ag-gregation specifically will obviously be important for AD imaging, as well as understanding Tau-
associated neuropathology of AD. Here, we report the first NIR ratiometric probe, CyDPA2, that targets Tau aggregates. The
specificity of CyPDA2 to aggregated Tau was evaluated with in vitro hyperphosphorylated Tau proteins (pTau), as well as ex vivo Tau
samples from AD human brain samples and the tauopathy transgenic mouse model, P301L. The characteristic enhancements of
absorption ratio and fluorescence intensity in CyDPA2 were observed in a pTau concentration-dependent manner. In addition,
fluorescence microscopy and gel staining studies demonstrated CyDPA2-labeled Tau aggregates. These data indicate that CyDPA2
is a promising imaging probe for studying Tau pathology and diagnosing AD at an early stage. (ajnmmi1301003)
Keywords: Near infrared (NIR), ratiometric, probe, Tau, Alzheimer’s disease (AD), imaging
Address correspondence to: Dr. Mingfeng Bai, Department of Radiology, University of Pittsburgh, 100 Technology Dr., Suite 452G
Pittsburgh, PA 15219. Tel: 412-624-2565; Fax: 412-624-2598; E-mail: baim@upmc.edu
Original Article
Alzheimer’s disease imaging with a novel Tau targeted near infrared ratiometric
probe
Hye-Yeong Kim, Urmi Sengupta, Pin Shao, Marcos J Guerrero-Muñoz, Rakez Kayed, Mingfeng Bai
Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15219, USA; Departments of
Neurology and Neuroscience & Cell Biology, George and Cynthia Mitchell Center for Neurodegenerative Diseases, University of
Texas Medical Branch, Gal-veston, Texas 77555-1045, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Received January 15, 2013; Accepted February 11, 2013; Epub March 8, 2013; Published March 18, 2013
Abstract: Neurofibrillary tangles (NFTs) have long been recognized as one of the pathological hallmarks in Alzheimer’s disease
(AD). Recent studies, however, showed that soluble aggregated Tau species, especially hyperphosphorylated Tau oligomers, which
are formed at early stage of AD prior to the formation of NFT, disrupted neural system integration. Unfortunately, little is known about
Tau aggregates, and few Tau targeted imaging probe has been reported. Successful development of new imaging methods that can
visualize early stages of Tau ag-gregation specifically will obviously be important for AD imaging, as well as understanding Tau-
associated neuropathology of AD. Here, we report the first NIR ratiometric probe, CyDPA2, that targets Tau aggregates. The
specificity of CyPDA2 to aggregated Tau was evaluated with in vitro hyperphosphorylated Tau proteins (pTau), as well as ex vivo Tau
samples from AD human brain samples and the tauopathy transgenic mouse model, P301L. The characteristic enhancements of
absorption ratio and fluorescence intensity in CyDPA2 were observed in a pTau concentration-dependent manner. In addition,
fluorescence microscopy and gel staining studies demonstrated CyDPA2-labeled Tau aggregates. These data indicate that CyDPA2
is a promising imaging probe for studying Tau pathology and diagnosing AD at an early stage. (ajnmmi1301003)
Keywords: Near infrared (NIR), ratiometric, probe, Tau, Alzheimer’s disease (AD), imaging
Address correspondence to: Dr. Mingfeng Bai, Department of Radiology, University of Pittsburgh, 100 Technology Dr., Suite 452G
Pittsburgh, PA 15219. Tel: 412-624-2565; Fax: 412-624-2598; E-mail: baim@upmc.edu
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