PT - JOURNAL ARTICLE AU - Chun-Jen Chen AU - Kazunori Bando AU - Hiroki Ashino AU - Kazumi Taguchi AU - Hideaki Shiraishi AU - Keiji Shima AU - Osuke Fujimoto AU - Chiemi Kitamura AU - Satoshi Matsushima AU - Keisuke Uchida AU - Yuto Nakahara AU - Hiroyuki Kasahara AU - Takao Minamizawa AU - Cheng Jiang AU - Ming-Rong Zhang AU - Maiko Ono AU - Masaki Tokunaga AU - Tetsuya Suhara AU - Makoto Higuchi AU - Kazutaka Yamada AU - Bin Ji TI - In Vivo SPECT Imaging of Amyloid-β Deposition with Radioiodinated Imidazo[1,2-<em>a</em>]Pyridine Derivative DRM106 in a Mouse Model of Alzheimer's Disease AID - 10.2967/jnumed.114.146944 DP - 2015 Jan 01 TA - Journal of Nuclear Medicine PG - 120--126 VI - 56 IP - 1 4099 - http://jnm.snmjournals.org/content/56/1/120.short 4100 - http://jnm.snmjournals.org/content/56/1/120.full SO - J Nucl Med2015 Jan 01; 56 AB - Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 (123/125I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aβ fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains. Method: The sensitivity of 125I-DRM106 for detecting Aβ deposition was compared with that of 125I-IMPY (2-(4′-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aβ plaques with 123I-DRM106 and a well-known amyloid PET agent, 11C-labeled Pittsburgh compound B (11C-PiB), in 29-mo-old transgenic mice and age-matched nontransgenic littermates. Additionally, we compared the binding characteristics of 125I-DRM106 with those of 11C-PiB and 11C-PBB3, which selectively bind to Aβ plaques and preferentially to tau aggregates, respectively, in postmortem AD brain sections. Results: Ex vivo autoradiographic analysis showed that measurement with 125I-DRM106 has a higher sensitivity for detecting Aβ accumulation than with 125I-IMPY in transgenic mice. SPECT imaging with 123I-DRM106 also successfully detected Aβ deposition in living aged transgenic mice and showed strong correlation (R = 0.95, P &lt; 0.01) in quantitative analysis for Aβ plaque detection by PET imaging with 11C-PiB, implying that sensitivity and quantitation of SPECT imaging with 123I-DRM106 are almost as good as 11C-PiB PET for the detectability of Aβ deposition. Further, the addition of nonradiolabeled DRM106 fully blocked the binding of 125I-DRM106 and 11C-PiB, but not 11C-PBB3, to AD brain sections, and 125I-DRM106 showed a lower binding ratio of the diffuse plaque–rich lateral temporal cortex to the dense-cored/neuritic plaque–rich hippocampal CA1 area, compared with 11C-PiB. Conclusion: All of these data demonstrated the high potential of 123I-DRM106 for amyloid imaging in preclinical and clinical application, and it might more preferentially detect dense-cored/neuritic amyloid deposition, which is expected to be closely associated with neuropathologic changes of AD.