RT Journal Article SR Electronic T1 In Vivo SPECT Imaging of Amyloid-β Deposition with Radioiodinated Imidazo[1,2-a]Pyridine Derivative DRM106 in a Mouse Model of Alzheimer's Disease JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 120 OP 126 DO 10.2967/jnumed.114.146944 VO 56 IS 1 A1 Chun-Jen Chen A1 Kazunori Bando A1 Hiroki Ashino A1 Kazumi Taguchi A1 Hideaki Shiraishi A1 Keiji Shima A1 Osuke Fujimoto A1 Chiemi Kitamura A1 Satoshi Matsushima A1 Keisuke Uchida A1 Yuto Nakahara A1 Hiroyuki Kasahara A1 Takao Minamizawa A1 Cheng Jiang A1 Ming-Rong Zhang A1 Maiko Ono A1 Masaki Tokunaga A1 Tetsuya Suhara A1 Makoto Higuchi A1 Kazutaka Yamada A1 Bin Ji YR 2015 UL http://jnm.snmjournals.org/content/56/1/120.abstract 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 < 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.