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P‐046: [I‐123] IMPY imaging in Alzheimer's disease and healthy controls
Author(s) -
Marek Kenneth,
Jennings Danna,
Tamagnan Gilles,
Koren Andre,
Skovronsky Daniel,
Seibyl John
Publication year - 2007
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2007.04.262
Subject(s) - bolus (digestion) , medicine , nuclear medicine , alzheimer's disease , pittsburgh compound b , positron emission tomography , pharmacology , disease
Background: -Amyloid plaque accumulation likely plays a critical role in AD etiology, and potentially in AD therapy. Imaging tracers targeting -amyloid would provide improved diagnostic accuracy and enable monitoring of amyloid reducing therapies for AD. IMPY is a modified thioflavin derivative with good binding affinity to preformed synthetic A 1-40 aggregates, excellent brain uptake, and selective plaque labeling in AD transgenic mouse models and in postmortem AD brain sections. Objective: To evaluate [I-123] IMPY (6-iodo-2-(4’-dimethylamino-)phenyl-imidazo[1,2-]pyridine) as an objective and quantifiable biomarker of -amyloid deposition in Alzheimer’s disease (AD) subjects and healthy controls (HC). Methods: In this ongoing study AD patients and HC undergo serial SPECT imaging after either a single bolus injection or a bolus injection followed by multiple mini-bolus injections of [I-123] IMPY. Subjects were evaluated prior to imaging with MMSE, ADAS-Cog. After the single bolus injection 15 serial, dynamic SPECT acquisitions were acquired over 2 hours. During the bolus plus mini-bolus injections scans were acquired for 90 minutes. All images within each reconstructed data set were aligned with SPM. Results were based on a standardized cortical volume of interest protocol. Venous blood was obtained to assess free plasma IMPY and metabolites. Results: 15 subjects; 8 AD patients (mean age 80, gender -6F,2M, mean MMSE 23) and 7 HC (mean age 69, gender -2F 5M, mean MMSE 29) have undergone [I-123] IMPY imaging. Following bolus injection cortical time activity data shows rapid uptake and washout. Analysis shows a T1/2 washout of [I-123] IMPY of 21.5 minutes (sd 5.3) for HS and 39.3 minutes (sd 19) for AD (p .052). Preliminary analysis of equilibrium distribution volume showed mean cortical to cerebellar ratios of 1.25 in AD subjects compared to 1.06 in HS. Conclusion: This pilot [I-123] IMPY study demonstrates a 25%-100% signal difference between well-characterized AD patients and older HC depending on the imaging outcome. These data suggest the feasibility of distinguishing AD and HC using quantitative [I-123] IMPY imaging outcomes. However, additional studies are required to more fully validate [I-123] IMPY as a potential tool for AD onset and progression.