J Nucl Med. 2007; 48 (Supplement 2):56P
Neurosciences: Neurology Amyloid Imaging in Dementia |
Comparison of the amyloid imaging agents [F-18]3-F-PIB and [C-11]PIB in Alzheimer's disease and control subjects
Chester Mathis1,
Brian Lopresti1,
Neal Mason1,
Julie Price1,
Nicole Flatt1,
Wenzhu Bi1,
Scott Ziolko1,
Steven DeKosky2 and
William Klunk3
1 Radiology;
2 Neurology;
3 Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania
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Objectives: [C-11]PIB has been successfully employed to assess brain amyloid-beta (Aß) deposition in Alzheimers disease (AD). Our ongoing efforts to develop an [F-18]-labeled Aß tracer have identified the 3-F analog of PIB (3-F-PIB) as a lead agent. PIB and 3-F-PIB have comparable lipophilicities (log PC18 PIB=1.2 and 3-F-PIB=1.7) and bind to Aß1-40 fibrils with high affinity (Ki PIB=4.3 nM and 3-F-PIB=5.9 nM). We report here a preliminary comparison of [F-18]3-F-PIB and [C-11]PIB in AD and control subjects. Methods: [C-11]PIB and [F-18]3-F-PIB were imaged using an ECAT HR+ scanner in 2 control (75 y/o F, MMSE=30; 55 y/o F, MMSE=30) and one AD subject (78 y/o F, MMSE = 28). For [C-11]PIB, dynamic emission data were collected for 90 min after injection (~15 mCi). For [F-18]3-F-PIB, dynamic emission data were collected over 250 min after injection (~10 mCi). Both [C-11]PIB and [F-18]3-F-PIB images were co-registered to SPGR MRIs for region of interest (ROI) definition and atrophy correction. ROIs included precuneus (PRC), frontal cortex (FRC), cerebellum (CER), and subcortical white matter (SWM), and ratios of regional to CER standardized uptake values (SUVR) were determined. Results: [F-18]3-F-PIB readily entered human brain, with uptake at 5 min in all subjects nearly identical to [C-11]PIB (3.1-4.5 SUV units). Following the injection of [F-18]3-F-PIB, ~2-fold greater retention of radioactivity was observed in AD cortical areas known to contain Aß plaques (eg, PRC and FRC) relative to that in control subjects. [F-18]3-F-PIB SUVR values (90-120) in PRC and FRC were similar (within 10%) to [C-11]PIB SUVR values (40-90) in all subjects, while higher non-specific binding was observed (~20%) in SWM for [F-18]3-F-PIB than for [C-11]PIB. Conclusions: [F-18]3-F-PIB shows uptake and retention characteristics closely matched to those of [C-11]PIB in cortical brain regions. Somewhat higher non-specific retention in white matter was observed for [F-18]3-F-PIB relative to [C-11]PIB, but this likely will not negatively impact the ability of [F-18]3-F-PIB to identify and quantify cortical Aß deposits.
Research Support (if any): NIH (NIA), DOE, DANA, Alz Assoc, GE Healthcare