Abstract
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Objectives To evaluate F-18 labeled 2-fluoro-8-hydroxy quinoline (HQ) for imaging amyloid plaques in AD transgenic (Tg) mice with PET.
Methods 8-benzyloxy-2-chloroquinoline was reacted with [K222][18F] in DMSO at 135o C followed by catalytic hydrogenation. The product was formulated with saline after HPLC purification in an overall synthesis time of 70 min (30% uncorrected radiochemical yield: specific activity >1 Ci/μmol). Control (B6) and Tg [mice with double mutation for AD (APP/PS1, strain B6C3-Tg, APPswe, PSEN1dE9), age 12 months, n=3] were imaged in a Siemens Inveon® PET-CT scanner. Image acquisition was started immediately after i.v. injection of the tracer (50-90 μCi) and continued up to 30 min. Tg mice were characterized by genotyping.
Results PET images showed high (8-10 %ID/g) and fast (1 min) uptake in mice brains and rapid washout of the tracer from the control mice brains while Tg mice had delayed washout. Activity in the brain as a function of time was expressed as a sum of two exponential functions with different slopes: f (t) = A1 * exp (-B1*t) + A2 * exp (-B2*t), where A1, A2, B1, B2 are fitting coefficients and were different (except for A1) for control (A1=104, A2=20.4, B1=1.32, B2=0.031) and AD (A1=104, A2=51, B1=1.46, B2=0.023) mice. Brain uptake (ID/g) ratio (AD/control) rapidly increased from 1.1 at one minute to 2.2 at 10 minutes post injection and reached 2.6 at 30 min. Brain uptake ratio (Y) vs. time (X) was expressed by the equation Y=1.36+0.36 * ln (X) indicating persistent increase with time.
Conclusions PET/CT images of AD mice brains showed discrete distribution and delayed washout of F-18 labeled HQ whereas control mice had very rapid washout. F-18 labeled HQ derivatives appear to be promising molecules for targeting elevated metal ions in amyloid plaques. These studies warrant further evaluation of this class of molecules as plaque imaging agents.
Research Support Studies were supported by Worsham Fund and NIH (NIA) Grant# 1RC1AG0330801