PT - JOURNAL ARTICLE AU - Pooja Patel AU - Daphne Collins AU - Mihaela Nistor AU - Balu Easwaramoorthy AU - Elizabeth Head AU - Jogesh Mukherjee TI - <sup>18</sup>F-Fluoropropyl curcumin: A potential PET tracer for imaging inflammation and Aβ-plaques DP - 2007 May 01 TA - Journal of Nuclear Medicine PG - 22P--22P VI - 48 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/48/supplement_2/22P.2.short 4100 - http://jnm.snmjournals.org/content/48/supplement_2/22P.2.full SO - J Nucl Med2007 May 01; 48 AB - 74 Objectives: Curcumin (CUR) is known to be anitinflammatory, antiamyloidogenic and anticarcinogenic and is known to reduce formation of β-amyloid (Aβ) plaques. CUR binds to Aβ plaques with Ki= 0.2 nM (Ryu et al., 2006). As a PET imaging agent based on CUR, we report: 1. Radiosynthesis of O-18F-fluoropropyl curcumin (18F-FPCur) in a two-step reaction, and 2. Binding of 18F-FPCur in transgenic mouse models Tg2576 (Aβ plaques) and 3xTg triple transgenic (expressing Aβ plaques and neurofibrillary tangles). Methods: 1-Bromo-3-18F-fluoropropane (18F-BFP)was prepared by reacting 1,3-dibromopropane with 18F-fluoride at 90°C in CH3CN for 20 mins. CUR was reacted with 18F-BFP in THF/K2CO3 at 80°C for 30 mins, purified on RP-HPLC (C18, CH3CN, CH3OH, H2O, CH3CO2H 41:23:36:1;1.5 ml/min). Binding to rat brain slices of 18F-FPCur was carried out at 37°C in 0.1 M TBS buffer containing 0.5% Tween, 0.1% BSA, pH 7.4 for 1hr. Sagittal brain sections (10 μm) were obtained from two transgenic models, Tg2576 and 3xTg and wild-type (WT) mice of comparable age. Binding of 18F-FPCur was determined by autroradiograms analyzed by OptiQuant Image Software. Adjacent mice brain sections were immunostained with an anti-Aβ antibody and thioflavin to confirm presence of Aβ plaques. Results: Radiolabeling and isolation of 18F-BFP as a THF solution occurred in &gt;40% radiochemical yield in 40 mins. Radiolabeling of CUR occurred in low yields- approx. 2-3% of the radioactivity computed from collected HPLC fractions. A protected precursor molecule for radiolabeling is underway. Rat brain slices had low levels of nonspecific binding. Transgenic mice brain sections revealed significant amount of binding in areas consistent with the presence of Aβ plaques. Cerebellum (Cb) was used as a reference region- areas rich in Aβ plaques such as hippocampus (Hp), cortex (Ctx) and brain stem (BS) showed greater 18F-FPCur binding: For 3xTg: Hp/Cb= 2.6; Ctx/Cb= 1.23; BS/Cb= 2.7; and for Tg2576: Hp/Cb=1.9; Ctx/Cb= 1.8; BS/Cb=1.2. Thus, cortical regions of Tg2576 model contain higher degree of Aβ plaques. Conclusions: 18F-FPCur was prepared in a 2-step reaction. Methods to improve yields are currently underway. Binding of 18F-FPCur in transgenic mouse models indicates potential as a PET imaging agent.