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¹⁸F-Fluoropropyl curcumin: Improved radiosynthesis and binding to β-amyloid plaques in a transgenic mouse model of Alzheimer’s disease

¹ University of California, Irvine, Irvine, California

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Objectives: O-¹⁸F-fluoropropyl curcumin (¹⁸F-FPCUR) has been synthesized and selectively labels β-amyloid (Aβ) plaques in brain slices (Patel et al., 2007). We report: 1. Improved radiosynthesis of ¹⁸F-FPCUR; 2. Evaluation of binding in transgenic mouse model Tg2576 expressing Aβ plaques 3. Comparison of ¹⁸F-FPCUR with ¹¹C-PIB binding in Tg2576 mice.

Methods: CUR-B₂O₃ complex was prepared to protect the diketone. 1-Bromo-3-¹⁸F-fluoropropane was reacted with CUR-B₂O₃ in THF with K₂CO₃ at 80 ^oC for 30 mins and deprotection with 1 N HCl for 5 mins and purified on RP HPLC (C-18, 55% CH₃CN, 45% citric acid 1%, 1.5 ml/min). Sagittal brain sections (10 µm thick) were obtained from Tg2576 and wild-type (WT) mice and treated with ¹⁸F-FPCUR at 37 ^oC in 0.1 M TBS buffer, 0.5% Tween, 0.1% BSA, pH 7.4 for one hr. Autoradiograms of ¹⁸F-FPCUR and ¹¹C-PIB were analyzed by OptiQuant. Sections were immunostained with anti-Aβ antibody and thioflavin to confirm presence of Aβ plaques.

Results: CUR-B₂O₃ complex radiolabeling was cleaner but yield was low (approx. 5 %). ¹⁸F-FPCUR eluted at 28 mins with specific activity of 1 Ci/µmol. ¹⁸F-FPCUR bound to Aβ plaques present in brain sections (15 mo old) confirmed by Aβ immunostaining. Compared to cerebellum (Cb) Aβ plaque rich regions, hippocampus (Hp) and cortex (Ctx) showed greater binding: Hp/Cb= 3.0 to 3.5; Ctx/Cb= 1.5. A significant reduction in ¹⁸F-FPCUR binding in HP was seen in the presence of 10 µM PIB (-70%) and 10 µM CUR (-75%). ¹¹C-PIB localized in Aβ plaque regions with ratios, Hp/Cb= 1.5; Ctx/Cb= 1.2 that were lower compared to ¹⁸F-FPCUR.

Conclusions: The higher binding ratios of ¹⁸F-FPCUR compared to ¹¹C-PIB may be due to the higher affinity of FPCUR (FPCUR Ki = 0.07 nM, Ryu et al., 2006; PIB Ki = 4.3 nM, Mathis et al., 2002).

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Patel, P. Articles by Mukherjee, J. PubMed Articles by Patel, P. Articles by Mukherjee, J.