Fluorine-18 labeling of three novel D-peptides by conjugation with N-succinimidyl-4-[18F]fluorobenzoate and preliminary examination by postmortem whole-hemisphere human brain autoradiography

Introduction: beta-Amyloid (A beta) plaques and neurofibrillary tangles are the main characteristics of Alzheimer's disease (AD). Positron emission tomography (PET), a high-resolution, sensitive, and noninvasive imaging technique, has been widely utilized in visualizing the localization of plaques and tangles and thereby distinguishing between AD and healthy controls. A small 12-mer D-enantiomeric peptide (amino acid sequence=QSHYRHISPAQV), denoted as D1, has high binding affinity to A beta in vitro in the sub-micromolar range, and consequently, its radiolabeled analogues have a potential as radioligands for visualizing amyloid plaques in vivo by PET. Aim: The aims of the present work were to develop three different potent D1 derivative peptides labeled with fluorine-18 and to examine them in the AD and control postmortem human brain by autoradiography (ARG). Methods: Three different D1 derivative peptides were radiolabeled with fluorine-18 ([F-18]ACI-87, [F-18]ACI-88, [F-18]ACI-89) using the prosthetic group N-succinimidyl-4-[F-18]fluorobenzoate ([F-18]SFB) and purified by high performance liquid chromatography (HPLC). Preliminary ARG measurements were performed in AD and control brains. Results: The three fluorine-18-labeled D-peptides were obtained in a total synthesis time of 140 min with radiochemical purity higher than 98%. The specific radioactivities of the three different D1 derivative peptides were between 9 and 113 GBq/mu mol. ARG demonstrated a higher radioligand uptake in the cortical gray matter and the hippocampus in the AD brain as compared to age-matched control brain. Conclusions: Fluorine-18 labeling of the three novel D1 derivative peptides using [F-18]SFB was successfully accomplished. Higher contrast between AD and control brain slices demonstrates their potential applicability for further use in vivo by PET. (C) 2012 Elsevier Inc. All rights reserved.