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

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• 作者：Mahabuba Jahan^a ; ^{mahabuba.jahan@ki.se} ; Sangram Nag^a ; Raisa Krasikova^a ; Urs Weber^b ; Andreas Muhs^b ; Andrea Pfeifer^b ; Christian Spenger^c ; Dieter Willbold^d ; ^e ; Balá ; zs Gulyá ; s^a ; Christer Halldin^a
• 关键词：Alzheimer's disease (AD) ; PET ; Fluorine-18 ; d-peptide ; 尾-Amyloid (A尾)
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 期刊代码：43_09698051
• 类别：ph
• 出版时间：April, 2012
• 卷：39
• 期：3
• 页码：315-323
• 文件大小：442 K

摘要

Introduction

尾-Amyloid (A尾) 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尾 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 ([¹⁸F]ACI-87, [¹⁸F]ACI-88, [¹⁸F]ACI-89) using the prosthetic group N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]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/渭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 [¹⁸F]SFB was successfully accomplished. Higher contrast between AD and control brain slices demonstrates their potential applicability for further use in vivo by PET.