Validation of an 18F-labeled biphenylalkyne as a positron emission tomography imaging agent for β-amyloid plaques

Wey, Shiaw-Pyng; Weng, Chi-Chang; Lin, Kun-Ju; Yao, Cheng-Hsiang; Yen, Tzu-Chen; Kung, Hank F.; Skovronsky, Daniel; Kung, Mei-Ping

doi:10.1016/j.nucmedbio.2009.01.013

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 411-417, May 2009

Validation of an ¹⁸F-labeled biphenylalkyne as a positron emission tomography imaging agent for β-amyloid plaques☆

Shiaw-Pyng Wey
- Department of Medical Imaging and Radiological Sciences, Graduate Institute of Medical Physics and Imaging Science, Chang Gung University, Taoyuan, 333 Taiwan
- Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, 333 Taiwan
- There authors contributed equally to this work.
Chi-Chang Weng
- Department of Medical Imaging and Radiological Sciences, Graduate Institute of Medical Physics and Imaging Science, Chang Gung University, Taoyuan, 333 Taiwan
- There authors contributed equally to this work.
Kun-Ju Lin
- Department of Medical Imaging and Radiological Sciences, Graduate Institute of Medical Physics and Imaging Science, Chang Gung University, Taoyuan, 333 Taiwan
- Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, 333 Taiwan
Cheng-Hsiang Yao
- Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, 333 Taiwan
Tzu-Chen Yen
- Department of Medical Imaging and Radiological Sciences, Graduate Institute of Medical Physics and Imaging Science, Chang Gung University, Taoyuan, 333 Taiwan
- Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, 333 Taiwan
Hank F. Kung
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Daniel Skovronsky
- Avid Radiopharmaceuticals Inc, Philadelphia, PA 19104, USA
Mei-Ping Kung
- Department of Medical Imaging and Radiological Sciences, Graduate Institute of Medical Physics and Imaging Science, Chang Gung University, Taoyuan, 333 Taiwan
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
- Corresponding author. Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA. Tel.: +1 215 662 3989; fax: +1 215 349 5035.

Received 9 December 2008; received in revised form 13 January 2009; accepted 23 January 2009. published online 31 March 2009.

Abstract

Aim

Recently, the feasibility of detecting amyloid plaques in the living brain by positron emission tomography (PET) imaging has been successfully demonstrated. As such, imaging β-amyloid (Aβ) plaques in the brain may further advance the differential diagnosis of the disease and allow clinicians to measure the effectiveness of therapeutic drugs aimed at lowering plaques in the brain. We report herein the preclinical validation of a potential ¹⁸F-labeled biphenylalkyne, AV-138, as a preliminary step toward developing the imaging agent for patients suspected of having Alzheimer's disease.

Methods

In vitro binding was carried out in the homogenates prepared from postmortem AD brains with [¹²⁵I]IMPY as the radioligand. [¹⁸F]AV-138 was successfully prepared using a tosylate precursor and Sumitomo modules for radiosynthesis. Similarly, specific binding of [¹⁸F]AV-138 (0.02–0.05 nM) to homogenates, prepared from gray and white matters of pooled AD patients and control subjects, was performed. Specific binding to Aβ plaques was measured by autoradiography in AD brain sections (n=11), and the same brain sections were fluorescently stained with thioflavin-S (TF-S). Images of both radiolabeling and fluorescent staining of plaques obtained by a phosphor imager were used for correlation image analysis.

Results

As expected, AV-138 displayed a high binding affinity (K_i=2.4±0.7 nM) in AD gray matter homogenates (due to its high level of Aβ plaque accumulation). Specific binding can be clearly measured in the AD gray matter homogenates, but not in the AD white matters. Control brain homogenates, due to a lack of Aβ plaques, also showed no specific binding. Furthermore, in vitro autoradiography of postmortem AD brain sections showed that the high binding signal of [¹⁸F]AV-138 was specifically due to Aβ plaques. Fluorescent staining of plaques with TF-S correlated well with the radiolabeling of [¹⁸F]AV-138 in AD brain sections (r>0.90).