心血管疾病与诊断

Comparison of 64Cu and 68Ga for Molecular Imaging of Atherosclerosis using the Apolipoprotein A-I Mimetic Peptide FAMP

Abstract

Eiji Yahiro, Emi Kawachi, Shin-Ichiro Miura, Takashi Kuwano, Satoshi Imaizumi, Atsushi Iwata, Koki Hasegawa, Tsuneo Yano, Yasuyoshi Watanabe, Yoshinari Uehara and Keijiro Saku

Background: Molecular imaging for detection of the atherosclerotic plaque burden has been highlighted as a modality for the diagnosis of atherosclerosis. We recently developed a novel and noninvasive positron emission tomography (PET) that was functionalized with an apolipoprotein (Apo) A-I mimetic peptide [known as Fukuoka University Apo A-I mimetic peptide (FAMP)] radiolabeled with gallium-68 (68Ga) - 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) to specifically image the status of atherosclerotic plaque in myocardial infarctionprone Watanabe heritable hyperlipidemic rabbits (WHHL-MI). Methods and Results: To achieve more sensitive molecular imaging, FAMP was modified with 4, 11 - bis (carboxymethyl) - 1, 4, 8, 11 - tetraazabicyclo (6.6.2) hexadecane (CB-TE2A) and radiolabeled with copper-64 (64Cu) for PET, and the ability of 64Cu-TE2A-FAMP to image plaque was compared with that of 68Ga-DOTA-FAMP. Japanese white normal (JW) and WHHL-MI rabbits were intravenously injected with 64Cu-CB-TE2A-FAMP or 68Ga- DOTA-FAMP, and subjected to continuous PET (25-30 MBq). Interestingly, 64Cu-CB-TE2A-FAMP was not taken up by atherosclerotic lesions in the aorta of WHHL-MI, whereas 68Ga-DOTA-FAMP was dramatically illuminated in the aorta of WHHL-MI. Moreover, 64Cu-CB-TE2A-FAMP was rapidly decomposed and 64Cu was excreted to the intestine, liver or urinary bladder in both JW and WHHL-MI rabbits. Conclusions: These results demonstrated that FAMP may be a target molecule for atherosclerotic molecular imaging with 68Ga-DOTA, but not with 64Cu-CB-TE2A. The selection of a suitable radio-nuclide and chelator might be important for HDL functioning imaging.