Comparison of 125I- and 111In-labeled peptide probes for in vivo detection of oxidized low-density lipoprotein in atherosclerotic plaques

• Published in: Annals of nuclear medicine Vol. 32; no. 6; pp. 425 - 429
• Main Authors: Temma, Takashi, Kondo, Naoya, Yoda, Keiko, Nishigori, Kantaro, Onoe, Satoru, Shiomi, Masashi, Ono, Masahiro, Saji, Hideo
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.07.2018; Springer Nature B.V
• Subjects: Accumulation; Amino acid sequence; Aorta; Arteriosclerosis; Atherosclerosis; Destabilization; Diethylenetriamine pentaacetic acid; High-performance liquid chromatography; Imaging; In vitro methods and tests; In vivo methods and tests; Inhibition; Intravenous administration; Lipophilicity; Liquid chromatography; Low density lipoprotein; Medical imaging; Medicine; Medicine & Public Health; Myocardial infarction; Nuclear Medicine; Peptides; Plaques; Probes; Rabbits; Radioactivity; Radiochemistry; Radiology; Short Communication; Stability analysis; Target recognition; Nuclear medical imaging; Oxidized low-density lipoprotein; WHHLMI rabbit; Peptide; Atherosclerosis
• ISSN: 0914-7187; 1864-6433
• DOI: 10.1007/s12149-018-1255-y

Objective Oxidized low-density lipoprotein (OxLDL) plays a pivotal role in atherosclerotic plaque destabilization, which suggests its potential as a nuclear medical imaging target. We previously developed radioiodinated 125 I-AHP7, a peptide probe carrying a 7-residue sequence from the OxLDL-binding protein Asp-hemolysin, for specific OxLDL imaging. Although 125 I-AHP7 recognized OxLDL, it had low stability. Thus, to improve stability, we designed radiolabeled 22-residue peptide probes, 125 I-AHP22 and 111 In-AHP22, which include the entire AHP7 sequence, and evaluated the stability, activity, and applications of these probes in vitro and in vivo. Methods Probes consisting of a 21-residue peptide derived from the Asp-hemolysin sequence and an N -terminal Cys or aminohexanoic acid for labeling with 125 I- N -(3-iodophenyl)maleimide or 111 In diethylene triamine pentaacetic acid were termed 125 I-AHP22 and 111 In-AHP22. An in vitro-binding inhibition assay with OxLDL was performed using 125 I-AHP7 as a radiotracer. Radioactivity accumulation in the atherosclerotic aorta and plasma intact fraction was evaluated 30 min after intravenous administration of probes in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. Results 125 I-AHP22 and 111 In-AHP22 were synthesized in ~ 360 and 60 min, respectively, with > 98% radiochemical purities after RP-HPLC purification. An in vitro-binding assay revealed similar or greater inhibition of OxLDL binding by both In-AHP22 and I-AHP22 compared to I-AHP7. The fraction of intact 125 I-AHP22 and 111 In-AHP22 in plasma was estimated to be approximately tenfold higher than that of 125 I-AHP7. Both probes were rapidly cleared from the blood. 111 In-AHP22 had a 2.3-fold higher accumulation in WHHLMI rabbit aortas compared to control rabbits, which was similar to 125 I-AHP7. However, 125 I-AHP22 accumulated to similar levels in aortas of WHHLMI and control rabbits due to high nonspecific accumulation in normal aortas that could be due to high lipophilicity. Conclusions 111 In-AHP22, easily prepared within 1 h, showed moderate affinity for OxLDL, high stability in vivo, and high accumulation in atherosclerotic aortas. 111 In-AHP22 could be a potential lead compound to develop future effective OxLDL imaging probes.