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Annals of Nuclear Medicine

, Volume 32, Issue 6, pp 425–429 | Cite as

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

  • Takashi Temma
  • Naoya Kondo
  • Keiko Yoda
  • Kantaro Nishigori
  • Satoru Onoe
  • Masashi Shiomi
  • Masahiro Ono
  • Hideo Saji
Short Communication
  • 128 Downloads

Abstract

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 125I-AHP7, a peptide probe carrying a 7-residue sequence from the OxLDL-binding protein Asp-hemolysin, for specific OxLDL imaging. Although 125I-AHP7 recognized OxLDL, it had low stability. Thus, to improve stability, we designed radiolabeled 22-residue peptide probes, 125I-AHP22 and 111In-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 125I-N-(3-iodophenyl)maleimide or 111In diethylene triamine pentaacetic acid were termed 125I-AHP22 and 111In-AHP22. An in vitro-binding inhibition assay with OxLDL was performed using 125I-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

125I-AHP22 and 111In-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 125I-AHP22 and 111In-AHP22 in plasma was estimated to be approximately tenfold higher than that of 125I-AHP7. Both probes were rapidly cleared from the blood. 111In-AHP22 had a 2.3-fold higher accumulation in WHHLMI rabbit aortas compared to control rabbits, which was similar to 125I-AHP7. However, 125I-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

111In-AHP22, easily prepared within 1 h, showed moderate affinity for OxLDL, high stability in vivo, and high accumulation in atherosclerotic aortas. 111In-AHP22 could be a potential lead compound to develop future effective OxLDL imaging probes.

Keywords

Atherosclerosis Oxidized low-density lipoprotein Peptide Nuclear medical imaging WHHLMI rabbit 

Notes

Funding

This work was partly supported by a Health and Labour Science Research Grant “Research on Noninvasive and Minimally Invasive Medical Devices” from the Ministry of Health, Labour and Welfare of Japan, and by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest.

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Copyright information

© The Japanese Society of Nuclear Medicine 2018

Authors and Affiliations

  1. 1.Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  2. 2.Department of Biofunctional AnalysisOsaka University of Pharmaceutical SciencesTakatsukiJapan
  3. 3.Laboratory of Physical ChemistryShowa Pharmaceutical UniversityMachidaJapan
  4. 4.Institute for Experimental AnimalsKobe University Graduate School of MedicineKobeJapan
  5. 5.Kyoto University Research Administration OfficeKyotoJapan

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