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125I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (125I-OI5V) imaging visualized augmented sigma-1 receptor expression according to the severity of myocardial ischemia

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

We aimed to explore how the severity of myocardial ischemia affects myocardial sigma-1 receptor (Sig-1R) expression using 125I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (125I-OI5V) imaging.

Methods and results

The left coronary artery was occluded for 30, 20, and 10 minute, to vary the severity of myocardial ischemia, followed by reperfusion. Dual-tracer autoradiography of the left ventricular short-axis slices was performed 3 and 7 days after reperfusion. 125I-OI5V was injected 30 minute before sacrifice and the area at risk (AAR) was evaluated by 99mTc-MIBI. Intense 125I-OI5V uptake was observed in the AAR and was significantly increased with increasing ischemia duration. To evaluate salvaged and nonsalvaged areas (preserved and decreased perfusion areas), triple-tracer autoradiography was performed 3 days after reperfusion. After dual-tracer autoradiography, 201Tl was injected 20 minute post 125I-OI5V injection. On triple-tracer autoradiography, the AAR/normally perfused area 125I-OI5V uptake ratio was positively correlated with the nonsalvaged area/whole left ventricular (LV) area ratio (P < .05). The AAR/normally perfused area 125I-OI5V uptake ratio was negatively correlated with the 201Tl uptake ratio of the AAR to normally perfused areas (P < .05). The comparison of the immunostaining distribution of 125I-OI5V and the macrophage marker CD68 revealed that 125I-OI5V was present mainly in, and immediately adjacent to the macrophage infiltration area.

Conclusions

Significant 125I-OI5V uptake in the AAR depends on the duration of ischemia and reduced 201Tl uptake; furthermore, 125I-OI5V was found in and around the macrophage infiltrate area. These results indicate that iodine-labeled OI5V is a promising tool for visualizing Sig-1R expression according to the ischemic burden.

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Abbreviations

AAR:

Area at risk

CD68:

Cluster of differentiation 68

DAPI:

4′,6-Diamidino-2-phenylindole

ER:

Endoplasmic reticulum

LCA:

Left coronary artery

LV:

Left ventricular

OI5V:

2-[4-(2-Iodophenyl)piperidino]cyclopentanol

ROI:

Region of interest

Sig-1R:

Sigma-1 receptor

99mTc-MIBI:

99mTc-hexakis 2-methoxyisobutyl isonitrile

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Disclosures

The authors declare that they have no conflict of interest.

Ethical approval

All experiments were approved by the Institute for Animal Studies of Kanazawa University (AP-173846). All applicable Japanese and institutional guidelines for the care and use of animals were followed.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Hiroshi Wakabayashi MD, PhD, Hiroshi Mori MD, PhD, Tomo Hiromasa MD, PhD, Norihito Akatani MD, Anri Inaki MD, PhD, Seigo Kinuya MD, PhD & Junichi Taki MD, PhD

  2. Division of Probe Chemistry for Disease Analysis, Research Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa, Ishikawa, Japan

    Takashi Kozaka PhD & Yoji Kitamura PhD

  3. Institute for Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan

    Kazuma Ogawa PhD

  4. Kanazawa Advanced Medical Center, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-0934, Japan

    Junichi Taki MD, PhD

Authors
  1. Hiroshi Wakabayashi MD, PhD
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  2. Hiroshi Mori MD, PhD
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  3. Tomo Hiromasa MD, PhD
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  9. Seigo Kinuya MD, PhD
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  10. Junichi Taki MD, PhD
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Corresponding author

Correspondence to Hiroshi Wakabayashi MD, PhD.

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Funding

This work has been supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP20K08047.

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All editorial decisions for this article, including selection of reviewers and the final decision, were made by guest editor Stephan Nekolla, MD.

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Wakabayashi, H., Mori, H., Hiromasa, T. et al. 125I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (125I-OI5V) imaging visualized augmented sigma-1 receptor expression according to the severity of myocardial ischemia. J. Nucl. Cardiol. 30, 653–661 (2023). https://doi.org/10.1007/s12350-022-03064-8

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