Elsevier

Journal of Nuclear Cardiology

Volume 29, Issue 6, December 2022, Pages 3432-3439
Journal of Nuclear Cardiology

Brief Report
Radioiodinated hypericin as a tracer for detection of acute myocardial infarction: SPECT-CT imaging in a swine model

https://doi.org/10.1007/s12350-022-02933-6Get rights and content

Abstract

Purpose

Hypericin (Hyp) is a natural compound with a newly discovered necrosis-avidity, which can be exploited as a necrosis-avid tracer once labeled with radioactive iodine as has been tested in rodent models. This study was to evaluate the effect of radioiodinated Hyp (131I-Hyp) for imaging detection of acute myocardial infarction (AMI) in conditions closer to clinical scenarios.

Methods

We established swine AMI models (n = 6) which were intravenously given 131I-Hyp and 99mTc-sestamibi and underwent SPECT-CT imaging with high- and low-energy collimators. The acquired SPECT images were fused with cardiac CT images and correlated with postmortem autoradiography and macro- and microscopic pathology. Tissue γ counting was performed to determine biodistribution of 131I-Hyp.

Results

131I-Hyp based SPECT indicated clearly hot regions on ventricular walls which were all histologically proved as AMI. Complementally, the hot AMI regions on 131I-Hyp SPECT (infarct/myoc ratio of 15.3 ± 7.7) were inversely cold regions on 99mTc-sestamibi SPECT (infarct/myoc ratio of 0.029 ± 0.021). Autoradiography of heart slices showed 9.8 times higher 131I-Hyp uptake in infarcted over normal myocardium. With γ counting, the mean 131I-Hyp uptake in infarcts was 10.69 ID%/g, 12.05 times of that in viable myocardium.

Conclusion

131I-Hyp shows a potential for clinical detection of AMI once I-131 is substituted by its isotope like I-124 or I-123 for PET or SPECT, respectively.

Introduction

Acute myocardial infarction (AMI) is a worldwide life-threatening disease and single photon emission computed tomography (SPECT) is a commonly used myocardial imaging technique. For evaluation of blood perfusion in myocardium, 99mTc labeled Sestamibi as a tracer for viable myocardium is extensively applied in clinical practice.1,2 On 99mTc-Sestamibi SPECT images, viable myocardium is usually presented as “hot spot” while infarcted myocardium as “cold spot”. Due to its nature of cold-spot imaging, sensitivity and specificity of 99mTc-Sestamibi SPECT for detection of AMI are unsatisfied.3 Therefore, hot-spot imaging with AMI tracers such as 99mTc-pyrophosphate and 111In-antimyosin have been developed as alternatives in a supplement setting.4

Necrosis-avid compounds such as porphyrin and non-porphyrin agents have been more recently explored as cardiac infarction sensitive contrast agents.5,6 Hypericin (Hyp) is a naturally occurring versatile small molecule, but newly discovered with a necrosis-avid property, which can be labeled with radioactive iodine such as 123I, 131I, and 124I, with a labeling rate over 90%.6 In previous studies, Hyp had been used as an AMI tracer in rodent models,7, 8, 9, 10 showing that Hyp presented extremely high accumulation in AMI that was clearly depicted on SPECT as a hot-spot. Radioiodinated Hyp deposited in AMI presented with a radiation dose (1.175 %ID/g) which was over an order of magnitude higher than that in normal myocardium (0.028 %ID/g), reaching an infarct-to-normal ratio of 42.0.7 This preliminary data established a possibility of clinical application of radioiodinated Hyp as a hot-spot tracer for AMI. However, the previous studies were all carried out on small animal models and imaged by using an animal micro-SPECT. To push radioiodinated Hyp to possible clinical use, we conducted this study, in which we delivered 131I-Hyp in a swine model of AMI, and imaged by a clinical set of SPECT-CT. A dual-energy acquisition system was applied to obtain cold-spot images by 99mTc-Sestamibi and hot-spot images by 131I-Hyp in the same SPECT-CT imaging session. And thereafter, postmortem autoradiography and histopathology were carried out to validate imaging findings.

Section snippets

Study Protocol

As shown in Figure 1, taking establishment of AMI models as point 0 on timeline, 131I-Hyp was intravenously (IV) administered at 6th hour, and 99mTc-sestamibi was given at 16.5th hour. SPECT-CT imaging with dual-energy acquisitions was performed at 18th hour (12 hour after 131I-Hyp and 1.5 hour after 99mTc-sestamibi injection). After imaging, the animal was sacrificed and postmortem examinations were performed including tissue γ counting, autoradiography, and macro-and micro-pathology.

AMI Model

Adhering

General Conditions

Altogether 6 swine AMI models were successfully made in this study. The animals were diagnosed as AMI according to characteristic ECG change and the values of cardiac enzymes, which were all consistent with postmortem macro- and microscopic histopathology (Figures 2, 3, 4). One extra animal died of uncorrectable ventricular arrhythmias during the procedure of balloon dilation. The AMI models underwent all the procedures of drug administration, imaging, and postmortem examinations.

SPECT-CT Imaging and Macroscopic Histochemical Pathology

Images of

Discussion

Application of necrosis-avid agent in heart disease has provided unique advantages on detection and demonstration of myocardial cell death. Several radio-labeled necrosis-avid agents have been tested as nuclear imaging tracers for AMI. Because most previous studies were carried out with rodent animal models,7,8,13 SPECT imaging had to be performed with animal specific micro-equipment. Some performed with clinical SPECT sets provided unsatisfied images.

The main objective of this study was to

New Knowledge Gained

The results of this preclinical study indicate radioiodinated hypericin could be a potentially ideal tracer for detection of infarcted myocardium in the AMI patients.

Disclosures

The authors report no conflict of interests in this study.

Funding

National Natural Science Foundation of China (Nos. 82072037, 81771944, 8201101264); National Hi-Technology Research and Development Program (No.2012AA022701); Liaoning Innovative Talents Supporting Program.

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