Radionuclide Imaging of Atherothrombotic Diseases

Abstract

Purpose of review: A variety of approaches and molecular targets have emerged in recent years for radionuclide-based imaging of atherosclerosis and vulnerable plaque using single photon emission computed tomography (SPECT) and positron emission tomography (PET), with numerous methods focused on characterizing the mechanisms underlying plaque progression and rupture. This review highlights the ongoing developments in both the preclinical and clinical environment for radionuclide imaging of atherosclerosis and atherothrombosis.

Recent findings: Numerous physiological processes responsible for the evolution of high-risk atherosclerotic plaque, such as inflammation, thrombosis, angiogenesis, and microcalcification, have been shown to be feasible targets for SPECT and PET imaging. For each physiological process, specific molecular markers have been identified that allow for sensitive non-invasive detection and characterization of atherosclerotic plaque.

Summary: The capabilities of SPECT and PET imaging continue to evolve for physiological evaluation of atherosclerosis. This review summarizes the latest developments related to radionuclide imaging of atherothrombotic diseases.

Keywords: PET; SPECT; atherosclerosis; atherothrombosis; molecular imaging; radionuclide imaging.

Figure 1.

⁶⁸Ga-pentixafor PET/CT imaging of abdominal aorta inflammation. Transaxial views of (A) CT and (B) fused PET/CT images reveal localization of ⁶⁸Ga-pentixafor uptake to regions of partial vascular calcification (denoted by white arrows). Sagittal views of (C) CT and (D) fused PET/CT images demonstrate ⁶⁸Ga-pentixafor uptake in partially calcified and non-calcified atherosclerotic lesions (dashed arrows). (This research was originally published in JNM. Weiberg, Thackeray, Daum, et al. Clinical Molecular Imaging of Chemokine Receptor CXCR4 Expression in Atherosclerotic Plaque Using ⁶⁸Ga-Pentixafor PET: Correlation with Cardiovascular Risk Factors and Calcified Plaque Burden. J Nucl Med. 2018;59:266–272. ©SNMMI.)

Figure 2.

⁶⁴Cu-NOTA-3–4A PET/CT imaging for detection of integrin expression in a mouse model of carotid artery atherosclerosis. (A) PET, CT, and fused PET/CT imaging 1 hour after injection of ⁶⁴Cu-NOTA-3–4A revealed radionuclide uptake in the site of the carotid artery atherosclerotic lesion. (B) Coronal PET images of carotid artery plaques at 1, 2, 4, and 24 hours after injection of ⁶⁴Cu-NOTA-3–4A without or with c(RGDyK), a blocking agent, which demonstrated suppression of ⁶⁴Cu-NOTA-3–4A uptake. (C) Quantitative analysis of radionuclide retention in organs at various time points following injection of ⁶⁴Cu-NOTA-3–4A, expressed as %ID/g. (D) Quantitative analysis of plaque–to–normal tissue ratios at various time points. %ID/g = percent injected dose per gram; B = blood; H = heart; K = kidney; Li = liver; M = muscle; N = normal vessel wall; P = plaque. (This research was originally published in JNM. Jiang, Tu, Kimura, et al. ⁶⁴Cu-Labeled Divalent Cystine Knot Peptide for Imaging Carotid Atherosclerotic Plaques. J Nucl Med. 2015;56:939–944. ©SNMMI.)

Figure 3.

In vivo ¹⁸F-NaF PET/CT imaging of the common carotid arteries. Transaxial views of (A) CT, (B) ¹⁸F-NaF PET, and (C) fused PET/CT images demonstrate bilateral uptake of ¹⁸F-NaF in common carotid artery plaques that is localized to sites of vascular calcification. (This research was originally published in JNM. Derlin, Wisotzki, Richter, et al. In Vivo Imaging of Mineral Deposition in Carotid Plaque Using ¹⁸F-Sodium Fluoride PET/CT: Correlation with Atherogenic Risk Factors. J Nucl Med. 2011;52:362–368. ©SNMMI.)