Application of a Novel CD206+ Macrophage-Specific Arterial Imaging Strategy in HIV-Infected Individuals

Abstract

Background: The ability to noninvasively assess arterial CD206+ macrophages may lead to improved understanding of human immunodeficiency virus (HIV)-associated cardiovascular disease.

Methods: We trialed a novel macrophage-specific arterial imaging technique.

Results: We demonstrated colocalization between technetium Tc 99m tilmanocept (99mTc-tilmanocept) and CD206+ macrophages ex vivo. In vivo application of 99mTc-tilmanocept single-photon emission computed tomography/computed tomography revealed high-level 99mTc-tilmanocept uptake across 20.4% of the aortic surface volume among HIV-infected subjects, compared with 4.3% among non-HIV-infected subjects (P = .009). Among all subjects, aortic high-level 99mTc-tilmanocept uptake was related to noncalcified aortic plaque volume (r = 0.87; P = .003) on computed tomographic angiography, and this relationship held when we controlled for HIV status.

Conclusion: These first-in-human data introduce a novel macrophage-specific arterial imaging technique in HIV.

Clinical trials registration: NCT02542371.

Keywords: HIV-associated cardiovascular disease; arterial inflammation; atherosclerosis..

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Ex vivo experiments on tissue-banked aortic samples from individuals with or without human immunodeficiency virus (HIV) infection and in vivo aortic high-level technetium Tc 99m tilmanocept (99mTc-tilmanocept) uptake and relationship to aortic noncalcified plaque in both groups of subjects. A, In tissue-banked aortic samples, the mean number of CD206+ macrophages per square millimeter was significantly higher among HIV-infected individuals (n = 10) than among non−HIV-infected individuals (n = 10) (P = .0002). B, Double-label immunofluorescence using a CD206 antibody and tilmanocept-Alexa Fluor 488 revealed a high and similar degree of colocalization of tilmanocept and CD206 in sections from HIV-infected (n = 10) and non−HIV-infected (n = 10) subjects (mean [standard deviation (SD)], 89.1% [6.3%] vs 86.3% [6.8%], respectively). The mean (SD) percentages of CD206+ tilmanocept-negative macrophages and CD206− tilmanocept-positive macrophages in HIV-infected (n = 10) versus non−HIV-infected (n = 10) subjects were 7.8% (7.0%) versus 10.4% (6.2%) and 3.1% (1.8%) versus 3.3% (2.1%), respectively. C, Aortic volume with high-level 99mTc-tilmanocept uptake was significantly increased in HIV-infected (n = 6) compared with non−HIV-infected (n = 3) subjects (P = .03). Results represent medians and interquartile ranges, with whiskers showing minimum and maximum values. Aortic volume with high-level 99mTc-tilmanocept uptake is shown to facilitate assessment of the relationship with total noncalcified coronary atherosclerotic plaque volume. The percentage of aortic volume with high-level 99mTc-tilmanocept uptake was significantly increased among HIV-infected (n = 6) compared with non−HIV-infected (n = 3) subjects (P = .009). Results represent means with SDs. D, Regression analysis demonstrating a significant relationship between aortic volume with high-level 99mTc-tilmanocept uptake at single-photon emission computed tomography/computed tomography and noncalcified aortic plaque volume (Pearson correlation coefficient [r] = 0.87; P = .003). HIV-infected subjects (n = 6) are represented as triangles, and non−HIV-infected control subjects (n = 3) as squares.

Figure 2.

Aortic technetium Tc 99m tilmanocept (99mTc-tilmanocept) single-photon emission computed tomography (SPECT)/computed tomography (CT) in human immunodeficiency virus (HIV)–infected and non−HIV-infected subjects. Axial cross-sections of the aorta from 99mTc-tilmanocept SPECT/CT scans are shown for HIV-infected (n = 6) and non−HIV-infected (n = 3) subjects. Aortic volume and the percentage of aortic volume with high-level 99mTc-tilmanocept uptake (>5 times muscle 99mTc-tilmanocept uptake) are displayed for each subject. The adjacent color scale indicates aortic 99mTc-tilmanocept uptake relative to muscle 99mTc-tilmanocept uptake, with red representing areas of high relative 99mTc-tilmanocept uptake. Abbreviation: 99mTc, metastable technetium isotope.