Imaging of atherosclerosis, targeting LFA-1 on inflammatory cells with (111)In-DANBIRT

BACKGROUND: (111)In-DOTA-butylamino-NorBIRT (DANBIRT) is a novel radioligand which binds to Leukocyte Function-associated Antigen-1 (LFA-1), expressed on inflammatory cells. This study evaluated (111)In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice. METHODS AND RESULTS: ApoE(−/−) mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of (111)In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of (111)In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1.7 ± 0.5. In vivo imaging results were validated by ex vivo SPECT/CT imaging, with a TBR up to 11.5 (range 2.6 to 11.5). Plaques, identified by Oil Red O lipid-staining on excised arteries, co-localized with (111)In-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed (111)In-DANBIRT uptake at plaque areas containing CD68 expressing macrophages and LFA-1 expressing inflammatory cells. Ex vivo incubation of a human carotid endarterectomy specimen with (111)In-DANBIRT (~ 950 nmol, ~ 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of (111)In-DANBIRT uptake and CD68 and LFA-1 expressing cells. CONCLUSIONS: Our results indicate the potential of radiolabeled DANBIRT as a relevant imaging radioligand for non-invasive evaluation of atherosclerotic inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12350-018-1244-5) contains supplementary material, which is available to authorized users.