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

Background. In-111-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 In-111-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice. Methods and Results. ApoE 2/2 mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of In-111-DANBIRT (similar to 200 pmol, similar to 40 MBq). Focal spots of In-111-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 In-111-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed In-111-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 In-111-DANBIRT (similar to 950 nmol, 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of In-111-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.