Imaging of atherosclerosis, targeting LFA-1 on inflammatory cells with 111In-DANBIRT
Background: 111In-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 111In-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 111In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of 111In-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 111In-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed 111In-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 111In-DANBIRT (~ 950 nmol, ~ 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of 111In-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.
|Keywords||Atherosclerosis, inflammation, molecular imaging, SPECT|
|Persistent URL||dx.doi.org/10.1007/s12350-018-1244-5, hdl.handle.net/1765/105282|
|Journal||Journal of Nuclear Cardiology|
Meester, E.J. (E. J.), Krenning, B.J, de Blois, R.H. (R. H.), Norenberg, J.P, de Jong, M. (M.), Bernsen, M.R, & van der Heiden, K. (2018). Imaging of atherosclerosis, targeting LFA-1 on inflammatory cells with 111In-DANBIRT. Journal of Nuclear Cardiology, 1–8. doi:10.1007/s12350-018-1244-5