Nanobodies Noninvasively Detect Atherosclerosis in Mice
Radiolabeled antibody fragments targeting VCAM1 accumulate in atherosclerotic plaques
FRIDAY, March 30 (HealthDay News) -- A radiolabeled antibody fragment targeting vascular cell adhesion molecule-1 (VCAM1) can noninvasively and specifically detect atherosclerotic plaques in mice, according to an experimental study published in the March 30 issue of Circulation Research.
Alexis Broisat, Ph.D., from the Université de Grenoble in La Tronche, France, and colleagues produced and tested 10 nanobodies (small antibody fragments) radiolabeled with technetium-99m (99mTc), targeting VCAM1, found in artery plaques. The nanobodies were screened in vitro on mouse and human recombinant VCAM1 proteins and endothelial cells, and in vivo screening was conducted in ApoE deficient mice. Specificity was demonstrated using a nontargeting control nanobody.
The researchers found that all of the nanobodies had nanomolar affinities for mouse VCAM1, and six cross-reacted with human VCAM1. A lead nanobody compound, cAbVCAM1-5, was cross-reactive for human VCAM1; cAbVCAM1-5 also demonstrated high lesion-to-control, lesion-to-heart, and lesion-to-blood ratios, while in vivo competition experiments demonstrated its binding specificity. Uptake of cAbVCAM1-5 in VCAM1-positive lesions was confirmed by autoradiography and immunohistochemistry.
"The 99mTc-labeled, anti-VCAM1 nanobody cAbVCAM1-5 allowed noninvasive detection of VCAM1 expression and displayed mouse and human crossreactivity," Broisat and colleagues conclude. "The nanobody technology might evolve into an important research tool for targeted imaging of atherosclerotic lesions and has the potential for fast clinical translation."