As previously reported,
Gadofluorine M-enhanced magnetic resonance imaging clearly demarcates
atherosclerotic plaques from the normal vessel wall. To date, the underlying mechanism has remained unknown.
Gadofluorine M is a
gadolinium-containing macrocyclic
contrast agent containing hydrophilic and hydrophobic moieties. To elucidate the mechanism of accumulation, fluorescently labeled and radioactively labeled derivates of
Gadofluorine M were used to determine affinity and specificity of
Gadofluorine M binding to blood serum and plaque components in vitro and for the distribution within the plaque of WHHL rabbits in vivo.
Gadofluorine M binds to
serum albumin, leading to a breakdown of
micelles after
intravenous injection. The affinity of
Gadofluorine M to
serum albumin is k(D) = 2 micromol/l.
Gadofluorine then penetrates the
atherosclerotic plaque while bound to
albumin and then accumulates within the extracellular, fibrous parts of the plaque by binding to
collagens,
proteoglycans and
tenascin, having the same affinity to these plaque constituents as to
albumin. In contrast, weak binding was determined to
LDL (k(D) = 2 mmol/l) and even no binding to
hyaluronic acid. The driving force of binding and accumulation is the hydrophobic moiety of the molecules interacting with hydrophobic plaque materials. Thus,
Gadofluorine M accumulates within the fibrous plaque or in the fibrous cap of a plaque containing high amounts of extracellular matrix components, but not in the
lipid-rich areas. In combination with high-resolution MRI,
Gadofluorine M might enable the detection of thin-cap
fibroatheromas, also named the vulnerable plaque.