Direct coupling of annexin A5 to VSOP yields small, protein-covered nanoprobes for MR imaging of apoptosis.
Annexin A5 (Anx) has been extensively used for imaging apoptosis by single-photon emission computed tomography, positron emission tomography, optical imaging and MRI. Recently we introduced ultrasmall Anx-VSOP (very small iron oxide particles)--the smallest high-relaxivity probe for MRI of apoptosis. Here we present a simplified method for the direct coupling of Anx to VSOP, which resulted in nanoparticles that are nearly completely covered with human Anx. These superparamagnetic nanoparticles are only 14.4 ± 2.3 nm in diameter and have higher T2* relaxivity. Compared with existing probes, the small size and the Anx shielding provide prerequisites for good biocompatibility and bioavailability in target tissues. In vitro characterization showed specific binding of Anx-VSOP to apoptotic cells, which led to a signal loss in T2*-weighted MR measurements, while control probe M1324-VSOP produced no such change. Exploratory MRI was done in vivo in a cardiac model of ischemia-reperfusion damage illustrating the potential of the probe for future studies.
Charité - University Medicine Berlin, Berlin, Germany.
Lena
L
Figge
Franziska
F
Appler
Howard H
HH
Chen
David E
DE
Sosnovik
Jörg
J
Schnorr
Oliver
O
Seitz
Matthias
M
Taupitz
Bernd
B
Hamm
Eyk
E
Schellenberger
D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D015335:Molecular Probes
D017304:Annexin A5; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D015335:Molecular Probes
Annexin A5; VSOP; apoptosis; magnetic resonance imaging; very small iron oxide particles