Albumin targeting of damaged muscle fibres in the mdx mouse can be monitored by MRI.
Increased sarcolemmal permeability has been implicated as a major pathological event in muscular dystrophies. In our study, we evaluated whether damaged muscle fibres can be specifically targeted using albumin as a carrier. We tagged human serum albumin (HSA) with Gadolinium (Gd) and systemically applied this compound (Gd-DTPA-HSA) to wildtype and dystrophin-deficient mdx mice. We performed magnetic resonance imaging before and after intravenous administration of Gd-DTPA-HSA and found localised signal enhancement only in mdx skeletal muscle. We also examined skeletal muscle after contrast enhanced magnetic resonance imaging using anti-human albumin antibodies and demonstrated intracellular accumulation of Gd-DTPA-HSA in clusters of damaged mdx muscle fibres. Comparison of magnetic resonance imaging and histological data emphasised the value of contrast agent enhanced magnetic resonance imaging for the in vivo assessment of fibre damage in muscular dystrophies. Furthermore, our data provide evidence that albumin can be used as a carrier to target covalently bound molecules to degenerating muscle fibres.
Amthor
Helge
H
Department of Paediatrics and Paediatric Neurology, University Hospital of Essen, Hufelandstrasse 55, Essen D-45122, Germany.
Egelhof
Thomas
T
McKinnell
Iain
I
Ladd
Mark E
ME
Janssen
Isabelle
I
Weber
Johannes
J
Sinn
Hannsjörg
H
Schrenk
Hans-Hermann
HH
Forsting
Michael
M
Voit
Thomas
T
Straub
Volker
V
D000818:Animals; D000906:Antibodies; D003287:Contrast Media / Q000493:pharmacokinetics*; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D011237:Predictive Value of Tests; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012709:Serum Albumin / Q000493:pharmacokinetics*
D000906:Antibodies; D003287:Contrast Media; D012709:Serum Albumin; D005682:Gadolinium