In vivo detection of intervertebral disk injury using a radiolabeled monoclonal antibody against keratan sulfate.
In the intervertebral disk, proteoglycans form the major part of the extracellular matrix, surrounding chondrocytelike disk cells. Keratan sulfate is a major constituent of proteoglycans.


METHODS
We have radioiodinated a monoclonal antibody raised against keratan sulfate. This antibody was injected into rats (n = 6), and the biodistribution was studied. A model of intervertebral disk injury was developed, and two tail disks in each animal with both acute (2 wk old) and subacute (7 wk old) injuries were studied for in vivo antibody uptake.


RESULTS
The biodistribution at 72 h was as follows: blood, 0.0018 percentage injected dose per gram of tissue (%ID/g); lung, 0.0106 %ID/g; esophagus, 0.0078 %ID/g; kidney, 0.0063 %ID/g; liver, 0.0047 %ID/g; spleen, 0.0046 %ID/g; heart, 0.0036 %ID/g; thyroid, 0.0034 %ID/g; muscle, 0.0017 %ID/g; and bone, 0.0016 %ID/g. In the subacute stage, a significant difference (P < 0.006) was found in antibody uptake between injured disks (n = 12) and adjacent healthy disks (n = 12). In vivo gamma imaging showed increased uptake in other animals having lumbar disk injuries (2, 7, and 17 d after injury). Cartilage tissue, such as the trachea, was studied separately and showed extremely high antibody uptake, 0.10 %ID/g. Rat trachea was also visualized on gamma images.


CONCLUSIONS
Our data suggest that antibodies against nucleus pulposus components, such as proteoglycans, can be used for in vivo detection of intervertebral disk injury. This finding is in spite of the minimal circulation present in intervertebral disks.
Kairemo
K J
KJ
Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland.
Lappalainen
A K
AK
Kääpä
E
E
Laitinen
O M
OM
Hyytinen
T
T
Karonen
S L
SL
Grönblad
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D007403:Intervertebral Disc / Q000000981:diagnostic imaging* / Q000293:injuries; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007632:Keratan Sulfate / Q000276:immunology*; D008297:Male; D016719:Radioimmunodetection; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D007632:Keratan Sulfate