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In Vivo Detection of Intervertebral Disk Injury Using a Radiolabeled Monoclonal Antibody Against Keratan Sulfate

Departments of Clinical Chemistry, Physical Medicine and Rehabilitation, and Thoracic and Cardiovascular Surgery, Helsinki University Central Hospital, Helsinki; and Faculty of Veterinary Medicine, Department of Clinical Veterinary Sciences, University of Helsinki, Helsinki, Finland

View larger version (38K): [in a new window]   FIGURE 1. Schematic diagram shows proteoglycan molecule and structural relationships between two main moieties, keratan sulfate and chondroitin sulfate. In intervertebral disk, proteoglycans form major part of extracellular matrix, surrounding chondrocytelike disk cells. Keratan sulfate was target molecule for studying experimental intervertebral disk injury in rats.

View larger version (24K): [in a new window]   FIGURE 2. Biodistribution after intravenous injection of 125I-labeled MAb against keratan sulfate at 72 h. Error bars stand for SD.

View larger version (18K): [in a new window]   FIGURE 3. Biodistribution in detail in thoracic organs after intravenous injection of 125I-labeled MAb against keratan sulfate at 72 h. Error bars stand for SD.

View larger version (23K): [in a new window]   FIGURE 4. Biodistribution in acute (2 wk) and subacute (7 wk) lesions after intravenous injection of 125I-labeled MAb against keratan sulfate at 72 h. Error bars stand for SD. Difference between healthy and injured disks in subacute lesions was statistically significant (P < 0.006).

View larger version (130K): [in a new window]   FIGURE 5. images 4 d after injection of 125I-labeled MAb against keratan sulfate in animals with both lumbar and tail disk injuries (injuries are 2 d old on left, 7 d old in middle, and 17 d old on right). Increased uptake in lumbar lesion in animals with 7- and 17-d-old injuries (solid arrows) is best seen in middle in lower back. Lesion size was approximately 2 x 2 mm. Similarly, tail disk injuries are localized in animals with 7- and 17-d-old injuries (solid arrows). Injection sites are seen (open arrows) in these animals and make tail uptake diffuse in animal with 7-d-old injury (no arrows). In animal with 2-d-old injury, lesions show no uptake. Tracheas were also visualized but, unfortunately, are masked here by high thyroid uptake because these animals were not blocked for thyroid.

View larger version (126K): [in a new window]   FIGURE 6. images 4 d after injection of 125I-labeled MAb against rat collagen III in animals with both lumbar and tail disk injuries (injuries are 2 d old on left, 7 d old in middle, and 17 d old on right). Lesions show no uptake. Trachea was not visualized in these animals.