Uptake of 67Ga in the lung of mice during bleomycin treatment

Changes of 67Ga uptake in the lungs and changes of components of the so-called ground substance of the lung connective tissues of mice were followed for 7 weeks after the start of bleomycin (BLM) administration (20 mg/kg body weight IP, twice weekly for 5 weeks; this treatment induced fibrosis of the lung). 67Ga uptake of the lung was elevated at 1 week, and reached a maximum at 5 weeks (3.00 +/- 0.11% dose/g lung), and then decreased slightly at 7 weeks. The uronic acid content in the 1.2 M NaCl-soluble fraction, which contained predominantly heparan sulfate (HS), was increased at 1 week, peaked at 3 weeks, and then remained unchanged up to 7 weeks. This pattern was similar to that of 67Ga accumulation in the lungs. The uronic acid content of the 0.4 M NaCl-fraction, which contained predominantly hyaluronic acid (HA), was decreased at 1 week, but increased to a maximum at 3 weeks, then decreased to about the initial level at 5 weeks and decreased further at 7 weeks. Lung hydroxyproline content, an index of collagen content, was increased at 3 weeks and continued to increased rapidly thereafter, reaching approximately 1.5 times the control value at 7 weeks. Serum iron, measured as an indicator of iron metabolism, was slightly increased at 3 weeks and there was a corresponding decrease of unsaturated iron-binding capacity (UIBC). No corresponding change of 67Ga uptake was apparent. These results indicate that HS increased before the collagen accumulation at an early stage of pulmonary fibrosis of the lung during BLM treatment of mice, and support our earlier proposal that HS is a major acceptor for 67Ga accumulation.