Development of Ga-67 labeled DFO-DAS-fibrinogen conjugate as a thrombus imaging agent.

A cluster method developed for labeling large molecular proteins with radioactive metal was applied for 67Ga-labeled fibrinogen. A large number of deferoxamine (DFO) was introduced to human fibrinogen using dialdehyde strarch (DAS) as a spacer-functional polymer. The synthesized DFO-DAS-fibrinogen mentioned above was easily labeled with GaCl3 (67Ga) solution (2 mCi/5 mg). The basic investigations found that 67Ga-DFO-DAS-fibrinogen was applicable to the diagnosis of thrombus, and clinical trials were carried out under the physician-sponsored IND. In our further investigation, improvement of the 67Ga-DFO-DAS-fibrinogen reagent was attempted to obtain high specific radioactivity. This was accomplished with the more familiar 67Ga citrate. From the results of a series of experiments, 67Ga-DFO-DAS-fibrinogen of a new composition labeled using 67Ga citrate with high specific radioactivity (2 mCi/3 mg) was prepared, and both reagents were evaluated as thrombus imaging agents from the chemical and biological aspects. The labeling efficiency and clottability of both 67Ga-DFO-DAS-fibrinogen conjugates were satisfactorily high, more than 95% and 80%, respectively. The biodistribution in rats showed that both 67Ga-DFO-DAS-fibrinogen conjugates were essentially the same. These results suggest that there are no significant differences between reagents. At present, the improved reagents are being supplied for the second clinical trials under physician-sponsored IND.