Radiolabeling and scintigraphic evaluation of Tc-99m labeled glutamic acid and its DTPA conjugate for brain/bone imaging

Glutamic acid (GAT) is an amino acid that is required for normal functioning of the brain and it is one of the very few nutrients that can cross intact blood brain barrier. It is also required for normal functioning and repairing of bones. So it was envisaged that the radiolabeling of GAT with Tc-99m could lead to development of a novel radiopharmaceutical for brain/bone imaging. It was also hypothesized that conjugation of GAT with DTPA would further enhance the brain uptake of the same while reducing bone uptake of GAT.

GAT-DTPA conjugate (1:2 molar ratio) was synthesized following the established procedure. Both GAT and GATDTPA were labeled with Tc-99m by direct labeling method. Labeling conditions (pH, stannous ion concentration and incubation time) were optimized to achieve the maximum labeling efficiency (>98%). In vitro stability of the labeled complexes was checked and the complexes were found to be stable for 24h. The labeled GAT and GAT-DTPA complexes were studied for blood clearance kinetics and scintigraphy in New Zealand albino rabbits and quantitative tissue distribution profile in strain A mice. Both the formulations cleared very rapidly from the systemic circulation and radioactivity <1% of the injected dose was observed in blood after 24h administration. There has been no statistical significant difference in the blood kinetics of both the formulations (P<0.05).

Scintigraphic images of the animals after 15 min of intravenous injection showed a significant accumulation of GAT-Tc-99m in both brain and bones, whereas the brain accumulation increased significantly upon injection of GAT-DTPA. The formulations cleared very rapidly as significant activity was also observed in liver, spleen, kidney and bladder of the animals. Finally, results of quantitative biodistribution study are in concordant with the scintigraphic study. The activity in the brain was almost doubled with GAT-DTPA-Tc-99m as compared to GAT-Tc-99m, while the activity in the bones was slightly reduced. A significant activity was recorded in liver, spleen and kidney that showed the very rapid clearance of the formulations.

It can be concluded from the results of that GAT-Tc-99m and GAT-DTPA-Tc-99m can be successfully used as bone/brain imaging agents for diagnosis of any abnormalities/disease condition/lesion in the brain/bones. Further more elaborative and comparative studies with the use of commercially available brain/bone imaging agents should be perform to assess the relative efficacy of the proposed radiopharmaceuticals before the same could be used for clinical trials.