Evaluation of Ga-DOTA-(D-Asp) as bone imaging agents: D-aspartic acid peptides as carriers to bone.

Ga-DOTA-(L-Asp) and Ga-DOTA-(L-Asp), which have been developed as bone imaging agents, showed a high accumulation in bone and a rapid blood clearance in mice. However, peptides composed of D-amino acids are more stable in vivo than those composed of their L-equivalents. In this study, Ga-DOTA-(D-Asp) (n = 2, 5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology and evaluated. In hydroxyapatite binding assay, binding of Ga-DOTA-(D-Asp) tended to increase with increasing length of the amino acid chain. Ga-DOTA-(D-Asp) and Ga-DOTA-(D-Asp) caused a high accumulation of radioactivity in the bones of the mice. However, the results for Ga-DOTA-(D-Asp) and Ga-DOTA-(L-Asp) were comparable. In urine analyses, the proportion of intact complex after injection of Ga-DOTA-(D-Asp) was significantly higher than that of Ga-DOTA-(L-Asp). Although Ga-DOTA-(D-Asp) was more stable than Ga-DOTA-(L-Asp), the properties of Ga-DOTA-(D-Asp) and Ga-DOTA-(L-Asp) as bone imaging agents may be comparable.