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

(67)Ga-DOTA-(L-Asp)(11) and (67)Ga-DOTA-(L-Asp)(14), 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, (67)Ga-DOTA-(D-Asp)(n) (n = 2, 5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology and evaluated. In hydroxyapatite binding assay, binding of (67)Ga-DOTA-(D-Asp)(n) tended to increase with increasing length of the amino acid chain. (67)Ga-DOTA-(D-Asp)(11) and (67)Ga-DOTA-(D-Asp)(14) caused a high accumulation of radioactivity in the bones of the mice. However, the results for (67)Ga-DOTA-(D-Asp)(n) and (67)Ga-DOTA-(L-Asp)(n) were comparable. In urine analyses, the proportion of intact complex after injection of (67)Ga-DOTA-(D-Asp)(14) was significantly higher than that of (67)Ga-DOTA-(L-Asp)(14). Although (67)Ga-DOTA-(D-Asp)(14) was more stable than (67)Ga-DOTA-(L-Asp)(14), the properties of (67)Ga-DOTA-(D-Asp)(n) and (67)Ga-DOTA-(L-Asp)(n) as bone imaging agents may be comparable.