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

摘要

⁶⁷Ga-DOTA-(L-Asp)11 and ⁶⁷Ga-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, ⁶⁷Ga-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 ⁶⁷Ga-DOTA-(D-Asp)n tended to increase with increasing length of the amino acid chain. ⁶⁷Ga-DOTA-(D-Asp)11 and ⁶⁷Ga-DOTA-(D-Asp)14 caused a high accumulation of radioactivity in the bones of the mice. However, the results for ⁶⁷Ga-DOTA-(D-Asp)n and ⁶⁷Ga-DOTA-(L-Asp)n were comparable. In urine analyses, the proportion of intact complex after injection of ⁶⁷Ga-DOTA-(D-Asp)14 was significantly higher than that of ⁶⁷Ga-DOTA-(L-Asp)14. Although ⁶⁷Ga-DOTA-(D-Asp)14 was more stable than ⁶⁷Ga-DOTA-(L-Asp)14, the properties of ⁶⁷Ga-DOTA-(D-Asp)n and ⁶⁷Ga-DOTA-(L-Asp)n as bone imaging agents may be comparable.