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

Abstract

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.