Radiosynthesis and Initial In Vitro Study of Radioiodinated-Labeled Oligo-Acidic Peptide Targeting Bone

Radiolabeling of poly-aspartic acid potential becomes carriers to deliver diagnostic and therapeutic agents to the bone and showed a high affinity for hydroxyapatite, the dominant mineral in the bone. Recently, we designed and synthesized the radiotracers, [125I]IB-D8-OH ([125I]8) and [125I]IB-D11-OH ([125I]9), as well as in vitro evaluated their affinities for hydroxyapatite. The peptide was prepared using the solid-phase peptide synthesis method and linked with a prosthetic group, N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE), to afford corresponding precursors for preparing radioiodinated peptides. The [125I]8 and [125I]9 were prepared using an iododestannylation reaction, with optimized labeling conditions by changing the reaction time and the temperature of the reaction. HPLC identified the labeled products, and their radiochemical yield, purity, stability in PBS(-), and affinity for hydroxyapatite were evaluated. The optimal labeling condition in this study used an oxidizing agent, N-chlorosuccinimide (NCS), which reacted for 15 minutes at room temperature in an acidic solution. This labeled method showed high labeling efficiency with radiochemical yield >94%, radiochemical purity >98%, and stable labeling. The [125I]8 and [125I]9 had a high affinity for hydroxyapatite. We developed [125I]-labeled poly-aspartic acid peptide with high stability in PBS(-) and murine plasma and had a high affinity for hydroxyapatite. The optimized radiolabeling methods could be used to prepare the other radiohalogenated-labeled oligopeptides using 123I, 124I, and 131I radionuclides instead of 125I radionuclide for diagnosis and therapeutic agents targeting bone. However, further studies should be required before clinical stage evaluation.