ArticleEJNMMI research2026
Beyond bisphosphonates: radiolabeled phosphopeptides for bone targeting.
Article in EJNMMI research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe efficacy of current bone-targeting agents, notably bisphosphonates, in the treatment of bone metastases remains limited by their systemic toxicity and excessively long half-life. This study aims to develop bone-targeting agents inspired by osteotropic peptides involved in the bone mineralization process. These agents are intended to provide an innovative alternative to bisphosphonates for precision bone targeting.
resultsOsteotropic peptides and phosphopeptides were obtained by solid-phase synthesis and conjugated to DOTA. The peptides were radiolabeled with gallium-68 or lutetium-177, and their binding affinity to bone was tested in vivo. Osteopontin and matrix extracellular phosphoglycoprotein (MEPE) derived peptides did not show strong binding to bone. Systematic variations in oligoglutamic acid chain length, as well as the positioning and clustering of phosphorylated serine residues, enabled the identification of an optimized phosphopeptide. Clustering phosphorylated sites within the peptide sequence provided significant advantages over phosphorylated moieties scattered throughout the peptide sequence. DOTA-pS4E8 showed the strongest affinity for bone, comparable to the clinically used bone targeting agent methylene bisphosphonate (MBP).
conclusionsThe novel phosphopeptides match the outstanding bone-targeting capabilities of bisphosphonates and show comparable pharmacokinetics. Owing to their peptidic nature and the consequently anticipated favorable toxicological profile, these agents warrant further investigation as versatile bone-targeting vectors.
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