Synthesis and Evaluation of Radiogallium Labeled Bone-Imaging Probes Using Oligo-γ-Carboxy Glutamic Acid Peptides as Carriers to Bone

Abstract

We investigated the importance of the carboxy group density in bone affinity during the development of peptidebased bone-seeking radiopharmaceuticals and carriers. Oligo-γcarboxy glutamic acid peptides [(Gla) n ] with higher carboxy group density than oligo-glutamic acid peptides [(Glu) n ] and oligoaspartic acid peptides [(Asp) n ] were chosen. Using the radiogallium chelator N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC), we synthesized [ 67 Ga]Ga-HBED-CC-(Gla) n (n = 1, 2, 5, 8, 11, or 14) with high yields. Hydroxyapatite-binding assays, biodistribution, and SPECT imaging showed higher affinity and bone accumulation for [ 67 Ga]Ga-HBED-CC-(Gla) n compared to [ 67 Ga]Ga-HBED-CC-(Glu) n . Notably, [ 67 Ga]Ga-HBED-CC-(Gla) 8 and [ 67 Ga]Ga-HBED-CC-(Gla) 11 exhibited superior bone accumulation and rapid blood clearance. SPECT/CT imaging with [ 67 Ga]Ga-HBED-CC-(Gla) 8 exclusively visualized the bone tissue. These findings support the potential use of [ 67 Ga]Ga-HBED-CC-(Gla) n as excellent bone-imaging PET probes, suggesting (Gla) n peptides are superior bone-seeking carriers.