Development of Structurally Identical Therapeutic and Diagnostic Agents for Image-Guided Boron Neutron Capture Therapy: c(RGD-BPA-K) Peptide with 125I/natI Albumin-Binding Moiety

The development of boron neutron capture therapy (BNCT) agents and structurally similar radiolabeled counterparts for diagnostic imaging is an area of significant interest. In this study, we designed structurally same compounds, c(RGD-BPA-K)(PEG 2 -(4-iodophenylbutyl)) (compound 1 ) and its radioiodinated counterpart, c(RGD-BPA-K)(PEG 2 -(4-[ 125 I]iodophenylbutyl)) ([ 125 I] 1 ), for efficient BNCT and SPECT/CT imaging, respectively. An albumin-binding moiety was introduced into the compound to enhance the blood circulation time and tumor accumulation. We evaluated the efficacy of compound 1 and [ 125 I] 1 in U87MG tumor-bearing mice using SPECT/CT imaging, biodistribution analysis, and inductively coupled plasma mass spectrometry. Both compound 1 and [ 125 I] 1 displayed similar pharmacokinetics, high blood retention, and substantial accumulation in U87MG tumors. This study highlights the potential of compound 1 and [ 125 I] 1 for SPECT/CT-guided BNCT. The structural identity between the therapeutic and diagnostic agents in BNCT can enhance its therapeutic efficacy. Further structural modifications to increase boron concentration in tumors, as well as thermal neutron irradiation studies, may be necessary to fully explore the potential of our novel BNCT agent.