64Cu-Labeled Boronic-Acid-Conjugated Porphyrin: A Novel Agent for PET Imaging and Boron Neutron Capture Therapy

ACS Med Chem Lett. 2025 Jul 22;16(8):1533-1537. doi: 10.1021/acsmedchemlett.5c00146. eCollection 2025 Aug 14.

Abstract

Radiometal-labeled porphyrin derivatives have emerged candidates for targeted brain tumor imaging and therapy. In this study, we synthesized a boronic-acid-conjugated porphyrin and radiolabeled it with 64Cu to evaluate its dual-function potential for PET imaging and boron neutron capture therapy (BNCT). The 64Cu-labeled 5,10,15,20-(tetra-4-dihydroxyborylphenyl)-porphyrin ([64Cu]-Cu-TDBP) exhibited excellent serum stability and significant uptake in U87MG cells. PET imaging in both xenograft and orthotopic models demonstrated time-dependent tumor accumulation, with selective localization in the brain tumor at 18 h post-injection (p.i.). The tumor-to-brain ratio increased from 7.2 at 4 h p.i. to 26.3 at 18 h p.i., alongside a rise in tumor boron concentration from 0.79 to 1.83 ppm over the same period. These results highlight the potential of [64Cu]-Cu-TDBP as a promising theranostic agent for precise brain tumor imaging and effective BNCT.

Keywords: 64Cu; Boron neutron capture therapy; Brain tumor; PET; Porphyrin.