Porphyrin-Based Brain Tumor-Targeting Agents: [ 64 Cu]Cu-porphyrin and [ 64 Cu]Cu-TDAP.

The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative, 5,10,15,20-(tetra- N , N -dimethyl-4-aminophenyl)porphyrin (TDAP), in which four N , N -dimethyl-4- p -phenylenediamine (DMPD) moieties are conjugated to the porphyrin labeled with the radiometal 64 Cu. DMPD affected the pharmacokinetics of porphyrin in terms of retention time in vivo and tumor-targeting ability relative to those of unmodified porphyrin. [ 64 Cu]Cu-TDAP showed stronger enhancement than [ 64 Cu]Cu-porphyrin in U87MG glioblastoma cells, especially in the cytoplasm and nucleus, indicating its tumor-targeting properties and potential use as a therapeutic agent. In the subcutaneous and orthotopic models of brain-tumor-bearing mice, [ 64 Cu]Cu-TDAP was clearly visualized in the tumor site via positron emission tomography imaging and showed a tumor-to-brain ratio as high as 13. [ 64 Cu]Cu-TDAP deserves attention as a new diagnostic agent that is suitable for the early diagnosis and treatment of brain tumors.