Physical properties and clinical translation advantages of 67Cu

Abstract: Abstract Copper-67 (⁶⁷Cu) demonstrates significant advantages in targeted radiotherapy for hematological malignancies, owing to its physical half-life (T₁/₂ = 61.83 h) that aligns with antibody pharmacokinetics, medium-range β⁻ particles (Eβ⁻ₘₐₓ = 577 keV, Rₘₐₓ ≈ 2 mm), and integrated diagnostic/therapeutic capabilities enabled by concomitant γ-ray emission (184.6 keV). The β⁻ particles precisely eradicate micro-metastases while overcoming antigen heterogeneity, and simultaneous SPECT imaging ensures biodistribution verification and dose monitoring. Key technological breakthroughs drive clinical translation: High-specific-activity production (>1850 GBq/mg) achieved via the photonuclear reaction ⁶⁸Zn(γ,p)⁶⁷Cu, and the bicyclic chelator CB-TE2Asignificantly reduces hepatic off-target accumulation. Compared to ⁹⁰Y, ⁶⁷Cu optimizes radiation dosimetry by increasing the tumor-to-bone marrow dose ratio by 3.5-fold, with pretargeting strategies further elevating this ratio to 4.1-fold. Clinical studies validate its efficacy: ⁶⁷Cu-lintuzumab achieved a 41% objective response rate in relapsed/refractory AML, while dual-targeting strategies yielded 35% minimal residual disease (MRD)-negative complete responses in antigen-escape acute lymphoblastic leukemia (ALL). Future efforts should address renal dose limitations, establish individualized dosimetry models using ⁶⁴Cu-PET, and expand applications through combination immunotherapies.