Targeting assay of a fusion protein applied in enzyme prodrug therapy

Tumor growth and metastasis are dependent on angiogenesis. The overexpression of integrin α_vβ₃ on angiogenic vessels and on numerous malignant human tumor cells suggests that these labeled ligands of integrin are potentially suitable for molecular imaging and in targeted therapy of tumors. In previous studies, we added a β-lactamase variant with reduced immunogenicity to the cyclic peptide RGD4C, resulting in the fusion protein RGD4CβL, which is suitable for use in targeted enzyme prodrug therapy (TEPT), a promising treatment for tumors. The targeting of the aforementioned fusion protein serves an important role in TEPT. In the present study, RGD4CβL was labeled with ¹²⁵I and the targeting effect on integrin-positive tumors was evaluated. The results demonstrated that the ¹²⁵I-RGD4CβL protein exhibited high levels of accumulation at the tumor site and rapid renal clearance, which revealed the potency and efficiency of RGD4CβL in TEPT.