Molecular Targeting Radiotherapy with Cyclo-RGDfK(C) Peptides Conjugated to ¹⁷⁷Lu-Labeled Gold Nanoparticles in Tumor-Bearing Mice

Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of α(v)β(3) integrin, thereby inhibiting angiogenesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable multimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of ¹⁷⁷Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare it with that of ¹⁷⁷Lu-AuNP or ¹⁷⁷Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [¹⁸F]fluor-deoxy-glucose-microPET/CT), histological characteristics and VEGF gene expression (by real-time polymerase chain reaction) in tumor tissues following treatment with ¹⁷⁷Lu-AuNP-RGD, ¹⁷⁷Lu-AuNP or ¹⁷⁷Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, ¹⁷⁷Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 ± 7.9 Gy). These results correlated with the observed therapeutic response, in which ¹⁷⁷Lu-AuNP-RGD significantly (p < 0.05) induced less tumor progression, less tumor metabolic activity, fewer intratumoral vessels and less VEGF gene expression than the other radiopharmaceuticals, a consequence of high tumor retention and a combination of molecular targeting therapy (multimeric RGD system) and radiotherapy (¹⁷⁷Lu). There was a low uptake in non-target organs and no induction of renal toxicity. ¹⁷⁷Lu-labeled gold nanoparticles conjugated to cyclo-RGDfK(C) demonstrate properties suitable for use as an agent for molecular targeting radiotherapy.