Multi-functional nanomaterial conjugates constructed with targeting ligands and therapeutic radioisotopes are key for the future clinical translation of radionanomedicine. However, the choice of the nanomaterial governs the in vivo oncological applications. In this study, recently introduced non-toxic, spherical (<50 nm) carbon nanospheres (CNS) have been modified at the surface for conjugation with integrin avb3-targeting peptide cRGDfK and macrocyclic chelator (DOTA). Herein we have investigated the potential of ¹⁷⁷Lu-labeled carbon nanospheres (¹⁷⁷Lu-DOTA-CNS–cRGDfK) for efficient nano-targeting of melanoma tumors expressing integrin avb3. To ascertain the specificity of ¹⁷⁷Lu-DOTA-CNS–cRGDfK in vivo, blocking studies with cold cRGDfK peptide as well as control experiments with radiolabeled nanoconjugate without the peptide (¹⁷⁷Lu-DOTA-CNS) were carried out. Significantly high tumor uptake of ¹⁷⁷Lu-DOTA-CNS–cRGDfK in comparison to that of ¹⁷⁷Lu-DOTA-CNS, fast urinary excretion and low uptake in the reticuloendothelial system (RES) establish the promising potential of the agent and indicate the future role of radiolabeled carbon nanospheres in radionanomedicine for efficient targeted therapy of numerous tumor sites.