The peptide fragment of human serum albumin that was identified as an inhibitor of C-X-C motif chemokine receptor 4 (CXCR4), termed EPI-X4, was investigated as a scaffold for the development of CXCR4-targeting radio-theragnostics. Derivatives of its truncated version JM#21 (ILRWSRKLPCVS) were conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and tested in Jurkat and Ghost-CXCR4 cells. Ligand-1, -2, -5, -6, -7, -8, and -9 were selected for radiolabeling. Molecular modeling indicated that 177Lu-DOTA incorporation C-terminally did not interfere with the CXCR4 binding. Lipophilicity, in vitro plasma stability, and cellular uptake hinted 177Lu-7 as superior. In Jurkat xenografts, all radioligands showed >90% washout from the body within an hour, with the exception of 177Lu-7 and 177Lu-9. 177Lu-7 demonstrated best CXCR4-tumor targeting. Ex vivo biodistribution and single-photon emission computed tomography (SPECT)/positron emission tomography (PET)/CT imaging of 177Lu-7/68Ga-7 showed the same distribution profile for both radioligands, characterized by very low uptake in all nontargeted organs except the kidneys. The data support the feasibility of CXCR4-targeting with EPI-X4-based radioligands and designate ligand-7 as a lead candidate for further optimization.