Here, we have prepared long-circulating PEGylated liposomes heavily loaded with 111In via the liposome-incorporated polylysine-based (PLL-based) polychelating amphiphilic polymer (PAP) and additionally modified with the monoclonal antibody 2C5 (mAb 2C5) possessing the nucleosome-restricted (NS-restricted) specificity and capable of specific recognition of a broad variety of live cancer cells via the cancer cell surface bound NSs. These liposomes have been tested as a tumor-specific contrast agent for the gamma-scintigraphic visualization of model tumors in mice. The tumor accumulation of mAb 2C5 modified liposomes prepared in this study was significantly (3-to-5-fold) higher than in the neighboring muscle tissue at all times after administration (6, 24, and 48 h) in mice bearing murine Lewis lung carcinoma (LLC) and human HT-29 tumors. The whole body direct gamma-imaging of LLC tumor bearing mice at different times has demonstrated the superior in vivo tumor accumulation of the targeted mAb 2C5 modified PAP-containing PEGylated liposomes compared to nontargeted liposomal control formulations, which resulted in better and faster tumor imaging as shown with LLC-bearing mice.