Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first-to our knowledge-method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with In to allow SPECT imaging. In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non-p53-specific In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. In vivo SPECT imaging showed enhanced uptake of In-anti-p53-TAT, versus In-mIgG-TAT, in high-expression p53 and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse-derived pancreatic ductal adenocarcinoma tumors. Imaging with In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53 pancreatic ductal adenocarcinoma tumors. We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.