Abstract
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. Methods: Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with (111)In to allow SPECT imaging. (111)In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non-p53-specific (111)In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of (111)In-anti-p53-TAT, versus (111)In-mIgG-TAT, in high-expression p53(R175H) 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 (111)In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53(R172H) pancreatic ductal adenocarcinoma tumors. Conclusion: We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.