Development of a highly specific and non-immunogenic reporter to monitor gene expression in vivo is critical for successful optimization ot gene and cell therapy protocols. Here we developed a membrane-anchored anti-polyethylene glycol (aPEG) eporter that can specifically bind PEGylated imaging probes to assess the location, extent and persistence of gene expression or transplanted cells in vivo. Functional aPEG reporters that were stably expressed on cells in vitro and in vivo selectively accumulated various PEGylated imaging probes and could be detected by optical imaging, magnetic resonance (MR) imaging and micro-positron emission tomography (micro-PET). The aPEG reporter displayed an imaging specificity comparable to HSV-tk but did not provoke immune responses or cause toxicity to the host. Importantly, a humanized aPEG reporter retained high imaging speciiicuy in subcutaneous and metastatic tumor models in vivo. Thus, the highly specific and non-immunogenic aPEG reporter may be paired with PEGylated probes to pro'ovide a valuable system to image gene expression or cell delivery in the clinic.
