Engineering AND-Gate Aptamer-Signal Base Conjugates for Targeted Magnetic Resonance Molecular Imaging of Metastatic Cancer

In vivo noninvasive molecular imaging requires precise recognition and in situ, real-time imaging of specific cellular and molecular signatures at the site of interest. However, this is often hindered by issues of current imaging probes relating to either the lack of active recognition or the overall nonspecific mechanism of action. Here, we present an aptamer-signal base conjugate (ApSC) concept to engineer AND-gate molecular tools for tumor-targeted molecular imaging. Superior to conventional synthetic methods for imaging probes, our design enables programmable and precise conjugation between recognition and signaling units in a modular synthesis manner with high fidelity for both the conjugating chemistry and binding affinity to the molecular target. Moreover, this design is endowed with simultaneous multivariate activation that readily adapts to tumor microenvironments for signal output, thus providing improved imaging specificity and sensitivity. Such a concept has been successfully shown in magnetic resonance imaging (MRI), the modality of choice for in vivo noninvasive molecular imaging. The engineered ApSC can produce amplified MR signals only after activation by the unique metabolism and dysregulation of redox balance in cancer. In mouse models of xenograft and metastatic breast cancer, the AND-gate molecular MRI probe elicits high imaging contrast in primary tumors and micrometastases. This study promises to provide synthetically accessible scaffolds that can be extended to a large library of advanced molecular imaging tools with varied imaging modalities and mechanisms of action for preventative, predictive, and personalized medicine.