Recently, our group developed a class of “AND-Gate”quenched contrast agents that require the multiplexed processing bymultiple tumor specific proteases in order to generate a fluorescencesignal (Figure S4a).26,37 Death-Cat-2, the best performing of this class of probes, is selectivelycleaved by both the tumor-associated executioner caspase-3 and thelysosomal cysteine cathepsins. This evidence concerns the gene CASP3 and neoplasm.