A typical molecular imaging probe, such as a fluorescently
labeled antibody, is introduced into a subject (animal, patient)
and washed out over time. Contrast is achieved by maximizing the
amount of signal at the target while minimizing that remaining
associated with nonspecific tissue. A host of factors, from
uptake, metabolism, and clearance of the probe to interference
by endogenous factors (e.g., autofluorescence) to sensitivity
and selectivity of the probe to timing of the imaging, can
impact the achievable signal to noise ratio (called tumor to
background ratio or TBR in oncology). Most currently available
probes are “always on”—that is, they continuously emit signal
(or in the case of fluorescently labeled probes, they always
fluoresce in response to excitation). The targeting moiety
should direct most of it to the organ, cell, or receptor of
interest, yet TBR often remains an issue. What if a probe only
emitted a signal when associated with its target? asked Hisataka
Kobayashi, M.D., Ph.D., chief scie