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 scientist in the National Cancer Institute's molecular imaging program. Dr. Kobayashi has been working on “activatable” probes that respond to biological processes. In one example, quenched fluorophores are conjugated to tumor-specific antibodies. Once bound, the probe is internalized where it can be activated by the acidic environment of the endolysosome.
Although fluorescent imaging is typically limited to very shallow depths, it can be used to guide open surgery—for example, in the brain—and most parts of the body (except the heart and brain) can be reached by using endoscopy as well. “We can go almost anywhere through the GI or urinary tract, or peritoneal or plural spaces,” Dr. Kobayashi pointed out.
He also uses different wavelength fluorophores and other different energy probes, to simultaneously query several discrete entities. In addition, MRI, nuclear, PET/CT, and optical can also be multiplexed to generate more information from the body, the radiologist added, “to detect things much better than the single modality.”