Exemplary embodiments include systems, methods, and compositions for the intra-operative detection of target tissue. At least one embodiment includes a fluorescence detection instrument that may be used for intra-operative detection of a fluorescent targeting agent, its binding site, and its interaction within cancer tissues. An exemplary embodiment is highly sensitive to the local deposition of fluorescence agents even at a low concentration. In at least one embodiment, the system includes a handheld navigation instrument that is usable to excite, detect, and report the fluorescent deposition of the targeting agent in real-time. In alternative embodiments, the system includes a wearable unit to excite, detect, and visually report the fluorescent deposition of the targeting agent to the user. The wearable unit includes eyewear that allow the user to perform image-guided surgery based on the near real-time fluorescence detection of the fluorescent targeting agent.