Biopsies of sentinel lymph nodes (SLNs) are used to determine whether tumour cells have begun to spread beyond the primary cancer site and whether lymphadectomy or systemic therapy is required. Locating which lymph node the cancer cells will drain to first — the SLN — using fluorescent dyes helps surgeons to biopsy the tissue quickly and efficiently. John Frangioni, Moungi Bawendi and colleagues now report a promising new approach for accurate SLN mapping, using nanotechnology.

Quantum dots (QDs) are fluorescent crystals that are typically less than 50 nm in diameter. These have potential for many biological applications; however, their development for bioimaging has been hampered by technical limitations. Frangioni's and Bawendi's groups previously developed QDs that fluoresce in the near-infrared (NIR) region of the spectrum to overcome the problem of poor sensitivity and poor resolution of visible QDs or conventional organic fluorescent dyes in vivo. For the current experiments, the dots were 15.8 nm diameter — well within the range that is required for retention in the SLN. They were also coated with polydentate phosphine to make them water soluble.

The authors showed that NIR dots are stable even at high fluence rates, unlike conventional NIR fluorophores, which rapidly photobleach — in fact, NIR dots seem to photobrighten slightly. They are also stable in 100% serum at 37°C for more than 30 minutes, indicating that they will survive prolonged exposure to bodily fluids at core body temperature.

So, the main technical problems have been addressed, but do these NIR QDs migrate to SLNs in vivo? The authors first showed that the dots entered the lymphatic system and migrated quickly to the SLN when injected intradermally in mice, as confirmed by re-injection with the standard SLN mapping agent — isosulfan blue — and by histological examination. They then injected 400 pmol of NIR QDs intradermally into the thigh of five pigs, which are about the same size as humans. Real-time imaging allowed a surgeon to follow the lymphatic flow and quickly identify the SLN, so minimizing incision inaccuracies. Because the NIR QDs are stable and the fluorescence is intense, the surgeon could easily see the SLN throughout the biopsy procedure and could also inspect the surgical site to ensure total resection of the node.

The next important step will be to examine the toxicity of the NIR QDs, as they contain three metals, which in their uncomplexed elemental forms cause acute and chronic toxicity. The current experiments — with very low doses of the complexed metals — did not reveal any short-term toxicity.