Techniques that accurately identify the sentinel lymph node in cancer

Table 1 Characteristics of common tracers

Blue dyes	Inherent low molecular weight of blue dyes translates into a very rapid migration into and subsequently out of the lymphatics with fairly low SLN retention, relying on surgeon expertize to identify, locate and remove the SLN before the dye spreads to other nodes[111] Better for localization of superficial lymph nodes Methylene blue (tetramethylthionine chloride, C16H18ClN3S) is a heterocyclic aromatic dye, a member of thiazine dyes[112] First line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy and has applications in the treatment of memory loss[112]. Has risk of skin necrosis observed with intradermal injection[113]. Excreted primarily in the urine and causes a green-blue discoloration of the urine which can also be observed in saliva and bile that disappears within a few days. Better safety profile when compared to Isosulfan Blue[114] Patent blue (Isosulfan Blue, Lymphazurin) has a vivid affinity for the lymphatics, with particle size small enough to travel through the lymph vessel but large to be trapped in the lymph nodes[115]
Radiolabelled colloid	Variable size, from 100-400 nm[24] Sulphide-based nanoparticles conjugated with Tc-99m are the most commonly used and available[116] Half life is approximately 6 h[116] As the radiocolloid emits high energy gamma radiation (140 keV) which is highly penetrating, allowing for its use in variable tissue depth, density and coloration[116] Gamma detection instruments are needed to localize tracer (hand held gamma probes, gamma cameras, SPECT)
Indocyanine green	ICG is a negatively charged ion tricarbocyanine dye belonging to the large family of cyanine dyes ICG fluoresces at about 800 nm and longer wavelengths, confines to the vascular compartment through binding with plasma proteins, has low toxicity and rapid excretion, almost exclusively into the bile[117] ICG is a low molecular weight contrast agent, and is both rapidly taken up into the lymphatics but also can diffuse from the lymphatics, reducing the local concentrations and contributing to background signal[116] and needs to be readministered
Tilmanocept (99mTc, Lymphoseek)	Radiopharmaceutical that accumulates in lymphatic tissues by binding to a mannose-binding protein on the surface of macrophages[101] The molecule, 99mTc-DTPA-mannosyl-dextran, is composed of a dextran backbone to which multiple units of mannose and DTPA are synthetically attached[101]

DTPA: Diethylenetriamine pentaacetic acid; SLN: Sentinel lymph node; ICG: Indocyanine green; SPECT: Single-photon emission computerized tomography.