Lymphoscintigraphy radiopharmaceuticals are radioactive particles that enter and move along lymphatic channels upon intradermal, subcutaneous, or intratissue injection.
Classical cancer surgery most often involved removal of the primary tumor and excision of the lymph nodes in the tumor’s most likely nodal drainage basins. While more complete nodal excisions statistically resulted in improved outcomes, the majority of the excised nodes did not harbor cancer cells. Moreover, a substantial number of patients developed lymphedema in the extremities that shared nodal drainage basins with the tumor. Thus, surgeons began to perform nodal labeling with injected methylene blue at the time of surgery. The idea was to tag, locate, and sample only the primary or sentinel nodes draining the tumor (1
). If these sentinel nodes were positive, nodal resection was performed; if not, no further nodal dissection was performed. While lymph node labeling with methylene blue is practical, it may be difficult to locate deeper nodes with this visual technique. Thus, lymphoscintigraphy was developed with the use of radioactive particle scintigraphy and intraoperative localization with the use of surgical gamma probes. Figure 15.1
demonstrates how an abdominal melanoma may spread along lymphatics to either axilla or groin nodes. Generally, if the first or sentinel node is cancer free, secondary nodes will also be cancer free and therefore do not require surgical sampling (2
compares the 99m
Tc-based radiopharmaceutical agents that have been used for lymphoscintigraphy (3
). Filtered 99m
Tc-sulfur colloid is most commonly used in the United States, while other colloids such as antimony trisulfide (Lymph-Flo®
) and nanocolloidal albumin (Nanocoll®
) are more commonly used in Europe. These agents are radioactive nanoparticles and when injected into tissue, they are mobilized along lymphatic channels. Smaller particles move more rapidly than larger particles with typical lymphatic flow rates of 30 mm/min.
) is an alternative small molecule (7 nm) agent which binds to CD206 receptor specific to reticuloendothelial cells including lymph nodes. As a small molecule, tilmanocept moves more rapidly than nanoparticles. As a CD206 receptor binding agent, tilmanocept may tag less
secondary nodes, thus potentially sparing less fruitful nodal excisions (4
• Schematic representation of the sentinel lymph node (SLN) concept, defined as the lymphatic station first encountered by tumor cells entering the lymphatic circulation. Photograph shows a primary cutaneous melanoma of the left abdominal wall and some afferent lymphatic channels draining to a left inguinal SLN (negative for the presence of metastases [SLNj]) and to two left axillary SLNs (one of which is positive for the presence of melanoma cells [SLN+]). SLN+, SLN positive for the presence of melanoma cells; SLNj, SLN negative for the presence of melanoma cells. Reprinted with permission from Manca et al. (2
Table 15.1 CHARACTERISTICS OF 99MTC-BASED RADIOPHARMACEUTICALS
Maximum Particle Size (nm)
Particle Size Range (nm)
About 7 (equivalence)
About 7 (equivalence)
Antimony trisulfide (Lymph-Flo®)
Sulfide nanocolloid (Lymphoscint®)
Nanocolloidal albumin (Nanocoll®)
Rhenium sulfide (Nanocis®)
Sulfur colloid (Sulfur colloid®)
Comparison of Nuclear Medicine-Labeled Particles
3,000 (with clumping)
Red blood cell
SIR-Spheres® Y-90 resin microspheres
TheraSphere® Glass Microspheres
This table shows the comparison of the 99mTc-based radiopharmaceutical agents that have been used for lymphoscintigraphy. Other particle-like nuclear medicine agents are also included for comparison. Reprinted by permission of Springer: Bluemel et al. (3). Copyright © 2015 Springer Nature.
DTPA, diethylene triamine pentaacetic acid; MAA, macro-aggregated albumin.
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