Comparison of ^99mTc-Tilmanocept and ^99mTc-Sulfur Colloid for Intraoperative Lymphatic Mapping and Sentinel Lymph Node Biopsy in Breast Cancer Patients

Objectives: Intraoperative lymphatic mapping (ILM) and sentinel lymph node biopsy (SLNB) have become standard-of-care in the surgical staging and treatment of breast cancer. ^99mTc-radiotracer agents and blue dye agents are used separately or in combination in ILM/SLNB. Historically, the most commonly used radiotracer for ILM/SLNB in patients with breast cancer was ^99mTc-Sulfur Colloid (^99mTc-SC) a non-synthetic, receptor non-specific LN mapping agent that is trapped by and accumulates in LNs. Recently, ^99mTc&#8209;Tilmanocept (^99mTc-TM), was approved for the indication of ILM/SLNB for breast cancer. ^99mTc-TM is a synthetic, receptor-specific macromolecule that accumulates within LNs via specific CD206 receptor targeting. ^99mTc-TM has a reported SLN localization rate of ≥97% with a false-negative rate of <3% and has demonstrated significantly less pain at the time of injection. This was a prospective single-center, randomized, parallel-group, double-blind study comparing ^99mTc-TM and ^99mTc-SC for ILM and SLNB in breast cancer patients. The endpoints were number of SLNs identified by utilization of an intraoperative gamma probe, uptake of vital blue dye (VBD), final histopathology of SLNs, and pain scores at the time of injection.

Methods: A total of 39 women (1 bilateral surgery), aged 18 or older, with a diagnosis of primary breast cancer who were eligible for surgery were enrolled in the study. Subjects received a single 0.5 mL intradermal injection of 0.5 mCi of ^99mTc labeled with either 50 µg of TM (n=18) or filtered SC (n=22). Immediately after injection, subjects were asked to verbally rate their level of discomfort using the Wong-Baker FACES pain rating scale, which ranges from a minimum score of 0 (no pain) to a maximum score of 10 (worst pain possible). After injection, preoperative imaging procedures were completed and then patients proceeded to surgery for lymphatic mapping where VBD was injected. During surgery, LNs were evaluated for radioactivity with a handheld gamma probe, where gamma counts had to satisfy the criteria of the 10% rule in order to be considered SLN. Any nodal count not meeting this threshold was considered a negative finding (not localized). All removed LNs were subjected to histopathological analysis. Results: There was no significant difference in the total number of LNs localized between groups with 28 LNs localized in subjects receiving ^99mTc-TM and 32 LNs localized in subjects receiving ^99mTc-SC. Nine (9) of the 28 LNs (32%) localized in the ^99mTc-TM group and 22 of the 32 LNs (69%) localized in the ^99mTc-SC group demonstrated uptake of VBD. Seven (7) LNs (25%) in the ^99mTc-TM group and 1 LN (3%) in the ^99mTc-SC group were identified as positive for malignancy on final histopathology. Of the LNs demonstrated as positive for malignancy on final histopathology, VBD uptake was demonstrated in 2/7 LNs in the ^99mTc-TM group and in 0/1 in the ^99mTc-SC group. Based on the Wong-Baker pain rating scale, the mean pain score in the ^99mTc-TM group was 0.53, which was significantly lower than the mean pain score of 1.57 observed in the ^99mTc-SC group (P=0.049). Conclusions: The number of SLNs localized intraoperatively was comparable for ^99mTc-TM and ^99mTc-SC (28 vs 32). There were more pathology-positive nodes in the ^99mTc-TM group vs the ^99mTc-SC group (7 vs 1). While VBD uptake was more prevalent in the ^99mTc-SC group compared to the ^99mTc-TM group (22 vs 9), the 1 lymph node in the ^99mTc-SC group demonstrated as positive for malignancy on final histopathology did not demonstrate VBD uptake. Pain at the time of injection was significantly less for subjects receiving ^99mTc-TM compared to those receiving ^99mTc-SC.