The efficacy of Tilmanocept in sentinel lymph mode mapping and identification in breast cancer patients: a comparative review and meta-analysis of the 99mTc-labeled nanocolloid human serum albumin standard of care

Abstract

Sentinel lymph node (SLN) mapping is common, however question remains as to what the ideal imaging agent is and how such an agent might provide reliable and stable localization of SLNs. (99m)Tc-labeled nanocolloid human serum albumin (Nanocoll) is the most commonly used radio-labeled colloid in Europe and remains the standard of care (SOC). It is used in conjunction with vital blue dyes (VBDs) which relies on simple lymphatic drainage for localization. Although the exact mechanism of Nanocoll SLN localization is unknown, there is general agreement that Nanocoll exhibits the optimal size distribution and radiolabeling properties of the commercially available radiolabel colloids. [(99m)Tc]Tilmanocept is a novel radiopharmaceutical designed to address these deficiencies. Our aim was to compare [(99m)Tc]Tilmanocept to Nanocoll for SLN mapping in breast cancer. Data from the Phase III clinical trials of [(99m)Tc]Tilmanocept's concordance with VBD was compared to a meta-analysis of a review of the literature to identify a (99m)Tc albumin colloid SOC. The primary endpoints were SLN localization rate and degree of localization. Six studies were used for a meta-analysis to identify the colloid-based SOC. Five studies (6,134 patients) were used to calculate the SOC localization rate of 95.91 % (CI 0.9428-0.9754) and three studies (1,380 patients) were used for the SOC SLN degree of localization of 1.6683 (CI 1.5136-1.8230). The lower bound of the confidence interval was used for comparison to Tilmanocept. Tilmanocept data included 148 patients, and pooled analysis revealed a 99.99 % (CI 0.9977-1.0000) localization rate and degree of localization of 2.16 (CI 1.964-2.3600). Tilmanocept was superior to the Nanocoll SOC for both endpoints (P < 0.0001).

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

“…The specific interaction of 99m Tc tilmanocept with the receptor permits the molecule to accumulate within the SLN, with minimal passage into distal lymph nodes. Phase I clinical trials in patients with breast cancer (12) and in those with melanoma (13) successfully demonstrated these properties, which were confirmed in phase II (14) and phase III (15) …”

In vivo albumin labeling and lymphatic imaging

“…The detection of SLNs is important in clinical cancer classification and treatment (30). Currently, presurgical diagnosis of SLNs is often based on the morphological changes observed by MR or CT scans.…”

99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization

“…Tokin et al retrospectively compared 99m Tc-tilmanocept with 99m Tc-nanocolloid human serum albumin in breast cancer patients who underwent intraoperative lymphatic mapping. Data analysis revealed a higher localization rate (proportion of patients with at least one localized lymph node) and degree of localization (average number of localized nodes per patient relative to patient population) for 99m Tc-tilmanocept than for 99m Tc-nanocolloid human serum albumin (P , 0.0001) (8).…”

“…The commonly used agents-unfiltered or filtered 99m Tc-SC, albumin-based colloids, and 99m Tc-antimony trisulfide colloid-do not exhibit all these characteristics. Furthermore, the ideal agent should have low radiation absorption, high biologic safety, rapid and stable 99m Tc labeling, and radiochemical purity (8). Vera et al reported the synthesis and preliminary biologic testing of a synthetic macromolecule, 99m Tcdiethylenetriaminepentaacetic acid (DTPA)-mannosyl-dextran (the same as 99m Tc-tilmanocept), for sentinel node detection and found that it exhibited the desired properties of rapid clearance from the injection site and low accumulation in distal nodes (9).…”