99mTc-Tilmanocept performance for sentinel node mapping in breast cancer, melanoma, and head and neck cancer: a systematic review and meta-analysis from a European expert panel

Purpose: Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, 99mTc-tilmanocept is of particular interest due to its low molecular weight and specific binding capability for the mannose receptors of lymphatic reticuloendothelial cells. In the current systematic review and meta-analysis, we aimed to provide an update from a European expert panel on the performance of 99mTc-tilmanocept for SN biopsy. Methods: A systematic literature search of the PubMed/Medline and Embase databases was performed to identify studies on the use of 99mTc-tilmanocept for SN identification in oncological patients. The articles' methodological quality was assessed before inclusion. The pooled estimates of the pre-/intraoperative detection rates (DR; proportion of patients with ≥ 1 SN identified) and/or pN + sensitivity (SN + /pN + patients ratio), with 95% confidence intervals (CIs), were calculated for breast cancer, melanoma, and head and neck cancer. Results: Twenty-four articles were included in the systematic review, and twenty-one provided data for the meta-analysis. According to data availability, the 99mTc-tilmanocept-estimated pooled preoperative and intraoperative DRs were 0.94 (95%CI, 0.88-1.01) and 0.99 (0.98-1.00) for breast cancer, 0.98 (0.96-0.99) and 1.00 (0.99-1.00) for melanoma, and 0.97 (0.93-1.02) and 0.99 (0.96-1.01) for head and neck carcinoma. Finally, the pooled sensitivity for nodal metastasis in melanoma was 0.97 (95% CI, 0.92-1.03). Conclusion: 99mTc-tilmanocept is a promising radiotracer for SN mapping in patients with breast cancer, melanoma, or head and neck cancer. We strongly believe that multicenter trials are still needed to assess if 99mTc-tilmanocept is superior to other radiotracers used in clinical routine.