title: A phase 2 study of (99m)Tc-tilmanocept in the detection of sentinel lymph nodes in melanoma and breast cancer.
abstract: BACKGROUND
  Several (99m)Tc-labeled agents that are not approved by the U.S. Food and Drug Administration are used for lymphatic mapping. A new low-molecular-weight mannose receptor-based, reticuloendothelial cell-directed, (99m)Tc-labeled lymphatic imaging agent, (99m)Tc-tilmanocept, was used for lymphatic mapping of sentinel lymph nodes (SLNs) from patients with primary breast cancer or melanoma malignancies. This novel molecular species provides the basis for potentially enhanced SLN mapping reliability.
  
  
  METHODS
  In a prospectively planned, open-label phase 2 clinical study, (99m)Tc-tilmanocept was injected into breast cancer and cutaneous melanoma patients before intraoperative lymphatic mapping. Injection technique, preoperative lymphoscintigraphy (LS), and intraoperative lymphatic mapping with a handheld gamma detection probe were performed by investigators per standard practice.
  
  
  RESULTS
  Seventy-eight patients underwent (99m)Tc-tilmanocept injection and were evaluated (47 melanoma, 31 breast cancer). For those whom LS was performed (55 patients, 70.5%), a (99m)Tc-tilmanocept hot spot was identified in 94.5% of LS patients before surgery. Intraoperatively, (99m)Tc-tilmanocept identified at least one regional SLN in 75 (96.2%) of 78 patients: 46 (97.9%) of 47 in melanoma and 29 (93.5%) of 31 in breast cancer cases. Tissue specificity of (99m)Tc-tilmanocept for lymph nodes was 100%, displaying 95.1% mapping sensitivity by localizing in 173 of 182 nodes removed during surgery. The overall proportion of (99m)Tc-tilmanocept-identified nodes that contained metastatic disease was 13.7%. Five procedure-related serious adverse events occurred, none related to (99m)Tc-tilmanocept.
  
  
  CONCLUSIONS
  Our results demonstrate the safety and efficacy of (99m)Tc-tilmanocept for use in intraoperative lymphatic mapping. The high intraoperative localization and lymph node specificity of (99m)Tc-tilmanocept and the identification of metastatic disease within the nodes suggest SLNs are effectively identified by this novel mannose receptor-targeted molecule.
authors.affiliation: California Pacific Medical Center and Sutter Pacific Medical Foundation and Research Institute, University of California, San Francisco, CA, USA. leongsx@cpmcri.org
authors.forename: Stanley P L
authors.initials: SP
authors.lastname: Leong
authors.forename: Julian
authors.initials: J
authors.lastname: Kim
authors.forename: Merrick
authors.initials: M
authors.lastname: Ross
authors.forename: Mark
authors.initials: M
authors.lastname: Faries
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
authors.forename: Wendy L Rich
authors.initials: WL
authors.lastname: Metz
authors.forename: Frederick O
authors.initials: FO
authors.lastname: Cope
authors.forename: Richard C
authors.initials: RC
authors.lastname: Orahood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D003911:Dextrans; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008351:Mannans; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D015609:Organotechnetium Compounds; D004369:Pentetic Acid; D011379:Prognosis; D011446:Prospective Studies; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D016284:Technetium Tc 99m Pentetate / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D003911:Dextrans; D008351:Mannans; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C431884:technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate