title: Improved detection of regional melanoma metastasis using 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide, a melanin-specific PET probe, by perilesional administration.
abstract: The efficacy of differing routes of administration of 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (18F-MEL050), a new benzamide-based PET radiotracer for imaging regional lymph node metastasis in melanoma, was assessed.
  
  
  METHODS
  B16-Black/6 metastatic melanoma cells harboring an mCherry transgene were implanted into the left-upper-foot surface of 49 C57 Black/6 mice as a model of popliteal lymph node (PLN) metastasis. Ultrasound scanning of the left PLN was performed at baseline and in combination with 18F-MEL050 PET on days 5, 9, and 14. Mice were divided into 2 groups to compare the results of tracer administration either subcutaneously at the tumor site (local) or in the lateral tail vein (systemic). After PET on each imaging day, 5 mice per group-including any with evidence of metastasis-were sacrificed for ex vivo validation studies including assessment of retained radioactivity and presence of the mCherry transgene as a surrogate of nodal tumor burden.
  
  
  RESULTS
  Nine mice were judged as positive for PLN metastasis by ultrasound at day 5, and 8 PLNs were positive on 18F-MEL050 PET, 3 after systemic and 5 after local administration. Ex vivo analysis showed that ultrasound correctly identified 90% of positive PLNs, with 1 false-positive. 18F-MEL050 PET correctly identified 60% of positive PLNs after systemic administration and 100% after local administration with no false-positive results by either route. The average node-to-background ratio for positive PLNs was 6.8 in the systemic-administration group and correlated with disease burden. In the local-administration group, the mean uptake ratio was 48, without clear relation to metastatic burden. Additional sites of metastatic disease were also correctly identified by 18F-MEL050 PET.
  
  
  CONCLUSIONS
  In addition to its potential for systemic staging, perilesional administration of 18F-MEL050 may allow sensitive and specific, noninvasive identification of regional lymph node metastasis in pigmented malignant melanomas.
authors.affiliation: Centre for Cancer Imaging and Translational Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Delphine
authors.initials: D
authors.lastname: Denoyer
authors.forename: Titaina
authors.initials: T
authors.lastname: Potdevin
authors.forename: Peter
authors.initials: P
authors.lastname: Roselt
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Neels
authors.forename: Laura
authors.initials: L
authors.lastname: Kirby
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.forename: Donna S
authors.initials: DS
authors.lastname: Dorow
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes; D008207:Lymphatic Metastasis; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000031:analogs & derivatives*; D016133:Polymerase Chain Reaction; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D014463:Ultrasonography
chemical_list: D005462:Fluorine Radioisotopes; D008543:Melanins; C543821:N-(2-(diethylamino)ethyl)-6-fluoronicotinamide; D019275:Radiopharmaceuticals; D009536:Niacinamide