title: Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging.
abstract: Sentinel lymph node (SLN) excision is included in various cancer guidelines to identify microscopic metastatic disease. Although effective, SLN excision is an invasive procedure requiring radioactive tracing. Novel imaging approaches assessing SLN metastatic status could improve or replace conventional lymph node excision protocols. In our first-in-human study, we used noninvasive multispectral optoacoustic tomography (MSOT) to image SLNs ex vivo and in vivo in patients with melanoma, to determine metastatic status. MSOT significantly improved the tumor metastasis detection rate in excised SLN (506 SLNs from 214 melanoma patients) compared with the conventional EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group protocol (22.9% versus 14.2%). MSOT combined with the near-infrared fluorophore indocyanine green reliably visualized SLNs in vivo in 20 patients, up to 5-cm penetration and with 100% concordance with (99m)Tc-marked SLN lymphoscintigraphy. MSOT identified cancer-free SLNs in vivo and ex vivo without a single false negative (189 total lymph nodes), with 100% sensitivity and 48 to 62% specificity. Our findings indicate that a noninvasive, nonradioactive MSOT-based approach can identify and determine SLN status and confidently rule out the presence of metastasis. The study further demonstrates that optoacoustic imaging strategies can improve the identification of SLN metastasis as an alternative to current invasive SLN excision protocols.
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Stoffels
authors.affiliation: iThera Medical GmbH, 81379 München, Germany. Institute for Biological and Medical Imaging, Technische Universität München, and Helmholtz Center Munich, 85764 München, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Morscher
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Helfrich
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hillen
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Leyh
authors.forename: Julia
authors.initials: J
authors.lastname: Lehy
authors.affiliation: iThera Medical GmbH, 81379 München, Germany.
authors.forename: Neal C
authors.initials: NC
authors.lastname: Burton
authors.affiliation: iThera Medical GmbH, 81379 München, Germany.
authors.forename: Thomas C P
authors.initials: TC
authors.lastname: Sardella
authors.affiliation: iThera Medical GmbH, 81379 München, Germany.
authors.forename: Jing
authors.initials: J
authors.lastname: Claussen
authors.affiliation: Department of Nuclear Medicine, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Thorsten D
authors.initials: TD
authors.lastname: Poeppel
authors.affiliation: Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Hagen S
authors.initials: HS
authors.lastname: Bachmann
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roesch
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Griewank
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Institute for Experimental Immunology and Imaging, Imaging Center Essen (IMCES), University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
authors.affiliation: Department of Dermatology, Venerology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. joachim.klode@uk-essen.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Klode
mesh_terms: D015331:Cohort Studies; D003952:Diagnostic Imaging; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000473:pathology*; D019047:Phantoms, Imaging; D061088:Photoacoustic Techniques / Q000379:methods*; D011300:Preoperative Care
chemical_list: D008543:Melanins; D007208:Indocyanine Green