title: First-in-human evaluation of a hybrid modality that allows combined radio- and (near-infrared) fluorescence tracing during surgery.
abstract: OBJECTIVE
  The clinical introduction of the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid, composed of a radioactive and a near-infrared (NIR) fluorescence component, has created the need for surgical (imaging) modalities that allow for simultaneous detection of both signals. This study describes the first-in-human use of a prototype opto-nuclear probe during sentinel node (SN) biopsy using ICG-(99m)Tc-nanocolloid.
  
  
  METHODS
  To allow for fluorescence tracing, a derivative of the conventional gamma probe technology was generated in which two optical fibers were integrated to allow for excitation (785 nm) and emission signal collection (> 810 nm). The ability of this opto-nuclear probe to detect the fluorescence signal of the hybrid tracer ICG-(99m)Tc-nanocolloid was firstly determined ex vivo in (non)SNs samples obtained from 41 patients who underwent hybrid tracer-based SN biopsy in the head and neck or urogenital area. In an in vivo proof-of-concept study in nine of these 41 patients, SNs were localized using combined gamma and fluorescence tracing with the opto-nuclear probe. Fluorescence tracing was performed in a similar manner as gamma tracing and under ambient light conditions.
  
  
  RESULTS
  Ex vivo, the gamma tracing option of the opto-nuclear probe correctly identified the SN in all 150 evaluated (non)SN samples. Ex vivo fluorescence tracing in the low-sensitivity mode correctly identified 71.7% of the samples. This increased to 98.9% when fluorescence tracing was performed in the high-sensitivity mode. In vivo fluorescence tracing (high-sensitivity mode) accurately identified the SNs in all nine patients (20 SNs evaluated; 100%).
  
  
  CONCLUSIONS
  This study demonstrates the first-in-human evaluation of a hybrid modality capable of detecting both gamma and fluorescence signals during a surgical procedure. Fluorescence tracing could be performed in ambient light.
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, C2-S zone, PO Box 9600, 2300 RC, Leiden, The Netherlands.|Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Nynke S
authors.initials: NS
authors.lastname: van den Berg
authors.affiliation: Eurorad S.A., 2 Rue Ettore Bugatti, 67201, Eckbolsheim, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Simon
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, C2-S zone, PO Box 9600, 2300 RC, Leiden, The Netherlands.|Department of Nuclear Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Gijs H
authors.initials: GH
authors.lastname: Kleinjan
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, C2-S zone, PO Box 9600, 2300 RC, Leiden, The Netherlands.|Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Engelen
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, C2-S zone, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Anton
authors.initials: A
authors.lastname: Bunschoten
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, C2-S zone, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
authors.affiliation: Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Tijink
authors.affiliation: Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Simon
authors.initials: S
authors.lastname: Horenblas
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Jacques
authors.initials: J
authors.lastname: Chambron
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, C2-S zone, PO Box 9600, 2300 RC, Leiden, The Netherlands. F.W.B.van_Leeuwen@lumc.nl.|Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. F.W.B.van_Leeuwen@lumc.nl.|Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. F.W.B.van_Leeuwen@lumc.nl.
authors.forename: Fijs W B
authors.initials: FWB
authors.lastname: van Leeuwen
mesh_terms: D000368:Aged; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry*; D007259:Infrared Rays; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D055100:Optical Fibers; D019047:Phantoms, Imaging; D011849:Radioactive Tracers; D021701:Sentinel Lymph Node Biopsy; D025321:Surgery, Computer-Assisted / Q000295:instrumentation / Q000379:methods*; D013668:Technetium Tc 99m Aggregated Albumin / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D011849:Radioactive Tracers; D013668:Technetium Tc 99m Aggregated Albumin; C083602:technetium Tc 99m nanocolloid; D007208:Indocyanine Green