title: A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye.
abstract: BACKGROUND
  Sentinel node (SN) biopsy in penile cancer is typically performed using a combination of radiocolloid and blue dye. Recently, the hybrid radioactive and fluorescent tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was developed to combine the beneficial properties of both radio-guidance and fluorescence imaging.
  
  
  OBJECTIVE
  To explore the added value of SN biopsy using ICG-(99m)Tc-nanocolloid in patients with penile carcinoma.
  
  
  METHODS
  Sixty-five patients with penile squamous cell carcinoma were prospectively included (January 2011 to December 2012). Preoperative SN mapping was performed using lymphoscintigraphy and single-proton emission computed tomography supplemented with computed tomography (SPECT/CT) after peritumoural injection of ICG-(99m)Tc-nanocolloid. During surgery, SNs were initially approached using a gamma probe, followed by patent blue dye and/or fluorescence imaging. A portable gamma camera was used to confirm excision of all SNs.
  
  
  METHODS
  Patients underwent SN biopsy of the cN0 groin and treatment of the primary tumour.
  
  
  METHODS
  The number and location of preoperatively identified SNs were documented. Intraoperative SN identification rates using radio- and/or fluorescence guidance were assessed and compared with blue dye. Statistical evaluation was performed using a two-sample test for equality of proportions with continuity correction.
  
  
  CONCLUSIONS
  Preoperative imaging after injection of ICG-(99m)Tc-nanocolloid enabled SN identification in all patients (a total of 183 SNs dispersed over 119 groins). Intraoperatively, all SNs identified by preoperative SN mapping were localised using combined radio-, fluorescence-, and blue dye guidance. Fluorescence imaging enabled visualisation of 96.8% of SNs, while only 55.7% was stained by blue dye (p<0.0001). The tissue penetration of the fluorescent signal, and the rapid flow of blue dye limited the detection sensitivity. A tumour-positive SN was found in seven patients.
  
  
  CONCLUSIONS
  ICG-(99m)Tc-nanocolloid allows for both preoperative SN mapping and combined radio- and fluorescence-guided SN biopsy in penile carcinoma patients and significantly improves optical SN detection compared with blue dye.
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Radiology, Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: o.r.brouwer@lumc.nl.
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Brouwer
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Radiology, Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nynke S
authors.initials: NS
authors.lastname: van den Berg
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Radiology, Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Mathéron
authors.affiliation: Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Henk G
authors.initials: HG
authors.lastname: van der Poel
authors.affiliation: Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Bas W
authors.initials: BW
authors.lastname: van Rhijn
authors.affiliation: Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Axel
authors.initials: A
authors.lastname: Bex
authors.affiliation: Department of Biostatistics, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Radiology, Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Renato A
authors.initials: RA
authors.lastname: Valdés Olmos
authors.affiliation: Department of Radiology, Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands; Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Fijs W B
authors.initials: FW
authors.lastname: van Leeuwen
authors.affiliation: Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Simon
authors.initials: S
authors.lastname: Horenblas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology*; D004396:Coloring Agents; D005453:Fluorescence; D006801:Humans; D007208:Indocyanine Green; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010412:Penile Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D011446:Prospective Studies; D011849:Radioactive Tracers; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D013668:Technetium Tc 99m Aggregated Albumin
chemical_list: D004396:Coloring Agents; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C083602:technetium Tc 99m nanocolloid; D007208:Indocyanine Green
keywords: Fluorescence; Hybrid; Image-guided surgery; Penile cancer; SPECT/CT; Sentinel node biopsy