Fluorescence guided surgery and tracer-dose, fact or fiction?

IntroductionFluorescence guidance is an upcoming methodology to improve surgical accuracy. Challenging herein is the identification of the minimum dose at which the tracer can be detected with a clinical-grade fluorescence camera. Using a hybrid tracer such as indocyanine green (ICG)-99mTc-nanocolloid, it has become possible to determine the accumulation of tracer and correlate this to intraoperative fluorescence-based identification rates. In the current study, we determined the lower detection limit of tracer at which intraoperative fluorescence guidance was still feasible.MethodsSize exclusion chromatography (SEC) provided a laboratory set-up to analyze the chemical content and to simulate the migratory behavior of ICG-nanocolloid in tissue. Tracer accumulation and intraoperative fluorescence detection findings were derived from a retrospective analysis of 20 head-and-neck melanoma patients, 40 penile and 20 prostate cancer patients scheduled for sentinel node (SN) biopsy using ICG-99mTc-nanocolloid. In these patients, following tracer injection, single photon emission computed tomography fused with computed tomography (SPECT/CT) was used to identify the SN(s). The percentage injected dose (% ID), the amount of ICG (in nmol), and the concentration of ICG in the SNs (in μM) was assessed for SNs detected on SPECT/CT and correlated with the intraoperative fluorescence imaging findings.ResultsSEC determined that in the hybrid tracer formulation, 41 % (standard deviation: 12 %) of ICG was present in nanocolloid-bound form. In the SNs detected using fluorescence guidance a median of 0.88 % ID was present, compared to a median of 0.25 % ID in the non-fluorescent SNs (p-value < 0.001). The % ID values could be correlated to the amount ICG in a SN (range: 0.003–10.8 nmol) and the concentration of ICG in a SN (range: 0.006–64.6 μM).DiscussionThe ability to provide intraoperative fluorescence guidance is dependent on the amount and concentration of the fluorescent dye accumulated in the lesion(s) of interest. Our findings indicate that intraoperative fluorescence detection with ICG is possible above a μM concentration.

[1]  Eben L. Rosenthal,et al.  In Vivo Fluorescence Immunohistochemistry: Localization of Fluorescently Labeled Cetuximab in Squamous Cell Carcinomas , 2015, Scientific Reports.

[2]  M. Kusano,et al.  ICG fluorescence imaging and navigation surgery , 2016 .

[3]  Michael Lassmann,et al.  Biodistribution and Radiation Dosimetry for the Chemokine Receptor CXCR4-Targeting Probe 68Ga-Pentixafor , 2015, The Journal of Nuclear Medicine.

[4]  P. Low,et al.  Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results , 2011, Nature Medicine.

[5]  A. Hemal,et al.  Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients. , 2014, European urology.

[6]  R. Swindell,et al.  Magnetic resonance appearance of normal inguinal nodes. , 2000, Clinical radiology.

[7]  F. V. van Leeuwen,et al.  Fluorescence guidance during radical prostatectomy. , 2014, European urology.

[8]  B. Harrison,et al.  Systematic review of intravenous methylene blue in parathyroid surgery , 2012, The British journal of surgery.

[9]  G. Luker,et al.  Targeted non-covalent self-assembled nanoparticles based on human serum albumin. , 2012, Biomaterials.

[10]  Carlo Cavedon,et al.  First human Cerenkography , 2013, Journal of biomedical optics.

[11]  Siavash Yazdanfar,et al.  Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met , 2015, Nature Medicine.

[12]  A. V. van Erkel,et al.  Luminescence-based Imaging Approaches in the Field of Interventional Molecular Imaging. , 2015, Radiology.

[13]  Tushar Tewari,et al.  Microdosing: Concept, Application and Relevance , 2010, Perspectives in clinical research.

[14]  M. Ying,et al.  Three-dimensional ultrasound measurement of cervical lymph node volume. , 2009, The British journal of radiology.

[15]  B. K. Mishra,et al.  Cyanines during the 1990s: A Review. , 2000, Chemical Reviews.

[16]  Lenka Vermeeren,et al.  Optimizing the colloid particle concentration for improved preoperative and intraoperative image-guided detection of sentinel nodes in prostate cancer , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[17]  John F. Thompson,et al.  Patterns of lymphatic drainage from the skin in patients with melanoma. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[18]  N. S. van den Berg,et al.  Optimisation of fluorescence guidance during robot-assisted laparoscopic sentinel node biopsy for prostate cancer. , 2014, European urology.

[19]  R. V. Valdés Olmos,et al.  Tracer-cocktail injections for combined pre- and intraoperative multimodal imaging of lymph nodes in a spontaneous mouse prostate tumor model. , 2011, Journal of biomedical optics.

[20]  C. Colyer,et al.  Non-covalent labeling of human serum albumin with indocyanine green: a study by capillary electrophoresis with diode laser-induced fluorescence detection. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[21]  N. S. van den Berg,et al.  A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye. , 2012, European urology.

[22]  G. Robertson,et al.  Sentinel node in head and neck cancer: Use of size criterion to upstage the no neck in head and neck squamous cell carcinoma , 2007, Head & neck.

[23]  Renato A. Valdés Olmos,et al.  SPECT/CT and a Portable γ-Camera for Image-Guided Laparoscopic Sentinel Node Biopsy in Testicular Cancer , 2011, The Journal of Nuclear Medicine.

[24]  N. S. van den Berg,et al.  Multimodal Surgical Guidance during Sentinel Node Biopsy for Melanoma: Combined Gamma Tracing and Fluorescence Imaging of the Sentinel Node through Use of the Hybrid Tracer Indocyanine Green-(99m)Tc-Nanocolloid. , 2015, Radiology.

[25]  A. Fischman,et al.  Comparison of standard-dose vs low-dose attenuation correction CT on image quality and positron emission tomographic attenuation correction. , 2008, Journal of the American College of Radiology : JACR.

[26]  Jan Grimm,et al.  Clinical Cerenkov Luminescence Imaging of 18F-FDG , 2014, The Journal of Nuclear Medicine.

[27]  Michael Hünerbein,et al.  Current trends and emerging future of indocyanine green usage in surgery and oncology , 2011, Cancer.

[28]  A. Norman,et al.  Normal pelvic lymph nodes: evaluation with CT after bipedal lymphangiography. , 1995, Radiology.