title: Image-guided tumor resection using real-time near-infrared fluorescence in a syngeneic rat model of primary breast cancer.
abstract: Tumor involvement of resection margins is found in a large proportion of patients who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging is an experimental technique to visualize cancer cells during surgery. To determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor-free resection margins, a protease-activatable NIR fluorescence probe and an intraoperative camera system were used in the EMR86 orthotopic syngeneic breast cancer rat model. Influence of concentration, timing and number of tumor cells were tested in the MCR86 rat breast cancer cell line. These variables were significantly associated with NIR fluorescence probe activation. Dosing and tumor size were also significantly associated with fluorescence intensity in the EMR86 rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance of tumor resection resulted in a complete resection of 17 out of 17 tumors with minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor-free margin of 0.2 ± 0.2 mm and 1.3 ± 0.6 mm, respectively). Moreover, the technique enabled identification of remnant tumor tissue in the surgical cavity. Histological analysis revealed that the NIR fluorescence signal was highest at the invasive tumor border and in the stromal compartment of the tumor. In conclusion, NIR fluorescence detection of breast tumor margins was successful in a rat model. This study suggests that clinical introduction of intraoperative NIR fluorescence imaging has the potential to increase the number of complete tumor resections in breast cancer patients undergoing breast-conserving surgery.
authors.affiliation: Department of Surgery, Leiden University Medical Center, ZA, Leiden, The Netherlands.
authors.forename: J Sven D
authors.initials: JS
authors.lastname: Mieog
authors.forename: Merlijn
authors.initials: M
authors.lastname: Hutteman
authors.forename: Joost R
authors.initials: JR
authors.lastname: van der Vorst
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.forename: Jouke
authors.initials: J
authors.lastname: Dijkstra
authors.forename: Eric L
authors.initials: EL
authors.lastname: Kaijzel
authors.forename: Frans
authors.initials: F
authors.lastname: Prins
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Vahrmeijer
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000601:surgery*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D008856:Microscopy, Fluorescence; D051381:Rats; D025321:Surgery, Computer-Assisted; D014185:Transplantation, Isogeneic; D023041:Xenograft Model Antitumor Assays