Rapid intraoperative visualization of breast lesions with γ-glutamyl hydroxymethyl rhodamine green

  • Sci Rep. 2015 Jul 13:5:12080. doi: 10.1038/srep12080.
Hiroki Ueo  1 ,  Yoshiaki Shinden  2 ,  Taro Tobo  3 ,  Ayako Gamachi  4 ,  Mitsuaki Udo  3 ,  Hisateru Komatsu  5 ,  Sho Nambara  5 ,  Tomoko Saito  5 ,  Masami Ueda  5 ,  Hidenari Hirata  5 ,  Shotaro Sakimura  5 ,  Yuki Takano  5 ,  Ryutaro Uchi  5 ,  Junji Kurashige  5 ,  Sayuri Akiyoshi  5 ,  Tomohiro Iguchi  5 ,  Hidetoshi Eguchi  5 ,  Keishi Sugimachi  5 ,  Yoko Kubota  6 ,  Yuichiro Kai  6 ,  Kenji Shibuta  6 ,  Yuko Kijima  7 ,  Heiji Yoshinaka  7 ,  Shoji Natsugoe  7 ,  Masaki Mori  8 ,  Yoshihiko Maehara  9 ,  Masayo Sakabe  10 ,  Mako Kamiya  10 ,  John W Kakareka  11 ,  Thomas J Pohida  11 ,  Peter L Choyke  12 ,  Hisataka Kobayashi  12 ,  Hiroaki Ueo  6 ,  Yasuteru Urano  13 ,  Koshi Mimori  5
Affiliations
  • 1. 1] Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838 [2] Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582.
  • 2. 1] Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838 [2] Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan.
  • 3. Department of Pathology, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838.
  • 4. Department of Pathology, Oita University, Yufu 879-5593, Japan.
  • 5. Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838.
  • 6. Ueo Breast Surgery Hospital, Oita 870-0854, Japan.
  • 7. Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan.
  • 8. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
  • 9. Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582.
  • 10. Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033.
  • 11. Signal Processing and Instrumentation Section, Division of Computational Bioscience, Center of Information Technology, National Institutes of Health, Bethesda, MD 20892-5624, USA.
  • 12. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1088, USA.
  • 13. 1] Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033 [2] Basic Research Program and CREST, Japan Science and Technology Agency, Tokyo 102-0076, Japan.
Abstract

We previously developed γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) as a tool to detect viable Cancer cells, based on the fact that the enzyme γ-glutamyltranspeptidase (GGT) is overexpressed on membranes of various Cancer cells, but is not expressed in normal tissue. Cleavage of the probe by GGT generates green fluorescence. Here, we examined the feasibility of clinical application of gGlu-HMRG during breast-conserving surgery. We found that fluorescence derived from cleavage of gGlu-HMRG allowed easy discrimination of breast Tumors, even those smaller than 1 mm in size, from normal mammary gland tissues, with 92% sensitivity and 94% specificity, within only 5 min after application. We believe this rapid, low-cost method represents a breakthrough in intraoperative margin assessment during breast-conserving surgery.