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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Surg. | doi: 10.3389/fsurg.2019.00045

Delta-aminlevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials

 Joseph F. Georges1, 2*, Amber Valeri1, 2,  Huan Wang3,  Aaron Brooking1, 2, Michael Kakareka1, 2, Steve S. Cho4, Zein Al-Atrache1,  Michael Bamimore1, Hany Osman5,  Joseph Ifrach1,  Si Yu3,  Carrie Li4,  Denah Appelt1, John Y. Lee6, Peter Nakaji7, Kristin Brill8 and Steven Yocom2
  • 1Philadelphia College of Osteopathic Medicine, United States
  • 2Cooper Health System, United States
  • 3Cooper Medical School of Rowan University, United States
  • 4Perelman School of Medicine, University of Pennsylvania, United States
  • 5Wellman Center for Photomedicine, Massachusetts General Hospital, United States
  • 6Hospital of the University of Pennsylvania, United States
  • 7Barrow Neurological Institute (BNI), United States
  • 8MD Anderson Cancer Center at Cooper, United States

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. However, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5-30mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources.

Keywords: protoporphhyrin IX (PpIX), Neurosurgery, 5ALA, Glioma, Endoscopy - methods, fluorescence, Surgery

Received: 15 Apr 2019; Accepted: 17 Jul 2019.

Copyright: © 2019 Georges, Valeri, Wang, Brooking, Kakareka, Cho, Al-Atrache, Bamimore, Osman, Ifrach, Yu, Li, Appelt, Lee, Nakaji, Brill and Yocom. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Joseph F. Georges, Philadelphia College of Osteopathic Medicine, Philadelphia, United States, joseph.georges@asu.edu