5-Aminolevulinic Acid Tumor Paint and Photodynamic Therapy for Chordoma: An In Vitro Study

Author(s): Shachar Kenan, Haixiang Liang, Ryan Nixon, Howard J. Goodman, Daniel A. Grande, Adam S. Levin

Wide resections of chordoma tumors are challenging for many reasons, primarily due to a lack of intraoperative visualization, leading to unacceptably high recurrence rates. Known techniques using five-aminolevulinic acid (5-ALA) for tumor paint and photodynamic therapy (PDT) may improve outcomes but have not been well described for chordomas. This study aimed to analyze chordoma cell response to 5-ALA tumor paint and PDT in vitro. Tumor paint: Human chordoma cells (MUG-Chor1) were cocultured with green fluorescence protein (GFP) rat adipose-derived stromal cells (ADS) with subsequent observation after 5-ALA exposure, visualized using filters to show GFP cells in green and 5-ALA positive cells in red color. PDT: MUG-Chor1 and ADS cells were exposed separately to 5-ALA followed by PDT treatment using 405-nm excitation and emission at 603-738-nm. Time-lapse images of live cells were captured every second for 15 minutes and then visualized sequentially at 50× speed. The tumor paint arm of the study successfully demonstrated selective red chordoma fluorescence, a finding which may facilitate visualization of a malignancy juxtaposed to surrounding benign healthy tissue. The second arm of the study, PDT, demonstrated selective chordoma cellular death, clearly evidenced by swelling and vesicle formation in contrast to the ADS control. The results of these experiments demonstrate the effective in vitro application of 5-ALA tumor paint and PDT on chordoma cells, documented visually using time-lapse photography. 5-ALA, with its double-edged applications of selective tumor identification and kill, may lead to transformative change in the management of soft tissue sarcomas.