In vivo visualization of GL261-luc2 mouse glioma cells by use of Alexa Fluor-labeled TRP-2 antibodies.
OBJECTIVE
For patients with glioblastoma multiforme, median survival time is approximately 14 months. Longer progression-free and overall survival times correlate with gross-total resection of tumor. The ability to identify tumor cells intraoperatively could result in an increased percentage of tumor resected and thus increased patient survival times. Available labeling methods rely on metabolic activity of tumor cells; thus, they are more robust in high-grade tumors, and their utility in low-grade tumors and metastatic tumors is not clear. The authors demonstrate intraoperative identification of tumor cells by using labeled tumor-specific antibodies.


METHODS
GL261 mouse glioma cells exhibit high expression of a membrane-bound protein called second tyrosinase-related protein (TRP-2). The authors used these cells to establish an intracranial, immunocompetent model of malignant glioma. Antibodies to TRP-2 were labeled by using Alexa Fluor 488 fluorescent dye and injected into the tail vein of albino C57BL/6 mice. After 24 hours, a craniotomy was performed and the tissue was examined in vivo by using an Optiscan 5.1 handheld portable confocal fiber-optic microscope. Tissue was examined ex vivo by using a Pascal 5 scanning confocal microscope.


RESULTS
Labeled tumor cells were visible in vivo and ex vivo under the respective microscopes.


CONCLUSIONS
Fluorescently labeled tumor-specific antibodies are capable of binding and identifying tumor cells in vivo, accurately and specifically. The development of labeled markers for the identification of brain tumors will facilitate the use of intraoperative fluorescence microscopy as a tool for increasing the extent of resection of a broad variety of intracranial tumors.
Neuro-Oncology Research.
Kathryn E
KE
Fenton
Nikolay L
NL
Martirosyan
Mohammed G
MG
Abdelwahab
Stephen W
SW
Coons
Mark C
MC
Preul
Adrienne C
AC
Scheck
D000818:Animals; D000912:Antibodies, Neoplasm / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000378:metabolism; D005910:Glioma / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods
D000912:Antibodies, Neoplasm; D005456:Fluorescent Dyes; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase