Background
5-ALA induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of two novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near-infrared), in a proof-of-principle study for fluorescence-guided glioma surgery.
Objective
To demonstrate CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and compare tumor (T) to normal brain (N) fluorescence ratios with 5-ALA.
Methods
CLR1501, CLR1502, 5-ALA were administered to mice with MRI-verified orthotopic U251 GBM and GSC-derived xenografts. Harvested brains were imaged using confocal microscopy (CLR1501), IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed.
Results
Excitation/emission peaks are 500/517nm for CLR1501, and 760/778nm for CLR1502. The observed T:N ratio of CLR1502 (9.28±1.08) was significantly higher (p<0.01) than CLR1501 (3.51±0.44 on confocal imaging; 7.23±1.63 on IVIS imaging) and 5-ALA (4.81±0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high contrast tumor visualization compatible with surgical applications.
Conclusion
CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor to brain fluorescence ratio similar to 5-ALA, whereas CLR1502 has a superior tumor to brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery.