Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection

Kyle I. Swanson, Paul A. Clark, Ray R. Zhang, Irawati K. Kandela, Mohammed Farhoud, Jamey P. Weichert, John S. Kuo*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    37 Scopus citations

    Abstract

    BACKGROUND: 5-Aminolevulinic acid (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 2 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 that CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and to compare tumor-to-normal brain (T:N) fluorescence ratios with 5-ALA. METHODS: CLR1501, CLR1502, and 5-ALA were administered to mice with magnetic resonance imaging-verified orthotopic U251 glioblastoma multiforme- and glioblastoma stem cell-derived xenografts. Harvested brains were imaged with confocal microscopy (CLR1501), the IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or the Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed. RESULTS: Excitation/emission peaks are 500/517 nm for CLR1501 and 760/778 nm for CLR1502. The observed T:N ratio for CLR1502 (9.28 ± 1.08) was significantly higher (P <.01) than for 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 that of 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.

    Original languageEnglish (US)
    Pages (from-to)115-123
    Number of pages9
    JournalNeurosurgery
    Volume76
    Issue number2
    DOIs
    StatePublished - 2015

    Keywords

    • Glioblastoma
    • Intraoperative imaging
    • Optical imaging
    • Tumor fluorescence

    ASJC Scopus subject areas

    • Surgery
    • Clinical Neurology

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