High Impact Manuscript: Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection

This article was approved by the Editor-in-Chief for inclusion in Neurosurgery’s High Impact Manuscript Services Program. The HIMS program is a combination of rapid review, author incentives, and promotion. To learn more about how to submit your manuscript for possible inclusion and receive benefits such as social media distribution, press coverage, cover art consideration, an invitation to present your work at the CNS Annual Meeting, waiver of publication charges and other exciting incentives, click here.

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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.

Click here for free full text access to Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection by Kuo et al.

Video Abstract

This article was approved by the Editor-in-Chief for inclusion in Neurosurgery’s High Impact Manuscript Services Program. The HIMS program is a combination of rapid review, author incentives, and promotion. To learn more about how to submit your manuscript for possible inclusion and receive benefits such as social media distribution, press coverage, cover art consideration, an invitation to present your work at the CNS Annual Meeting, waiver of publication charges and other exciting incentives, click here.