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Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection. | LitMetric

Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection.

Neurosurgery

*Department of Neurological Surgery, ‡Cellular and Molecular Biology Training Program, ¶Department of Radiology, ‖Department Medical Physics, and #Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; §Cellectar Biosciences, Inc, Madison, Wisconsin; **Department of Surgery, National University of Singapore, Singapore.

Published: February 2015

AI Article Synopsis

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343207PMC
http://dx.doi.org/10.1227/NEU.0000000000000622DOI Listing

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