Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection

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

doi:10.1227/neu.0000000000000622

Cited by 57 publications

(66 citation statements)

References 43 publications

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“…122,123 Kuo et al developed two APC-based cancer-selective fluorescent probes CLR1501 (32) and CLR1502 (33) for discriminating tumors from normal brain tissue in fluorescence-guided glioma surgery. 123,124 These two probes provided high tumorto-normal brain contrast in fluorescence discrimination with glioblastoma multiforme and glioblastoma stem cell-derived xenografts in mouse models. Moreover, 33 showed a superior tumor-to-brain fluorescence ratio compared with 5-aminolevulinic acid, which is the current standard for fluorescence-guided neurosurgery.…”

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confidence: 99%

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

et al. 2017

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Surgical resection of solid tumors is currently the gold standard and preferred therapeutic strategy for cancer. Chemotherapy drugs also make a significant contribution by inhibiting the rapid growth of tumor cells and these two approaches are often combined to enhance treatment efficacy. However, surgery and chemotherapy inevitably lead to severe side effects and high systemic toxicity, which in turn results in poor prognosis. Precision medicine has promoted the development of treatment modalities that are developed to specifically target and kill tumor cells. Advances in in vivo medical imaging for visualizing tumor lesions can aid diagnosis, facilitate surgical resection, investigate therapeutic efficacy, and improve prognosis. In particular, the modality of fluorescence imaging has high specificity and sensitivity and has been utilized for medical imaging. Therefore, there are great opportunities for chemists and physicians to conceive, synthesize, and exploit new chemical probes that can image tumors and release chemotherapy drugs in vivo. This review focuses on small molecular ligand-targeted fluorescent imaging probes and fluorescent theranostics, including their design strategies and applications in clinical tumor treatment. The progress in chemical probes described here suggests that fluorescence imaging is a vital and rapidly developing field for interventional surgical imaging, as well as tumor diagnosis and therapy.

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confidence: 99%

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

et al. 2017

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“…19,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] The long-term interest in the intraoperative NIR fluorescence visualization is driven by the development of new agents capable of improved delineation of brain tumor margins. Examples of dyes include various derivatives of NIR fluorescent dye currently undergoing preclinical or clinical evaluations, such as BLZ-100, a chlorotoxin-ICG conjugate; 36,37 CLR1502, an alkylphopholine derivative of a cyanine dye; 40,41 anti-EGFR antibody fragments conjugated to IRDye 800 CW; 42,43 and others. 44 We believe that the ability to simultaneously visualize the surgical field and contrast agent within the augmented microscope will enable broad implementation of image guidance in surgeries.…”

Section: Discussionmentioning

confidence: 99%

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images

et al. 2015

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Abstract. Intraoperative applications of near-infrared (NIR) fluorescent contrast agents can be aided by instrumentation capable of merging the view of surgical field with that of NIR fluorescence. We demonstrate augmented microscopy, an intraoperative imaging technique in which bright-field (real) and electronically processed NIR fluorescence (synthetic) images are merged within the optical path of a stereomicroscope. Under luminance of 100,000 lx, representing typical illumination of the surgical field, the augmented microscope detects 189 nM concentration of indocyanine green and produces a composite of the real and synthetic images within the eyepiece of the microscope at 20 fps. Augmentation described here can be implemented as an add-on module to visualize NIR contrast agents, laser beams, or various types of electronic data within the surgical microscopes commonly used in neurosurgical, cerebrovascular, otolaryngological, and ophthalmic procedures.

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“…Unconjugated free FITC was removed by cation exchange Capto MMC mixed-mode chromatography in 20 mM phosphate at pH 6.5 and anion exchange Capto adhere mixed-mode chromatography in 50 mM Tris-HCl at pH 8. 6. In both cases, FITC-labeled IgG bound to the column, while free negatively charged FITC flowed through the Capto MMC column.…”

Section: Fitc Labelingmentioning

confidence: 97%

“…Targeted delivery of anti-cancer drugs and radioactive isotopes using cancer-specific antibodies, lipids and other compounds is currently being studied extensively as next generation biopharmaceuticals or diagnostic reagents (1)(2)(3)(4)(5)(6)(7)(8). When antibodies and drugs are combined to make antibody-drug conjugates (ADC), also known as armed antibodies, the conjugation of what is often a hydrophobic drug to the antibody has the potential to alter the chemical and physical properties of the ADC.…”

Section: Introductionmentioning

confidence: 99%