A folate receptor-specific activatable probe for near-infrared fluorescence imaging of ovarian cancer

Lee, Hawon; Kim, Jisu; Kim, Hyun‐Jin; Kim, Youngmi; Choi, Yongdoo

doi:10.1039/c4cc02301c

Cited by 46 publications

(33 citation statements)

References 20 publications

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“…Increasing evidence shows that folate receptors are overexpressed on the surface of many cancer cells, and targeting these receptors through covalently tethering a folic acid moiety to an effector domain has been a longstanding concept. Using this folic acid dually as a quenching moiety and homing beacon, Lee et al 31 explored the targeting of ovarian cancer using an activatable probe that remains quenched through intramolecular charge transfer between the effector domain, dye ATTO655, and folic acid (Figure 11). The isolating linker in this case is uniquely constructed to cleave in the presence of cathepsin B.…”

Section: Activatable Nir Imaging Agentsmentioning

confidence: 99%

“…(A) The final probe used in (B) cellular experiments in SKOV3 cells expressing the folic acid receptor without a folic acid receptor inhibitor present and with a folate acid receptor inhibitor present and (C) in vivo data showing rapid clearance of the free dye after 30 min and high SBR imaging of the tumor tissue when using the FSA probe. Reproduced with permission from ref 31. Copyright 2014 Royal Society of Chemistry.…”

Section: Figurementioning

confidence: 99%

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Tissue-Specific Near-Infrared Fluorescence Imaging

et al. 2016

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CONSPECTUS Near-infrared (NIR) fluorescence light has been widely utilized in clinical imaging by providing surgeons highly specific images of target tissue. The “NIR window” from 650 to 900 nm is especially useful due to several special features such as minimal autofluorescence and absorption of biomolecules in tissue, as well as low light scattering. Compared with visible wavelengths, NIR fluorescence light is invisible, thus allowing highly sensitivity real-time image guidance in human surgery without changing the surgical field. The benefit of using NIR fluorescence light as a clinical imaging technology can be attributed to its molecular fluorescence as an exogenous contrast agent. Indeed, whole body preoperative imaging of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) remains important in diagnostic utility, but they lack the efficacy of innocuous and targeted NIR fluorophores to simultaneously facilitate the real-time delineation of diseased tissue while preserving vital tissues. Admittedly, NIR imaging technology has been slow to enter clinical use mostly due to the late-coming development of truly breakthrough contrast agents for use with current imaging systems. Therefore, clearly defining the physical margins of tumorous tissue remains of paramount importance in bioimaging and targeted therapy. An equally noteworthy yet less researched goal is the ability to outline healthy vital tissues that should be carefully navigated without transection during the intraoperative surgery. Both of these paths require optimizing a gauntlet of design considerations to obtain not only an effective imaging agent in the NIR window but also high molecular brightness, water solubility, biocompatibility, and tissue-specific targetability. The imaging community recognizes three strategic approaches which include (1) passive targeting via the EPR effect, (2) active targeting using the innate overall biodistribution of known molecules, and (3) activatable targeting through an internal stimulus, which turns on fluorescence from an off state. Recent advances in nanomedicine and bioimaging offer much needed promise toward fulfilling these stringent requirements as we develop a successful catalog of targeted contrast agents for illuminating both tumors and vital tissues in the same surgical space by employing spectrally distinct fluorophores in real time. These tissue-specific contrast agents can be versatile arsenals to physicians for real-time intraoperative navigation as well as image-guided targeted therapy. There is a versatile library of tissue-specific fluorophores available in the literature, with many discussed herein, which offers clinicians an array of possibilities that will undoubtedly improve intraoperative success and long-term postoperation prognosis.

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Section: Activatable Nir Imaging Agentsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Tissue-Specific Near-Infrared Fluorescence Imaging

et al. 2016

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“…Choi et al developed a folate receptor-specific probe (23) for NIR fluorescence imaging of ovarian tumors in vivo. 97 The probe was synthesized by conjugating folate to the ATTO655 fluorophore via a cathepsin B-cleavable peptide spacer. The fluorescence emission from the fluorophore was effectively quenched by folate.…”

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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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“…Preclinical advances in near-infrared fluorescence imaging have been made as well. To wit, Terwisscha van Scheltinga et al targeted HER2 and vascular endothelial growth factor using IRDye 800CW–labeled monoclonal antibodies (34), whereas Lee et al targeted folate receptor-α with an activatable near-infrared fluorescence probe that emits fluorescence only after cleavage of a linker by the lysosomal enzyme cathepsin B (35). …”

Section: Optical Imagingmentioning

confidence: 99%

Molecular Imaging of Ovarian Cancer

et al. 2016

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Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer.

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A folate receptor-specific activatable probe for near-infrared fluorescence imaging of ovarian cancer

Cited by 46 publications

References 20 publications

Tissue-Specific Near-Infrared Fluorescence Imaging

Tissue-Specific Near-Infrared Fluorescence Imaging

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

Molecular Imaging of Ovarian Cancer

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