Chemical Re-engineering of Chlorotoxin Improves Bioconjugation Properties for Tumor Imaging and Targeted Therapy

Akcan, Muharrem; Stroud, Mark R.; Hansen, Stacey; Clark, Richard J.; Daly, Norelle L.; Craik, David J.; Olson, James M.

doi:10.1021/jm101018r

Cited by 85 publications

(94 citation statements)

References 31 publications

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“…The Cy5.5 conjugation resulted in a mixture of mono-, di-, and tri-labeled probes because CTX contains three lysine residues. 155 Substitution of the lysines at positions 15 and 23 with either alanine or arginine would result in a Lys27 monolabeled peptide that retained the stability and in vivo half-life properties of CTX.…”

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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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“…CTX was developed into an optical imaging agent by the Olson group through conjugation with a Cy5.5 NIR fluorophore (Veiseh, et al, 2007). Because CTX contains three lysine residues, Cy5.5 conjugation resulted in a mixture of mono-, di-, and tri-labeled probes (Akcan, et al, 2011). This posed a regulatory and manufacturing problem for translation to the clinic and required re-engineering of the CTX peptide to replace Lys15 and Lys23 with alanine or arginine (Akcan, et al, 2011).…”

Section: Affinity-based Probesmentioning

confidence: 99%

A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application

Garland

Yim

Bogyo

2016

Cell Chemical Biology

223

188

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The Precision Medicine Initiative aims to use advances in basic and clinical research to develop therapeutics that selectively target and kill cancer cells. Under the same doctrine of precision medicine, there is an equally important need to visualize these diseased cells to enable diagnosis, facilitate surgical resection and monitor therapeutic response. Therefore, there is a great opportunity for chemists to develop chemically tractable probes that can image cancer in vivo. This review focuses on recent advances in the development of optical probes as well as their current and future applications in the clinical management of cancer. The progress in probe development described here suggests that optical imaging is an important and rapidly developing field of study that encourages continued collaboration between chemists, biologists and clinicians to further refine these tools for interventional surgical imaging, as well as for diagnostic and therapeutic applications.

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“…Other promising candidates for target biomolecules for cancer imaging include the prostatespecific membrane antigen (PSMA), 57,58 cycloxygenase-2 (COX-2) 59,60 and chlorotoxin venom (CTX). 61,62 A preclinical study 63 and Phase I clinical trial of the NIR optical imaging agent for CTX have been completed, and its safety and promising results were demonstrated (NCT02496065).…”

Section: Biomedical Analysis By Optical Imagingmentioning

confidence: 99%

In Vivo Molecular Imaging for Biomedical Analysis and Therapies

Ogawa

Takakura

2018

ANAL. SCI.

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In vivo molecular imaging is a powerful tool to analyze the human body. Precision medicine is receiving high attention these days, and molecular imaging plays an important role as companion diagnostics in precision medicine. Nuclear imaging with PET or SPECT and optical imaging technologies are used for in vivo molecular imaging. Nuclear imaging is superior for quantitative imaging, and whole-body analysis is possible even for humans. Optical imaging is superior due to its ease of use, and highly targeted specific imaging is possible with activatable agents. However, with optical imaging using fluorescence, it is difficult to obtain a signal from deep tissue and quantitation is difficult due to the attenuation and scattering of the fluorescent signal. Recently, to overcome these issues, optoacoustic imaging has been used in in vivo imaging. In this article, we review in vivo molecular imaging with nuclear and optical imaging and discuss their utility for precision medicine.

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Chemical Re-engineering of Chlorotoxin Improves Bioconjugation Properties for Tumor Imaging and Targeted Therapy

Cited by 85 publications

References 31 publications

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application

In Vivo Molecular Imaging for Biomedical Analysis and Therapies

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