We have been investigating the rational design and in vivo applications of target-cell specific activatable probes. Designing these probes based on their photo-chemical (e.g. activation strategy), pharmacological (e.g. biodistribution), and biological (e.g. target specificity) properties has recently allowed the rational design and synthesis of target-cell specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photo-chemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include: self-quenching, homo- and hetero-fluorescence resonance energy transfer (FRET), H-dimer formation and photon-induced electron transfer (PeT). In addition, the repertoire is further expanded by the option for reversibility or irreversibility of the signal emitted using the aforementioned mechanisms. Given the wide range of photochemical mechanisms and properties, target-cell specific activatable probes possess considerable flexibility and can be adapted to specific diagnostic needs. From a translational viewpoint, including considerations of both the clinical value and regulatory approval requirements, several clinically applicable candidates including indocyanine green labeled antibodies or a small molecular gamma-glutamyltransferase activatable probe, which are designed to be used during surgical or endoscopic procedures, have been tested.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011512-03
Application #
9153961
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Mochida, Ai; Ogata, Fusa; Nagaya, Tadanobu et al. (2018) Activatable fluorescent probes in fluorescence-guided surgery: Practical considerations. Bioorg Med Chem 26:925-930
Slooter, Maxime D; Handgraaf, Henricus J M; Boonstra, Martin C et al. (2018) Detecting tumour-positive resection margins after oral cancer surgery by spraying a fluorescent tracer activated by gamma-glutamyltranspeptidase. Oral Oncol 78:1-7
Nakamura, Yuko; Mochida, Ai; Nagaya, Tadanobu et al. (2017) A topically-sprayable, activatable fluorescent and retaining probe, SPiDER-?Gal for detecting cancer: Advantages of anchoring to cellular proteins after activation. Oncotarget 8:39512-39521
Ito, Kimihiro; Mitsunaga, Makoto; Nishimura, Takashi et al. (2017) Near-Infrared Photochemoimmunotherapy by Photoactivatable Bifunctional Antibody-Drug Conjugates Targeting Human Epidermal Growth Factor Receptor 2 Positive Cancer. Bioconjug Chem 28:1458-1469
Shen, Zhenhua; Prasai, Bijeta; Nakamura, Yuko et al. (2017) A Near-Infrared, Wavelength-Shiftable, Turn-on Fluorescent Probe for the Detection and Imaging of Cancer Tumor Cells. ACS Chem Biol 12:1121-1132
Sinharay, Sanhita; Randtke, Edward A; Jones, Kyle M et al. (2017) Noninvasive detection of enzyme activity in tumor models of human ovarian cancer using catalyCEST MRI. Magn Reson Med 77:2005-2014
Nagaya, Tadanobu; Nakamura, Yu A; Choyke, Peter L et al. (2017) Fluorescence-Guided Surgery. Front Oncol 7:314
Nakamura, Yuko; Harada, Toshiko; Nagaya, Tadanobu et al. (2016) Dynamic fluorescent imaging with the activatable probe, ?-glutamyl hydroxymethyl rhodamine green in the detection of peritoneal cancer metastases: Overcoming the problem of dilution when using a sprayable optical probe. Oncotarget :
Radenkovic, Dina; Kobayashi, Hisataka; Remsey-Semmelweis, Ernö et al. (2016) Quantum dot nanoparticle for optimization of breast cancer diagnostics and therapy in a clinical setting. Nanomedicine 12:1581-92
Shinden, Yoshiaki; Ueo, Hiroki; Tobo, Taro et al. (2016) Rapid diagnosis of lymph node metastasis in breast cancer using a new fluorescent method with ?-glutamyl hydroxymethyl rhodamine green. Sci Rep 6:27525

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