TY - JOUR
T1 - A Fluorescent Probe for Rapid, High-Contrast Visualization of Folate-Receptor-Expressing Tumors In Vivo
AU - Numasawa, Koji
AU - Hanaoka, Kenjiro
AU - Saito, Naoko
AU - Yamaguchi, Yoshifumi
AU - Ikeno, Takayuki
AU - Echizen, Honami
AU - Yasunaga, Masahiro
AU - Komatsu, Toru
AU - Ueno, Tasuku
AU - Miura, Masayuki
AU - Nagano, Tetsuo
AU - Urano, Yasuteru
N1 - Funding Information:
This work was supported in part by JSPS KAKENHI Grant Numbers JP18H04609 and JP16H05099 to K.H. and JP26110005 to Y.Y., SENTAN, JST to K.H, and Hoansha Foundation and Daiichi Sankyo Foundation of Life Science to K.H. This work was also supported by a grant JSPS Core-to-Core program, A. Advanced Research Networks and a Grant-in-Aid for Scientific Research on Innovative Areas “Singularity Biology (No.8007)” (JP19H05414 to K.H.) of The Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/4/6
Y1 - 2020/4/6
N2 - Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR-α) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near-infrared (NIR) region (650–900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR-α show high non-specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR-1, utilizing a Si-rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker. This probe exhibits very low background fluorescence and afforded a tumor-to-background ratio (TBR) of up to 83 in FR-expressing tumor-bearing mice within 30 min. Thus, FolateSiR-1 has the potential to contribute to the research in the field of biology and the clinical medicine.
AB - Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR-α) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near-infrared (NIR) region (650–900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR-α show high non-specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR-1, utilizing a Si-rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker. This probe exhibits very low background fluorescence and afforded a tumor-to-background ratio (TBR) of up to 83 in FR-expressing tumor-bearing mice within 30 min. Thus, FolateSiR-1 has the potential to contribute to the research in the field of biology and the clinical medicine.
KW - cancer
KW - chromophores
KW - fluorescent probes
KW - imaging
KW - vitamins
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U2 - 10.1002/anie.201914826
DO - 10.1002/anie.201914826
M3 - Article
C2 - 31984590
AN - SCOPUS:85080050029
SN - 1433-7851
VL - 59
SP - 6015
EP - 6020
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 15
ER -
