Abstract
Purpose
Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results.
Procedures
In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin).
Results
We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650–680 nm) and near-infrared (~740–800 nm) regions.
Conclusions
This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.
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References
Brand C, Abdel-Atti D, Zhang Y et al (2014) In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent. Bioconjug Chem 25:1323–1330
Kimura RH, Cheng Z, Gambhir SS, Cochran JR (2009) Engineered knottin peptides: a new class of agents for imaging integrin expression in living subjects. Cancer Res 69:2435–2442
Seibold U, Wangler B, Schirrmacher R, Wangler C (2014) Bimodal imaging probes for combined PET and OI: recent developments and future directions for hybrid agent development. BioMed Research Int 2014:153741
Press OW, Shan D, HowellClark J et al (1996) Comparative metabolism and retention of iodine-125, yttrium-90, and indium-111 radioimmunoconjugates by cancer cells. Cancer Res 56:2123–2129
Ferl GZ, Kenanova V, Wu AM, DiStefano JJ (2006) A two-tiered physiologically based model for dually labeled single-chain Fv-Fc antibody fragments. Mol Cancer Ther 5(6):1550–1558
Griffiths GL, Govindan SV, Sgouros G et al (1999) Cytotoxicity with Auger electron-emitting radionuclides delivered by antibodies. Int J Cancer J Int Du Cancer 81:985–992
Knowles SM, Zettlitz KA, Tavare R et al (2014) Quantitative immunoPET of prostate cancer xenografts with 89Zr- and 124I-labeled anti-PSCA A11 minibody. J Nucl Med Off Publ Soc Nucl Med 55:452–459
Hamzei N, Samkoe KS, Elliott JT et al (2014) Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors. Austin J Biomed Eng 1(1)
Thurber GM, Wittrup KD (2012) A mechanistic compartmental model for total antibody uptake in tumors. J Theor Biol 314:57–68
Williams SP (2012) Tissue distribution studies of protein therapeutics using molecular probes: molecular imaging. AAPS J 14:389–399
Bhatnagar S, Deschenes E, Liao J et al (2014) Multichannel imaging to quantify four classes of pharmacokinetic distribution in tumors. J Pharm Sci 103:3276–3286
Gioux S, Choi HS, Frangioni JV (2010) Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation. Mol Imaging 9:237–255
Laughney AM, Kim E, Sprachman MM et al (2014) Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin. Sci Transl Med 6:261ra152
Thurber GM, Yang KS, Reiner T et al (2013) Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo. Nat Commun 4:1504
Thurber GM, Reiner T, Yang KS et al (2014) Effect of small-molecule modification on single-cell pharmacokinetics of PARP inhibitors. Mol Cancer Ther 13:986–995
Jose J, Burgess K (2006) Benzophenoxazine-based fluorescent dyes for labeling biomolecules. Tetrahedron 62:11021–11037
Kessel D (1990) Photodynamic therapy of neoplastic disease. CRC Press, Inc, Boca Raton
Arden-Jacob J, Frantzeskos J, Kemnitzer NU et al (2001) New fluorescent markers for the red region. Spectrochim Acta A Mol Biomol Spectrosc 57:2271–2283
Luo FR, Yang Z, Dong H et al (2005) Correlation of pharmacokinetics with the antitumor activity of cetuximab in nude mice bearing the GEO human colon carcinoma xenograft. Cancer Chemother Pharmacol 56:455–464
Devaraj NK, Upadhyay R, Hatin JB et al (2009) Fast and sensitive pretargeted labeling of cancer cells through a tetrazine/trans-cyclooctene cycloaddition. Angew Chem Int Ed 48:7013–7016
Conner KP, Rock BM, Kwon GK et al (2014) Evaluation of near infrared fluorescent labeling of monoclonal antibodies as a tool for tissue distribution. Drug Metab Dispos Biol Fate Chem 42:1906–1913
Yang X, Shi C, Tong R et al (2010) Near IR heptamethine cyanine dye-mediated cancer imaging. Clin Cancer Res Off J Am Assoc Cancer Res 16:2833–2844
Shapiro AB, Corder AB, Ling V (1997) P-Glycoprotein-mediated Hoechst 33342 transport out of the lipid bilayer. Eur J Biochem/FEBS 250:115–121
Thorpe SR, Baynes JW, Chroneos ZC (1993) The design and application of residualizing labels for studies of protein catabolism. FASEB J 7:399–405
Thurber GM, Weissleder R (2011) A systems approach for tumor pharmacokinetics. PLoS One 6(9):e24696
Acknowledgments
We thank the University of Michigan Biointerfaces Institute for use of the plate reader. Funding was provided by NIH grant 1K01DK093766 (GMT).
Conflict of Interest
The authors declare that they have no conflict of interest.
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Cilliers, C., Liao, J., Atangcho, L. et al. Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents. Mol Imaging Biol 17, 757–762 (2015). https://doi.org/10.1007/s11307-015-0851-7
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DOI: https://doi.org/10.1007/s11307-015-0851-7