Synthesis and Characterization of (89)Zr-Labeled Ultrasmall Nanoparticles.
The ultrasmall nanoparticle AGuIX is a versatile platform that tolerates a range of chemical diversity for theranostic applications. Our previous work showed that AGuIX clears rapidly from normal tissues, while durably accumulating within the tumor microenvironment. On this basis, AGuIX was used to detect tumor tissue with Gd(3+) enhanced MRI and can sensitize tumors to radiation therapy. As we begin the translation of AGuIX, we appreciated that coupling AGuIX to a long-lived radioisotope would help to more completely measure the magnitude and duration of its retention within the tumor microenvironment. Therefore, we developed (89)Zr-DFO-AGuIX. AGuIX was coupled to DFO and then to (89)Zr in ∼99% radiochemical yield. Stability studies showed that (89)Zr-DFO-AGuIX did not dissociate after 72 h. In animals bearing U87MG xenografts, it was detectable at levels above background for 72 h. Lastly, (89)Zr-DFO-AGuIX did not accumulate in inflammatory abscesses in vivo, highlighting its specificity for well vascularized tumors.
Department of Radiology and Biomedical Imaging, University of California San Francisco , 185 Berry Street, Lobby 6, Suite 350, San Francisco, California 94107, United States.
Charles
C
Truillet
Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon , 69622 Villeurbanne cedex, France.
Eloise
E
Thomas
Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon , 69622 Villeurbanne cedex, France.
Francois
F
Lux
Department of Radiology and Biomedical Imaging, University of California San Francisco , 185 Berry Street, Lobby 6, Suite 350, San Francisco, California 94107, United States.
Loc T
LT
Huynh
Institut Lumière Matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon , 69622 Villeurbanne cedex, France.
Olivier
O
Tillement
Department of Radiology and Biomedical Imaging, University of California San Francisco , 185 Berry Street, Lobby 6, Suite 350, San Francisco, California 94107, United States.
Michael J
MJ
Evans
D000818:Animals; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods; D011854:Radiochemistry / Q000379:methods; D019275:Radiopharmaceuticals / Q000737:chemistry*; D015040:Zirconium / Q000737:chemistry*
D019275:Radiopharmaceuticals; D015040:Zirconium
AGuIX; cancer; nanoparticle; positron emission tomography