Synthesis and Characterization of ⁸⁹Zr-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 Gd³⁺ 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 ⁸⁹Zr-DFO-AGuIX. AGuIX was coupled to DFO and then to ⁸⁹Zr in ∼99% radiochemical yield. Stability studies showed that ⁸⁹Zr-DFO-AGuIX did not dissociate after 72 h. In animals bearing U87MG xenografts, it was detectable at levels above background for 72 h. Lastly, ⁸⁹Zr-DFO-AGuIX did not accumulate in inflammatory abscesses in vivo, highlighting its specificity for well vascularized tumors.