Intracellular Co-Assembly of Hybrid Gadolinium and Gallium-68 Nanoparticles Simultaneously Enhance PET and T ₁ -Weighted MR Imaging of Tumor

High Resolution Image Download MS PowerPoint Slide The incompatible amounts between positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) contrast agents are a major obstacle in clinical tumor PET/MR imaging. Herein, by employing a biocompatible condensation reaction, we report an enzyme-instructed in situ coassembly strategy and demonstrate its utility for PET/MR bimodality imaging of tumors. Under the catalysis of endoprotease legumain, the 68 Ga-based probe Ac-Ala-Ala-Asn-Cys(StBu)-Lys(DOTA- 68 Ga)-CBT ( 1- 68 Ga ) and the Gd-based probe Ac-Ala-Ala-Asn-Cys(StBu)-Lys(DOTA-Gd)-CBT ( 1-Gd ) coassembled to form hybrid gadolinium and gallium-68 nanoparticles ( 68 Ga/Gd-NPs ), permitting the concurrent enhancement of PET and the T 1 -weighted MR imaging of tumors in mice. In vivo results showed that coinjection of 1- 68 Ga and 1-Gd resulted in significantly higher PET and MRI contrast in legumain-overexpressed C6 tumors compared to tumors treated with 1- 68 Ga or 1-Gd alone, as well as tumors pretreated with a legumain inhibitor, indicating superior simultaneous PET and MR imaging signal enhancement following coassembly. Thus, the specific targeting and high compatibility of this coassembly strategy offer an alternative approach to improve the stoichiometry matching of PET tracers and MRI contrast agents while also enhancing tumor-selective PET/MR imaging.