A tunable one-pot three-component synthesis of an ¹²⁵I and Gd-labelled star polymer nanoparticle for hybrid imaging with MRI and nuclear medicine

The successful treatment of a disease via individualized treatment protocols relies on an early and accurate diagnosis. Advances to imaging hardware, such as hybrid PET/MRI scanners, have overcome the inherit disadvantages associated with the individual imaging modality. However, well-designed multimodal contrast agents are essential to optimally exploit hybrid PET/MRI systems. Herein, we show that core-cross-linked azide-functional star polymer nanoparticles can be simultaneously labelled with a radioisotope (radioiodine) and a clinically-used MRI contrast agent (Gd-DOTA) by exploiting an elegant copper-catalyzed one-pot three-component reaction creating an iodotriazole. The nanoparticles have a longitudinal relaxivity of 5.7 mM^-1 s^-1 at 7 T (as compared to 3.8 mM^-1 s^-1 for commercially available Gd-DTPA), and a radiochemical yield of 58% was achieved. Furthermore, we show that the radioiodine content can be fine-tuned without affecting the final Gd-DOTA loading. While we have demonstrated the versatility of the approach with ¹²⁵I, an isotope widely used in biological research, the availability of various radioiodine isotopes enables potential applications in SPECT (¹²³I), PET (¹²⁴I) and in theranostics by combining radioimmunotherapy (¹³¹I) with MRI.