Evaluation of 89Zr-DFO Functionalized Manganese-Iron Oxide Core-Shell Nanoparticles as a HER2-Targeted Multimodal Imaging Candidate Nanoplatform.

Hybrid multimodal imaging agents combining magnetic resonance imaging (MRI) and positron emission tomography (PET) capabilities offer potential for accurate tumor detection and monitoring. In our previous study, we synthesized manganese-loaded, mesoporous silica-coated superparamagnetic iron oxide nanoparticles functionalized with trastuzumab (Fe3O4-mSi-NH2-Mn-Tra), which demonstrated dual T1/T2 MRI contrast enhancement and selective cytotoxicity against HER2-positive breast cancer cells in vitro. In the current study, the nanoparticle was labeled with Zirconium-89 (89Zr) to evaluate its potential as a HER2-targeted PET imaging agent- candidate. Radiolabeling was performed using the p-isothiocyanatobenzyl-desferrioxamine (p-NCS-Bz-DFO) chelator, 89Zr-DFO-Fe3O4-mSi-NH2-Mn-Tra was labeled of 78 ± 2%. The labeled nanoparticles demonstrated high colloidal stability in PBS for up to 24 h and lipophilic (log P = 2.23 ± 0.24). In in vitro uptake studies, radiolabeled nanoparticles showed receptor-specific internalization in HER2-positive SKBR-3 cells (65.25% at 2 h), whereas the uptake was limited in HER2-negative MDA-MB-231 cells (20.22% at 4 h). When the receptor was blocked with trastuzumab, the uptake results was reduced by 11.14 ± 1.2%, confirming HER2-mediated binding. In vivo biodistribution studies in rats have shown that the radiolabeled nanoparticles accumulate in the reticuloendothelial organs (liver 15.53 ± 7.6% ID/g at 120 min) and renal excretion. These results suggest that 89Zr-DFO-Fe3O4-mSi-NH2-Mn-Tra nanoparticles may serve as a promising HER2-targeted PET/MRI candidate nanoplatform for further preclinical evaluation.