Preparation And Biological Properties Of SPECT/MRI Dual-Modality Imaging Agents

Cancer seriously affects people’s health,and early diagnosis can greatly improve the survival rate of patients.Diagnostic imaging is currently the most effective and intuitive diagnostic modality in clinical practice,which includes various imaging modalities.However,since each imaging modality has its advantages and disadvantages,it is impossible to obtain all the key information about the diseased tissue with only one imaging modality.For example,MRI(magnetic resonance imaging)guarantees high-resolution imaging but has low sensitivity,while PET(positron emission tomography)or SPECT(single photon emission computed tomography),which rely on radionuclides,have high sensitivity and low resolution.The combination of these two imaging modalities complements each other to obtain both the highsensitivity physiological information provided by SPECT and PET imaging and the high-resolution deconvolution information provided by MRI imaging.Currently,devices on multimodal imaging(MRI and nuclear medicine dual-modality imaging)are moving to the clinic,but corresponding matching multimodal imaging probes are still under development and need more research.To address this above situation,this paper attempts to modify,functionalize,and radiolabel superparamagnetic iron oxide nanoparticles based on them as the core for SPECT/MRI dual-modality imaging.Firstly,three dopamine-derived ligands:dopamine(DA),levodopa(LDOPA),3,4-dihydroxyphenylpropionic acid(DHCA)modified iron oxide nanoparticles were synthesized,all of which have a suitable particle size,good water solubility,stability,magnetic properties.Among them,Fe3O4-DHCA nanoparticles have the smallest particle size,the best stability,the best magnetic properties,so using Fe3O4-DHCA as the core for functionalization is the best choice.We then grafted NH2-PEG2000-NH2 on top of Fe3O4-DHCA nanoparticles to further increase their water solubility and biocompatibility and functionalized them with RGDyk peptide and diethylenetriaminepentaacetic acid(DTPA).labeling,and the final synthesis of RGD-Fe3O4-PEG-DTPA nanoparticles to achieve SPECT/MRI dualmodality imaging.We investigated the synthesized RGD-Fe3O4-PEG-DTPA nanoparticles and found that they have a good 99mTc labeling rate capable of being used for SPECT imaging and good MR relaxation properties for MRI T2 imaging.In vivo SPECT and MRI imaging in tumor-bearing mice also demonstrated their ability to target、tumor sites over time,with the best imaging results at 6 h.The biological tissue distribution results also indicate that at 6 h the tumor site has the highest uptake of 4.82%ID/g and the highest tumor-to-flesh ratio of 5.17,while its metabolic processes are also seen,demonstrating its ability to be safely excreted over time.These results all indicate the potential of bimodal probes developed based on magnetic iron oxide nanoparticles for the evaluation and diagnosis of malignant tumors.Finally,we tried different ligands such as luteinizing hormone-releasing hormone(LHRH)and 2-hydrazinyl hypochlorous acid(HYNIC)to functionalize them,but in the process of 99mTc labeling,we found that Fe3O4-PEG-LHRH-HYNIC nanoparticles have poor thermal stability and will agglomerate with the increase of temperature,which eventually led to poor labeling rate and imaging effect and could not be used for SPECT/MRI dual-modality imaging.In conclusion,this paper explored SPECT/MRI dual-modality probes based on superparamagnetic iron oxide nanoparticles,and finally synthesized probes capable of SPECT/MRI dual-modality,which are potentially valuable for promoting the application of SPECT/MRI dual-modality imaging.