Construction And Application Of MRI/SPECT Dual-modality Molecular Imaging Probe

Cancer is one of the most important diseases that threaten human health.Its early diagnosis is the key for human beings to overcome cancer.Nowadays,magnetic resonance imaging and nuclear medicine imaging are important methods for clinical diagnosis of tumors.However,they both have their own pros and cons.For example,magnetic resonance imaging has the advantages of safety,non-invasiveness,high spatial resolution,and freedom from tissue depth,while its sensitivity is low.Nuclear medicine imaging has high specificity and sensitivity,but the special resolution is low,which makes it difficult to accurately locate lesions.It can be seen that the use of single magnetic resonance or nuclear medicine imaging technology have already not been able to meet the needs of the early diagnosis of the tumor,and may even lead to undiagnosis,misjudgement or misdiagnosis of the tumor,thereby delaying the best treatment time.Therefore,exploiting the complementary advantages of magnetic resonance imaging and nuclear medicine imaging to develop dual-modality molecular imaging technology of magnetic resonance/nuclear medicine and the overcoming the defects of single-modality imaging has become an important means to improve the accuracy of tumor diagnosis.Due to the rapid development of nanotechnology and medical imaging,imaging equipment capable of realizing dual-modality imaging of magnetic resonance/nuclear medicine has become clinically advanced.However,the dual-modality molecular imaging probe for magnetic resonance/nuclear medicine is still in the basic research stage and needs further development.In view of the current status of dual-modality molecular imaging probes for magnetic resonance/nuclear medicine,a stable and reliable radioactive labeling method was developed based on magnetic Fe3O4 nanoparticles.First,monodisperse oil-soluble Fe3O4 nanoparticles were prepared by high-temperature thermal decomposition.Using diphosphate acid polyethylene glycol(PEG)derivatives as ligands,Fe3O4 nanoparticles with good water solubility and colloidal stability were obtained by ligand exchange method.Then we radioactively label 125 I on the surface of nanoparticles.The results show that by introducing Gd3+,it is coordinated with the phosphate group of PEG,which can cross-link PEG ligands on the surface of nanoparticles and improve the binding stability of ligands and nanoparticles.Therefore,it is beneficial to improve the radionuclide labeling stability of labeled nanoparticles both in vivo and in vitro.In spite of this,after entering into the body,125I-labeled Fe3O4 nanoparticle may undergo serious deiodination,and,as a result,the behavior of Fe3O4 nanoparticles in vivo will not be accurately traced.In order to solve the problem of deiodination in vivo,based on the above work,we labeled the metal radionuclide 99 mTc with the phosphate groups on the surface of the nanoparticles.Similar to Gd3+,99 mTc can also cross-link the surface ligands with the phosphate groups,which can increase the radionuclide labeling stability while achieving the radionuclide 99 mTc labeling.Compare with radioactive iodine labeling,in vivo tracking of nanoparticles is more accurate because there is no deiodination in vivo through 99 mTc labelingFinally,we exploited the developed 99 mTc labeling method to label Fe3O4 nanoparticles with different sizes and studied their pharmacokinetic behavior in mice,rats and rabbits.Which lays the foundation for the further application of magnetic resonance/nuclear bimodal molecular imaging probes based on Fe3O4 nanoparticles.