ABSTRACT
Cherenkov radiation (CR) derived from the decay of diagnostic and therapeutic radionuclides is currently being studied by the scientific community to determine if these emissions can be harnessed for cancer detection and therapy. While Cherenkov luminescence imaging (CLI) has been studied in the preclinical and clinical settings, Cherenkov radiation-induced cancer therapy (CRICT) is a relatively new area of research that harnesses the emitted photons to kill cancer cells through free radical generation and DNA damage. Nanoparticles seem well suited for developing a theranostic platform that would allow researchers to visualize therapy delivery and also generate the reactive oxygen species necessary to kill cancer cells. Herein, we report the preparation of an 89Zr-TiO2-MnO2 nanocomposite that incorporates transferrin onto the nanoparticle surface to enhance cancer cell growth inhibition. The incorporation of the positron emission tomography (PET) radioisotope 89Zr (half-life: 3.3 days) allowed for the detection of the nanoparticle using PET and for the creation of Cherenkov emissions that interacted with the nanoparticle surface to generate free radicals for therapy delivery. After preparation, these systems were observed to be stable in various media and provided excellent tumor growth control after being intratumorally injected into mice bearing CT-26 tumors. These results demonstrate that a therapeutically efficient CRICT platform can be generated using commercially available and affordable materials.
Subject(s)
Neoplasms , Radioisotopes , Mice , Animals , Zirconium , Precision Medicine , Manganese Compounds/pharmacology , Oxides , Positron-Emission Tomography , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/radiotherapyABSTRACT
64Cu and 67Cu are theragnostic pair radionuclides with promising application in the nuclear medicine. 64Cu is PET nuclide for the non-invasive diagnosis and 67Cu is beta emitter for therapy of various cancers. This study discusses optimization efforts in the production of these radioactive coppers carried out with 30 MeV cyclotron. Optimized conditions include target preparation, chemical separation, and quality control. The production routes of 64Cu and 67Cu were studied based on the nuclear reactions of 64Ni(p,n)64Cu and 70Zn(p,α)67Cu. The produced 64Cu and 67Cu have >99.9% of the radionuclidic purity. The yield at the end of bombardment (EOB) of 64Cu and 67Cu is 28.5 MBq/µAh and 67Cu is 0.58 MBq/µAh, respectively.
ABSTRACT
Mood abnormalities related to major depressive disorder (MDD) seem to result from disturbances in pathways connecting the fronto-limbic and subcortical, both regions known to be involved in the processing of emotional information. Using functional magnetic resonance imaging (fMRI), we measured neural responses to viewing images of sad, angry and neutral faces in 21 patients with MDD and 15 healthy controls. When shown pictures of sad faces, patients with MDD relative controls showed decreased activations bilaterally in the dorsolateral prefrontal cortex, inferior orbitofrontal cortex (OFC), medial OFC, caudate, and hippocampus. We also found significant group differences under the angry face condition, bilaterally, in the inferior OFC and medial OFC areas. Our findings indicate that decreased activations in the fronto-limbic and subcortical regions in response to affectively negative stimuli may be associated with pathophysiology of MDD.