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lüll Osteotropic Radiolabeled Nanophotosensitizer for Imaging and Treating Multiple Myeloma Tang R; Zheleznyak A; Mixdorf M; Ghai A; Prior J; Black KCL; Shokeen M; Reed N; Biswas P; Achilefu SACS Nano 2020[Apr]; 14 (4): 4255-4264Rapid liver and spleen opsonization of systemically administered nanoparticles (NPs) for in vivo applications remains the Achilles' heel of nanomedicine, allowing only a small fraction of the materials to reach the intended target tissue. Although focusing on diseases that reside in the natural disposal organs for nanoparticles is a viable option, it limits the plurality of lesions that could benefit from nanomedical interventions. Here we designed a theranostic nanoplatform consisting of reactive oxygen (ROS)-generating titanium dioxide (TiO(2)) NPs, coated with a tumor-targeting agent, transferrin (Tf), and radiolabeled with a radionuclide ((89)Zr) for targeting bone marrow, imaging the distribution of the NPs, and stimulating ROS generation for cell killing. Radiolabeling of TiO(2) NPs with (89)Zr afforded thermodynamically and kinetically stable chelate-free (89)Zr-TiO(2)-Tf NPs without altering the NP morphology. Treatment of multiple myeloma (MM) cells, a disease of plasma cells originating in the bone marrow, with (89)Zr-TiO(2)-Tf generated cytotoxic ROS to induce cancer cell killing via the apoptosis pathway. Positron emission tomography/X-ray computed tomography (PET/CT) imaging and tissue biodistribution studies revealed that in vivo administration of (89)Zr-TiO(2)-Tf in mice leveraged the osteotropic effect of (89)Zr to selectively localize about 70% of the injected radioactivity in mouse bone tissue. A combination of small-animal PET/CT imaging of NP distribution and bioluminescence imaging of cancer progression showed that a single-dose (89)Zr-TiO(2)-Tf treatment in a disseminated MM mouse model completely inhibited cancer growth at euthanasia of untreated mice and at least doubled the survival of treated mice. Treatment of the mice with cold Zr-TiO(2)-Tf, (89)Zr-oxalate, or (89)Zr-Tf had no therapeutic benefit compared to untreated controls. This study reveals an effective radionuclide sensitizing nanophototherapy paradigm for the treatment of MM and possibly other bone-associated malignancies.|*Multiple Myeloma/diagnostic imaging/drug therapy[MESH]|Animals[MESH]|Mice[MESH]|Positron Emission Tomography Computed Tomography[MESH]|Positron-Emission Tomography[MESH]|Radioisotopes[MESH]|Tissue Distribution[MESH]|Zirconium[MESH] |