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Solid lipid nanoparticles (SLNs) are submicrometer (1-1000 nm) colloidal carriers developed in the past decade as an alternative system to traditional carriers (emulsions, liposomes, and polymeric nanoparticles) for intravenous applications. Because of their potential as drug carriers, there is much interest in understanding the in vivo biodistribution of SLNs following intravenous (i.v.) injection. Positron emission tomography (PET) is an attractive method for investigating biodistribution but requires a radiolabeled compound. In this work, we describe a method to radiolabel SLN for in vivo PET studies. A copper specific chelator, 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (BAT), conjugated with a synthetic lipid, was incorporated into the SLN. Following incubation with (64)CuCl(2) for 1 h at 25 °C in 0.1 M NH(4)OAc buffer (pH 5.5), the SLNs (∼150 nm) were successfully radiolabeled with (64)Cu (66.5% radiolabeling yield), exhibiting &gt;95% radiolabeled particles following purification. The (64)Cu-SLNs were delivered intravenously to mice and imaged with PET at 0.5, 3, 20, and 48 h post injection. Gamma counting was utilized post imaging to confirm organ distributions. Tissue radioactivity (% injected dose/gram, %ID/g), obtained by quantitative analysis of the images, suggests that the (64)Cu-SLNs are circulating in the bloodstream after 3 h (blood half-life ∼1.4 h), but are almost entirely cleared by 48 h. PET and gamma counting demonstrate that approximately 5-7%ID/g (64)Cu-SLNs remain in the liver at 48 h post injection. Stability assays confirm that copper remains associated with the SLN over the 48 h time period and that the biodistribution patterns observed are not from free, dissociated copper. Our results indicate that SLNs can be radiolabeled with (64)Cu, and their biodistribution can be quantitatively evaluated by in vivo PET imaging and ex vivo gamma counting.

Novel Method to Label Solid Lipid Nanoparticles with 64Cu for Positron Emission Tomography Imaging

Novel Method to Label Solid Lipid Nanoparticles with ⁶⁴Cu for Positron Emission Tomography Imaging