Cancer is still one of the most serious diseases for humanity. Internal radiation therapy with alpha particles is a promising method to battle cancer, but it is currently limited to easily accessible tumors. A more advanced and selective method for alpha radiation therapy that will have better outcomes, fewer side effects, and higher efficacy is needed. A promising alternative is a two-step approach in which super paramagnetic iron oxide nanoparticles (SPION’s) are first delivered to the cancer cells and then receive the radiotherapeutics in a targeted manner. One of the most important conditions for this strategy is retention of SPIONs at the cell membranes in order to ensure in vivo click-reaction between the azide-functionalized nanoparticles and cyclooctyne-conjugated radiotracer. The goal of this study is to observe the behavior of two types of SPION’s on the glioblastoma multiforme (GBM) cancer cell line U87 and to verify whether the nanoparticles are internalized by the cancer cells or stay on the outside of the membrane. This has been done by growing U87 spheroids, incubating them with the nanoparticles, performing a cryosection on these spheroids, photographing the slices of the cryosection with a fluorescence microscope and analyzing the iron-content of the slices with inductively coupled plasma optical emission spectrometry (ICP-OES). The second part of the study concerns the preliminary in vitro click-reaction of the nanoparticles by adding beta emitter 177Lu coupled to DOTA-cyclooctyne complex to spheroids that were incubated with the nanoparticles. The fluorescence microscope analysis concludes that the nanoparticles functionalized with polyethylene glycol (PEG) penetrate the U87 spheroids less than the nanoparticles without PEG. The azide click reaction between the nanoparticles and 177Lu-DOTA-cyclooctyne complex was observed and showed more cell damage to the spheroid incubated with nanoparticles then the spheroids that were only treated with 177LuDOTA-cyclooctyne.