Book Description

Nuclear medicine, including the use of radioactive materials for imaging and therapy, has its role well estabilished. For nuclear medicine applications, not only the choice of radioisotope with characteristics that matchs the application purpose, but also the isotope "carrier" needs to be taken into account, as it "controls" the radiotracer biodistribution and other important biological interactions. Noteworthy, these "carriers" can be of any type, such as nanomaterial or antibodybased. Since nuclear medicine can be as multidisciplinary as the biomedical engineering field, herein, I have chosen to explore both routes of achieving molecular imaging and cancer theranostics: using nanoparticle and antibody-based probes. In chapter 2, we have demonstrated the synthesis of size-optimized ultrasmall porous silica nanoparticles (UPSN), with improved pharmacokinetics, i.e. prolonged blood circulation half-life and reasonably fast systemic clearance. We have systematically investigated the influence of vascular architecture and stromal microenvironment on the accumulation and retention of as-designed UPSN in two different triplenegative breast cancer models. After successfully determining that UPSN can highly accumulate in tumor tissues through EPR effect, we decided, in chapter 3, to evaluate if the same nanoparticles could act as a nanocarrier of a theranostic isotopic pair 86/90Y. In that chapter, we demonstrated that the nanoparticles, when radiolabeled with 86Y, were selectively taken up by tumors cells and were clearly visualized through PET imaging at all time points investigated. 90YDOTA-UPSN provided promising therapeutic results by significantly reducing tumor volumes when compared to all the other groups investigated and by significantly increasing average survival. In chapter 4, we have employed a theranostic approach using the isotopic pair 86Y/90Y targeting tissue factor in a pancreatic cancer model through the use of ALT836 monoclonal antibody. We demonstrated that the anti-TF monoclonal antibody, when radiolabeled with 86Y, allowed PET imaging of pancreatic cancer tumor tissue with excellent tumor contrast and could allow for dosimetric calculation of potential dose that would be received with its isotopic pair 90Y. When radiolabeled with 90Y, ALT836 provided evidence of anti-tumor effects and increased average survival. We have evaluated and characterized the ability of 52Mn-labeled YY146, a specific antibody targeting human CD146 to act as a CD146-specific breast tumor imaging agent, with capability of delineating different CD146 expressions. PET imaging, for up to 7 days, of mice bearing three different breast tumors were carried out and revealed radiotracer uptake in tumors that strongly (r2=0.98, p