Immuno-PET imaging of cancer using small antibody fragments: development and preclinical validation of 18F-radiolabeled nanobodies towards personalised medicine

Positron emission tomography (PET) is becoming the driving force of molecular imaging. This imaging technique detects distribution of radiopharmaceuticals in the body allowing rapid measurement of metabolic changes. Hence, PET-probes enable rapid diagnosis and individual assessment of treatment response as path towards providing personalised medicine. Fluorine-18 (18F) is a particularly suitable and attractive radioisotope for PET-imaging due to its availability at high activities and relatively long half-life (t1/2 109.8 min) permitting multistep
synthesis and distribution of 18F-radiopharmaceuticals to other clinical services. In contrast to full size antibodies, radiolabeled smaller antibody fragments like camelid single-domain antibody-fragments, Nanobodies, are attractive tools for targeted molecular imaging. These Nanobodies benefit from easier generation, improved tissue penetration and their short circulatory half-life, which matches the half-life of 18F. This thesis is aimed at developing and comparing radiochemical synthesis procedures for incorporating the PET radioisotope 18F in the Nanobody molecule. After optimization of different labeling strategies, subsequent preclinical validation of the new PET tools in tumor models was studied to evaluate their utility and value. Clinical translation of these Nanobody
based PET probes empowers the improved diagnosis and evaluation of
response to anticancer therapy.