The Development and Biodistribution of an antiCD3-F(ab¿¿¿)2 Radiotracer for PET/CT Imaging

Undergraduate: Luke Soliman

Faculty Advisor: Matthew Parrott
Department: Chemistry

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The activation of tumor-infiltrating lymphocytes (TILs) has become a prominent immunotherapy technique for the treatment of various cancers. However, the ability to evaluate the patient response to these treatments has been limited because it relies on counting the number of immune cells that are recruited during therapy. One novel, unexploited approach for monitoring the efficacy of immunotherapy is to quantify immune cells by way of positron emission tomography-computed tomography (PET/CT) imaging. The CD3 antigen, which is uniquely present in T-cell receptors at all stages of T-cell development, makes it a useful target for the imaging of T-cells. Thus, the CD3 antigen is also a natural point of interest for the early evaluation of the efficacy of immunotherapy. To target the CD3 antigen, we use antiCD3 antibody fragments, rather than full antibodies, because they exhibit better tissue penetration, more rapid clearance from the blood, and thus less radioactive exposure to the patient. Overall, this project takes advantage of techniques in enzymatic proteolysis and antibody binding behavior to evaluate the biodistribution of an antiCD3-F(ab¿¿¿)2 fragment in vivo ¿¿¿ and serves as a basis for subsequent development of antiCD3 fragments as powerful diagnostic tools for evaluating the efficacy of cancer immunotherapy treatments.