**4. Antibody-Based Probes**

Antibodies are high-affinity molecules with strict targeting abilities that are used for highly specific binding [97]. The development and translational use of antibody therapeutics have shaped the model of molecular targeted therapy and immunotherapy. The high affinity of monoclonal antibodies for their targets promotes the rational and efficacious use of antibody therapeutics [98]. We have advocated that PET imaging with radiolabeled antibodies or antibody fragments (i.e., immunoPET) provides a powerful platform for visualizing the tumor targets, selecting suitable patients for targeted therapies or immunotherapies, and assessing the therapeutic responses thereafter [19]. The first-generation monoclonal antibodies (mAbs) were of murine origin, making them immunogenic, limited for their clinical use. Consequently, chimeric mAbs, humanized mAbs, and complete human mAbs were produced to solve this issue [98]. One limitation of the full-size antibody probes is their considerable size (~150 kDa), which leads to a long circulatory half-life and reduced tissue penetration [99]. To ameliorate the imaging quality and efficiency and accelerate clinical translation, some smaller molecule substitute probes have been investigated, including antigen-binding fragments (Fabs) and engineered Fab variants, single-chain variable fragments (scFv), diabodies, minibodies (~25–100 kDa), and other types of therapeutic proteins, such as affibodies and nanobodies [19]. Facilitated by these developments, multiple antibodies, and antibody derivatives have been designed as either imaging probes or therapeutic agents to induce cancer cell death and elicit host immune effector responses in TC [19].
