**12.1 Cancer imaging**

*Advances in Precision Medicine Oncology*

effective use in therapy [50].

*Different characteristics of antibody fragments.*

**Figure 2.**

In the 1980s, researchers isolated and screened a heavy chain of the murine antibody for its binding to lysosomes [49]. It was called a single domain antibody' (dAb) as it contained only a heavy or light chain and had a meager molecular weight (15 kDa). However, it had drawbacks like poor solubility and aggregation, and a major issue was that the fragments did not retain the original's binding efficacy [49]. Components from animals such as camels, llamas, and fish such as sharks were used as more soluble, but they suffered from immunogenicity issues. Efforts like immunization and bioengineering to reduce agglomeration were carried out for

Later the above types were converted from univalent to multivalent through protein engineering, which was then used to target multiple entities at once [51]. These multivalent fragments show slower dissociation from the receptor and high functionality. One great example of multivalent fragments is a 'diabody' formed by linking light and heavy chain by a single chain variable fragment to be self-assembled into a dimer [52]. Diabodies have an advantage such as moderate molecular weight, multivalency which give them characteristics like improved penetration in tissue, rapid clearance. These diabodies bind to tumor antigen as well as to CD3 cells to kill tumors through T-cell mediated toxicity. The mini body is another type of synthesized antibody fragment, which is a pair of single chains of variable fragments interconnected by-CH3 bonds, and a variable region specific for any antigen is attached to this pair. Minibodies are more suitable for targeted radiotherapy because they show better uptake and are cleared faster as compared to other types of fragments and are cleared rapidly. In the structure of the Mini body, the single variable region can be replaced by a cytotoxic agent, radioisotope, for its delivery. Nanobody is the shortest antibody fragment. It is isolated from camelid heavy

chains of variable antibody region. It is produced by making phage viral coat cover the desired fragment. As these antibodies do not have light chains, they are structurally different than normal antibodies. They have a concave antigen-binding region larger than other antibodies. Hydrophilic structures replace the usual hydrophobic amino acid residue. Such adjustments allow antigen-binding property even in the absence of light region. Another specific property is its ability to cross

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blood–brain barrier.

Antibodies that bind to the target can be coupled with a radionuclide, fluorescent molecules to obtain images of cancer. Antibodies that have longer half-life need more time for imaging and may blur the image. These fragments have a short half-life and higher permeability, which allow easy detection. Techniques such as Positron emission tomography (PET), Computed tomography (CT), Single-photon emission computed tomography (SPECT) are now being performed where the antibody fragments are employed [53].
