Molecular nuclear imaging, a medical imaging procedure, offers pictures of what is going on inside the human body, recognized as the visualization, characterization, and measurement of biological processes at molecular and cellular levels. A convenient approach of molecular imaging in vivo consists of administration and visualization of a molecular nuclear imaging tracer, a.k.a. probe or radiotracer, which comprises a targeting vehicle bound to a detectable radiolabel. Various types of compounds have been used as the targeting vehicles, including small organic compounds, peptides, proteins, conventional antibodies, antibody-derived fragments, etc.
Single-domain antibody fragments (sdAbs), a.k.a. VHH molecules, are engineered from special heavy-chain-only antibodies of camelids (e.g. camels, alpacas, and llamas). The heavy-chain-only antibodies contain a single variable domain (VHH) with two constant domains. Retaining the similar targeting affinity of conventional antibodies, sdAbs are merely 10 percent the molecular weight (12–15 kDa).
To be a perfect imaging tracer it is essential to find and bind the target receptor as fast as possible, with a minimal uptake in non-targeted organs and to clear rapidly the unbound fraction from blood. In the recent years, sdAb has been found to be an ideal type of targeting vehicle for molecular imaging due to its tiny size and unique structure.
The stable and soluble sdAb probes can find and bind their specific antigen with high affinities and specificities. The small size of sdAbs allows imaging within hours after injection of the imaging tracer.
Whole-body targeted molecular nuclear imaging offers a new non-invasive method for detecting biomarker expression (such aswhole-body PD-L1 expressionand Tumor Infiltration Lymphocyte bio-distribution), complementary to available method of immunohistochemistry that is based on biopsy samples. This invasive clinical procedure provides no information other than the biopsy specimen, which does NOT reflect expression of the entire human body.