Nanobodies: From Discovery to Translational Imaging and Therapy
Nanobodies are single-domain antibody fragments derived from the variable region (VHH) of heavy-chain-only antibodies naturally present in camelids. With a molecular weight of approximately 15 kDa, they are about one-tenth the size of conventional IgG antibodies. Despite their small size, they retain full antigen-binding capacity and exhibit high affinity, specificity, and remarkable stability under chemical and thermal stress.
Discovery at the VUB
Nanobodies were discovered in the early 1990s at the VUB by the research group of Raymond Hamers. The identification of functional heavy-chain-only antibodies in camelids represented a paradigm shift in antibody biology. Subsequent work demonstrated that the isolated VHH could function as a fully independent antigen-binding unit, forming the basis of nanobody technology.
The VUB has since become an international center of excellence in nanobody research, advancing their molecular engineering, production, and translational applications across diagnostics and therapeutics.
Structural and Functional Advantages
Nanobodies possess several characteristics that make them uniquely suited for molecular imaging and radionuclide therapy:
Small size and monomeric structure, enabling deep tumor penetration
Rapid blood clearance, resulting in high target-to-background ratios
High solubility and stability, facilitating chemical modification
Ease of recombinant production, allowing scalable and cost-efficient manufacturing
Compatibility with site-specific conjugation strategies, ensuring controlled labeling with radionuclides or fluorophores
Importantly, their rapid pharmacokinetics align well with short-lived radionuclides used in nuclear imaging, enabling same-day imaging protocols.