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Radiolabeled nanobodies for tumor targeting: From bioengineering to imaging and therapy
Majid Piramoon1, Fatemeh Khodadust2, Seyed Jalal Hosseinimehr3
1Department of Medicinal Chemistry and Radiopharmacy, School of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran; Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
Abstract:
So far, numerous molecules and biomolecules have been evaluated for tumor targeting purposes for radionuclide-based imaging and therapy modalities. Due to the high affinity and specificity against tumor antigens, monoclonal antibodies are appropriate candidates for tumor targeting. However, their large size prevents their comprehensive application in radionuclide-based tumor imaging or therapy, since it leads to their low tumor penetration, low blood clearance, and thus inappropriate tumor-to-background ratio. Nowadays, the variable domain of heavy-chain antibodies from the Camelidae family, known as nanobodies (Nbs), turn into exciting candidates for medical research. Considering several innate advantages of these new tumor-targeting agents, including excellent affinity and specificity toward antigen, high solubility, high stability, fast washout from blood, convenient production, ease of selection, and low immunogenicity, it assumes that they may overcome generic problems of monoclonal antibodies, their fragments, and other vectors used for tumor imaging/therapy. After three decades of Nbs discovery, the increasing number of their preclinical and clinical investigations, which have led to outstanding results, confirm their application for tumor targeting purposes. This review describes Nbs characteristics, the diagnostic and therapeutic application of their radioconjugates, and their recent advances.
Insights
Nanobodies (Nbs), derived from Camelidae heavy-chain antibodies, show promise for tumor targeting in imaging and therapy. Their small size and advantageous properties overcome limitations of traditional monoclonal antibodies, enabling better tumor penetration and imaging.
Area of Science:
- Biotechnology
- Immunology
- Radiopharmaceutical Science
Background:
- Monoclonal antibodies are used for tumor targeting but face limitations due to large size, impacting tumor penetration and imaging.
- Nanobodies (Nbs), variable heavy-chain domains from Camelidae, offer potential advantages over larger antibodies.
Purpose of the Study:
- To review the characteristics of nanobodies (Nbs) for tumor targeting.
- To discuss the diagnostic and therapeutic applications of radioconjugated Nbs.
- To highlight recent advances in Nb-based tumor targeting.
Main Methods:
- Review of preclinical and clinical investigations of nanobodies for tumor targeting.
- Analysis of nanobody characteristics, including affinity, specificity, solubility, stability, and immunogenicity.
- Evaluation of radioconjugated nanobodies for diagnostic and therapeutic applications.
Main Results:
- Nanobodies exhibit excellent affinity and specificity for tumor antigens.
- Their small size facilitates better tumor penetration and faster blood clearance compared to monoclonal antibodies.
- Preclinical and clinical studies demonstrate outstanding results for Nb-based tumor targeting.
Conclusions:
- Nanobodies are promising agents for radionuclide-based tumor imaging and therapy, overcoming limitations of conventional antibodies.
- Their favorable properties support their application in advanced cancer diagnostics and therapeutics.
- Continued research and clinical investigations confirm the potential of nanobodies in oncology.
