Approaches to Radiolabeling Nanobodies for Biomedical Applications

Molecular imaging plays a vital role in diagnosing diseases, monitoring treatments, and evaluating therapeutic efficacy by enabling noninvasive visualization of biological processes. Nanobodies, single-domain antibodies derived from camelids, have emerged as promising candidates for a wide range of biomedical applications due to their unique properties, including small size, high affinity, rapid clearance, and deep-tissue penetration. While effective radiolabeling techniques remain a major challenge to fully realize their clinical potential, this review aims to present recent advances in nanobody radiolabeling, focusing on radionuclides like 64Cu, 68Ga, 89Zr, and 111In, along with their associated chelators and conjugation methods. We highlight the development of innovative chelators, including p-SCN-Bn-HOPO and desferrioxamine derivatives that enhance specificity and stability, as well as advances in conjugation techniques that influence biodistribution and pharmacokinetics. These findings highlight the essential role of nanobody-based molecular imaging for precise diagnostics and targeted therapy.