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.