Unlocking the power of affibody conjugated radioactive metallopharmaceuticals for targeted cancer diagnosis and therapy

Abstract

Cancer is the second-largest death-causing disease after cardiovascular diseases. Effective research on cancer diagnosis and subsequent elimination plays a vital role in reducing the cancer-related death toll. Radiotherapy is one of the best strategies that could kill masses of solid tumour tissues; however, the efficacy is limited due to the bystander effect. This issue could be solved by the emergence of targeted delivery of radiometallic complexes, enabling clinicians to monitor the tumour regions and effectively destroy the tumour. Affibody® molecules are a class of synthetic peptides known as antibody mimics having the binding sites of an antibody. The specificity of affibodies is found to be greater than that of antibodies due to their small size. This review intends to highlight the recent developments in the field of affibody-targeted radiometallopharmaceuticals. These approaches could be essential for early cancer detection, tumour staging, and monitoring the response to therapy and could produce better therapeutic outcomes. In an attempt to provide ideas and inspiration for the researchers to design affibody-conjugated radiopharmaceuticals that are clinically applicable, we have provided an in-depth exploration of the various types of affibody-conjugated radiopharmaceuticals that are currently in clinical trials and various other pre-clinically tested conjugates in this article. Only a few review reports on affibody-conjugated radiometallopharmaceuticals, typically focusing on a specific molecular target or radionuclides reported. In this review, we provide a comprehensive overview of most radiometals, such as ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁵⁵Co, ⁵⁷Co, ⁴⁴Sc, ^99mTc, ⁸⁹Zr, ⁹⁰Y, ²¹¹At, ¹⁸⁸Re, and ¹⁷⁷Lu, choice of chelators, and potential cancer-associated molecular targets such HER2, EGFR or HER1, HER3, IGF-1R, PDGFRβ, VEGFR2, PD-L1, CAIX, PD-L1, neonatal Fc receptor (FcRn) and B7-H3. This approach highlights the advancements made over the past twenty years in affibody conjugates for radio imaging and therapy in oncology.