Balancing innovation and accessibility in infection imaging: lessons from the [99mTc]Tc-besilesomab paradox

Infection imaging plays a crucial role in clinical decision making, guiding antibiotic therapy and surgical management. Nuclear medicine offers molecular level approaches using three main techniques: [ 18 F]FDG PET/CT, radiolabelled white blood cell (WBC) scintigraphy, and anti-granulocyte monoclonal antibody scintigraphy with [ 99m Tc]Tc-besilesomab. Among these, [ 99m Tc]Tc-besilesomab was developed to simplify infection imaging compared with in vitro WBC labelling, improving accessibility for hospitals without cell-labelling facilities. However, its use is restricted by the need for prior testing for human anti-mouse antibodies (HAMA) to prevent hypersensitivity reactions. In recent years, significant regulatory changes in the European framework for in vitro diagnostics (IVDR 2017/746) have coincided with the withdrawal of the quantitative HAMA enzyme-linked immunosorbent assay from the market and its replacement with a qualitative rapid test. Although this shift aimed to streamline in vitro testing procedures, it has complicated the interpretation of HAMA results and raised concerns about diagnostic accessibility. In some centres, an increase in positive results has been observed with rapid tests, suggesting that patients may be inappropriately excluded from [ 99m Tc]Tc-besilesomab imaging. This situation highlights a paradox: a radiopharmaceutical designed to improve accessibility is now constrained by regulatory and methodological factors. The issue also reflects a broader challenge in nuclear medicine, ensuring patient safety and compliance without limiting access to essential diagnostic tools. This debate argues that restoring accessibility to [ 99m Tc]Tc-besilesomab immunoscintigraphy requires both technological and regulatory innovation. Developing quantitative point-of-care HAMA assays, promoting humanised or nanobody-based tracers, and establishing harmonised European guidelines could help balance patient safety with diagnostic availability. The [ 99m Tc]Tc-besilesomab case exemplifies how well-intentioned regulatory transitions may have unintended consequences, underscoring the need for a pragmatic equilibrium between innovation, safety, and accessibility in infection imaging.