Selection of the optimal macrocyclic chelators for labeling with

Radionuclide molecular imaging is a promising tool that becomes increasingly important as targeted cancer therapies are developed. To ensure an effective treatment, a molecular stratification of the cancer is a necessity. To accomplish this, visualization of cancer associated molecular abnormalities in vivo by molecular imaging is the method of choice. ADAPTs, a novel type of small protein scaffold, have been utilized to select and develop high affinity binders to different proteinaceous targets. One of these binders, ADAPT6 selectively interacts with human epidermal growth factor 2 (HER2) with low nanomolar affinity and can therefore be used for its in vivo visualization. Molecular design and optimization of labeled anti-HER2 ADAPT has been explored in several earlier studies, showing that small changes in the scaffold affect the biodistribution of the domain. In this study, we evaluate how the biodistribution properties of ADAPT6 is affected by the commonly used maleimido derivatives of the macrocyclic chelators NOTA, NODAGA, DOTA and DOTAGA with the aim to select the best variants for SPECT and PET imaging. The different conjugates were labeled with

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