SpineAssist offers enhanced performance in spinal surgery when compared to free-hand surgeries, by increasing placement accuracy and reducing neurologic risks. In addition, 49% of the cases reported herein used a percutaneous approach, highlighting the contribution of SpineAssist in procedures without anatomic landmarks.
Incorporation of a mercaptoacetyl-containing chelating sequence during chemical synthesis enabled site-specific (99m)Tc labelling of the Z(HER2:342) Affibody molecule with preserved targeting capacity.
Affibody molecules present a new class of affinity proteins, which utilizes a scaffold based on a 58-amino acid domain derived from protein A. The small (7 kDa) Affibody molecule can be selected to bind to cell-surface targets with high affinity. An Affibody molecule (Z HER2:342 ) with a dissociation constant (K d ) of 22 pM for binding to the HER2 receptor has been reported earlier. Preclinical and pilot clinical studies have demonstrated the utility of radiolabeled Z HER2:342 in imaging of HER2-expressing tumors. The small size and cysteine-free structure of Affibody molecules enable complete peptide synthesis and direct incorporation of radionuclide chelators. The goal of this study was to evaluate if incorporation of the natural peptide sequences cysteine-diglycine (CGG) and cysteine-triglycine (CGGG) sequences would enable labeling of Affibody molecules with 99m Tc. In a model monomeric form, the chelating sequences were incorporated by peptide synthesis. The HER2-binding affinity was 280 and 250 pM for CGG-Z HER2:342 and CGGG-Z HER2:342, respectively. Conjugates were directly labeled with 99m Tc with 90% efficiency and preserved the capacity to bind specifically to HER2-expressing cells. The biodistribution in normal mice showed a rapid clearance from the blood and the majority of organs (except kidneys). In the mice bearing SKOV-3 xenografts, tumor uptake of 99m Tc-CGG-Z HER2:342 was HER2-specific and a tumorto-blood ratio of 9.2 was obtained at 6 h postinjection. Gamma-camera imaging with 99m Tc-CGG-Z HER2:342 clearly visualized tumors at 6 h postinjection. The results show that the use of a cysteine-based chelator enables 99m Tclabeling of Affibody molecules for imaging.
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