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- W2965635772 abstract "252 Introduction: The development of bifunctional chelators (BFCs) that can stably chelate zirconium-89 (89Zr) while being conjugated to targeting molecules is an area of active research (1). A recent publication described the extraordinary stability of the radiolabeled tetraazamacrocycle, 89Zr-DOTA in vivo (2). This work extends this research and examines the influence of macrocycle structure on the stability of these radiometal complexes. Methods: The non-radioactive Zr-tetraazamacrocycle complexes, Zr-NOTA, Zr-PCTA and Zr-TRITA were prepared using standard procedures, and the molecular structure of each complex was elucidated using single crystal x-ray diffraction analysis. The radioactive analogs were prepared using 89ZrCl4. In vitro, the radiometal complexes were challenged with exogenous chelating ligands, biologically relevant metal ions and human serum. Biodistribution and small animal PET studies were conducted in normal mice to examine the in vivo behavior of each radiometal complex. Results: Single crystal analysis revealed each Zr-complex to be octa-coordinate. Radiochemical studies revealed 89Zr-PCTA and 89Zr-NOTA to be extraordinarily inert to exogenous ligand, metal and serum challenge in vitro. Furthermore, biodistribution studies revealed rapid systemic clearance and low tissue retention of radioactivity. For example, mice injected with 89Zr-PCTA or 89Zr-NOTA retained less radioactivity in their kidney tissue than did mice receiving 89Zr-DFO (89Zr-PCTA vs. 89Zr-NOTAvs. 89Zr-DFO; mean %ID/g ± SD; [one-way ANOVA value, p value]: kidney (72 h): 0.15 ± 0.01 vs. 0.30 ± 0.023 vs. 0.69 ± 0.098; [F(3, 136), p" @default.
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- W2965635772 date "2018-05-01" @default.
- W2965635772 modified "2023-09-28" @default.
- W2965635772 title "Zirconium-89 tetraazamacrocycle complexes: the influence of macrocycle structure on stability" @default.
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