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- W1551240223 abstract "1186 Objectives 89Zr-desferrioxamine (DFO) complexes are widely used in immunoPET applications despite recent observations suggesting instability of the radiometal chelate in vivo. These observations have stimulated interest in the development of new chelators that would form 89Zr-complexes that are more stable in vivo. This report describes the synthesis, radiochemistry and biological evaluation of novel 2-hydroxyisophthalamide (IAM) and 3-hydroxy-2-oxopyridine (HOPO) ligands (A and B) as chelators for 89Zr. Methods All ligands were synthesized using novel, high dilution procedures. These ligands were radiolabeled with 89Zr with purity and reaction progress monitored by radio-TLC and radio-HPLC. Stability of each complex was evaluated in PBS, 50 mM DTPA and human serum and compared with 89Zr-DFO. Lipophilicty (LogP) values using a water:octanol partition were also determined. Results Formation of the 89Zr-HOPO complexes was complete and quantitative after 30 minutes at room temperature, but the formation of 89Zr-IAM required more rigorous reaction conditions. After seven days, transchelation was observed in all complexes with the relative order of stability to DTPA challenge being 89Zr-HOPO-A>89Zr-HOPO-B>89Zr-DFO > 89Zr-IAM. In addition, the89Zr-IAM and 89Zr-HOPO complexes were observed to be more lipophilic than 89Zr-DFO [(89Zr-IAM vs. 89Zr-HOPO-A vs. 89Zr-HOPO-B vs. 89Zr-DFO): -2.65±0.03 vs. -1.53 ±0.04 vs. -1.58 ±0.02 vs. -2.68±0.04]. Conclusions Both 89Zr-HOPO complexes demonstrated greater lipophilicity and greater stability against DTPA challenge when compared with 89Zr-DFO while 89Zr-IAM demonstrated comparable lipophilicity and was less stable to DTPA challenge. The results of comparative biodistribution studies with 89Zr-DFO will be highlighted, and the utility of these novel ligands as 89Zr chelators will be discussed. Research Support This work was supported by Wake Forest Health Sciences." @default.
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- W1551240223 date "2014-05-01" @default.
- W1551240223 modified "2023-09-23" @default.
- W1551240223 title "Radiochemistry and biological evaluation of novel 2-hydroxyisophthalamide and 3-hydroxy-2-oxopyridine ligands as chelators for 89Zr" @default.
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