Preclinical evaluation of Affibody molecule for PET imaging of human pancreatic islets derived from stem cells

Affibody 分子用于干细胞来源的人类胰岛 PET 成像的临床前评估

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作者:Pierre Cheung #, Julia Thorngren #, Bo Zhang, Svitlana Vasylovska, Francesco Lechi, Jonas Persson, Stefan Ståhl, John Löfblom, Olle Korsgren, Jonas Eriksson, Joey Lau #, Olof Eriksson #

Background

Beta-cell replacement

Conclusion

Targeting of DGCR2 is a promising approach for in vivo detection of stem-cell-derived islets grafts by molecular imaging. The synthesis of [18F]ZDGCR2:AM106 was successfully performed via a pretargeting method to label a site-specific covalently bonded fluorine-18 to the Affibody molecule. However, the rapid washout of [18F]ZDGCR2:AM106 from the stem-cell-derived islets graft indicates that dissociation kinetics can be improved. Further studies using alternative binders of similar classes with improved binding potential are warranted.

Results

[18F]ZDGCR2:AM106 was successfully synthesized with high radiochemical purity and yield via a pretargeting approach. [18F]ZDGCR2:AM106 retained binding to recombinant human DCGR2 as well as to cryosectioned stem-cell-derived islets, but in vivo binding to native pancreatic tissue in both rat and pig was low. However, in vivo uptake of [18F]ZDGCR2:AM106 in stem-cell-derived islets transplanted in the immunodeficient mice was observed, albeit only within the early imaging frames after injection of the radiotracer.

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