10.1021/acs.bioconjchem.5b00447.s001
Kasey
J. Clear
Kasey
J.
Clear
Kara M. Harmatys
Kara M.
Harmatys
Douglas R. Rice
Douglas R.
Rice
William R. Wolter
William R.
Wolter
Mark A. Suckow
Mark A.
Suckow
Yuzhen Wang
Yuzhen
Wang
Mary Rusckowski
Mary
Rusckowski
Bradley D. Smith
Bradley D.
Smith
Phenoxide-Bridged Zinc(II)-Bis(dipicolylamine) Probes
for Molecular Imaging of Cell
Death
American Chemical Society
2016
probe
fluorescence imaging contrast
Cell DeathCell death
vivo imaging performance
PS
mouse thymus atrophy model
cell death imaging agent
Zn 2BDPA coordination complexes
vivo biodistribution profile
mouse thymus atrophy
imaging agents
cell death
report cell death
2016-02-10 15:48:31
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Phenoxide_Bridged_Zinc_II_Bis_dipicolylamine_Probes_for_Molecular_Imaging_of_Cell_Death/2077966
Cell
death is involved in many pathological conditions, and there
is a need for clinical and preclinical imaging agents that can target
and report cell death. One of the best known biomarkers of cell death
is exposure of the anionic phospholipid phosphatidylserine (PS) on
the surface of dead and dying cells. Synthetic zincĀ(II)-bisĀ(dipicolylamine)
(Zn<sub>2</sub>BDPA) coordination complexes are known to selectively
recognize PS-rich membranes and act as cell death molecular imaging
agents. However, there is a need to improve in vivo imaging performance
by selectively increasing target affinity and decreasing off-target
accumulation. This present study compared the cell death targeting
ability of two new deep-red fluorescent probes containing phenoxide-bridged
Zn<sub>2</sub>BDPA complexes. One probe was a bivalent version of
the other and associated more strongly with PS-rich liposome membranes.
However, the bivalent probe exhibited self-quenching on the membrane
surface, so the monovalent version produced brighter micrographs of
dead and dying cells in cell culture and also better fluorescence
imaging contrast in two living animal models of cell death (rat implanted
tumor with necrotic core and mouse thymus atrophy). An <sup>111</sup>In-labeled radiotracer version of the monovalent probe also exhibited
selective cell death targeting ability in the mouse thymus atrophy
model, with relatively high amounts detected in dead and dying tissue
and low off-target accumulation in nonclearance organs. The in vivo
biodistribution profile is the most favorable yet reported for a Zn<sub>2</sub>BDPA complex; thus, the monovalent phenoxide-bridged Zn<sub>2</sub>BDPA scaffold is a promising candidate for further development
as a cell death imaging agent in living subjects.