An NIR-II Probe with High PSMA Affinity Demonstrates an Unexpected Excellent Bone Imaging Ability

(S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic
acid (EuK) is a known binder toward the prostate-specific membrane
agent (PSMA) with strong affinity, making it a popular choice for
prostate cancer medicine development. However, during the probe modification,
a new EuK-based PSMA tetramer, Bone-1064, was discovered
to have an unexpected and intense uptake in bone, which has not yet
been reported in any previous studies yet. After administration, Bone-1064 allowed for high contrast visualization of the bone
from surrounding tissues with a signal-to-background ratio of 10.22
at 24 h postinjection. In contrast, the tumor had a blurry contour,
and the maximum tumor-to-normal-tissue ratio was only 2.22. Further
imaging studies revealed that Bone-1064 binds specifically
to hydroxyapatite in bone tissues, instead of PSMA. Overall, Bone-1064 is an excellent bone probe with a unique structure
that can be used for NIR-II fluorescence imaging in animal models.
Meanwhile, this modification study might also inspire further PSMA
probe designations.