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

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Radiochemistry

Background:

• Prostate-specific membrane antigen (PSMA) targeted probes are crucial for prostate cancer diagnostics and therapeutics.
• The probe (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acid (EuK) is a known PSMA binder.
• Modification of EuK led to the development of a novel tetramer, Bone-1064.

Purpose of the Study:

• To investigate the unexpected bone uptake of the novel EuK-based PSMA tetramer, Bone-1064.
• To characterize the binding properties and imaging capabilities of Bone-1064.
• To evaluate Bone-1064 as a potential imaging agent for bone tissue.

Main Methods:

• Synthesis and modification of EuK-based PSMA tetramer (Bone-1064).
• In vivo near-infrared-II (NIR-II) fluorescence imaging in animal models.
• Quantitative analysis of signal-to-background and tumor-to-normal-tissue ratios.
• In vitro binding studies to identify the target of Bone-1064.

Main Results:

• Bone-1064 exhibited intense and specific uptake in bone tissues, achieving a high signal-to-background ratio of 10.22 at 24 hours post-injection.
• In contrast, tumor visualization was poor, with a maximum tumor-to-normal-tissue ratio of only 2.22.
• Binding assays confirmed that Bone-1064 specifically targets hydroxyapatite in bone, not PSMA.

Conclusions:

• Bone-1064 is an effective bone-targeting probe for NIR-II fluorescence imaging, distinct from its intended PSMA binding.
• This finding reveals a new class of bone imaging agents and highlights the potential for unexpected target discovery during probe development.
• The study suggests Bone-1064's utility in animal models for bone imaging and may inspire new PSMA probe designs.