Design, Synthesis, and Evaluation of a Novel-Labeled Small Molecule Inhibitor-Based PET/SPECT Tracer Targeting HSP90.

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Heat shock protein 90 (HSP90) inhibitors are emerging cancer therapeutics.
• Therapeutic efficacy is linked to tumor HSP90 expression, requiring in vivo detection methods.
• Current probes face limitations in subtype specificity and off-target organ accumulation.

Purpose of the Study:

• To develop and optimize an HSP90-targeted radiotracer for improved in vivo tumor detection.
• To address limitations of existing probes, including off-target accumulation and subtype specificity.
• To evaluate the translational potential of the novel radiotracer in clinical settings.

Main Methods:

• Development and chemical optimization of an HSP90-targeted radiotracer.
• In vivo evaluation in colorectal and gastric cancer models to assess tumor uptake and biodistribution.
• Clinical evaluation for tumor delineation and imaging contrast.

Main Results:

• Enhanced tumor uptake in colorectal (10.02 ± 2.05% ID/g) and gastric (5.02 ± 0.08% ID/g) cancer models.
• Reduced off-target accumulation in liver (∼2% ID/g) and kidneys (∼5% ID/g).
• High tumor-to-muscle ratios (23.28 ± 9.70 and 16.73 ± 2.80) and clinical imaging with SUVmax ∼ 5.

Conclusions:

• The optimized radiotracer demonstrates significant potential for in vivo HSP90 expression imaging.
• This probe facilitates accurate tumor delineation and high-contrast imaging in clinical settings.
• The developed radiotracer can support comprehensive cancer management and guide HSP90 inhibitor therapy.