E-Urea-K-Based PSMA Imaging Served as an Alternative in Assessing Tumor Neovascularization via Targeting CD31

Area of Science:

• Nuclear Medicine
• Oncology
• Molecular Imaging

Background:

• Prostate-specific membrane antigen (PSMA) imaging is crucial in prostate cancer diagnostics.
• Tumor neovascularization is a key factor in cancer progression and treatment response.
• The potential of E-urea-K-based PSMA-targeted (EK-PSMA) imaging to reflect tumor neovascularization requires further investigation.

Purpose of the Study:

• To determine the correlation between PSMA imaging and tumor neovascularization in prostate cancer.
• To explore EK-PSMA imaging as a potential indicator of tumor neovascularization.
• To identify key molecular factors involved in EK-PSMA imaging related to neovascularization.

Main Methods:

• Establishment of 22Rv1 mouse models for SPECT/CT imaging with ^99mTc-HYNIC-ALUG.
• Pearson correlation analysis to assess relationships between tracer uptake and tumor characteristics (size, metabolism, cell phenotypes like CD31, VEGF, Ki-67).
• Molecular docking and antibody-targeted blockade experiments in various tumor models (PSMA-positive and negative) to validate findings.

Main Results:

• Strong positive correlations were found between tracer uptake and CD31 (r=0.82) and tumor size (r=0.99).
• Molecular docking revealed affinity of E-urea-K to both PSMA and CD31.
• CD31 antibody blockade partially reduced tracer uptake in non-PSMA-expressing tumors, with a high correlation (r=0.99) between CD31 and tracer uptake when PSMA-positive models were excluded.

Conclusions:

• CD31 is identified as a mutual target for EK-PSMA imaging.
• EK-PSMA imaging serves as a viable method for assessing tumor neovascularization.
• This imaging approach is particularly valuable for evaluating neovascularization in PSMA-negative tumors.