Targeting VPAC1 Receptors for Imaging Glioblastoma

Purpose: Scintigraphic imaging of malignant glioblastoma (MG) continues to be challenging. We hypothesized that VPAC1 cell surface receptors can be targeted for positron emission tomography (PET) imaging of orthotopically implanted MG in a mouse model, using a VPAC1-specific peptide [ ⁶⁴ Cu]TP3805.

Procedures: The expression of VPAC1 in mouse GL261 and human U87 glioma cell lines was determined by western blot. The ability of [ ⁶⁴ Cu]TP3805 to bind to GL261 and U87 cells was studied by cell-binding. Receptor-blocking studies were performed to validate receptor specificity. GL261 tumors were implanted orthotopically in syngeneic T-bet knockout C57BL/6 mouse brain (N = 15) and allowed to grow for 2-3 weeks. Mice were injected i.v., first with ~ 150 μCi of 2-deoxy-2-[ ¹⁸ F]fluoro-D-glucose ([ ¹⁸ F]FDG) then 24 h later with ~ 200 μCi of [ ⁶⁴ Cu]TP3805. In another set of tumor-bearing mice, (N = 5), ionic [ ⁶⁴ Cu]Cl ₂ was injected as a control. Mice were imaged at a 2-h post-injection using an Inveon micro-PET/CT, sacrificed and % ID/g of [ ⁶⁴ Cu]TP3805 and [ ⁶⁴ Cu]Cl ₂ were calculated in a tumor, normal brain, and other tissues. For histologic tissue examination, 3-μm thick sections of the tumors and normal brain were prepared, digital autoradiography (DAR) was performed, and then the sections were H&E stained for histologic examination.

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