Tumor targeting with radiolabeled alpha(v)beta(3) integrin binding peptides in a nude mouse model

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Alpha(v)beta(3) integrin is upregulated on tumor endothelial cells and tumor cells, making it a target for cancer therapy.
• Arg-Gly-Asp (RGD) peptides bind to alpha(v)beta(3) integrin, offering a strategy to block tumor angiogenesis.
• Radiolabeled RGD peptides are promising for targeted tumor imaging and therapy due to selective integrin expression.

Purpose of the Study:

• To evaluate the in vivo behavior of radiolabeled dimeric RGD peptide E-[c(RGDfK)](2).
• To assess the potential of these radiolabeled peptides for alpha(v)beta(3) integrin-targeted ovarian carcinoma xenograft imaging and therapy.

Main Methods:

• Radiolabeling of E-[c(RGDfK)](2) with (111)In/(90)Y using DOTA chelator and with (99m)Tc using HYNIC chelator.
• In vivo biodistribution studies in NIH:OVCAR-3 ovarian carcinoma xenograft model in BALB/c nude mice.
• Therapeutic efficacy assessment using (90)Y-DOTA-E-[c(RGDfK)](2) in tumor-bearing mice.

Main Results:

• High and specific tumor uptake of (111)In-DOTA-E-[c(RGDfK)](2) and (99m)Tc-HYNIC-E-[c(RGDfK)](2) was observed.
• Tumor uptake was confirmed to be specific for alpha(v)beta(3) integrin via control peptide studies.
• A single injection of (90)Y-DOTA-E-[c(RGDfK)](2) significantly delayed tumor growth and improved median survival.

Conclusions:

• Radiolabeled RGD peptides demonstrate high and specific tumor uptake in an ovarian carcinoma xenograft model.
• The therapeutic administration of (90)Y-DOTA-E-[c(RGDfK)](2) resulted in significant tumor growth delay.
• These radiolabeled RGD peptides hold potential for both peptide receptor radionuclide imaging and targeted radionuclide therapy.