Does imaging αvβ3 integrin expression with PET detect changes in angiogenesis during bevacizumab therapy?

Area of Science:

• Oncology
• Molecular Imaging
• Radiochemistry

Background:

• Growing interest in molecular imaging markers for tumor-induced angiogenesis.
• Radiolabeled arginine, glycine, aspartate (RGD) peptides are used for PET imaging of αvβ3 integrins in tumor vasculature.
• Limited data exists on the impact of angiogenesis inhibitors on RGD peptide tumor uptake.

Purpose of the Study:

• To investigate the effect of bevacizumab therapy on the tumor uptake of (68)Ga-NODAGA-c(RGDfK) peptide.
• To correlate peptide uptake with changes in tumor microvasculature and αvβ3 integrin expression during antiangiogenic treatment.

Main Methods:

• Utilized Positron Emission Tomography (PET) to measure (68)Ga-NODAGA-c(RGDfK) peptide uptake in αvβ3-negative squamous cell carcinoma xenografts (A-431 and FaDu) during bevacizumab therapy.
• Assessed tumor growth, microvascular density, vascular morphology, permeability, and αvβ3 integrin expression.

Main Results:

• Bevacizumab significantly inhibited A-431 tumor growth, reduced microvascular density and αvβ3 integrin expression, and normalized vasculature within 7 days.
• (68)Ga-NODAGA-c(RGDfK) uptake in A-431 tumors increased at day 7 and decreased only after 3 weeks of therapy.
• Bevacizumab showed minor effects on tumor growth and peptide uptake in FaDu xenografts.

Conclusions:

• Uptake of radiolabeled RGD peptides does not always decrease with effective antiangiogenic therapy.
• Early decreases in αvβ3 integrin expression during therapy may not be immediately reflected by reduced RGD peptide uptake.
• PET imaging with RGD peptides requires careful interpretation in the context of antiangiogenic treatment timelines.