Integrin PET imaging during therapy may not tell the whole story

Anti-angiogenesis drugs have been making waves as treatments for some cancers. Researchers have been developing new biomarkers to map the progress of these therapies, including those that target integrin expression. However, a new study published online yesterday in the Journal of Nuclear Medicine indicates that integrin expression imaging may not provide a mirror image of the impact of peptide therapy as it occurs.

Scientists have developed peptides such as aspartate, arginine and glycine in order to glean information from αvb3 integrins in the micro-vessels around tumor vasculature. But more research is needed to see how anti-angiogenisis therapies alter the uptake of these biomarkers. 

Svetlana N. Rylova, PhD, from the German Cancer Consortium (DKTK) in Heidelberg, and colleagues assessed the effects of bevacizumab therapy in αvb3-negative squamous cell carcinoma cell lines (A-431 and FaDu) on the uptake of Ga-68-NODAGA-c(RGDfK), a peptide PET imaging agent.

Results of the study showed substantial inhibition of A-431 tumors and decreased vascular density and morphology, tumor necrosis and avb3 integrin expression within seven days of bevacizumab treatment. Conversely, Ga-68 NODAGA-c(RGDfK) uptake spiked on the seventh day of treatment and remained high until after three weeks of therapy.

Only minor changes in tumor growth and Ga-68-NODAGA-c(RGDfK) uptake were found in the Fadu xenografts.

“Our findings indicate that several factors such as vascular normalization and tumor necrosis can modulate uptake of RGD peptides during treatment with bevacizumab,” wrote Rylova et al. “Consequently, tumor uptake of RGD peptides does not necessarily reflect changes of avb3 expression by intratumoral blood vessels early in the course of therapy.”

Further study is needed to replicate these findings before any conclusion can be made about integrin imaging during peptide therapy.