Monitoring tumour response to anti-angiogenic therapy with an F18-labeled angiogenesis imaging agent

Objectives The RGD-binding integrins α_v^β3 and α_v^β5, play key roles in tumour angiogenesis. We examined an [¹⁸F] labeled small peptide (AH111585) containing an RGD (Arg-Gly-Asp) sequence. AH111585 binds with high affinity (nM) to α_v^β3 and α_v^β5 integrins, which are highly expressed on tumour neovasculature. In this study, [¹⁸F]AH111585 was used to examine the response of human glioblastoma xenografts to treatment with anti-angiogenic therapy.

Methods U87 tumour uptake of [¹⁸F]AH111585 was determined by microPET imaging (% id/g) following administration of anti-angiogenic therapies, such as Sutent and Avastin. Tumour microvessel density (MVD) was also analysed post-therapy.

Results Dymanic mircoPET imaging of [¹⁸F]AH111585 uptake demonstrated that tumour uptake peaked ~30 mins post-injection of the tracer (5% id/g). Whole body biodistribution studies confirmed rapid clearance of [¹⁸F]AH111585 from the blood with predominantly urinary excretion. Following administration of a clinically relevant anti-angiogenic therapy, a reduction in [¹⁸F]AH111585 tumour uptake was demonstrated compared to vehicle controls. Skeletal muscle, used as a reference tissue, demonstrated equivalent [¹⁸F]AH111585 uptake pre- and post-therapy. A reduction in MVD was also seen in anti-angiogenic therapy treated tumours.

Conclusions The data demonstrate that [¹⁸F]AH111585 can detect changes in tumour uptake following acute anti-angiogenic therapy. The results suggest this imaging agent may provide clinically important information to guide patient management and monitor response to anti-angiogenic therapies.