[18F]FPRGD2 imaging of abraxane therapy response

Objectives Suitably labeled RGD peptides have been increasingly used to imaging βvβ expression in both preclinical and clinical settings for tumor angiogenesis imaging. The ability of integrin imaging in monitoring cancer therapy response is not known. Herein we report a longitudinal PET imaging study using a [¹⁸F]FPRGD2 to follow paclitaxel chemotherapy.

Methods Mice bearing orthotopic MDA-MB-435 breast cancer xenografts were treated with paclitaxel or Abraxane® (human serum albumin (HSA)–stabilized paclitaxel particles) and then subjected to small-animal PET imaging studies with [¹⁸F]-FB-PEG3-E[c(RGDyK)]₂ ([¹⁸F]FPRGD2). The correlation between tumor growth status and the uptake of [¹⁸F]FPRGD2 at time points post therapy onset was assessed.

Results Abraxane showed significantly better anti-tumor effect than paclitaxel. [¹⁸F]FPRGD2 PET imaging was performed at baseline, 1 dose, 1 week and 2 weeks post treatment. All the treated mice (n = 8/group) showed an increased uptake of [¹⁸F]FPRGD2 after a single dose treatment (2.51±0.29 %ID/g for therapy vs. 2.24±0.17 %ID/g for baseline). The tumor uptake was decreased to 1.84±0.08 %ID/g at 1-week and increased to 2.59±0.66 %ID/g at 2-week time points. Tumor growth measured by caliper showed tumor regression at 1 week (V_t/V₀ = 0.6±0.032) and some regrowth of the shrank tumors after 2 weeks since Abraxane treatment.

Conclusions [¹⁸F]FPRGD2 is an exciting angiogenesis tracer that is potentially useful for therapy response monitoring. Early increase of tumor uptake of [¹⁸F]FPRGD2 is indicative of positive tumor response to therapy before delayed tumor growth and/or tumor regression may happen.