In vivo monitoring of tumor response to chemotherapy by PET/NIRF imaging of cell death using a novel phosphatidylserine-targeted molecular probe

Objectives This study aims to apply PET/NIRF imaging with a novel DPA-containing probe (18F-PS-TumorVue®) to visualize and evaluate cell death induced by Paclitaxel in a U87MG tumor xenograft model.

Methods The response of U87MG cells to Paclitaxel treatment was determined by flow cytometry, fluorescence staining, and cell uptake study. Established U87MG tumors in nude mice were daily treated with a combination of All-Trans Retinoic Acid (ATRC) (1.5 µg/kg) and Paclitaxel (45 µg/kg). Longitudinal PET imaging was performed before treatment and at day 3, 6, and 9 post-treatment. A direct tissue biodistribution study was performed to confirm the accuracy of PET quantification. NIRF imaging was carried out with 19F-PS-TumorVue® before treatment and at day 4, 7, and 11 post-treatment.

Results After 15 h of Paclitaxel treatment, the strong red fluorescence signal was identified in the cytosol of the treated U87MG cells with PSVue643® (a DPA-containing dye) but not on the untreated cells. The fluorescent signal was effectively blocked by co-incubation with excess amount of unlabeled Zn-DPA. About 1.5% of 18F-PS-TumorVue® uptake in Paclitaxel-treated U87MG cells was determined after 1 hr incubation, which is higher than 0.69% and 0.39% observed for 18F-FP-DPA (single modality compound) and 18F-FP-Dye (negative control). The cell death was clearly visualized by 18F-PS-TumorVue® PET after treatment. The tumor uptake, which was observed at day 9 after treatment, was significantly higher than that in the untreated tumors (8.23±0.35 vs. 1.69±0.42%ID/g, p<0.05). The NIRF imaging results are consistent with the findings by PET.

Conclusions PET/NIRF imaging with PS-TumorVue® is sensitive enough to allow visualization of Paclitaxel induced cell death in U87MG tumor xenograft model. Fully quantitative imaging of tumor response to therapy with PS-TumorVue® offers the potential to provide early assessment of cancer treatment efficacy.

Research Support This work was supported by the USC Department of Radiology.