Abstract
Abstract Aim: Nanoparticle-assisted photothermal therapy relies on photo-absorbing agents that accumulate in tumors and upon irradiation with near-infrared light, generate hyperthermal temperatures sufficient to ablate surrounding cancerous tissue. In this study, we used small animal PET imaging to compare the tracers 18F-FDG and 18F-FLT, that are glucose and thymidine analogues respectively, for the assessment of silica-gold nanoshell (NS)-assisted photothermal therapy in a colorectal cancer mouse model. Method: Mouse colorectal tumors (CT26) were established subcutaneously in female Balb/c mice by inoculation of ~ 3x105 cells. When the tumors reached a volume of ~150 mm3, the animals were divided into treatment groups receiving either: NS and laser irradiation (NS group), saline and laser irradiation (saline group), or NS but no laser irradiation (sham group). 24 h after intravenous injection of either NS or saline, the tumors were irradiated for 5 minutes with an 807 nm diode laser with an intensity of 1.5 W/cm2 (day 0) meanwhile the temperature development was monitored using thermographic imaging. To evaluate the treatment response, all animals were PET/CT scanned with either 18F-FDG or 18F-FLT the day before treatment (baseline) and two days after treatment (day 2). In addition, the change in tumor volume was assessed by CT imaging on day 7. Throughout the study, tumor growth was monitored using caliper measurements and animals were euthanized when the tumor volume exceeded 1,000 mm3. Regions of interest were manually drawn on the entire tumor volume on co-registered PET and CT images and the PET tracer uptake quantified as the mean percentage of injected dose per grams of tissue (%ID/g). Results: During laser irradiation, NS-laden tumors reached hyperthermal temperatures that led to inhibited tumor growth and improved survival compared to the saline and sham treated groups. In the NS group, PET imaging showed a reduction in tumor uptake of 18F-FDG of nearly 50% at day 2 compared to baseline. In the saline and sham groups the tumor uptake of 18F-FDG was at comparable levels at baseline and day 2. In addition, a positive correlation was found between the change in tumor uptake between baseline and day 2 and the change in tumor volume on day 7 in all animals scanned with 18F-FDG. Preliminary data from animals scanned with 18F-FLT indicates that the tumor uptake is also strongly reduced after NS-assisted photothermal therapy and that the change in 18F-FLT uptake correlates with inhibited tumor growth on day 7. Conclusion: Both 18F-FDG and 18F-FLT PET imaging show great potential for early evaluation of the treatment response after nanoparticle-assisted photothermal therapy and preliminary data suggest that both tracers can be used to predict treatment outcome. Citation Format: Kamilla Norregaard, Jesper Tranekjaer Joergensen, Marina Simón Martín, Lene B. Oddershede, Andreas Kjaer. Comparison of 18F-FDG and 18F-FLT PET imaging for early response monitoring of nanoparticle-assisted photothermal cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2869. doi:10.1158/1538-7445.AM2017-2869
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