Abstract 2868: 18F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal therapy
Authors: Jesper Tranekjaer Joergensen, Kamilla Norregaard, Marina Simón Martín, Fredrik Melander, Lotte K. Kristensen, Pól Martin Bendix, Thomas L. Andresen, Lene B. Oddershede, Andreas Kjaer
Journal: Cancer Research (2017)

Abstract Aim: Nanoparticle-assisted photothermal therapy is a new promising therapeutic strategy that utilizes photo-absorbing nanoparticles irradiated with near infrared light to generate a local temperature increase in tumor tissue. Here we used small animal 18F-FDG PET/CT to evaluate the treatment response of silica-gold nanoshell (NS)-assisted photothermal therapy in human tumor xenografts in mice. Method: NMRI nude mice had ~ 106 human neuroendocrine tumor cells (H727) inoculated into the left flank. After 4-5 weeks, animals were divided into three groups: one receiving NS and laser irradiation (NS group, n = 9), one receiving saline and laser irradiation (saline group, n = 9), and one receiving NS but no laser irradiation (sham group, n = 5). All animals were PET scanned with 18F-FDG one day before treatment (baseline), followed by iv administration of either NS or saline. Approximately 24 hours after injection, the animals were placed on a laser treatment platform and the tumors were irradiated with an 807 nm diode laser for 5 minutes using a laser intensity of 1.8 W/cm2. During irradiation, the temperature at the surface of the tumor was measured using thermographic imaging. The mice were 18F-FDG PET scanned again at day 1 after treatment and tumor growth was followed by caliper measurements with the humane endpoint defined as a tumor volume of 1,000 mm3. PET and CT images were co-registered, and regions of interest were manually drawn on whole tumor regions. 18F-FDG uptake was quantified as mean percentage of injected dose per grams of tissue (%ID/g) and the treatment response was evaluated based on the reduction in tumor uptake of 18F-FDG between baseline and day 1. Results: Thermographic imaging showed that the tumor surface on average reached 49.2 ± 3.3 °C in the NS group. In comparison, the average temperatures reached 44.5 ± 1.9 °C in the saline group and 33 ± 1.0 °C in the sham group. This was consistent with an overall inhibited tumor growth, as well as improved survival in the NS group compared to the sham and saline groups. The tumor accumulation of 18F-FDG uptake was comparable between groups at baseline but PET imaging revealed a significant reduction in tumor uptake at day 1 in the NS group ( 84 ± 8 % (day 1/baseline)) compared to the saline (= 108 ± 21 %; p &amp;lt; 0.01) and sham (= 110 ± 11 %; p &amp;lt; 0.05) groups. Moreover, the change in 18F-FDG tumor uptake (day 1/baseline), was used to stratify animals into responders and non-responders, where the responding group matched inhibited tumor growth and improved survival. Conclusion: In this study we showed that 18F-FDG PET could be used for early response monitoring of the therapeutic outcome of nanoparticle-assisted photothermal therapy in human tumor xenografts in mice. Based on this, we suggest that PET can also be used for optimization of therapy, both for guiding treatment planning and early identification of non-responders for which the treatment strategy should then be changed. Citation Format: Jesper Tranekjaer Joergensen, Kamilla Norregaard, Marina Simón Martín, Fredrik Melander, Lotte K. Kristensen, Pól Martin Bendix, Thomas L. Andresen, Lene B. Oddershede, Andreas Kjaer. 18F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal 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 2868. doi:10.1158/1538-7445.AM2017-2868