Abstract
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Objectives Nano-sized drugs and particles passively accumulate in tumor tissue through the leaky tumor vasculature, known as enhanced permeability and retention (EPR) effect. This can be exploited for different treatment strategies. Among these is nanoparticle-assisted photothermal therapy that is based on the enhanced light-to-heat conversion of metallic nanoparticles when irradiated with resonant light. Nanoparticles localized in the tumor strongly absorb the incoming light and efficiently translate it into heat that ablate or inflict irreversible damage to nearby cancer cells. However, the heating is very local, thus sparing tissue surrounding the tumor. Here we use small animal 18FDG PET/CT to evaluate the treatment response of nanoparticle-assisted photothermal therapy in human tumor xenografts in mice.
Methods Human neuroendocrine lung carcinoid (H727) tumor xenografts were established in the left flank of female NMRI nude mice. The tumors were allowed to grow until they reached a volume of ~ 150 mm3 whereupon they were matched into 3 treatment groups: one receiving nanoparticles and laser irradiation (nanoparticle group), a control group receiving saline and laser irradiation (saline group), and a control group receiving nanoparticles but no laser irradiation (sham group). The animals were scanned with 18FDG PET/CT the day before treatment (baseline), and at day 1 and day 3 after therapy. After the baseline 18FDG PET/CT scan, the animals were injected with nanoparticles or saline via the tail vein. Approximately 24 hours after injection the animals were placed on a laser treatment platform and the tumors were irradiated with an 808 nm diode laser for 5 minutes. During laser irradiation, the temperature at the surface of the tumor area was measured using thermographic imaging. After therapy, the change in tumor volume (= ½(length x width2)) was followed by caliper measurements with the humane endpoint defined as a tumor volume 蠅 1,000 mm3. PET and CT images were co-registered and regions of interests (ROIs) were manually drawn on whole tumor regions from which the 18FDG uptake was quantified as mean percentage of injected dose per grams of tissue (%ID/g).
Results The treatment of tumors with nanoparticles and laser irradiation led to a delayed increase in tumor volume as well as improved survival times compared to mice in the saline and sham groups. Moreover, the treatment response was evaluated by the reduction in 18FDG uptake after treatment calculated as the ratio between the mean 18FDG uptake at day 1 and at baseline as well as the ratio between day 3 and baseline. Figure 1a shows representative PET/CT images of a nanoparticle treated mouse where the 18FDG uptake is markedly reduced at day 1 compared to baseline. Preliminary data suggest that there is a reduction in the mean 18FDG uptake between day 1 and baseline in the nanoparticle group compared to the saline and sham groups. Finally, thermographic imaging showed that the tumor surface temperature in the nanoparticle group overall reached higher temperatures than in the other two groups (see example of a mouse from the nanoparticle group in Fig. 1b), consistent with the better treatment effect observed for the nanoparticle group.
Conclusions Preliminary data in this study shows that 18FDG PET can be used for early response evaluation of nanoparticle-assisted photothermal therapy. In addition, as the treatment response was found to be somewhat heterogeneous, we suggest that 18FDG PET can also be used for optimization of the treatment protocol.