Abstract
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Objectives Vascular targeted photodynamic therapy using WST-11 (VTP-TS), is a focal ablative treatment, currently in multi-center clinical trials of localized prostate cancer. Photosensitization of WST-11 by near infra-red illumination generates reactive oxygen/nitrogen species within the tumor blood vessels, which in turn causes intratumoral vascular occlusion. Thus, we hypothesized that VTP might increase the intratumoral half-life of radiopharmaceuticals and thereby improve the efficacy of targeted radiotherapy. We tested this hypothesis in prostate cancer xenografts treated with 90Y-labeled DOTA-AR06 (a bombesin antagonist), WST11 and a combination of both therapies.
Methods Groups of mice (n=8-13) bearing PC3 xenografts were treated with either WST11 (9 mg/kg), 90Y-DOTA-AR06 (14.8 MBq), combination of both, or vehicle. For VTP the tumor was illuminated with a laser for 10 min (150 mW/cm2 at 753 nm). For combination therapy, VTP was performed 4 h after 90Y-DOTA-AR06 injection. The radiotracer uptake in xenografts was followed with Cerenkov luminescence imaging in order to estimate the amount of 90Y retained in the xenografts.
Results VTP-TS significantly increased the intratumoral residency time of 90Y 1.3 fold (P < 0.05). 90Y-DOTA-AR06 alone at the selected dose had no significant effect on tumor growth. VTP alone decreased tumor volume by 59% at 4 weeks (p<0.01). Combination treatment caused complete tumor regression in 6/12 of animals, and decreased tumor volume by 72% at day 4 weeks (p<0.01 for comparison with 90Y-DOTA-AR06; p<0.05 for comparison with VTP).
Conclusions VTP-TS can increase the intratumoral trapping of radiopharmaceuticals. A combination of VTP and targeted radiotherapy with GRPr antagonists should be further evaluated for minimally invasive, focal therapy of early prostate cancer.
Research Support NIH grants P50-CA84638, R24CA83084, P30CA08748.