Radiation Biology

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SU_42_2425 - Novel Radiation-Activated Photodynamic (radioPDT) Nanoparticles for Treating Deep-Seated Tumors

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Novel Radiation-Activated Photodynamic (radioPDT) Nanoparticles for Treating Deep-Seated Tumors
D. Dinakaran1,2, H. Chen2, B. Warkentin1, P. Kumar2, N. H. Usmani2, R. Narain2, J. D. Lewis2, and R. B. Moore2; 1Cross Cancer Institute, Edmonton, AB, Canada, 2University of Alberta, Edmonton, AB, Canada

Introduction: Current challenges in prostate radiotherapy (RT) involves balancing the benefits of dose escalation to tumors while minimizing dose and toxicity to organs-at-risk, such as the rectum, bladder, and urethra. Photodynamic therapy (PDT) uses photosensitizers (PS) that, when exposed to light, generate reactive singlet oxygen species to cause significant tumor cytotoxicity. Despite the significant clinical benefits shown in phase III clinical trials for prostate PDT, its use is limited in treating deep-seated tumors due to minimal tissue penetrance of the activating light. By exploiting the greater depth penetration of X-rays, radiation-activated PDT (radioPDT) can augment radiotherapy’s efficacy for deep-seated tumors. This is done with scintillating nanoparticles (NSC) to convert X-rays to light for PDT. Prostate tumors can be hypoxic, and hypoxia’s effect on radioPDT is unknown. This is important since both RT and PDT are oxygen-dependent.

Purpose/Objective(s): We are now reporting the potential of our novel radioPDT nanoparticle (NP) in hypoxic conditions by evaluating singlet oxygen yield, cancer cell death, and in vivo toxicity. We also investigate our NP’s potential as a diagnostic agent.

Materials/Methods: We developed a novel radioPDT NP by encapsulating NSCs (lanthanum fluoride) and PS (protoporphyrin) into nanospheres (PEG-PLGA). Therapeutic potential was evaluated via singlet oxygen yield and an in vitro cell viability assay in normoxic (20% O2) and hypoxic (≤1% O2) conditions under radiation and light PDT. Diagnostic properties were evaluated via CT and MRI, as well as by X-ray imaging of in vivo distribution characteristics using a chorioallantoic membrane (CAM) chick embryo model. An acute radioPDT NP toxicity study in C57/BL mice was performed by escalating NP concentrations; behavioral and weight changes over 48 hours were monitored, and post-mortem vital organ histopathology was done.

Results: In vitro assays show virtually no toxicity in prostate cancer and fibroblast cell lines when NPs were not activated, however cancer cell killing was increased by up to 50% (p<0.001) over RT alone, when activated. Imaging showed appreciable signal yield with CT enhancement of 39.6 HU/ La ppm and a MRI T1 relaxivity constant of 1.12x10-7 ms/ La ppm. CAM studies showed preferential tumor-targeting. Mice studies showed no significant weight, behavioral, or histopathologic changes in doses up to 1000mg/kg.

Conclusion: radioPDT is a novel method of enhancing RT efficacy and minimizing toxicity. Preliminary in vitro data shows radioPDT significantly augments RT, even in hypoxia, via singlet oxygen production, with minimal in vivo toxicity observed. Future in vivo studies exploring diagnostic and therapeutic potential are planned.

Author Disclosure: D. Dinakaran: Research Grant; Astellas. H. Chen: None. B. Warkentin: None. P. Kumar: None. N.H. Usmani: None. R. Narain: None. J.D. Lewis: None. R.B. Moore: Research Grant; Astellas.

Deepak Dinakaran, MD, (PhD)

Biography:
Deepak Dinakaran, MD, (PhD), PGY-3 Radiation Oncology

I am an PGY-3 resident in radiation oncology in the University of Alberta, Canada and am concurrently completing a PhD in experimental oncology. I am interested in translational science research into novel therapies using advanced radiation techniques in combination with nanoparticles. I am specifically interested in radiation-activated cytotoxic agents and immunotherapies.

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