Abstract 1328: Imaging tumor oxygenation during interstitial photodynamic therapy

Abstract Background: Interstitial photodynamic therapy (I-PDT) is a promising treatment for patients with large locally advanced or deeply seated tumors. In I-PDT, light is administered to activate a photosensitive drug (photosensitizer), which, in the presence of oxygen, results in the production of reactive oxygen species. In previous preclinical studies, we demonstrated that the light dose rate (irradiance, mW/cm2) is a main predictor of tumor response to I-PDT. The objective of this investigational study was to perform electron paramagnetic resonance oxygen imaging (EPROI) during I-PDT of locally advanced murine tumors to investigate how changes in the delivered light irradiance, mW/cm2, correlate to changes in tumor oxygenation. Methods: C3H mice with locally advanced squamous cell carcinoma (SCC7), between 260-740 mm3, were treated with I-PDT using the photosensitizer porfimer sodium administered at a dose of 5.0 mg/kg via tail vein injection. Interstitial light was delivered through two 2-cm light diffuser optical fibers placed 6 ± 1 mm apart in the tumor 24 ± 2 hours post the photosensitizer injection. The light intensity delivered from each fiber was either 60 mW/cm, which is associated with low light irradiance and low cure rate (n = 4) or 100 mW/cm, which is associated with high light irradiance and high cure rate (n=3). Partial oxygen pressure (pO2) maps were acquired prior to and during I-PDT using a 25 mT/720 MHz EPROI instrument and tris(8-carboxyl-2, 2, 6, 6-tetra(2-(1-hydroxy-2, 2-d2-ethyl))benzo[1, 2-d:4, 5-d’]bis(1, 3)dithiol-4-yl) methyl trityl as the oxygen-sensitive contrast agent. Trityl was delivered to mice via intra-peritoneal injection (300μL, 36.1mM) followed by three intra-tumor injections (50μL, 20mM each). pO2 maps were derived with following acquisition and reconstruction parameters: pulse sequence - inversion recovery electron spin echo, π/2 and π pulse lengths- 60 ns, spin-echo delay - 400 ns, 16-step phase-cycling, 828 projections, 1.5 G/cm gradient, 9 delays - 204 ns to 40 μs, TR - 45 μs, acquisition time: ∼9 min, filtered back projection reconstruction, image resolution 1.32 x 1.32 x 1.32 mm^3, R1-pO2 calibration - slope: 111.23 torr/μs-1 & intercept: 0.16 μs-1. Results: The mean pre-treatment pO2 was 9.74 ± 2.37 torr. The average decrease in pO2 as measured with EPROI was 77.8 ± 17.4% (n = 3) for the 100 mW/cm cohort and 63.0 ± 9.4% (n = 4) for the 60 mW/cm cohort. Conclusion and Discussion: In conventional PDT, in which the light is administered to the tumor surface, a high irradiance is associated with high oxygen consumption and poor tumor response. In contrast to conventional PDT, the results from this study suggest that a high irradiance, which induces a high oxygen consumption, is required to obtain high cure rates and local tumor response following I-PDT. Future experiments are ongoing to correlate changes in the tissue oxygenation during I-PDT with the delivered light irradiance and overall tumor response. Citation Format: Emily Oakley-Gawrys, Irene Canavesi, Navin Viswakarma, Boris Epel, Mrignayani Kotecha, Gal Shafirstein. Imaging tumor oxygenation during interstitial photodynamic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1328.