Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI

Abstract

Antivascular photodynamic therapy (PDT) of tumors with palladium-bacteriopheophorbide (TOOKAD) relies on in situ photosensitization of the circulating drug by local generation of cytotoxic reactive oxygen species, which leads to rapid vascular occlusion, stasis, necrosis and tumor eradication. Intravascular production of reactive oxygen species is associated with photoconsumption of O(2) and consequent evolution of paramagnetic deoxyhemoglobin. In this study we evaluate the use of blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for real-time monitoring of PDT efficacy. Using a solid tumor model, we show that TOOKAD-PDT generates appreciable attenuation (25-40%) of the magnetic resonance signal, solely at the illuminated tumor site. This phenomenon is independent of, though augmented by, ensuing changes in blood flow. These results were validated by immunohistochemistry and intravital microscopy. The concept of photosensitized BOLD-contrast MRI may have intraoperative applications in interactive guidance and monitoring of antivascular cancer therapy, PDT treatment of macular degeneration, interventional cardiology and possibly other biomedical disciplines.

Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment

“…As rapid destruction of tumour tissue after ADMP06-mediated PDT makes histological assessment of vascular effects difficult, we sought to further examine vascular perfusion effects using MRI. This imaging modality has previously been successfully used to investigate photosensitiser vascular-targeting mechanism of action both in the experimental (Gross et al, 2003;Huang et al, 2006) and in the clinical context . Our data indicate that vascular perfusion is significantly decreased within 3 h after ADPM06-induced treatment.…”

Contrast-Enhanced MRI-Guided Photodynamic Cancer Therapy with a Pegylated Bifunctional Polymer Conjugate

“…MRI is a non-invasive imaging modality and has several advantages over other imaging modalities since it provides three-dimensional anatomic images with high spatial resolution. The combination of MRI with photodynamic therapy provides image-guidance for laser irradiation (14,15), and non-invasive assessment of the therapeutic efficacy of PDT (16). Previously, we have shown that contrast-enhanced MRI-guided photodynamic therapy using a bifunctional polymer conjugate containing an MRI contrast agent and a photosensitizer is effective for tumor imaging and cancer treatment (17).…”

Homologous Adaptation to Oxidative Stress Induced by the Photosensitized Pd-bacteriochlorophyll Derivative (WST11) in Cultured Endothelial Cells

“…As described in Fig. 1, the preconditioning (P) of cells for oxidative stress was performed at 1, 2, or 3 M (P (1), (2), or (3) , corresponding to LD 5 , LD 20 , or LD 50 , respectively), whereas the challenge (C) was performed at 5 or 10 M (C (5) or (10) , corresponding to LD 80 or LD 90 , respectively). As can be seen from this experiment, the survival of non-adapted (P (0) ) C (5) cells was only 21%, whereas that of adapted P (1), (2) ϩ C (5) cells increased to 28 and 55%, respectively (Fig.…”

“…HSPs are important modifying factors in cellular responses to a variety of physiologically relevant conditions such as hyperthermia, exercise, metabolic challenge, aging, and oxidative stress (1,16,19). Furthermore, lipid peroxides that are also a feature of bacteriochlorophyll-based PDT (8,10) were shown to directly participate in the induction of cytoprotective, stress-tolerance-induced proteins such as HSPs, as demonstrated in a mouse brain model (20). Antioxidants such as the ROS scavengers CuZn superoxide dismutase 1 and catalase may also undergo changes (level and activity) in response to oxidative stress (3,21).…”