Detection of Treatment Success after Photodynamic Therapy Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Abstract

Early evaluation of response to therapy is crucial for selecting the optimal therapeutic follow-up strategy for cancer patients. PDT is a photochemistry-based treatment modality that induces tumor tissue damage by cytotoxic oxygen radicals, generated by a pre-injected photosensitive drug upon light irradiation of tumor tissue. Vascular shutdown is an important mechanism of tumor destruction for most PDT protocols. In this study, we assessed the suitability of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to evaluate treatment efficacy within a day after photodynamic therapy (PDT), using the tumor vascular response as a biomarker for treatment success.Methods: DCE-MRI at 7 T was used to measure the micro-vascular status of subcutaneous colon carcinoma tumors before, right after, and 24 h after PDT in mice. Maps of the area under the curve (AUC) of the contrast agent concentration were calculated from the DCE-MRI data. Besides, tracer kinetic parameters including Ktrans were calculated using the standard Tofts-Kermode model. Viability of tumor tissue at 24 h after PDT was assessed by histological analysis.Results: PDT led to drastic decreases in AUC and Ktrans or complete loss of enhancement immediately after treatment, indicating a vascular shutdown in treated tumor regions. Histological analysis demonstrated that the treatment induced extensive necrosis in the tumors. For PDT-treated tumors, the viable tumor fraction showed a strong correlation (ρ ≥ 0.85) with the tumor fraction with Ktrans > 0.05 min-1 right after PDT. The viable tumor fraction also correlated strongly with the enhanced fraction, the average Ktrans, and the fraction with Ktrans > 0.05 min-1 at 24 h after PDT. Images of the viability stained tumor sections were registered to the DCE-MRI data, demonstrating a good spatial agreement between regions with Ktrans > 0.05 min-1 and viable tissue regions. Finally, 3D post-treatment viability detection maps were constructed for the tumors of three mice by applying a threshold (0.05 min-1) to Ktrans at 24 h after PDT. As a proof of principle, these maps were compared to actual tumor progression after one week. Complete tumor response was correctly assessed in one animal, while residual viable tumor tissue was detected in the other two at the locations where residual tumor tissue was observed after one week.Conclusion: This study demonstrates that DCE-MRI is an effective tool for early evaluation of PDT tumor treatment.

Impact of genotypic and phenotypic differences in sarcoma models on the outcome of photochemical internalization (PCI) of bleomycin

“…In the MRI analysis of PDT and PCI treated tumours in Paper 2 it was observed that the peripheral zone was resistant to vascular shutdown, a finding previously reported by several authors [4,[132][133][134]. In the MES-SA tumors there also seemed to be remaining uptake of contrast agent in areas corresponding with a high pre-treatment uptake along the strands of fibrous tissue containing blood vessels.…”

“…However, not all studies point in the same direction regarding tumour vasculature and treatment effects. The treatment resistant tumour periphery was studied after PDT treatment of CT26.WT (colon carcinoma), but the authors were unable to identify blood vessels in this area after treatment and proposed that PDT only works well in vascularized tumours [134].…”

Noninvasive assessment and therapeutic monitoring of drug-resistant colorectal cancer by MR molecular imaging of extradomain-B fibronectin

“…Among the widely reported magnetic nanoparticle (MNP) studies 24 , MRI-based detection of iron oxide nanoparticles targeting human tumor antigen underglycosylated mucin 1 (uMUC1) 25 , and nanoaggregation of probe scaffolds specific to pro-apoptotic caspases 26 , has been used to monitor chemotherapeutic response of colon xenografts. Vascular volume fraction (VVF), K-Ras mutation, EGFR, and α v β 3 have been used as surrogate markers for MRI of CRC with some success 27 - 29 . Novel theranostic approaches, combining MRI, DCE-MRI and diverse therapies like photodynamic therapy and MXene-based nanoplatforms, have also been reported for other models of cancer 30 - 32 .…”

Cancer Theranostics: Bridging Conventional and Nano-photodynamic Therapy

“…16 Magnetic resonance imaging (MRI) can be used to evaluate treatment efficacy of PDT in cancer treatment automatically instead of histopathologic assessment. 17 PDT has several potential benefits compared with standard treatments. The most important criteria for PDT include the choice of photosensitizer and the wavelength of light.…”