Background: The majority of cancers upregulate their transferrin receptor (Tf-R) to satisfy their higher Fe3+ requirements for proliferation. TLD-1433 can bind to transferrin to form Rutherrin, which is a promising photosensitizer with stable chemical structure and higher tissue selectivity.
Methods: To investigate the effect of Rutherrin®-mediated photodynamic treatment (PDT), we used non-small lung cancer cell lines H2170, A549, and H460. Subcutaneous tumors were treated with Rutherrin-mediated PDT, 4hrs post intravenous administration. The treatment parameters10 mg/kg Rutherrin and 600 Jcm-2 808 nm radiation. In an orthotopic A549 tumor model, the presence of tumor after inoculation in lungs was confirmed by microCT. Tissue samples were collected for Inductively Coupled Mass Spectrometry to quantify the Rutherrin concentrations via a Ru isotope in tumor and normal lung tissue.
Results: Evaluation of TfR expression by flow cytometric and western blotting showed that almost all cancer cells express TfR. In in-vitro cytotoxicity assay, all cancer cell lines showed high cell kill by PDT at 100nM Rutherrin concentrations. In the subcutaneous tumor model, PDT after Rutherrin injection significantly inhibited the tumor growth and histopathology showed extensive necrosis at 24 hrs, which was confirmed with lowered Ki67 staining. In an orthotopic model, the lung lobe with tumor retained more Rutherrin than the contralateral lung, showing specific tumor uptake.
Conclusion: These results support the hypothesis that safe and efficient Rutherrin-mediated PDT is feasible due to improved photosensitizer localization to lung tumors tissue. Selective irradiation of the cancer lesions by strategic placement of the light source remains a requirement.
Tomonari Kinoshita, Manjunatha Ankathatti Munegowda, Hitoshi Igai, Kosuke Fujino, Chang Young Le Lee, Hideki Ujiie, Arkady Mandel, Lothar D. Lilge, and Kazuhiro Yasufuku, "Targeting non-small cell lung cancer by novel TLD-1433-mediated photodynamic therapy (Conference Presentation)," Proc. SPIE 10476, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVII, 104760B (Presented at SPIE BiOS: January 27, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2287493.5751476563001.
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