In-Vivo Optical Monitoring of the Efficacy of Epidermal Growth Factor Receptor Targeted Photodynamic Therapy: The Effect of Fluence Rate
by
Wei Peng 1,2,†, Henriette S. de Bruijn 1,*,†
, Timo L. M. ten Hagen 3, Kristian Berg 4,5, Jan L. N. Roodenburg 2, Go M. van Dam 6, Max J. H. Witjes 2 and Dominic J. Robinson 1
Wei Peng 1,2,†, Henriette S. de Bruijn 1,*,†, Timo L. M. ten Hagen 3, Kristian Berg 4,5, Jan L. N. Roodenburg 2, Go M. van Dam 6, Max J. H. Witjes 2 and Dominic J. Robinson 1
1
ErasmusMC Cancer Institute, Department of Otolaryngology and Head & Neck Surgery, Center for Optical Diagnostics and Therapy, Dr. Molenwaterplein 40, 3015 GD Rotterdam, The Netherlands
2
Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
3
ErasmusMC, Laboratory of Experimental Oncology, Department of Pathology, Dr. Molenwaterplein 40, 3015 GD Rotterdam, The Netherlands
4
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Boks 1072 Blindern, NO-0316 Oslo, Norway
5
Department of Pharmacy, School of Pharmacy, University of Oslo, Boks 1072 Blindern, NO-0316 Oslo, Norway
6
Department of Surgery, Nuclear Medicine and Molecular Imaging and Intensive Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(1), 190; https://doi.org/10.3390/cancers12010190
Received: 17 December 2019 / Revised: 8 January 2020 / Accepted: 9 January 2020 / Published: 13 January 2020
(This article belongs to the Special Issue Photodynamic Therapy (PDT) in Oncology)
Targeted photodynamic therapy (PDT) has the potential to improve the therapeutic effect of PDT due to significantly better tumor responses and less normal tissue damage. Here we investigated if the efficacy of epidermal growth factor receptor (EGFR) targeted PDT using cetuximab-IRDye700DX is fluence rate dependent. Cell survival after treatment with different fluence rates was investigated in three cell lines. Singlet oxygen formation was investigated using the singlet oxygen quencher sodium azide and singlet oxygen sensor green (SOSG). The long-term response (to 90 days) of solid OSC-19-luc2-cGFP tumors in mice was determined after illumination with 20, 50, or 150 mW·cm−2. Reflectance and fluorescence spectroscopy were used to monitor therapy. Singlet oxygen was formed during illumination as shown by the increase in SOSG fluorescence and the decreased response in the presence of sodium azide. Significantly more cell death and more cures were observed after reducing the fluence rate from 150 mW·cm−2 to 20 mW·cm−2 both in-vitro and in-vivo. Photobleaching of IRDye700DX increased with lower fluence rates and correlated with efficacy. The response in EGFR targeted PDT is strongly dependent on fluence rate used. The effectiveness of targeted PDT is, like PDT, dependent on the generation of singlet oxygen and thus the availability of intracellular oxygen.
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Keywords:
targeted; EGFR; photosensitizer; photodynamic therapy; intravital microscopy; growth delay
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MDPI and ACS Style
Peng, W.; de Bruijn, H.S.; ten Hagen, T.L.M.; Berg, K.; Roodenburg, J.L.N.; van Dam, G.M.; Witjes, M.J.H.; Robinson, D.J. In-Vivo Optical Monitoring of the Efficacy of Epidermal Growth Factor Receptor Targeted Photodynamic Therapy: The Effect of Fluence Rate. Cancers 2020, 12, 190.
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