Theranostics 2019; 9(9):2727-2738. doi:10.7150/thno.31225

Research Paper

Use of Porphysomes to detect primary tumour, lymph node metastases, intra-abdominal metastases and as a tool for image-guided lymphadenectomy: proof of concept in endometrial cancer

Lauren Philp1,2✉, Harley Chan3, Marjan Rouzbahman4, Marta Overchuk5, Juan Chen6, Gang Zheng1,5,6,7✉, Marcus Q. Bernardini1,8

1. Institute of Medical Science, University of Toronto, Toronto, ON, Canada
2. Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada
3. Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, ON, Canada
4. Department of Pathology, Princess Margaret Cancer Center, University Health Network, Toronto ON, Canada,
5. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada
6. Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
7. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
8. Division of Gynecologic Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada

Abstract

Objective: To investigate Porphysome fluorescence image-guided resection (PYRO-FGR) for detection of uterine tumour, metastatic lymph nodes and abdominal metastases in a model of endometrial cancer.

Methods: White New Zealand rabbits were inoculated with VX2 cells via intra-myometrial injection. At 30 days, Porphysomes were administered intravenously. At 24 h the abdomen was imaged and fluorescent tissue identified (PYRO-FGR). After complete resection of fluorescent tissue, fluorescence-negative lymph nodes and peritoneal biopsies were removed. Histopathology including ultra-staging and analysis by a pathologist was used to detect tumour. Fluorescence signal to background ratio (SBR) was calculated and VX2 (+) tissue compared to VX2 (-) tissue. Biodistribution was calculated and Porphysome accumulation in fluorescent VX2 (+) tissue compared to fluorescent VX2 (-) and non-fluorescent VX2 (-) tissue.

Results: Of 17 VX2 models, 10 received 4 mg/kg of Porphysomes and 7 received 1 mg/kg. Seventeen tumours (UT), 81 lymph nodes (LN) and 54 abdominal metastases (AM) were fluorescence-positive and resected. Of these, 17 UT, 60 LN and 45 AM were VX2 (+), while 16 LN and 5 AM were VX2 (-). Nine specimens were excluded from analysis. Thirty-one LN and 53 peritoneal biopsies were fluorescence-negative and resected. Of these, all LN and 51/53 biopsies were VX2 (-) with only 2 false-negative biopsies. Sensitivity and specificity of PYRO-FGR for VX2 (+) tissue was 98.4% / 80.0% overall, 100% / 100% for UT, 100% / 66.0 % for LN and 95.7% / 91.4% for AM. Increased SBR and biodistribution was observed in VX2 (+) tissue vs. VX2 (-) tissue.

Conclusions: Porphysomes are a highly sensitive imaging agent for intra-operative detection and resection of uterine tumour, metastatic lymph nodes and abdominal metastases.

Keywords: Fluorescence guided surgery, Optical Imaging, Porphyrin nanoparticle, Porphysome, Endometrial Cancer

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How to cite this article:
Philp L, Chan H, Rouzbahman M, Overchuk M, Chen J, Zheng G, Bernardini MQ. Use of Porphysomes to detect primary tumour, lymph node metastases, intra-abdominal metastases and as a tool for image-guided lymphadenectomy: proof of concept in endometrial cancer. Theranostics 2019; 9(9):2727-2738. doi:10.7150/thno.31225. Available from http://www.thno.org/v09p2727.htm