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

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.

The Dark Side: Photosensitizer Prodrugs

“…In addition, they also observed the persistence of nanovesicles at the tumor site after 24 h and 48 h post-injection [79]. Another example of the diagnostic utility of these nanoparticles was shown by Philp et al, who used porphysomes to guide the detection and real-time resection of primary tumors, lymph nodes and abdominal metastasis in rabbits [80].…”

Multiplexed NIR‐II Probes for Lymph Node‐Invaded Cancer Detection and Imaging‐Guided Surgery

“…Tumor metastasis monitoring/detection is the key for tumor staging and therapeutic decision‐making as well as prognosis. Since tumor cells spread mainly through lymphatic vessels to distant organs/tissues, the adjacent lymph nodes (LNs), sentinel LNs, are usually excised for tumor metastasis detection through biopsy . If the sentinel LNs are free of cancer, this indicates that cancer is unlikely to have spread and that removal of additional LNs is unnecessary; vice versa.…”

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

“…Rapamycin was found to more effectively inhibit tumor growth in PTEN-negative EC tumors compared to PTEN-positive [38]. Similar to SLN-mapping using fluorescent dyes in humans, fluorescence-guided resection of primary tumor and metastatic lymph nodes in an orthotopic rabbit model of EC yielded overall good sensitivity and specificity overall [39].…”