Modalities for image- and molecular-guided cancer surgery.

BACKGROUND: Surgery is the cornerstone of treatment for many solid tumours. A wide variety of imaging modalities are available before surgery for staging, although surgeons still rely primarily on visual and haptic cues in the operating environment. Image and molecular guidance might improve the adequacy of resection through enhanced tumour definition and detection of aberrant deposits. Intraoperative modalities available for image- and molecular-guided cancer surgery are reviewed here. METHODS: Intraoperative cancer detection techniques were identified through a systematic literature search, with selection of peer-reviewed publications from January 2012 to January 2017. Modalities were reviewed, described and compared according to 25 predefined characteristics. To summarize the data in a comparable way, a three-point rating scale was applied to quantitative characteristics. RESULTS: The search identified ten image- and molecular-guided surgery techniques, which can be divided into four groups: conventional, optical, nuclear and endogenous reflectance modalities. Conventional techniques are the most well known imaging modalities, but unfortunately have the drawback of a defined resolution and long acquisition time. Optical imaging is a real-time modality; however, the penetration depth is limited. Nuclear modalities have excellent penetration depth, but their intraoperative use is limited by the use of radioactivity. Endogenous reflectance modalities provide high resolution, although with a narrow field of view. CONCLUSION: Each modality has its strengths and weaknesses; no single technique will be suitable for all surgical procedures. Strict selection of modalities per cancer type and surgical requirements is required as well as combining techniques to find the optimal balance.

Preclinical uPAR-targeted multimodal imaging of locoregional oral cancer.

OBJECTIVES: Establishing adequate resection margins and lymphatic mapping are crucial for the prognosis of oral cancer patients. Novel targeted imaging modalities are needed, enabling pre- and intraoperative detection of tumour cells, in combination with improved post-surgical examination by the pathologist. The urokinase-receptor (uPAR) is overexpressed in head and neck cancer, where it is associated with tumour progression and metastasis. MATERIAL AND METHODS: To determine suitability of uPAR for molecular imaging of oral cancer surgery, human head and neck tumours were sectioned and stained for uPAR to evaluate the expression pattern compared to normal mucosa. Furthermore, metastatic oral squamous carcinoma cell line OSC-19 was used for targeting uPAR in in vivo mouse models. Using anti-uPAR antibody ATN-658, equipped with a multimodal label, the in vivo specificity was investigated and the optimal dose and time-window were evaluated. RESULTS: All human oral cancer tissues expressed uPAR in epithelial and stromal cells. Hybrid ATN-658 clearly visualized tongue tumours in mice using either NIRF or SPECT imaging. Mean fluorescent TBRs over time were 4.3±0.7 with the specific tracer versus 1.7±0.1 with a control antibody. A significant difference in TBRs could be seen between 1nmol (150µg) and 0.34nmol (50µg) dose groups (n=4, p<0.05). Co-expression between BLI, GFP and the NIR fluorescent signals were seen in the tongue tumour, whereas human cytokeratin staining confirmed presence of malignant cells in the positive cervical lymph nodes. CONCLUSION: This study shows the applicability of an uPAR specific multimodal tracer in an oral cancer model, combining SPECT with intraoperative guidance.