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ERC

SURVIVE Report Summary

Project ID: 323105
Funded under: FP7-IDEAS-ERC
Country: Netherlands

Mid-Term Report Summary - SURVIVE (Integrating cancer detection and SURgery Via molecular Imaging)

The aim of this ERC-advanced grant proposal is to develop strategies that will connect cancer detection and surgery via tumor-specific molecular imaging techniques. This will lead to personalized patient-, or even tumor-specific treatment strategies. In addition, it will provide a tool for the selection of patients that, following preoperative (neoadjuvant) treatment, would benefit from additional (minimally invasive) surgery and identify patients who may be treated non-operatively. If pathological complete response (pCR) after neoadjuvant treatment can be predicted accurately, surgery could potentially be avoided. Further optimization of non-invasive imaging strategies for response monitoring is therefore crucial as sensitivity of current conventional imaging modalities is not yet sufficient.
To achieve this, this project develops tumor-targeted tracers that are both radioactive and fluorescent, allowing preoperative surgical planning and intraoperative resection margin assessment. In the first phase of this project several novel synthesis routes have been developed. Novel symmetric and asymmetric near-infrared molecules with superior manufacturability, stability and photophysical properties have been prepared and analyzed. An asymmetric dye has been selected for further development and conjugation to a multimodal (PET and near infrared) label for monoclonal antibody trastuzumab. Moreover, a novel synthetic route for the synthesis of cGMP-grade cRGD has been designed and a robust synthesis protocol is now available for the preparation of multimodal labels for trastuzumab and cRGD.
In vivo experiments showed high tumor-to-background ratios of fluorescence imaging and SPECT up to 7 days post injection of 1 nmol trastuzumab-DTPA[111In]-NIRD5. Importantly, fluorescence signals in tumors remained very stable, allowing sufficient time for preoperative nuclear imaging for surgical planning and intraoperative fluorescence imaging for margin assessment. An new fluorescence imaging system optimized for NIRD5 is being developed to ensure maximal sensitivity.
Using intraoperative navigation, surgeons should be able to locate a surgical instrument relative to the navigation target and the anatomy. At the same time, the surgeon should be able to identify critical structures (e.g. nerves, blood vessels). To address these clinical requirements, a novel interactive focus-and-context multi-view direct volume rendering visualization approach has been developed. Our approach guarantees an unobstructed view of the navigated instrument tip in the context of the surrounding anatomy, allowing a precise visual estimate of the tool’s position in the anatomy at all times. We developed first a first prototype 3D interactive segmentation tool, which allows the easy switching between multiple co-registered patient scans. One could for example start navigation on a CT scan, then switch to an MR scan when approaching a region that is better visible in this modality.
The benefits of surgical navigation and fluorescence imaging are combined by integrating a robot-integrated fluorescence laparoscope with the surgical navigation system. This hybrid navigation setup allows the use of both guidance via pre- or intraoperative patient scans and the real-time intraoperative guidance via fluorescence imaging. The first phantom experiments performed suggest that SPECT-based navigation of the robot-integrated fluorescence laparoscope is feasible and may aid fluorescence-guided surgery, both in laparoscopic and open surgical procedures.
To date, available imaging modalities are not sufficiently sensitive to accurately predict a pathologic complete response (pCR) in breast cancer patients who have undergone neoadjuvant therapy and will undergo surgery according to the current standard. Our novel imaging modalities aim to improve surgical planning and the predictive value for a pCR.
With regards to rectal cancer patients, we can conclude that DW-MRI and FDG-PET/CT are acceptable imaging modalities to assess response of the tumor to chemo-radiotherapy. This is in line with conclusions of the expert panel discussions. However, tumor-targeted PET imaging might be of added value, as accuracy for lymph node assessment remains insufficient with currently available imaging modalities.

Reported by

ACADEMISCH ZIEKENHUIS LEIDEN - LEIDS UNIVERSITAIR MEDISCH CENTRUM
Netherlands
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