Trial Information

Validation of Uptake of a VEGF-targeted Optical Fluorescent Imaging Tracer in Surgical Specimens of Breast Cancer and Application of Pre- and Intra-operative Human Molecular Fluorescence Imaging Techniques. A Multicenter Feasibility Study

There is a need for better visualization of presence and extent of breast cancer to improve
breast cancer management. Molecular imaging of breast cancer associated targets is a
promising method to improve visualization. Vascular endothelial growth factor (VEGF) has
proven to be a valid target for molecular imaging with radioactive labeled tracers. However
in view of radiation safety, infrastructure, costs and stability, fluorescent labeling of
bevacizumab (a VEGF targeting humanized monoclonal antibody) has potential advantages over
radioactive labeling. Therefore recently the near-infrared fluorescent tracer
bevacizumab-IRDye 800CW has been developed. In mice the fluorescent signal was clearly
present in tumor tissue and could be visualized intra-operatively. The tracer was also
approved for administration to patients in a microdose (tracer dose).

In this prospective multicenter feasibility study the new tracer bevacizumab-IRDye 800CW
will be administered to a maximum of 30 patients with proven breast cancer 3 days before
surgery. Part of the surgical specimen will after surgery extensively be investigated by
macroscopy and microscopy to determine the uptake of the tracer in tumor tissue, surrounding
normal tissue and lymph nodes. To detect the tracer before surgery, two different
pre-operative imaging methods are used: MSOT (in the UMCG en FDOT in the UMCU. During
surgery the intra-operative MFRI camera is available at both centers to detect the
fluorescent signal.

The study consists of a total of five study procedure related patient visits.

1. During a screening visit, eligibility will be evaluated and patient characteristics
will be collected.

2. During the administration visit, 3 days before surgery, 4.5 mg of bevacizumab-IRDye
800CW will be administered intravenously, followed by 4 hours observation. Also before
and 4 hours after tracer injection pre-operative optical imaging will take place (in
the UMC Groningen, the hand-held MSOT system will be used and in the UMC Utrecht, the
FDOT system will be used) and blood samples are taken.

3. A third visit, approximately 36 hours after tracer administration, another
pre-operative optical imaging procedure will take place.

4. At the day of surgery, first a blood sample will be taken and the last pre-operative
optical imaging procedure will take place, followed by standard surgery. During
surgery, the MFRI camera will be used to detect a fluorescent signal before and after
incision an after removal of the tumor. Part of the surgical specimen will after
surgery extensively be investigated by macroscopy and microscopy to determine the
uptake of the tracer in tumor tissue, surrounding normal tissue and lymph nodes.

5. At an outpatient visit (approximately 10 days after surgery) (visit 5), the last blood
sample will be taken.