INTRAOPERATIVE REAL TIME IMAGING WITH A DUAL RADIOACTIVE/FLUORESCENCE MODALITY FOR SENTINEL NODE LOCALIZATION. A FEASIBILITY STUDY INCLUDING REPRODUCIBILITY OF MULTIMODALITY LYMPHATIC MAPPING WITH A COCKTAIL TRACER CONTAINING 99mTc NANOCOLLOID /ICG

Lymphoscintigraphy can determine the lymphatic pattern and the location of the
lymph nodes with direct drainage from the tumor site, the sentinel nodes. The
sentinel node is likely to be the first node to harbor tumor cells, which may
lead to change the patients* management. Preoperative lymphoscintigraphy in
combination with intraoperative blue dye and gamma probe detection has led to
sentinel node retrieval rates of 99% in melanoma and more than 95% in breast
cancer, in the past 15 years. The technique has been adopted for other
malignancies for better staging and to diminish the morbidity of the standard
surgical approaches. However, in some conditions sentinel nodes are difficult
to be found. This is the case for sentinel nodes located in the neck in
patients with cutaneous melanoma and oral cavity malignancies. Also in patients
with melanomas of the upper part of the trunk sentinel nodes may be located in
areas difficult to explore. Finally, in almost a third of breast cancer
patients sentinel nodes outside of the axilla are seen and in only 80% of the
cases these sentinel nodes can be retrieved. Against this background the
introduction of a portable gamma camera for real time intraoperative imaging
and a 99mTc-nanocolloid tracer and Indocyanine Green (ICG) cocktail for
simultaneous radioactive and fluorescence detection may enable the localization
of sentinel nodes difficult to retrieve. In the present study we will explore
the feasibility of this diagnostic combination in patients with melanoma of the
head/neck or the upper part of the trunk, patients with oral malignancies and
patients with a medially located breast tumor and demonstrated lymphatic
drainage outside the axilla. At the same time we will assess the
reproducibility of the lymphatic drainage using the tracer cocktail in
comparison with the patterns of the standard 99mTc -nanocolloid.

1. To explore whether the intraoperative combination of a portable gamma
camera for real time imaging and a 99mTc nanocolloid/ICG cocktail for
simultaneous radioactive and fluorescence detection is suitable to retrieve
sentinel nodes in difficult anatomical areas in patients with malignancies
characterized by superficial drainage patterns.
2. To establish the reproducibility of the 99mTc nanocolloid/ICG cocktail in
comparison to the standard 99mTc -nanocolloid.

This is a prospective feasibility study involving cancer patients scheduled for
sentinel node localization in areas of difficult surgical exploration. In this
study intraoperative sentinel node localization using a portable gamma camera
and a dual-labeled 99mTc/ICG tracer will be performed in addition to the
standard sentinel node procedure. At the same time lymphatic patterns of
99mTc-nanocolloid and the cocktail will be compared. The hypothesis to be
tested is that this diagnostic combination will be reproducible, suitable and
effective in the localization of the sentinel node in anatomical areas with a
recognised surgical difficulty degree.
The patients will be investigated in addition to the standard sentinel node
procedure by re-injecting the dual-tracer. Subsequently patients will be
operated within 4 hours after tracer administration. Sentinel node retrieval
rates will be recorded and both the length of the surgical procedure and the
acceptation degree by the surgeon will be evaluated using special formularies.
Furthermore early gamma camera images of both tracers will be compared for
reproducibility. It is expected that fluorescent sentinel node visualisation
rates will be similar to radioactive sentinel node rates for melanoma and oral
cavity malignancies. In the case of internal mammary sentinel nodes it is
expected that fluorescent sentinel node rate (>90%) will be significantly
higher than blue dye (30%). It is also expected that sentinel node retrieval
rate will be more than 90% in all patient categories.

Allergic reactions or other adverse effects following administration of
99mTc-nanocolloid have not been described. The total dosage of radioactivity is
within the limits that are recommended.
Allergic reactions to the fluorescence component ICG in the cocktail are not
expected. ICG is a FDA approved agent for human use. This compound has been
safely applied in humans.