MR lymphography and magnetic sentinel lymph node biopsy in melanoma patients measured with DiffMag

The sentinel lymph nodes (SLN) are the first lymph nodes (LN) to drain the
tumor site and therefore the first LN to bare metastases. Hence the importance
to investigate these LN for the best treatment strategy. The current method for
SLN detection in e.g. melanoma and breast cancer patients uses radioactive
tracer (Tc99-m). Due to the use of radioisotopes, this procedure suffers from
several disadvantages such as limited availability, strict rules and
regulations, degradation time in patient and radioactive load for user and
patient.
To overcome the limitations of a radioactive tracer, a magnetic SLNB was
developed which is facilitated by super paramagnetic iron-oxide (SPIO)
nanoparticles. This potentially offers numerous benefits making surgery
planning more flexible: no exposure to radiation, easy accessibility of the
tracer, long shelf time, long half time in the patient. Several aspects of this
magnetic procedure have been investigated in previous studies. However,
currently available commercial product for perioperative detection of
SPIO-enhanced LNs (Sentimag®, Endomagnetics, ltd., United Kingdom) is hampered
by a relatively low detection depth, biological noise, and effects of surgical
equipment. Therefore, with the current Sentimag® probe, the surgeons need to
switch to plastic or carbon equipment and the system needs to be balanced prior
to each measurement, which increases the surgery time by 20%.
A new and effective way to localize magnetic particles is differential
magnetometry (DiffMag). This patented detection principle, developed by
Magnetic Detection & Imaging (MD&I) group at University of Twente (UT),
utilizes the nonlinear magnetic response of nanoparticles. An additional
advantage of SPIOs is their visibility on MRI, which could map the nodes
preoperatively. Especially in patients with melanomas on the abdomen or back,
this would be very useful to see which lymph node stations are connected to the
melanoma. In addition, studies have shown that SPIOs are absorbed into lymph
nodes in different ways, depending on the presence of metastases. SPIO-enhanced
MR lymphography could therefore provide an opportunity for a non-invasive
preoperative assessment of nodal status.
In this pilot study we want to evaluate the clinical use of the DiffMag
handheld probe, and compare the detection and usability of the DiffMag with the
radioactive detection and the detection of the SentiMag for the furthur
optimazation of DiffMag. Moreover, we want to map the lymph nodes
preoperatively using MR lymphography. In addition, ex vivo MRI will be used to
examine the possibility of assessing the nodal status.

In this pilot study we want to evaluate the clinical use of the DiffMag
handheld probe, and compare the detection and usability of the DiffMag with the
radioactive detection and the detection of the SentiMag for furthur
optimazation of DiffMag magnetometer. Moreover, we want to map the lymph nodes
preoperatively using MR lymphography. In addition, ex vivo MRI will be used to
examine the possibility of recognizing metastases in LN.

Experimental, minimally invasive, pilot study in melanoma patients.

Injection of Magtrace, pre- and post-injection a MRI scan will be made. During
surgery, the sentinel lymph node will be traced with the SentiMag and DiffMag
in addition to the conventional procedure.

This research will not be beneficial to the subject. However, the results of
the study will be used to optimize the SLNB procedure. The study outcomes are
used to progress to a radiation-free and minimally invasive procedure. The
benefits are concerning the future patient group, including not only melanoma
patients, but also breast cancer patients and potentially all solid cancers
eligible for SLNB.
The study won*t delay diagnosis or treatment, the MRI scans and Magtrace
injection will be scheduled as much as possible with regular hospital visits.
The possible delay of the surgical date will be in the order of days and the
time between surgery and treatment will always be according to the national
guidelines. The extra time will be a maximum of 15-20 minutes.
The only burden is the extra injection of iron containing particles, with an
effective amount of iron which is lower than the amount of iron injected safely
in previous studies. The patient will not experience any side effects from the
two in-vivo MRI scans in this study. Prior to MRI, patients follow the standard
questionnaire that applies to all other MRI examinations in the hospital. With
the questionnaire will be determined if the patient is suitable for the MRI
examinations.