Sentinel Node Localisation and Staging With Superparamagnetic Iron Oxide-enhanced MRI and Magtrace®/Sentimag® in Patients With Malignant Melanoma of the Extremities. The MAGMEN Feasibility Study

Background Sentinel node biopsy (SNB) is a well-established technique for nodal staging of malignant disease, including breast cancer and malignant melanoma. The sentinel node (SN) is the first lymph node to receive cancer cells in a given lymph node basin. The status of the SN is often the most important prognostic factor, and determines potential adjuvant therapy and follow-up. The SN is detected by injection of a radioactive isotope (Technetium 99m) and a blue dye around the tumour or the scar following primary resection. This is achieved by a lymphoscintigraphy which is usually performed the day before surgery which necessitates a nuclear medicine department. At the time of surgery, a blue dye (Patent blue) is injected at the same area prior to incision. Thereafter the SN is identified by a handheld gamma-probe and the dye which colours the sentinel node blue. The so called hot and blue lymph node is removed surgically and sent to pathology for staging.

The mortality of cutaneous malignant melanoma is high, especially when diagnosed in an advanced stage [4]. Accurate staging and prediction of outcome largely depend on the identification and examination of the SN. SNB is recommended in Sweden for melanomas with a Breslow thickness more than 1 mm. About 20% of SNs in patients with melanoma are positive, which affects follow-up and also potentially adjuvant therapies that recently have been approved.

SNB is a surgical technique with associated risk for complications, mainly seroma, infections and lymph-edema. If nodal status could be determined by imaging, the dissection of the sentinel node biopsy could be avoided. However, current imaging techniques, such as MRI, CT and ultrasound are not accurate enough to stage the lymph nodes preoperatively. Motomura et al. recently reported a technique where superparamagnetic iron-oxide (SPIO) is injected into the tumour in patients with breast cancer, followed by MRI scan. They found a 100% sensitivity and 96% specificity for node staging when being compared to SNB.

There has been an increasing interest in using SPIO for identifying the sentinel node in breast cancer and recent publications showed great accuracy when SPIO was used as the only tracer. The agent was injected intra tumoral or subcutaneously under the areola before surgery and the SN(s) was/were detected by use of a handheld probe (Sentimag, Endomagnetics Ltd). The Sentimag is a magnetometer, which measures the strength of the magnetic field created by the iron oxide particles in the SPIO. It is a handheld device that signals when it is close enough to a magnetic field. The method was compared for feasibility and sensitivity to the current method used for identifying the SN (Technetium and Patent blue) and it was found to be at least as reliable and accurate.

Concerning melanoma, the SPIO method has not been used except recently when the MELAMAG trial was published. SPIO was compared to blue dye and radioisotope for identification of sentinel node in clinically node negative patients with melanoma. 97.7% of patients had a sentinel node identified with the standard technique, whereas 95.3% were identified with the magnetic tracer.