Sentinel lymph node mapping with superparamagnetic iron oxide for melanoma: a pilot study in healthy participants to establish an optimal MRI workflow protocol

Loeki Aldenhoven, Caroline Frotscher, Rachelle Körver-Steeman, Milou H Martens, Damir Kuburic, Alfred Janssen, Geerard L Beets, James van Bastelaar, Loeki Aldenhoven, Caroline Frotscher, Rachelle Körver-Steeman, Milou H Martens, Damir Kuburic, Alfred Janssen, Geerard L Beets, James van Bastelaar

Abstract

Background: Current pre-operative Sentinel Lymph Node (SLN) mapping using dual tracing is associated with drawbacks (radiation exposure, logistic challenges). Superparamagnetic iron oxide (SPIO) is a non-inferior alternative for SLN mapping in breast cancer patients. Limited research has been performed on SPIO use and pre-operative MRI in melanoma patients to identify SLNs. METHODS: Healthy participants underwent MRI-scanning pre- and post SPIO-injection during 20 min. Workflow protocols varied in dosage, massage duration, route of administration and injection sites. The first lymph node showing a susceptibility artefact caused by SPIO accumulation was considered as SLN.

Results: Artefacts were identified in 5/6 participants. Two participants received a 0.5 ml subcutaneous injection and 30-s massage, of which one showed an artefact after one hour. Four participants received a 1.0 ml intracutaneous injection and two-minute massage, leading to artefacts in all participants. All SLNs were observed within five minutes, except after lower limb injection (30 min).

Conclusion: SPIO and pre-operative MRI-scanning seems to be a promising alternative for SLN visualization in melanoma patients. An intracutaneous injection of 1.0 ml SPIO tracer, followed by a two-minute massage seems to be the most effective technique, simplifying the pre-operative pathway. Result will be used in a larger prospective study with melanoma patients.

Trial registration: ClinicalTrials.gov (NCT05054062) - September 9, 2021.

Keywords: Magnetic iron oxide nanoparticles; Melanoma; Sentinel lymph node biopsy; Surgical oncology.

Conflict of interest statement

Not applicable.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Detailed information about SPIO injections and time of appearance of SLNs
Fig. 2
Fig. 2
Pre- and post-injection (0.5 ml) T1-weighted coronal images of the anterior upper trunk in participant one. A Image before tracer injection. B Image of injection site showing a large decrease in signal. C Image of lymphatic tracer uptake in right axillary LN, one hour post-injection. The first LN showing a large decreased signal and therefore considered to be the SLN, indicated with the white circle
Fig. 3
Fig. 3
Pre- and post-injection (1.0 ml) T1-weighted coronal images of the upper limb, lower arm. A Image before tracer injection. B Image of injection site showing a large decrease in signal in LN tract, indicated with the white arrows. C Image of lymphatic tracer uptake in right axillary LN, five minutes post-injection. The first LN showing a large decreased signal and therefore considered to be the SLN, indicated with the white circle
Fig. 4
Fig. 4
Post-injection (1.0 ml) T1-weighted coronal images of the anterior upper trunk. A Image after tracer injection. Lymphatic uptake towards upper body is indicated with the white arrows and lymphatic uptake towards groins is indicated with the black arrows. B Image showing a large decrease in signal in groin lymph vessels. C Image of lymphatic tracer uptake in both groin LNs, five minutes post-injection. The first LN showing a large decreased signal and therefore considered to be the SLN, indicated with the black circle
Fig. 5
Fig. 5
Skin discoloration of the lower arm after 1.0 ml intracutaneous SPIO injection. A Two hours post-injection. B Five weeks post-injection. C Five months post-injection

References

    1. Stiegel E, Xiong D, Ya J, Funchain P, Isakov R, Gastman B, Vij A. Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma. J Am Acad Dermatol. 2018;78(5):942–948. doi: 10.1016/j.jaad.2018.01.030.
    1. Keung EZ, Gershenwald JE. The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: implications for melanoma treatment and care. Expert Rev Anticancer Ther. 2018;18(8):775–784. doi: 10.1080/14737140.2018.1489246.
    1. Thompson JF, Uren RF, Shaw HM, McCarthy WH, Quinn MJ, O’Brien CJ, Howman-Giles RB. Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy. J Am Coll Surg. 1999;189(2):195–204.
    1. Thill M, Kurylcio A, Welter R, van Haasteren V, Grosse B, Berclaz G, Polkowski W, Hauser N. The Central-European SentiMag study: sentinel lymph node biopsy with superparamagnetic iron oxide (SPIO) vs. radioisotope. Breast. 2014;23(2):175–179. doi: 10.1016/j.breast.2014.01.004.
    1. Karakatsanis A, Olofsson H, Stålberg P, Bergkvist L, Abdsaleh S, Wärnberg F. Simplifying Logistics and Avoiding the Unnecessary in Patients With Breast Cancer Undergoing Sentinel Node Biopsy. A Prospective Feasibility Trial of the Preoperative Injection of Super Paramagnetic Iron Oxide Nanoparticles. Scand J Surg. 2018;107(2):130–137. doi: 10.1177/1457496917738867.
    1. Shams S, Lippold K, Blohmer JU, Röhle R, Kühn F, Karsten MM: A Pilot Study Evaluating the Effects of Magtrace® for Sentinel Node Biopsy in Breast Cancer Patients Regarding Care Process Optimization, Reimbursement, Surgical Time, and Patient Comfort Compared With Standard Technetium(99). Ann Surg Oncol 2020.
    1. Alvarado MD, Mittendorf EA, Teshome M, Thompson AM, Bold RJ, Gittleman MA, Beitsch PD, Blair SL, Kivilaid K, Harmer QJ, Hunt KK. SentimagIC: A Non-inferiority Trial Comparing Superparamagnetic Iron Oxide Versus Technetium-99m and Blue Dye in the Detection of Axillary Sentinel Nodes in Patients with Early-Stage Breast Cancer. Ann Surg Oncol. 2019;26(11):3510–3516. doi: 10.1245/s10434-019-07577-4.
    1. Mok CW, Tan SM, Zheng Q, Shi L. Network meta-analysis of novel and conventional sentinel lymph node biopsy techniques in breast cancer. BJS Open. 2019;3(4):445–452. doi: 10.1002/bjs5.50157.
    1. Endomag (2021). Endomag - magtrace - overview. Retrieved on March 16, 2021. [].
    1. Piñero-Madrona A, Torró-Richart JA, de León-Carrillo JM, de Castro-Parga G, Navarro-Cecilia J, Domínguez-Cunchillos F, Román-Santamaría JM, Fuster-Diana C, Pardo-García R. Superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast cancer: A comparative non-inferiority study. European Journal of Surgical Oncology (EJSO) 2015;41(8):991–997. doi: 10.1016/j.ejso.2015.04.017.
    1. Ghilli M, Carretta E, Di Filippo F, Battaglia C, Fustaino L, Galanou I, Di Filippo S, Rucci P, Fantini MP, Roncella M. The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment. Eur J Cancer Care. 2017;26(4):e12385. doi: 10.1111/ecc.12385.
    1. Pouw JJ, Grootendorst MR, Bezooijen R, Klazen CA, De Bruin WI, Klaase JM, Hall-Craggs MA, Douek M, Ten Haken B. Pre-operative sentinel lymph node localization in breast cancer with superparamagnetic iron oxide MRI: the SentiMAG Multicentre Trial imaging subprotocol. Br J Radiol. 2015;88(1056):20150634. doi: 10.1259/bjr.20150634.
    1. Piñero-Madrona A, Nicolás-Ruiz F, Rull-Ortuño R, Vidal-Sicart S, Cabañas-Montero J, Rioja-Martín ME, Rodríguez-Fernández R, Gil-Olarte MÁ, González-García B, Sánchez JH. Correlation between ferromagnetic and isotopic tracers for sentinel lymph node detection in cutaneous melanoma: IMINEM study. J Surg Oncol. 2021;123(2):654–659. doi: 10.1002/jso.26303.
    1. Anninga B, White SH, Moncrieff M, Dziewulski P, Geh JLC, Klaase J, Garmo H, Castro F, Pinder S, Pankhurst QA, Hall-Craggs MA, Douek M, MELAMAG MulticentreTrialists Group Magnetic Technique for Sentinel Lymph Node Biopsy in Melanoma: The MELAMAG Trial. Ann Surg Oncol. 2016;23(6):2070–2078. doi: 10.1245/s10434-016-5113-7.
    1. Katsarelias D, Petrusson H, Leonhardt H, Zaar P, Mattsson J, Bagge RO. Sentinel Node Localisation and Staging with Superparamagnetic Iron Oxide-Enhanced MRI and Sentimag in Patients with Malignant Melanoma. The MAGMEN Feasibility Study. EJSO. 2020;46(2):e131. doi: 10.1016/j.ejso.2019.11.341.
    1. Pouw JJ, Ahmed M, Anninga B, Schuurman K, Pinder SE, Van Hemelrijck M, Pankhurst QA, Douek M, Ten Haken B. Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model. Int J Nanomedicine. 2015;10:1235–1243. doi: 10.2147/IJN.S76962.
    1. Douek M, Klaase J, Monypenny I, Kothari A, Zechmeister K, Brown D, Wyld L, Drew P, Garmo H, Agbaje O, Pankhurst Q, Anninga B, Grootendorst M, Ten Haken B, Hall-Craggs MA, Purushotham A, Pinder S. SentiMAG Trialists Group: Sentinel node biopsy using a magnetic tracer versus standard technique: the SentiMAG Multicentre Trial. Ann Surg Oncol. 2014;21(4):1237–1245. doi: 10.1245/s10434-013-3379-6.
    1. Hersi AF, Pistiolis L, Dussan Luberth C, Vikhe-Patil E, Nilsson F, Mohammed I, Olofsson Bagge R, Wärnberg F, Eriksson S, Karakatsanis A. Optimizing Dose and Timing in Magnetic Tracer Techniques for Sentinel Lymph Node Detection in Early Breast Cancers: The Prospective Multicenter SentiDose Trial. Cancers (Basel) 2021;13(4):693. doi: 10.3390/cancers13040693.
    1. Conduct Science. Magnetic Resonance Imaging (MRI) in Research (April 25, 2019). Retrieved on March 24, 2021. [].
    1. Endomagnetics. Highlights of instructions for use - Magtrace (July, 2018). Retrieved on March 24, 2021. [].
    1. Sysmex Europe, Endomagnetics: Sentimag - Magnetic localisation of sentinel lymph nodes - easy flexible and effective. Retrieved on March 24, 2021. .
    1. Karakatsanis A, Hersi AF, Pistiolis L, Olofsson Bagge R, Lykoudis PM, Eriksson S, Wärnberg F. SentiNot Trialists Group: Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study) Br J Surg. 2019;106(6):720–728. doi: 10.1002/bjs.11110.
    1. Wärnberg F, Stigberg E, Obondo C, Olofsson H, Abdsaleh S, Wärnberg M, Karakatsanis A. Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery. Ann Surg Oncol. 2019;26(5):1247–1253. doi: 10.1245/s10434-019-07239-5.

Source: PubMed

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