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Within-patient comparison between [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy and [99mTc]Tc-tilmanocept lymphoscintigraphy for sentinel lymph node detection in oral cancer: a pilot study

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Abstract

Purpose

To compare sentinel lymph node (SLN) identification using [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy to [99mTc]Tc-tilmanocept lymphoscintigraphy (including SPECT/CT) in early-stage oral cancer. Furthermore, to assess whether reliable intraoperative SLN localization can be performed with a conventional portable gamma-probe using [99mTc]Tc-tilmanocept without the interference of [68Ga]Ga-tilmanocept in these patients.

Methods

This prospective within-patient comparison pilot study evaluated SLN identification by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy compared to conventional lymphoscintigraphy using [99mTc]Tc-tilmanocept (~ 74 MBq) in 10 early-stage oral cancer patients scheduled for SLN biopsy. After conventional [99mTc]Tc-tilmanocept lymphoscintigraphy, patients underwent peritumoral administration of [68Ga]Ga-tilmanocept (~ 10 MBq) followed by PET/CT acquisition initiated 15 min after injection. Intraoperative SLN localization was performed under conventional portable gamma-probe guidance the next day; the location of harvested SLNs was correlated to both lymphoscintigraphic images in each patient.

Results

A total of 24 SLNs were identified by [99mTc]Tc-tilmanocept lymphoscintigraphy, all except one were also identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy. [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy identified 4 additional SLNs near the injection site, of which two harbored metastases. Lymphatic vessels transporting [68Ga]Ga-tilmanocept were identified by PET/CT lymphoscintigraphy in 80% of patients, while draining lymphatic vessels were visualized by [99mTc]Tc-tilmanocept lymphoscintigraphy in 20% of patients. Of the 33 SLNs identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy, 30 (91%) were intraoperatively localized under conventional gamma-probe guidance.

Conclusion

[68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy provided more accurate identification of SLNs and improved visualization of lymphatic vessels compared to [99mTc]Tc-tilmanocept lymphoscintigraphy. When combined with peritumoral administration of [99mTc]Tc-tilmanocept, SLNs detected by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy can be reliably localized during surgery under conventional gamma-probe guidance.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

References

  1. D’Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med. 2015;373(6):521–9. https://doi.org/10.1056/NEJMoa1506007.

  2. de Bree R, de Keizer B, Civantos FJ, Takes RP, Rodrigo JP, Hernandez-Prera JC, et al. What is the role of sentinel lymph node biopsy in the management of oral cancer in 2020? Eur Arch Otorhinolaryngol. 2021;278(9):3181–91. https://doi.org/10.1007/s00405-020-06538-y.

    Article  PubMed  Google Scholar 

  3. Garrel R, Poissonnet G, Moyà Plana A, Fakhry N, Dolivet G, Lallemant B, et al. Equivalence randomized trial to compare treatment on the basis of sentinel node biopsy versus neck node dissection in operable T1–T2N0 oral and oropharyngeal cancer. J Clin Oncol. 2020;38(34):4010–8. https://doi.org/10.1200/JCO.20.01661.

    Article  PubMed  Google Scholar 

  4. den Toom IJ, Boeve K, Lobeek D, Bloemena E, Donswijk ML, de Keizer B, et al. Elective neck dissection or sentinel lymph node biopsy in early stage oral cavity cancer patients: the Dutch experience. Cancers (Basel). 2020;12(7):1783. https://doi.org/10.3390/cancers12071783.

    Article  CAS  Google Scholar 

  5. Murer K, Huber GF, Haile SR, Stoeckli SJ. Comparison of morbidity between sentinel node biopsy and elective neck dissection for treatment of the n0 neck in patients with oral squamous cell carcinoma. Head Neck. 2011;33(9):1260–4. https://doi.org/10.1002/hed.21622.

    Article  PubMed  Google Scholar 

  6. Mahieu R, de Maar JS, Nieuwenhuis ER, Deckers R, Moonen C, Alic L, et al. New developments in imaging for sentinel lymph node biopsy in early-stage oral cavity squamous cell carcinoma. Cancers (Basel). 2020;12(10):3055. https://doi.org/10.3390/cancers12103055.

    Article  CAS  Google Scholar 

  7. Alkureishi LW, Ross GL, Shoaib T, Soutar DS, Robertson AG, Thompson R, et al. Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial. Ann Surg Oncol. 2010;17(9):2459–64. https://doi.org/10.1245/s10434-010-1111-3.

    Article  PubMed  Google Scholar 

  8. Pedersen NJ, Jensen DH, Hedbäck N, Frendø M, Kiss K, Lelkaitis G, et al. Staging of early lymph node metastases with the sentinel lymph node technique and predictive factors in T1/T2 oral cavity cancer: a retrospective single-center study. Head Neck. 2016;38(Suppl 1):E1033–40. https://doi.org/10.1002/hed.24153.

    Article  PubMed  Google Scholar 

  9. Stoeckli SJ, Huebner T, Huber GF, Broglie MA. Technique for reliable sentinel node biopsy in squamous cell carcinomas of the floor of mouth. Head Neck. 2016;38(9):1367–72. https://doi.org/10.1002/hed.24440.

    Article  PubMed  Google Scholar 

  10. den Toom IJ, Mahieu R, van Rooij R, van Es RJJ, Hobbelink MGG, Krijger GC, et al. Sentinel lymph node detection in oral cancer: a within-patient comparison between [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid. Eur J Nucl Med Mol Imaging. 2020. https://doi.org/10.1007/s00259-020-04984-8.

    Article  Google Scholar 

  11. Flach GB, Tenhagen M, de Bree R, Brakenhoff RH, van derWaal I, Bloemena E, et al. Outcome of patients with early stage oral cancer managed by an observation strategy towards the N0 neck using ultrasound guided fine needle aspiration cytology: no survival difference as compared to elective neck dissection. Oral Oncol. 2013;49(2):157–64.

    Article  PubMed  Google Scholar 

  12. Heuveling DA, Flach GB, van Schie A, van Weert S, Karagozoglu KH, Bloemena E, et al. Visualization of the sentinel node in early-stage oral cancer: limited value of late static lymphoscintigraphy. Nucl Med Commun. 2012;33(10):1065–9. https://doi.org/10.1097/MNM.0b013e3283571089.

    Article  PubMed  Google Scholar 

  13. Heuveling DA, van Schie A, Vugts DJ, Hendrikse NH, Yaqub M, Hoekstra OS, et al. Pilot study on the feasibility of PET/CT lymphoscintigraphy with 89Zr-nanocolloidal albumin for sentinel node identification in oral cancer patients. J Nucl Med. 2013;54(4):585–9. https://doi.org/10.2967/jnumed.112.115188.

    Article  CAS  PubMed  Google Scholar 

  14. Heuveling DA, Karagozoglu KH, Van Lingen A, Hoekstra OS, Van Dongen GAMS, De Bree R. Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium-labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe. EJNMMI Res. 2018;8(1):15. https://doi.org/10.1186/s13550-018-0368-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kasbollah A, Eu P, Cowell S, Deb P. Review on production of 89Zr in a medical cyclotron for PET radiopharmaceuticals. J Nucl Med Technol. 2013 Mar;41(1):35–41. https://doi.org/10.2967/jnmt.112.111377.

  16. Stroup SP, Kane CJ, Farchshchi-Heydari S, James CM, Davis CH, Wallace AM, et al. Preoperative sentinel lymph node mapping of the prostate using PET/CT fusion imaging and Ga-68-labeled tilmanocept in an animal model. Clin Exp Metastasis. 2012;29(7):673–80. https://doi.org/10.1007/s10585-012-9498-9.

    Article  PubMed  Google Scholar 

  17. Lee HJ, Barback CV, Hoh CK, Qin Z, Kader K, Hall DJ, et al. Fluorescence-based molecular imaging of porcine urinary bladder sentinel lymph nodes. J Nucl Med. 2017;58(4):547–53. https://doi.org/10.2967/jnumed.116.178582.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Qin Z, Hoh CK, Hall DJ, Vera DR. A tri-modal molecular imaging agent for sentinel lymph node mapping. Nucl Med Biol. 2015;42(12):917–22. https://doi.org/10.1016/j.nucmedbio.2015.07.011.

    Article  CAS  PubMed  Google Scholar 

  19. Anderson KM, Barback CV, Qin Z, Hall DJ, Hoh CK, Vera DR, et al. Molecular imaging of endometrial sentinel lymph nodes utilizing fluorescent-labeled tilmanocept during robotic-assisted surgery in a porcine model. PLoS ONE. 2018;13(7): e0197842. https://doi.org/10.1371/journal.pone.0197842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017 67(2):93–99. https://doi.org/10.3322/caac.21388.

  21. Brierley JD, Gospodarowicz M, Wittekind C. UICC TNM Classification of Malignant Tumours. 8th ed. Chichester, UK: Wiley; 2017.

    Google Scholar 

  22. Ebrahimi A, Gil Z, Amit M, Yen TC, Liao CT, Chaturvedi P, et al. Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: an international multicenter retrospective study. JAMA Otolaryngol Head Neck Surg. 2014;140(12):1138–48. https://doi.org/10.1001/jamaoto.2014.1548.

    Article  PubMed  Google Scholar 

  23. Alkureishi LW, Burak Z, Alvarez JA, Ballinger J, Bilde A, Britten AJ et al.; European Association of Nuclear Medicine Oncology Committee; European Sentinel Node Biopsy Trial Committee. Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma. Ann Surg Oncol. 2009;16(11):3190–210. https://doi.org/10.1245/s10434-009-0726-8.

  24. Dhawan I, Sandhu SV, Bhandari R, Sood N, Bhullar RK, Sethi N. Detection of cervical lymph node micrometastasis and isolated tumour cells in oral squamous cell carcinoma using immunohistochemistry and serial sectioning. J Oral Maxillofac Pathol. 2016;20(3):436–444.

  25. Yoneyama H, Tsushima H, Kobayashi M, Onoguchi M, Nakajima K, Kinuya S. Improved detection of sentinel lymph nodes in SPECT/CT images acquired using a low- to medium-energy general-purpose collimator. Clin Nucl Med. 2014;39(1):e1-6. https://doi.org/10.1097/RLU.0b013e31828da362.

    Article  PubMed  Google Scholar 

  26. Giammarile F, Schilling C, Gnanasegaran G, Bal C, Oyen WJG, Rubello D, et al. The EANM practical guidelines for sentinel lymph node localisation in oral cavity squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2019;46(3):623–37. https://doi.org/10.1007/s00259-018-4235-5.

    Article  PubMed  Google Scholar 

  27. Flach GB, van Schie A, Witte BI, Olmos RA, Klop WM, Hoekstra OS, et al. Practice variation in defining sentinel lymph nodes on lymphoscintigrams in oral cancer patients. Eur J Nucl Med Mol Imaging. 2014;41(12):2249–56. https://doi.org/10.1007/s00259-014-2843-2.

    Article  PubMed  Google Scholar 

  28. Collamati F, Bocci V, Castellucci P, De Simoni M, Fanti S, Faccini R, et al. Radioguided surgery with β radiation: a novel application with Ga68. Sci Rep. 2018;8(1):16171. https://doi.org/10.1038/s41598-018-34626-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hicks RJ, HofmanMS. Is there still a role for SPECT-CT in oncology in the PET-CT era? Nat Rev Clin Oncol. 2012;9(12):712–20. https://doi.org/10.1038/nrclinonc.2012.188.

  30. Ellner SJ, Hoh CK, Vera DR, Darrah DD, Schulteis G, Wallace AM. Dose-dependent biodistribution of [(99m)Tc]DTPA-mannosyl-dextran for breast cancer sentinel lymph node mapping. Nucl Med Biol. 2003;30(8):805–10. https://doi.org/10.1016/j.nucmedbio.2003.10.001.

    Article  CAS  PubMed  Google Scholar 

  31. Flach GB, Tenhagen M, de Bree R, Brakenhoff RH, van der Waal I, Bloemena E, et al. Outcome of patients with early stage oral cancer managed by an observation strategy towards the N0 neck using ultrasound guided fine needle aspiration cytology: no survival difference as compared to elective neck dissection. Oral Oncol. 2013;49(2):157–64. https://doi.org/10.1016/j.oraloncology.2012.08.006.

    Article  PubMed  Google Scholar 

  32. Brands MT, Smeekens EAJ, Takes RP, Kaanders JHAM, Verbeek ALM, Merkx MAW, et al. Time patterns of recurrence and second primary tumors in a large cohort of patients treated for oral cavity cancer. Cancer Med. 2019;8(12):5810–9. https://doi.org/10.1002/cam4.2124.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands

    Rutger Mahieu, Dominique N. V. Donders & Remco de Bree

  2. Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands

    Gerard C. Krijger, Remmert de Roos, John L. M. M. Bemelmans, Rob van Rooij & Bart de Keizer

  3. Department of Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands

    F. F. Tessa Ververs

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Correspondence to Bart de Keizer.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by UMC Utrecht’s Ethics Committee (no. 19/697). This study was registered in the Netherlands Trial Register (accessible via: https://www.trialregister.nl/): registration number NL8433. In addition, this study was registered in EudraCT (accessible via: https://eudract.ema.europa.eu/): registration number 2019–004914-32.

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Written informed consent was obtained from all participants included in this study.

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The authors declare no competing interests.

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This article is part of the Topical Collection on Oncology - Head and Neck.

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Mahieu, R., Donders, D.N.V., Krijger, G.C. et al. Within-patient comparison between [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy and [99mTc]Tc-tilmanocept lymphoscintigraphy for sentinel lymph node detection in oral cancer: a pilot study. Eur J Nucl Med Mol Imaging 49, 2023–2036 (2022). https://doi.org/10.1007/s00259-021-05645-0

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