Medical Radiology and Radiation Safety. 2023. Vol. 68. № 5

DOI:10.33266/1024-6177-2023-68-5-88-95

A.A. Medvedeva, A.N. Rуbina, R.V. Zeltchan, O.D. Bragina, A.V. Doroshenko,
E.Iu. Garbukov, N.A. Tarabanovskaya, L.A. Tashireva, V.I. Chernov

Radionuclide Diagnosis of Sentinel Lymph Nodes in Breast cancer with a Radiopharmaceutical Based on Technetium-99m Labeled Gamma Aluminum Oxide

Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia

Contact person: A.A. Medvedeva, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


ABSTRACT 

Аim: To analyze the results of radionuclide diagnostics of sentinel lymph nodes (SLN) in patients with breast cancer (BC) with the radiotracer Sentiscan, 99mTc (manufacturer “MedicorPharma-Ural”) using the multimodal SPECT/CT at the stage of visualization.

Material and methods: The study was retrospective, it included 48 patients with BC with clinical stage T2-3N0M0, who underwent radionuclide diagnostics of SLN and SPECT/CT was performed at the imaging stage. The images were evaluated visually, the intensity of the radiotracer accumulation in the lymph nodes (LN) was analyzed, SUVmax was used as a quantitative parameter. Intraoperative detection of SLN with subsequent histological examination was also carried out with the calculation of the level of the radiotracer accumulation.

Results: On tomoscintigrams, LNs were visualized in 43 patients out of 48, intraoperatively ‒ in 46 cases, in 2 patients, accumulation of the radiotracer in the LN projection was noted neither according to SPECT/CT, nor intraoperatively. When analyzing the intensity of the radiotracer accumulation according to SPECT/CT data, a rather large scatter of SUVmax‒35 [10‒104]. Sentinel were considered LNs with the level of the radiotracer accumulation in them of at least 10 % of the most intense node. According to SPECT/CT data, 165 lymph nodes were identified, the average number of lymph nodes detected in one patient was 2 [1‒3], the maximum number was 6 lymph nodes. In all patients, the lymph nodes were determined in the projection of the 1st level, in 25 cases ‒ in the projection of other zones of regional lymphatic outflow. The total number of lymph nodes removed during surgery was n=247, on average 3 [2‒5] lymph nodes were removed in one patient, with a maximum of 8 nodes.

Conclusion: The sensitivity of radionuclide diagnostics of SLN with Sentiscan, 99mTc was 89.6 % according to SPECT/CT and 95.8 % according to the results of intraoperative detection. The use of multimodal imaging provides information on the exact anatomical localization of the lymph nodes. In the absence of scintigraphic visualization of the radiotracer redistribution in the lymphatic collector, intraoperative detection does not lose its relevance.

Keywords: breast cancer, sentinel lymph node, radionuclide colloid, single photon emission computed tomography, gamma probe

For citation: Medvedeva AA, Rуbina AN, Zeltchan RV, Bragina OD, Doroshenko AV, Garbukov EIu, Tarabanovskaya NA, Tashire-
va LA, Chernov VI. Radionuclide Diagnosis of Sentinel Lymph Nodes in Breast cancer with a Radiopharmaceutical Based on Technetium-99m Labeled Gamma Aluminum Oxide. Medical Radiology and Radiation Safety. 2023;68(5):88–95. (In Russian). DOI:10.33266/1024-6177-2023-68-5-88-95

 

References

1. Cabañas R.M. An Approach for the Treatment of Penile Cancer. Cancer. 1977;39:456-466.

2. Morton D. Technical Details of Intraoperative Lymphatic Mapping for Early Stage Melanoma. Arch Surg. 1992;127;4:392. DOI: 10.1001/ archsurg.1992.01420040034005.

3. Alex J.C., Krag D.N. The Gamma-Probe-Guided Resection of Radiolabeled Primary. Lymph Nodes. Surg. Oncol. Clin. N Am. 1996;5;1:33–41.

4. Boada A., Tejera-Vaquerizo A., Ribero S., Puig S., Moreno-Ramírez D., Quaglino P., Osella-Abate S., Cassoni P., Malvehy J., Carrera C., Pigem R., Barreiro-Capurro A., Requena C., Traves V., Manrique-Silva E., Fernández-Orland A., Ferrandiz L., García-Senosiain O., Fernández-Figueras M.T., Ferrándiz C, Nagore E. Factors Associated with Sentinel Lymph Node Status and Prognostic Role of Completion Lymph Node Dissection for Thick Melanoma. Eur. J. Surg. Oncol. 2020;46;2:263–271. doi: 10.1016/j.ejso.2019.09.189. 

5. Lafuente-Sanchis A., Olmo A., Carretero J., Alcacer Fernandez-Coronado J., Estors-Guerrero M., Martínez-Hernández N.J., Cremades A., Zúñiga A., Alcacer J., Farras R., Cuenca M., Galbis-Caravajal J.M. Clinical Significance of Epithelial-mesenchymal Transition-related Markers Expression in the Micrometastatic Sentinel Lymph Node of NSCLC. Clin. Transl. Oncol. 2020;22;3:381–391. doi: 10.1007/s12094-019-02138-3.

6. Ni J.S., Janz T.A., Nguyen S.A., Lentsch E.J. Predictors of Occult Lymph Node Metastasis in Cutaneous Head and Neck Melanoma. World J. Otorhinolaryngol Head Neck Surg. 2019;5;4:200–206. doi: 10.1016/j.wjorl.2019.02.003.

7. Touhami O., Grégoire J., Renaud M.C., Sebastianelli A., Plante M. Performance of Sentinel Lymph Node (SLN) Mapping in High-risk Endometrial Cancer. Gynecol Oncol. 2017;147;3:549–553. doi: 10.1016/j.ygyno.2017.09.014.

8. Moo T.A., Sanford R., Dang C., Morrow M. Overview of Breast Cancer Therapy. PET Clin. 2018;13;3:339–354. doi: 10.1016/j.cpet.2018.02.006.

9. Plichta J.K. Breast Cancer Prognostic Staging and Internal Mammary Lymph Node Metastases: a Brief Overview. Chin. Clin. Oncol. 2019;8:1–11. DOI: 10.21037/cco.2019.01.09.

10. Chernov V.I., Dudnikova E.A., Zelchan R.V., Kravchuk T.L., Danilova A.V., Medvedeva A.A., Sinilkin I.G., Bragina O.D., Goldberg V.E., Goldberg A.V., Frolova I.G. The First Experience of Using 99mTc-1-Thio-d-Glucose for Single-Photon Emission Computed Tomography Imaging of Lymphomas. Siberian Journal of Oncology. 2018;17;4:81-87 (In Russ.).

11. Bragina O., Chernov V., Zelchan R., Medvedeva A., Schulga A., Vorobyeva A., Orlova A., Deyev S., Tolmachev V., Konovalova E., Garbukov E., Tashireva L., Sorensen J. Phase I trial of 99mTc-(He)3-G3, a Darpin-based Probe for Imaging of Her2 Expression in Breast Cancer. Journal of Nuclear Medicine. 2022;63;4:528-535. 

12. Chernov V.I., Medvedeva A.A., Sinilkin I.G., Zelchan R.V., Bragina O.D, Development Radiopharmaceuticals for Nuclear Medicine in Oncology. Meditsinskaya Vizualizatsiya = Medical Visualization. 2016;2:63-66 (In Russ.).

13. Zhang Jing-Jie, Zhang Wan-Chun, An Cai-Xia, Li Xiao-Min, Ma Le. Comparative Research on 99mTc-Rituximab and 99mTc-sulfur Colloid in Sentinel Lymph Node Imaging of Breast Cancer. BMC Cancer. 2019;19;1:956. doi: 10.1186/s12885-019-6197-9.

14. Unkart J.T., Hosseini A., Wallace A.M. Tc-99m Tilmanocept Versus Tc-99m Sulfur Colloid in Breast Cancer Sentinel Lymph Node Identification: Results from a Randomized, Blinded Clinical Trial. J. Surg. Oncol. 2017;116;7:819–823.

15. Krivorotko P.V., Kanayev S.V., Semiglazov V.F., Novikov S.N., Krzhivitskiy P.I., Semenov I.I., Turkevich E.A., Busko E.A., Donskikh R.V., Bryantseva Zh.V., Piskunov E.A., Trufanova E.S., Chernaya A.V. Methodological Problems of Sentinel Lymph Node Biopsy in Patients with Breast Cancer. Problems in Oncology. 2015;61;3:418-423 (In Russ.).

16. Giammarile F., Alazraki N., Aarsvold J.N., Audisio R.A., Glass E., Grant S.F., Kunikowska J., Leidenius M., Moncayo V.M., Uren R.F., Oyen W.J.G., Olmos R.A.V., Sicart S.V. The EANM and SNMMI Practice Guideline for Lymphoscintigraphy and Sentinel Node Localization in Breast Cancer. European Journal of Nuclear Medicine and Molecular Imaging. 2013;40:1932–1947.

17. Navalkissoor S., Wagner T., Gnanasegaran G. SPECT/CT in Imaging Sentinel Nodes. ClinTransl Imaging. 2015;3;3:203–215. doi: 10.1007/s40336- 015-0113-3. 

18. Olmos V.R.A., Rietbergen D.D.D., Vidal-Sicart S. SPECT/CT and Sentinel Node Lymphoscintigraphy. ClinTransl Imaging. 2014;2;6:491–504. doi: 10.1007/s40336-014-0087-6.

19. Mucientes R.J., Farge B.L., Cardona A.J., Moreno E.A., Delgado-Bolton R, Izarduy P.L., Rodríguez R.C., Lapeña G.L., González M.A., Román S.J.M., Carreras D.J.L. SPECT-CT: a New Tool for Localisation of Sentinel Lymph Nodes in Breast Cancer Patients. Rev. Esp. Med. Nucl. 2008;27;3:183-190.

20. Krzhivitskiy P.I., Kanayev S.V., Novikov S.N., Chernaya A.V., Krivorotko P.V., Semiglazov V.F., Semenov I.I., Ponomareva O.I., Ilin N.D., Zhukova L.A. Use of SPECT-CT for Visualization of Sentinel Lymph Nodes in Breast Cancer Patients. Problems in Oncology. 2015;61;4:624-626 (In Russ.).

21. Krzhivitskiy P.I., Kanayev S.V., Novikov S.N., Novikov R.V., Semenov I.I., Ponomareva O.I., Ilin N.D., Petrova A.S. The Use of SPECT-CT for Visualization of Sentinel Lymph Nodes and Lymph Drainage Pathways in Prostate Cancer Patients. Problems in Oncology. 2016;62;2:272-276 (In Russ.).

22. Kanayev S.V., Novikov S.N., Krzhivitskiy P.I., Radzhabova Z.A., Kotov M.A., Ponomareva O.I., Girshovich M.M., Artemyev S.S., Artemyeva A.S., Melnik Yu.S. SPECT-CT for Visualization of Sentinel Lymph Nodes and Lymph Flow from Tongue Cancer. Problems in Oncology. 2019;65;2:250-255 (In Russ.).

23. Jimenez-Heffernan A., Ellmann A., Sado H., Huić D., Bal C., Parameswaran R., Giammarile F., Pruzzo R., Kostadinova I., Vorster M., Almeida P., Santiago J., Gambhir S., Sergieva S., Calderon A., Young G.O., Valdes-Olmos R., Zaknun J., Magboo V.P., Pascual T.N. Results of a Prospective Multicenter International Atomic Energy Agency Sentinel Node Trial on the Value of SPECT/CT Over Planar Imaging in Various Malignancies. J. Nucl. Med. 2015;56;9:1338-1344. doi: 10.2967/jnumed.114.153643.

24. Pouw B., Hellingman D., Kieft M., Vogel W.V., van Os K.J., Rutgers E.J., Valdés Olmos R.A., Stokkel M.P. The Hidden Sentinel Node in Breast Cancer: Reevaluating the Role of SPECT/CT and Tracer Reinjection. Eur. J. Surg. Oncol. 2016;42;4:497-503. doi: 10.1016/j.ejso.2015.12.009.

25. Varlamova N.V., Skuridin V.S., Nesterov E.A., Larionova L.A., Chernov V.I. The Study of Cumulative Propertiesradiopharmaceutical Nanocolloid, 99mtс-Al2o3 in Rats. Bulletin of the Novosibirsk State University. Series: Biology, Clinical Medicine. 2015;13;2:40–44 (In Russ.).

26. Varlamova N.V., Stasyuk E.S., Titskaya A.A., Sinilkin I.G., Larionova L.A., SHerstoboyev E.Yu., Trofimova E.S., Ligacheva A.A., Skuridin V.S. The Study of the Allergenic Pproperties of the Radiopharmaceutical “Nanocolloid, 99mTc-Al2O3” in the Experiment. Modern Technologies in Medicine. 2015;4:72–77 (In Russ.).

27. Skuridin V.S., Chernov V.I., Varlamova N.V., Nesterov E.A., Sinilkin I.G., Zelchan R.V. Study of Functional Fitness Radiopharmaceuticals “Nanocolloids,99mTc-Al2O3” for Scintigraphic and Intraoperative Identification of “Sentinel” Lymph Nodes. Diagnostic and Interventional Radiology. 2015;3:76–80 (In Russ.).

28. Zelchan R.V., Medvedeva A.A., Sinilkin I.G., Bragina O.D., Chernov V.I., Stasyuk E.S., Ilina E.A., Skuridin V.S. Study of the Functional Suitability of the Tumoritropic Radiopharmaceutical 99mTc-1-Thio-6-Glucose in the Experiment. Molecular Medicine. 2018;16;3:54-57
(In Russ.).

29. Sinilkin I.G., Chernov V.I., Kolomiyets L.A., Slonimskaya E.M., Medvedeva А.А., Zelchan R.V., Chernyshova A.L., Doroshenko A.V., Lyapunov A.Yu. The First Clinical Experiment with a New Domestic Radiopharmaceutical 99mTc-Aluminum Gamma-Oxide for Imaging Sentinel Lymph Nodes in Malignant Tumors. Medical visualization. 2016;2:57-62 (In Russ.).

30. McMasters K.M., Reintgen D.S., Ross M.I., Wong S.L., Gershenwald J.E., Krag D.N., Noyes R.D., Viar V., Cerrito P.B., Edwards M.J. Sentinel Lymph Node Biopsy for Melanoma: How Many Radioactive Nodes should be Removed? Ann. Surg. Oncol. 2001;8;3:192–197.

31. Boughey J.C., Suman V.J., Mittendorf E.A., Ahrendt G.M., Wilke L.G., Taback B., Leitch A.M., Kuerer H.M., Bowling M., Flippo-Morton T.S., Byrd D.R., Ollila D.W., Julian T.B., McLaughlin S.A., McCall L., Symmans W.F., Le-Petross H.T., Haffty B.G., Buchholz T.A., Nelson H., Hunt K.K., Alliance for Clinical Trials in Oncology. Sentinel Lymph Node Surgery after Neoadjuvant Chemotherapy in Patients with Node-positive Breast Cancer: the ACOSOG Z1071 (Alliance) Clinical Trial. JAMA. 2013;310;14:1455–1461. doi: 10.1001/jama.2013.278932.

32. Kuehn T., Bauerfeind I., Fehm T., Fleige B., Hausschild M., Helms G., Lebeau A., Liedtke C., von Minckwitz G., Nekljudova V., Schmatloch S., Schrenk P., Staebler A., Untch M. Sentinel-Lymph-Node Biopsy in Patients with Breast Cancer before and after Neoadjuvant Chemotherapy (SENTINA): a Prospective, Multicentre Cohort Study. Lancet Oncol. 2013;14;7:609–618. doi: 10.1016/S1470-2045(13)70166-9.

33. Krag D., Anderson S., Julian T., et al. Technical Outcomes of Sentinel-Lymph-Node Resection and Conventional Axillary-Lymphnode Dissection in Patients with Clinically Node-negative Breast Cancer: Results from the NSABP B-32 Randomised Phase III Trial. Lancet Oncol. 2007;8;10:881–888.

34. Li S., Liu F., Chen K., Rao N., Xie Y., Su F., Zhu L. The Extent of Axillary Surgery is Associated with Breast Cancer-specifc Survival in T1–2 Breast Cancer Patients with 1 or 2 Positive Lymph Nodes: a SEER-population Study. Medicine. 1995;14:e3254.

35. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology, Breast Cancer. Version. 1.2018.

36. Cheng G., Kurita S., Torigian D.A., Alavi A. Current Status of Sentinel Lymph-node Biopsy in Patients with Breast Cancer. Eur. J. Nucl. Med. Mol. Imaging. 2011;38:562-575.

37. Magnoni F., Corso G., Gilardi L., Pagan E., Massari G., Girardi A., Ghidinelli F., Bagnardi V., Galimberti V., Grana C.M., Veronesi P. Does Failed Mapping Predict Sentinel Lymph Node Metastasis in cN0 Breast Cancer? Future Oncol. 2022;18;2:193-204. doi: 10.2217/fon-2021-0470.

38. Giammarile F., Alazraki N., Aarsvold J.N., Audisio R.A., Glass E., Grant S.F., Kunikowska J., Leidenius M., Moncayo V.M., Uren R.F., Oyen W.J., Valdés Olmos R.A., Vidal Sicart S. The EANM and SNMMI Practice Guideline for Lymphoscintigraphy and Sentinel Node Localization in Breast Cancer. Eur. J. Nucl. Med. Mol. Imaging. 2013;40;12:1932-1947. doi: 10.1007/s00259-013-2544-2. 

 

 

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Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Medvedeva A.A.: collection and analysis of literary material, concept and design development, data analysis and interpretation, text writing; Chernov V.I.: concept and design development, scientific text editing, final approval for manuscript publication; Rybina A.N., Zelchan R.V., Bragina O.D.: research concept development, development research design, data analysis, text editing; Doroshenko A.V., Garbukov E.Yu., Tarabanovskaya N.I., Tshireva L.A.: material collection, data analysis, statistical data processing, text editing.

Article received: 20.04.2023. Accepted for publication: 27.05.2023.