Radionuclide imaging of HER2/neu expression in metastatic axillary lymph nodes in breast cancer patients: comparing the efficacy of [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3
О. D. Bragina,
L. А. Tashireva,
Е. Yu. Garbukov,
М. А. Vostrikova,
А. А. Romanova,
S. М. Deyev,
М. Е. Borodina,
V. I. Chernov https://doi.org/10.20538/1682-0363-2025-1-14-21
Abstract
Aim. To conduct a direct comparative analysis of single-photon emission computed tomography (SPECT-CT) with [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 in patients with HER2-positive breast cancer (BC) with axillary lymph node metastases.
Materials and methods. The analysis included 8 patients with HER2-positive BC with axillary lymph node metastases before the systemic treatment. All patients were injected with [99mTc]Tc-ADAPT6 (500 µg) and [99mTc] Tc-(HE)3-G3 (3,000 µg) with an interval of 3–4 days. The SPECT-CT scans of the chest and upper abdomen were performed after 2 hours for [99mTc]Tc-ADAPT6 and after 4 hours for [99mTc]Tc-(HE)3-G3. The accumulation of radiopharmaceuticals was assessed by measuring the maximum standardized uptake values (SUVmax) in metastatic axillary lymph nodes, projections of the contralateral axillary lymph nodes, liver, latissimus dorsi muscle, and spleen. Additionally, mALN-to-background and mALN-to-reference organs ratios were calculated for each patient.
Results. Comparison of the mALN-to-background ratio revealed the advantage of [99mTc]Tc-ADAPT6 (38.93 (16.56–56.02)) over [99mTc]Tc-(HE)3-G3 (19.39 (8.43–34.52)), p = 0.0391. The comparative analysis of the accumulation of the studied radiopharmaceuticals in the reference organs demonstrated higher SUVmax for [99mTc] Tc-(HE)3 -G3 in the liver and spleen (4.44 (2.85–9.08) and 2.47 (1.28–4.41), respectively) than for [99mTc]Tc-ADAPT6 (2.98 (1.96–3.65) and 0.43 (0.14–0.62), respectively), p = 0.01 and p = 0.04. Comparison of the SUVmax ratios in mALN and reference organs showed higher values of mALN / spleen for [99mTc]Tc-ADAPT6 (5.93 (1.04–11.85)) compared to [99mTc]Tc-(HE)3-G3 (1.83 (0.46–4.54)), p = 0.02. Conclusion. According to the results of the performed analysis, the diagnostic advantage of [99mTc]Tc-ADEPT6 for the detection of) HER2/neu expression in metastatic lymph nodes in breast cancer patients was revealed.
Supporting agencies: The work was performed at the expense of the grant from the Russian Ministry of Science and Higher Education No. 075-15-2024-536.
About the Authors
О. D. Bragina
Cancer Research Institute, Tomsk National Research Medical Center (Russian Academy of Sciences);
National Research Tomsk Polytechnic University (NR TPU)
Russian Federation
Competing Interests:
Russian Federation
5, Kooperativny Str., Tomsk, 634009;
30, Lenina Av., Tomsk, 634050
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
L. А. Tashireva
Cancer Research Institute, Tomsk National Research Medical Center (Russian Academy of Sciences)
Russian Federation
Competing Interests:
Russian Federation
5, Kooperativny Str., Tomsk, 634009
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
Е. Yu. Garbukov
Cancer Research Institute, Tomsk National Research Medical Center (Russian Academy of Sciences)
Russian Federation
Competing Interests:
Russian Federation
5, Kooperativny Str., Tomsk, 634009
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
М. А. Vostrikova
Cancer Research Institute, Tomsk National Research Medical Center (Russian Academy of Sciences)
Russian Federation
Competing Interests:
Russian Federation
5, Kooperativny Str., Tomsk, 634009
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
А. А. Romanova
Cancer Research Institute, Tomsk National Research Medical Center (Russian Academy of Sciences)
Russian Federation
Competing Interests:
Russian Federation
5, Kooperativny Str., Tomsk, 634009
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
S. М. Deyev
National Research Tomsk Polytechnic University (NR TPU);
Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences;
National Research Center «Kurchatov Institute»
Russian Federation
Competing Interests:
Russian Federation
30, Lenina Av., Tomsk, 634050;
16/10, Miklukho – Maklaya Str., Moscow, 117997;
1, Akademika Kurchatova Str., Moscow, 123098
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
М. Е. Borodina
P. Hertsen Moscow Oncology Research Institute
Russian Federation
Competing Interests:
Russian Federation
3, 2nd Botkinsky Proyezd Str., Moscow, 125284
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
V. I. Chernov
Cancer Research Institute, Tomsk National Research Medical Center (Russian Academy of Sciences);
National Research Tomsk Polytechnic University (NR TPU);
National Research Center «Kurchatov Institute»
Russian Federation
Competing Interests:
Russian Federation
5, Kooperativny Str., Tomsk, 634009;
30, Lenina Av., Tomsk, 634050;
1, Akademika Kurchatova Str., Moscow, 123098
Competing Interests:
The authors declare the absence of obvious or potential conflict of interest related to the publication of this article.
References
1. Тюляндин С.А., Артамонова Е.В., Жигулев А.Н., Жукова Л.Г., Королева И.А., Пароконная А.А. и др. Практические рекомендации по лекарственному лечению рака молочной железы. Практические рекомендации RUSSCO, часть 1. Злокачественные опухоли. 2023;3:157–165. DOI: 10.18027/2224-5057-2023-13-3s2-1-157-200.
2. Апанасевич В.И., Артамонова Е.В., Ашрафян Л.А., Бесова Н.С., Бирюкова А.М., Божок А.А. и др. Золотой стандарт профилактики, диагностики, лечения и реабилитации больных РМЖ. 2024:17–30.
3. Helfgott R., Mittlböck М., Miesbauer М. The influence of breast cancer subtypes on axillary ultrasound accuracy: A retrospective single center analysis of 583 women. Eur. J. Surg. Oncol. 2019;45(4):538–543. DOI: 10.1016/j.ejso.2018.10.001.
4. Гордеева О.О., Жукова Л.Г., Колядина И.В., Ганьшина И.П. Оценка рецепторного статуса первичной опухоли молочной железы и синхронных регионарных метастазов: их клиническая и прогностическая роль. Сибирский онкологический журнал. 2019;18(2):78–82. DOI: 10.21294/1814-4861-2019-18-2-78-82.
5. Lower E.E., Khan S., Kennedy D., Baughman R.P. Discordance of the estrogen receptor and HER-2/neu in breast cancer from primary lesion to first and second metastatic site. Breast Cancer – Targets and Therapy. 2017;9:515–520. DOI: 10.2147/BCTT.S137709.
6. Han L., Li L., Wang N., Xiong Y., Li Y., Gu Y. Relationship of epidermal growth factor receptor expression with clinical symptoms and metastasis of invasive breast cancer. Interferon Cytokine Res. 2018;38(12):578–582. DOI: 10.1089/jir.2018.0085.
7. Брагина О.Д., Деев С.М., Чернов В.И., Толмачев В.М. Эволюция таргетной радионуклидной диагностики HER2-позитивного рака молочной железы. Acta Naturae. 2022;14(2):4–15. DOI: 10.32607/actanaturae.11611.
8. Tolmachev V., Orlova A., Sorensen J. The emerging role of radionuclide molecular imaging of HER2 expression in breast cancer. Semin. Cancer Biol. 2021;72:185–197. DOI: 10.1016/j.semcancer.2020.10.005.
9. Pernas S., Tolaney S.M. HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther. Adv. Med. Oncol. 2019;11:1758835919833519. DOI: 10.1177/1758835919833519.
10. Bragina O.D., Tashireva L.A., Loos D.M., Chernov V.I., Hober S., Tolmachev V.M. Evaluation of approaches for the assessment of HER2 expression in breast cancer by radionuclide imaging using the scaffold protein [99mTc]Tc-ADAPT6. Pharmaceutics. 2024;16(4):445. DOI: 10.3390/pharmaceutics16040445.
11. Брагина О.Д., Таширева Л.А., Лоос Д.М., Вторушин С.В., Шульга А.А., Коновалова Е.Н. и и др. Оценка экспресии рецептора HER2/neu в ткани метастатических лимфатических узлов у больных раком молочной железы с применением препарата [99mTс]Tс-(HE)3-G3. Acta Naturae. 2024;16(2):64–71. DOI: 10.32607/actanaturae.27448.
12. Wolff A.C., Hammond M.E.H., Allison K.H., Harvey B.E., Mangu P.B., Bartlett J.M. et al. Human epidermal growth factor receptor 2 testing in breast cancer: American society of clinical oncology / College of American pathologist clinical practice guideline focused update. Pathol. Lab. Med. 2018;142(11):1364–1382. DOI: 10.5858/arpa.2018-0902-SA.
13. Chernov V., Rybina A., Zelchan R., Medvedeva A., Bragina O., Lushnikova N. et al. Phase I trial of [99mTc]TcmaSSS-PEG2-RM26, a bombesin analogue antagonistic to gastrin-releasing peptide receptors (GRPRs), for SPECT imaging of GRPR expression in malignant tumors. Cancers. 2023;15(6):1631. DOI: 10.3390/cancers15061631.
14. Брагина О.Д., Чернов В.И., Гарбуков Е.Ю., Дорошенко А.В., Воробьева А.Г., Орлова А.М. и др. Возможности радионуклидной диагностики HER2-позитивного рака молочной железы с использованием меченных технецием-99m таргетных молекул: первый опыт клинического применения. Бюллетень сибирской медицины. 2021;20(1):23–30. DOI: 10.20538/1682-0363-2021-1-23-30.
15. Bragina O., Chernov V., Larkina M., Rybina A., Zelchan R., Garbukov E. et al. Phase I clinical evaluation of 99mTc-labeled affibody molecule for imaging of HER2 expression in breast cancer. Theranostics. 2023;13(14):4858–4871. DOI: 10.7150/thno.86770.
16. Tolmachev V., Bodenko V., Oroujeni M., Deyev S., Konovalova E., Shulga A. et al. Direct in vivo comparison of 99mTc-labeled scaffold proteins, DARPin G3 and ADAPT6, for visualization of HER2 expression and monitoring of early response for trastuzumab therapy. Int. J. Mol. Sci. 2022;23(23):15181. DOI: 10.3390/ijms232315181.
17. Bragina O., Chernov V., Schulga A., Konovalova E., Hober S., Deyev S. et al. Direct intra-patient comparison of scaffold protein-based tracers, [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3, for imaging of HER2-positive breast cancer. Cancers. 2023;15(12):3149. DOI: 10.3390/cancers15123149.
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For citations:
Bragina О.D., Tashireva L.А., Garbukov Е.Yu., Vostrikova М.А., Romanova А.А., Deyev S.М., Borodina М.Е., Chernov V.I. Radionuclide imaging of HER2/neu expression in metastatic axillary lymph nodes in breast cancer patients: comparing the efficacy of [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3. Bulletin of Siberian Medicine. 2025;24(1):14-21. https://doi.org/10.20538/1682-0363-2025-1-14-21
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