Preview

Bulletin of Siberian Medicine

Advanced search

A direct comparison of the diagnostic efficacy of alternative scaffoldbased radiopharmaceuticals [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 in patients with HER2-positive breast cancer

https://doi.org/10.20538/1682-0363-2023-3-6-13

Abstract

Aim. To perform a direct comparison of the diagnostic efficacy of [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE) -G3 in HER2-positive breast cancer patients before the systemic treatment.

Materials and methods. The study included 11 patients with HER2-positive breast cancer (T1–4N0–2M0–1) before the initiation of systemic treatment. All patients underwent a radionuclide examination with [99mTc]TcADAPT6 and [99mTc]Tc-(HE) -G3 with the interval of 3–4 days. Single-photon emission computed tomography (SPECT) /computed tomography (CT) was performed 2 and 4 hours after [99mTc]Tc-ADAPT6 and [99mTc]Tc(HE)3-G3 administration, respectively.

Results. The analysis of [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE) -G3 distribution showed their high uptake in the kidneys and liver. Breast tumors were visualized in all cases. The average tumor uptake of [99mTc]Tc-ADAPT6 was 4.7 ± 2.1, which was significantly higher than in the [99mTc]Tc-(HE)3-G3 injection (3.5 ± 1.7) (p < 0.005, paired t-test). The tumor-to-background ratio (15.2 ± 7.4 and 19.6 ± 12.4, respectively) had no statistical differences in both cases (p > 0.05, paired t-test). Liver metastases were visualized in patients 1 and 5 and corresponded to the projection of metastases according to contrast-enhanced abdominal CT. The accumulation of [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 in the projection of metastases in both cases was significantly higher compared to the primary tumor (1.3 and 1.7 times higher in patient 1; 2.2 and 3.5 times higher in patient 5, respectively).

Conclusion. Both [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 demonstrated the diagnostic efficacy in visualizing a primary HER2-positive tumor in breast cancer patients. However, [99mTc]Tc-ADEPT6 had higher accumulation values, which makes it a more promising diagnostic agent.

About the Authors

O. D. Bragina
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of the Russian Academy of Sciences; National Research Tomsk Polytechnic University
Russian Federation

5, Kooperativny Str., Tomsk, 634009,

30, Lenina Av., Tomsk, 634050



S. M. Deyev
National Research Tomsk Polytechnic University; Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Russian Federation

30, Lenina Av., Tomsk, 634050,

16/10, Miklukho-Maklaya Str., Moscow, 117997



E. Yu. Garbukov
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of the Russian Academy of Sciences
Russian Federation

5, Kooperativny Str., Tomsk, 634009



V. E. Goldberg
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of the Russian Academy of Sciences
Russian Federation

5, Kooperativny Str., Tomsk, 634009



V. I. Chernov
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of the Russian Academy of Sciences; National Research Tomsk Polytechnic University
Russian Federation

5, Kooperativny Str., Tomsk, 634009,

30, Lenina Av., Tomsk, 634050



V. M. Tolmachev
National Research Tomsk Polytechnic University; Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Uppsala University
Russian Federation

30, Lenina Av., Tomsk, 634050,

16/10, Miklukho-Maklaya Str., Moscow, 117997,

7, Dag Hammarskjöldsväg, Segerstedthuset, Uppsala



References

1. 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.

2. 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.

3. 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.

4. 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.

5. Bragina O.D., Deyev S.M., Chernov V.I., Tolmachev V.M. Evolution of targeted radionuclide diagnosis of HER2-positive breast cancer. Acta Naturae. 2022;14(2):4–15. DOI: 10.32607/actanaturae.11611.

6. Shilova O.N., Deyev S.M. DARPins: Promising scaffolds for theranostics. Acta Naturae. 2019;11(4):42–53. DOI: 10.32607/20758251-2019-11-4-42-53/

7. Брагина О.Д., Чернов В.И., Зельчан Р.В., Синилкин И.Г., Медведева А.А., Ларкина М.С. Альтернативные каркасные белки в радионуклидной диагностике злокачественных образований. Бюллетень сибирской медицины. 2019;18(3):125– 133. DOI: 10.20538/1682-0363-2019-3-125-133/

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. 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.

10. Bragina O., Chernov V., Schulga A., Konovalova E., Garbukov E., Vorobyeva A. et al. 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. DOI: 10.2967/jnumed.121.262542.

11. 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.

12. Lindbo S., Garousi J., Åstrand M., Honarvar H., Orlova A., Hober S. et al. Influence of histidine-containing tags on the biodistribution of ADAPT scaffold proteins. Bioconjug Chem. 2016;27(3):716–726. DOI: 10.1021/ACS.BIOCONJCHEM.5B00677.

13. Vorobyeva A., Schulga A., Konovalova E. et al. Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3. Sci. Rep. 2019;9(1):9405. DOI: 10.1038/S41598-019-45795-8.


Review

For citations:


Bragina O.D., Deyev S.M., Garbukov E.Yu., Goldberg V.E., Chernov V.I., Tolmachev V.M. A direct comparison of the diagnostic efficacy of alternative scaffoldbased radiopharmaceuticals [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 in patients with HER2-positive breast cancer. Bulletin of Siberian Medicine. 2023;22(3):6-13. https://doi.org/10.20538/1682-0363-2023-3-6-13

Views: 454


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)