Use of [18F]FLT/PET for assessing the tumor evolution and monitoring the antitumor activity of rosmarinic acid in a mouse 4T1 breast tumor model

Authors

  • Jousie Michel Pereira Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)
  • Brígida Gomes de Almeida Schirmer Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)
  • Marina Rios Araujo Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)
  • Leonardo T. C. Nascimento Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)
  • Andrea Vidal Ferreira Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)
  • Aline de Biasi Bassani Gonçalves Universidade Federal de Minas Gerais
  • Lucíola da Silva Barcelos Universidade Federal de Minas Gerais
  • Geovanni Dantas Cassali Universidade Federal de Minas Gerais
  • Marina Bicalho Silveira Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)
  • Juliana Batista da Silva Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)
  • Carlos Malamut Centro de Desenvolvimento da Tecnologia Nuclear (CDTN)

DOI:

https://doi.org/10.15392/2319-0612.2023.2300

Keywords:

[18F]FLT/PET, rosmarinic acid, 4T1 mammary tumor, lung metastasis

Abstract

The use of the tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine ([18F]FLT) in positron emission tomography (PET) has been shown to be an effective tool for assessing tumor aggressiveness and early response to therapy. In this study, we investigated the applicability of [18F]FLT/PET to study the antitumor and anti–lung metastatic effects of rosmarinic acid (RA) in highly invasive breast cancer. 4T1 mammary carcinoma cells were injected into the flank of female Balb/c mice. The animals were treated daily with RA until day 21 after the inoculation of tumor cells. [18F]FLT/PET imaging was used to evaluate the response of primary tumors and lung metastases to RA treatment. PET Images showed a decreased [18F]FLT uptake in the lungs of mice after RA treatment. The antitumor effect of RA appears to be related to the inhibition of cell migration, cell proliferation, and blood vessel formation in the primary tumor. Furthermore, the inflammatory response was modulated by RA, which reduced the accumulation of mast cells and neutrophils in the primary tumor and of macrophages in the lungs. In conclusion, [18F]FLT/PET demonstrates the antitumor and antimetastatic effects of RA in a 4T1 breast tumor model. Furthermore, the findings suggest that RA modulates tumor angiogenesis and inflammation, resulting in antitumor and antimetastatic effects in a 4T1 breast carcinoma model.

Downloads

Download data is not yet available.

References

LUO, C.; LI, N.; LU, B.; CAI, J.; LU, M.; ZHANG, Y.; et al. Global and regional trends in incidence and mortality of female breast cancer and associated factors at national level in 2000 to 2019. Chin Med J (Engl), v. 135, p. 42–51, 2022.

WILKINSON, L.; GATHANI, T. Understanding breast cancer as a global health concern. Br J Radiol, v. 95, 2022.

GIAQUINTO, A.N.; SUNG, H.; MILLER, K.D.; KRAMER, J.L.; NEWMAN, L.A.; MINIHAN, A.; et al. Breast Cancer Statistics, 2022. CA Cancer J Clin, v. 72, p. 524–541, 2022.

GALLICCHIO, L.; DEVASIA, T.P.; TONOREZOS, E.; MOLLICA, M.A.; MARIOTTO, A. Estimation of the Number of Individuals Living With Metastatic Cancer in the United States. JNCI J Natl Cancer Inst, v. 114, p. 1476–1483, 2022.

HOWLADER, N.; NOONE, A.M.; KRAPCHO, M.; MILLER, D.; BISHOP, K.; KOSARY, C.L.; YU, M.; RUHL, J.; TATALOVICH, Z.; MARIOTTO, A.; LEWIS, D.R.; CHEN, H.S.; FEUER, E.J.C.K (eds). SEER Cancer Statistics Review, 1975-2014. National Cancer Institute, Bethesda, MD, https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017.

PAYDARY, K.; SERAJ, S.M.; ZADEH, M.Z.; EMAMZADEHFARD, S; SHAMCHI, S.P.; GHOLAMI, S.; et al. The Evolving Role of FDG-PET/CT in the Diagnosis, Staging, and Treatment of Breast Cancer. Mol Imaging Biol, v. 21, p. 1–10, 2019.

HADEBE, B.; HARRY, L.; EBRAHIM, T.; PILLAY, V.; VORSTER, M. The Role of PET/CT in Breast Cancer. Diagnostics, v. 13, p. 597, 2023.

MING, Y.; WU, N.; QIAN, T.; LI, X.; WAN, D.Q.; LI, C.; et al. Progress and Future Trends in PET/CT and PET/MRI Molecular Imaging Approaches for Breast Cancer. Front Oncol, v.10, 2020.

CRIȘAN, G.; MOLDOVEAN-CIOROIANU, N.S.; TIMARU, D-G.; ANDRIEȘ, G.; CAINAP, C.; CHIȘ, V. Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade. Int J Mol Sci, v. 23, p. 5023, 2022.

ROMINE, P.E.; PETERSON, L.M.; KURLAND, B.F.; BYRD, D.W.; NOVAKOVA-JIRESOVA, A.; MUZI, M.; et al. 18F-fluorodeoxyglucose (FDG) PET or 18F-fluorothymidine (FLT) PET to assess early response to aromatase inhibitors (AI) in women with ER+ operable breast cancer in a window-of-opportunity study. Breast Cancer Res, v. 23, p. 88, 2021.

XU, W.; YU, S.; XIN, J.; GUO, Q. 18F-FLT and 18F-FDG PET-CT imaging in the evaluation of early therapeutic effects of chemotherapy on Walker 256 tumor-bearing rats. Exp Ther Med, v.12, p. 4154–4158, 2016.

ALWADANI B, DALL’ANGELO S, FLEMING IN. Clinical value of 3’-deoxy-3’-[18F]fluorothymidine-positron emission tomography for diagnosis, staging and assessing therapy response in lung cancer. Insights Imaging, v. 12, p. 90, 2021.

HISHAR, H.; PRICE, R.; FATHINUL, F.; AHMAD, S.; EDIE, L.; WING, F.; ASSUNTA, C.; NORDIN, A.J. Potential of 3’-fluoro-3’ deoxythymidine as a cellular proliferation marker in PET oncology examination. Pertanika J Sci Technol, v. 24, p. 41–52, 2016.

PETERSEN, M.; SIMMONDS, M.S.J. Rosmarinic acid. Phytochemistry, v. 62, p. 121–125, 2003.

ADOMAKO-BONSU, A.G.; CHAN, S.L.; PRATTEN, M.; FRY, J.R. Antioxidant activity of rosmarinic acid and its principal metabolites in chemical and cellular systems: Importance of physico-chemical characteristics. Toxicol In Vitro, v. 40, p. 248–255, 2017.

CAO, W.; HU, C.; WU, L.; XU, L.; JIANG, W. Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular carcinoma by suppression of NF-κB signaling in H22 tumor-bearing mice. J Pharmacol Sci. Elsevier Ltd, v. 132, p. 131–137, 2016.

YOOU, M.; PARK, C.L.; KIM, M-H.; KIM, H-M.; JEONG, H-J. Inhibition of MDM2 expression by rosmarinic acid in TSLP-stimulated mast cell. Eur J Pharmacol, v.771, p. 191–198, 2016.

ROCHA, J; EDUARDO-FIGUEIRA, M.; BARATEIRO, A.; FERNANDES, A.; BRITES, D.; BRONZE, R.; et al. Anti-inflammatory Effect of Rosmarinic Acid and an Extract of Rosmarinus officinalis in Rat Models of Local and Systemic Inflammation. Basic Clin Pharmacol Toxicol, v.116, p. 398–413, 2015.

HAN, Y-H.; KEE, J-Y.; HONG, S-H. Rosmarinic Acid Activates AMPK to Inhibit Metastasis of Colorectal Cancer. Front Pharmacol, v. 9, p. 68, 2018.

PULASKI, B. A.; OSTRAND-ROSENBERG, S. Mouse 4T1 breast tumor model. Curr Protoc Immunol. Chapter 20: Unit 20.2. 2001.

NASCIMENTO, L.T.C.; SILVEIRA, M.B.; FERREIRA, S.M.Z.M.D.; SILVA, J.B. Comparison between Two Ethanolic Solutions for 3’-Deoxy-3’-[18F]Fluorothymidine Elution. Adv Chem Eng Sci, v. 07, p. 23–33, 2017.

CASSINI-VIEIRA, P.; MOREIRA, C.; DA SILVA, M.; BARCELOS, L.S. Estimation of Wound Tissue Neutrophil and Macrophage Accumulation by Measuring Myeloperoxidase (MPO) and N-Acetyl-β-D-glucosaminidase (NAG) Activities. BIO-PROTOCOL, v. 5, 2015.

FURTADO, R.A.; DE ARAUJO, F.R.R.; RESENDE, F.A.; CUNHA, W.R.; TAVARES, D.C. Protective effect of rosmarinic acid on V79 cells evaluated by the micronucleus and comet assays. J Appl Toxicol, v. 30, p. 254–259, 2010.

ZHANG, L.; MIZUMOTO, K.; SATO, N.; OGAWA, T.; KUSUMOTO, M.; NIIYAMA, H.; et al. Quantitative determination of apoptotic death in cultured human pancreatic cancer cells by propidium iodide and digitonin. Cancer Lett. v.142, p. 129–137, 1999.

BAKHEET, S.M.B.; POWE, J.; KANDIL, A.; EZZAT, A.; ROSTOM, A.; AMARTEY, J. F-18 FDG Uptake in Breast Infection and Inflammation. Clin Nucl Med, v. 25, p. 100, 2000.

FILHO, G.B. Bogliolo - Patologia Geral, 4th ed., Rio de Janeiro: Guanabara Koogan; 2009. p. 233-282.

TAO, K.; FANG, M.; ALROY, J.; SAHAGIAN, G.G. Imagable 4T1 model for the study of late stage breast cancer. BMC Cancer, v. 8, p. 228, 2008.

MORI. M.; FUJIOKA, T.; ICHIKAWA, R.; INOMATA, R.; KATSUTA, L.; YASHIMA, Y.; et al. Comparison of 18F-fluorothymidine Positron Emission Tomography/Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Breast Cancer. Tomography, v. 8, p. 2533–2546, 2022.

WESOLOWSKI, R.; STOVER, D.G.; LUSTBERG, M.B.; SHOBEN, A.; ZHAO, M.; MROZEK, E.; et al. Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study. Oncologist, v. 25, p. e1158–e1169, 2020.

SU, T-P.; HUANG, J-S.; CHANG, P-H.; LUI, K-W.; HSIEH, JC-H.; NG, S-H.; et al. Prospective comparison of early interim 18F-FDG-PET with 18F-FLT-PET for predicting treatment response and survival in metastatic breast cancer. BMC Cancer, v. 21, p. 908, 2021.

XU, Y.; JIANG, Z.; JI, G.; LIU, J. Inhibition of bone metastasis from breast carcinoma by rosmarinic acid. Planta Med, v. 76, p. 956–962, 2010.

XU, Y.; XU, G.; LIU, L.; XU, D.; LIU, J. Anti-invasion effect of rosmarinic acid via the extracellular signal-regulated kinase and oxidation-reduction pathway in Ls174-T cells. J Cell Biochem, v. 111, p. 370–9, 2010.

JENSEN, M.M.; KJAER, A. Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET: a comprehensive review of pre-clinical studies. Am J Nucl Med Mol Imaging, v. 5, p. 431–456, 2015.

DE ALMEIDA SCHIRMER BG, DE ARAUJO MR, SILVEIRA MB, PEREIRA JM, VIEIRA LC, ALVES CG, et al. Comparison of [18F]Fluorocholine and [18F]Fluordesoxyglucose for assessment of progression, lung metastasis detection and therapy response in murine 4T1 breast tumor model. Appl Radiat Isot, v. 140, p. 278–288, 2018.

LANDSKRON G, DE LA FUENTE M, THUWAJIT P, THUWAJIT C, HERMOSO MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res, v. 2014, p. 149185, 2014.

LAVALLE G., BERTAGNOLLI A., TAVARES WL., FERREIRA MAN., CASSALI G. Mast cells and angiogenesis in canine mammary tumor. Arq Bras Med Veterinária e Zootec, v. 62, p. 1348–1351, 2010.

SONI A, REN Z, HAMEED O, CHANDA D, MORGAN CJ, SIEGAL GP, et al. Breast Cancer Subtypes Predispose the Site of Distant Metastases. Am J Clin Pathol, v. 143, p. 471–478, 2015.

BUCK AK, SCHIRRMEISTER H, MATTFELDT T, RESKE SN. Biological characterisation of breast cancer by means of PET. Eur J Nucl Med Mol Imaging, v. 31 Suppl 1, p. S80-7, 2004.

ĐILAS S, KNEZ Ž, ČETOJEVIC-SIMIN D, TUMBAS V, ŠKERGET M, ČANADANOVIC-BRUNET J, et al. In vitro antioxidant and antiproliferative activity of three rosemary (Rosmarinus officinalis L.) extract formulations. Int J Food Sci Technol, v. 47, p. 2052–2062, 2012.

GONZALEZ-VALLINAS M, REGLERO G, RAMIREZ DE MOLINA A. Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy. Nutrition and Cancer, p. 1221–1229, 2015.

YESIL-CELIKTAS, O.; SEVIMLI, C.; BEDIR, E.; VARDAR-SUKAN, F. Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines. Plant Foods Hum Nutr, v. 65, p. 158–163, 2010.

BERDOWSKA, I.; ZIELINSKI, B.; FECKA, I.; KULBACKA, J.; SACZKO, J.; GAMIAN A. Cytotoxic impact of phenolics from Lamiaceae species on human breast cancer cells. Food Chem, v. 141, p. 1313–1321, 2013.

GALUN, E. Liver inflammation and cancer: The role of tissue microenvironment in generating the tumor-promoting niche (TPN) in the development of hepatocellular carcinoma. Hepatology, v. 63, p. 354–356, 2016.

TARIQ, M.; ZHANG, J.; LIANG, G.; DING, L.; HE, Q.; YANG, B. Macrophage Polarization: Anti-Cancer Strategies to Target Tumor-Associated Macrophage in Breast Cancer. J Cell Biochem, v. 118, p. 2484–2501, 2017.

HOLLMEN, M.; KARAMAN, S.; SCHWAGER, S.; LISIBACH, A.; CHRISTIANSEN, A.J.; MAKSIMOW, M.; et al. G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer. Oncoimmunology, v. 5, p. e1115177, 2016.

YOUN, J-I.; NAGARAJ, S.; COLLAZO, M.; GABRILOVICH, D.I. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol, v. 181, p. 5791–802, 2008.

WCULEK, S.K.; MALANCHI, I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature, v. 528, p. 413–417, 2015.

Downloads

Published

2023-09-30

Issue

Section

Articles

How to Cite

Use of [18F]FLT/PET for assessing the tumor evolution and monitoring the antitumor activity of rosmarinic acid in a mouse 4T1 breast tumor model. Brazilian Journal of Radiation Sciences, Rio de Janeiro, Brazil, v. 11, n. 3, p. 1–23, 2023. DOI: 10.15392/2319-0612.2023.2300. Disponível em: https://bjrs.org.br/revista/index.php/REVISTA/article/view/2300.. Acesso em: 4 may. 2024.

Similar Articles

1-10 of 138

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)

1 2 > >>