Skip to main content
Log in

Synthesis and in vitro evaluation of 99mTc radiolabeled lapatinib (LPT) and its PLGA formulation

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

Lapatinib-(LPT) is a dual tyrosine kinase inhibitor that has important effects on the targeted therapy of various tumours. The current study is aimed to use a novel tracer strategy including Technetium-99 m-(99mTc) radiolabeled LPT and its poly(lactic-co-glycolic acid)-(PLGA) encapsulated formulation-(LPT-PLGA). In vitro bioaffinity of the [99mTc]Tc-LPT and [99mTc]Tc-LPT-PLGA was evaluated by using cell culture methods on human breast adenocarcinoma (MDA-MB-231), cervix adenocarcinoma and human ovarian (MDAH-2774) cancer cell lines. Radiochemical yield were over 95% and both compounds were examined high incorporation values on HeLa and MDAH cell lines. Current results may contribute to develope as the encapculated agents including radiotracer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Mukama T, Kharazmi E, Xu X, Sundquist K, Sundquist J, Brenner H et al (2020) Risk-adapted starting age of screening for relatives of patients with breast cancer. JAMA Oncol 6(1):68–74. https://doi.org/10.1001/jamaoncol.2019.3876

    Article  PubMed  Google Scholar 

  2. Wu P, Zhu Y, Liu S, Xiong H (2021) Modular design of high-brightness pH-activatable near-infrared BODIPY probes for noninvasive fluorescence detection of deep-seated early breast cancer bone metastasis: remarkable axial substituent effect on performance. ACS Cent Sci 7(12):2039–2048. https://doi.org/10.1021/acscentsci.1c01066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Xia W, Gerard CM, Liu L et al (2005) Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene 24:6213–6221. https://doi.org/10.1038/SJ.ONC.1208774

    Article  CAS  PubMed  Google Scholar 

  4. Liu H, Ruan S, Larsen ME et al (2023) Trastuzumab-resistant breast cancer cells-derived tumor xenograft models exhibit distinct sensitivity to lapatinib treatment in vivo. Biol Proced Online 25:19. https://doi.org/10.1186/s12575-023-00212-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Moreira C, Kaklamani V (2010) Lapatinib and breast cancer: current indications and outlook for the future. Expert Rev Antican Therapy 10:1171–1182. https://doi.org/10.1586/ERA.10.113

    Article  CAS  Google Scholar 

  6. Gui X, Li H, Yan Y, Zhang R (2020) Efficacy of lapatinib combined with capecitabine in patients with HER2-positive metastatic breast cancer in a real-world study. Oncol Lett 20:1–6. https://doi.org/10.3892/ol.2020.12241

    Article  Google Scholar 

  7. Long-term clinical outcome of trastuzumab and lapatinib for HER2-positive metastatic colorectal cancer | elsevier enhanced reader. https://reader.elsevier.com/reader/sd/pii/S1533002820300943?token=7AE073F65595ABE78047CEAF3FA1E40F7DFCD7099BBE4A9766CFD83390DD497554954CF60849A6895BD445DD8EFA4DEF&originRegion=eu-west-1&originCreation=20210826082556. Accessed 26 Aug 2021.

  8. Ju SS, Jiao S (2018) Prolonged overall survival in metastatic gastric cancer treated with ipilimumab and lapatinib. J Cancer Res Ther 14:1589. https://doi.org/10.4103/JCRT.JCRT_508_17

    Article  CAS  PubMed  Google Scholar 

  9. Lapatinib/Paclitaxel polyelectrolyte nanocapsules for overcoming multidrug resistance in ovarian cancer | Elsevier Enhanced Reader. https://reader.elsevier.com/reader/sd/pii/S1549963411005223?token=2F286C8238C45C1834C5D43C558C8FA985F0DA285981543F2F1B0D6E85CCE30A32F21EC9B8F7DE6A93A31ACAE18D042A&originRegion=eu-west-1&originCreation=20210826082906. Accessed 26 Aug 2021.

  10. Kreuter J (1996) Nanoparticles and microparticles for drug and vaccine delivery. J Anat 189(3):503–505

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Jena KK (2011) Biodegradable polymers (pla and plga ) based nanoparticles in protein and plasmid dna delivery. pp 1–47

  12. Biber Muftuler FZ (2023) A perspective on PLGA encapsulated radio agents. J Radioanal Nucl Chem 332:511–515. https://doi.org/10.1007/s10967-023-08798-4

    Article  CAS  Google Scholar 

  13. Zj H, Sj W, Zq W et al (2015) Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation. Cancer Sci 106:1429–1437. https://doi.org/10.1111/CAS.12737

    Article  Google Scholar 

  14. Khan M, Zhao Z, Arooj S et al (2020) Lapatinib plus local radiation therapy for brain metastases from HER-2 positive breast cancer patients and role of trastuzumab: a systematic review and meta-analysis. Front Oncol 10:576926. https://doi.org/10.3389/fonc.2020.576926

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tada H, Miyashita M, Gonda K et al (2018) Abstract P2–09–28: New quantitative diagnostic method by fluorescence nanoparticle for HER2 positive breast cancer treated with neoadjuvant lapatinib and trastuzumab: the neo lath study (JBCRG-16TR). Cancer Research 78:P2-09-P2-28. https://doi.org/10.1158/1538-7445.SABCS17-P2-09-28

    Article  Google Scholar 

  16. 99mTc-labeled-2-arylbenzoxazole derivatives as potential Aβ imaging probes for single-photon emission computed tomography | Elsevier Enhanced Reader. https://reader.elsevier.com/reader/sd/pii/S0223523414009738?token=AE10736E021309FF541BF7046DD2430D9D1EB82DAAF365F110E7E5B8E3051B1A05D6DD143592E56DB4781E0BE21C7017&originRegion=eu-west-1&originCreation=20210826085531. Accessed 26 Aug 2021.

  17. PII: S0969–8051(99)00010–4 | Elsevier enhanced reader. https://reader.elsevier.com/reader/sd/pii/S0969805199000104?token=A529438A6ED6A833352E57796D59D005D4D240ACBC7F2BB36A2B4B409A0EA53DAC0C6C9842C9BF5B7CB7B293A5EFDC7C&originRegion=eu-west-1&originCreation=20210826085258. Accessed 26 Aug 2021.

  18. Singh UV, Bisht KS, Rao S et al (1996) Plumbagin-loaded PLGA microspheres with reduced toxicity and enhanced antitumour efficacy in mice. Pharm Pharmacol Commun 2:407–409. https://doi.org/10.1111/J.2042-7158.1996.TB00643.X

    Article  CAS  Google Scholar 

  19. Pitchika S, Sahoo SK (2022) Paclitaxel and lapatinib dual loaded chitosan-coated PLGA nanoparticles enhance cytotoxicity by circumventing MDR1-mediated trastuzumab resistance in HER2 positive breast cancers: in-vitro and in-vivo studies. Journal of Drug Delivery Science and Technology 73:103445. https://doi.org/10.1016/j.jddst.2022.103445

    Article  CAS  Google Scholar 

  20. Zajdel A et al (2019) Cytotoxic effect of paclitaxel and lapatinib co-delivered in polylactide- co-poly(ethylene glycol) micelles on HER-2-negative breast cancer cells. Pharmaceutics 11:169. https://doi.org/10.3390/PHARMACEUTICS11040169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sharma B, Jeet Singh V, Chawla PA (2021) Epidermal growth factor receptor inhibitors as potential anticancer agents: an update of recent progress. Bioorg Chem 116:105393

    Article  CAS  PubMed  Google Scholar 

  22. Chandran S, Harmey J, Toomey S (2023) Inhibition of the IGF signalling pathway in MDA-MB-231 triple-negative breast cancer cells. Royal College of Surgeons in Ireland. Journal contribution. https://hdl.handle.net/10779/rcsi.23276843.v1

  23. Levit SL, Tang C (2021) Polymeric nanoparticle delivery of combination therapy with synergistic effects in ovarian cancer. Nanomaterials 11(4):1048. https://doi.org/10.3390/nano11041048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Feng S, Ren Y, Li H, Tang Y, Yan J, Shen Z, Zhang H, Chen F (2021) Cancer cell-membrane biomimetic boron nitride nanospheres for targeted cancer therapy. Int J Nanomedicine 2021:16

    Google Scholar 

  25. Basuli F et al (2011) A first synthesis of 18F-radiolabeled lapatinib: a potential tracer for positron emission tomographic imaging of ErbB1/ErbB2 tyrosine kinase activity. J Labelled Comp Radiopharm 54(9):633–36. https://doi.org/10.1002/jlcr.1898

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Current work is supported by Ege University Scientific Research Projects Coordination (contract no 2017-TIP-044). We would like to thank Pál Ferenc to check for grammatical and language mistakes. The authors also thank Nese Kavcar, Fatmagul Gedik, Oyku Madenci for the technical assistance during the assays.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fazilet Zumrut Biber Muftuler.

Ethics declarations

Conflicts of interest

The authors state that there is no confict of interest to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gokulu, S.G., Karatay, K.B., Bilgi, A. et al. Synthesis and in vitro evaluation of 99mTc radiolabeled lapatinib (LPT) and its PLGA formulation. J Radioanal Nucl Chem 333, 665–672 (2024). https://doi.org/10.1007/s10967-023-09292-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-023-09292-7

Keywords

Navigation