Lapatinib-Based Radioagents for Application in Nuclear Medicine
Source abstract
Abstract
Lapatinib is an approved therapeutic agent for the treatment of HER2-positive breast cancer. It has a high affinity for the non-receptor cytoplasmic tyrosine kinases of the EGFR and HER2 receptors. It is a type II inhibitor, with Kiapp values of 3 nM and 13 nM, respectively. The dissociation rate of the lapatinib–receptor complex is notably slow compared with many other kinase inhibitors. Although the literature contains numerous reports on radiolabelled ligands for HER-family receptors, studies on radiolabelled tyrosine kinase inhibitors are far fewer, and only few focus specifically on radiolabelled lapatinib. The aim of this review is to compile and discuss the chemical and biological data on lapatinib-based radiopharmaceuticals with potential applications in the diagnosis and treatment of HER2-positive tumours.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: HER2/EGFR in Cancer Research · Radiopharmaceutical Chemistry and Applications · Lung Cancer Treatments and Mutations
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland
Funding
International Atomic Energy Agency
References (49)
Show source-provided references
1. Molecular subtypes and local-regional control of breast cancer10.1016/j.soc.2017.08.005 ↗
2. Breast cancer10.1016/S0140-6736(20)32381-3 ↗
3. Lapatinib: A novel dual tyrosine kinase inhibitor with activity in solid tumors10.1345/aph.1G387 ↗
4. Lapatinib: A novel EGFR/HER2 tyrosine kinase inhibitor for cancer10.1358/dot.2006.42.7.985637 ↗
5. HER family in cancer progression: From discovery to 2020 and beyond10.1016/bs.acr.2020.04.001 ↗
6. Assessment of epidermal growth factor receptor (EGFR, ErbB1) and HER2 (ErbB2) protein expression levels and response to lapatinib (Tykerb, GW572016) in an expanded panel of human normal and tumour cell lines10.1111/j.1365-2184.2007.00455.x ↗
7. Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies10.1200/JCO.2005.12.157 ↗
8. A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): Relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells10.1158/0008-5472.CAN-04-1168 ↗
9. Human metabolism of lapatinib, a dual kinase inhibitor: Implications for hepatotoxicity10.1124/dmd.111.040949 ↗
10. Lapatinib plus capecitabine for HER2-positive advanced breast cancer10.1056/NEJMoa064320 ↗
11. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: A prospective study10.1093/neuonc/nou141 ↗
12. Lapatinib: A dual inhibitor of human epidermal growth factor receptor tyrosine kinases10.1016/j.clinthera.2008.08.008 ↗
13. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells10.1158/0008-5472.CAN-05-1182 ↗
14. Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells10.18632/oncotarget.12597 ↗
15. Expression of p95HER2, a Truncated Form of the HER2 Receptor, and Response to Anti-HER2 Therapies in Breast Cancer10.1093/jnci/djk134 ↗
16. Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: Effects on insulin-like growth factor I signaling10.1158/1535-7163.MCT-06-0423 ↗
17. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline10.1200/JCO.2015.61.1459 ↗
18. HER2 amplification status in breast cancer: A comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis scoring techniques10.1136/jcp.2004.023424 ↗
19. Guidelines for human epidermal growth factor receptor 2 testing: Biologic and methodologic considerations10.1200/JCO.2007.14.8197 ↗
20. Chromogenic in situ hybridization: A practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples10.1016/S0002-9440(10)64785-2 ↗
21. The correlation between dual-color chromogenic in situ hybridization and fluorescence in situ hybridization in assessing HER2 gene amplification in breast cancer10.1097/PDM.0b013e31817f5227 ↗
22. Radiopharmaceuticals and their applications in medicine10.1038/s41392-024-02041-6 ↗
23. Ge, S., Li, J., Yu, Y., Chen, Z., Yang, Y., Zhu, L., Sang, S., and Deng, S. (2021). Review: Radionuclide Molecular Imaging Targeting HER2 in Breast Cancer with a Focus on Molecular Probes into Clinical Trials and Small Peptides. Molecules, 26.10.3390/molecules26216482 ↗
24. The Radiolabeled HER3 Targeting Molecules for Tumor Imaging
25. Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging10.3390/molecules201219816 ↗
26. Lapatinib and 17AAG reduce 89Zr-trastuzumab-F(ab’)2 uptake in SKBR3 tumor xenografts10.1021/mp3002182 ↗
27. Affibody-mediated PET imaging of HER3 expression in malignant tumours10.1038/srep15226 ↗
28. Efficient [18F]AlF Radiolabeling of ZHER3:8698 Affibody Molecule for Imaging of HER3 Positive Tumors10.1021/acs.bioconjchem.6b00259 ↗
29. 89Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment10.1080/19420862.2017.1371382 ↗
30. Neuregulins and their receptors: A versatile signaling module in organogenesis and oncogenesis10.1016/S0896-6273(00)80324-4 ↗
31. Protein tyrosine kinases and cancer
32. Specificity within the EGF family/ErbB receptor family signaling network10.1002/(SICI)1521-1878(199801)20:1<41::AID-BIES7>3.0.CO;2-V ↗
33. Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein10.1074/jbc.M110.206193 ↗
34. FDA-approved small-molecule kinase inhibitors10.1016/j.tips.2015.04.005 ↗
35. Mechanism of activation and inhibition of the HER4/ErbB4 kinase10.1016/j.str.2007.12.016 ↗
36. PET imaging with small-molecule tyrosine kinase inhibitors: TKI-PET10.1016/j.drudis.2012.06.016 ↗
37. A first synthesis of 18F-radiolabeled Lapatinib: A potential tracer for positron emission tomographic imaging of erbb1/erbb2 tyrosine kinase activity10.1002/jlcr.1898 ↗
38. Facile synthesis of 18F-labeled Lapatinib for imaging with positron emission tomography
39. Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer10.1186/s13550-015-0103-5 ↗
40. Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer10.1007/s11095-011-0601-8 ↗
41. Synthesis, physicochemical and biological evaluation of technetium- 99m labeled lapatinib as a novel potential tumor imaging agent of Her-2 positive breast cancer10.1016/j.ejmech.2014.09.080 ↗
42. Synthesis and in vitro evaluation of 99mTc radiolabeled lapatinib (LPT) and its PLGA formulation10.1007/s10967-023-09292-7 ↗
43. 153Sm-labeled Fe3O4@lapatinib nanoparticles as a potential therapeutic agent for breast cancer: Synthesis, quality control, and In Vivo evaluation10.1039/D3TB01957H ↗
44. Combined PET and near-infrared fluorescence probe based on lapatinib targeting HER2 for in vivo tumor imaging10.1016/j.bioorg.2025.108550 ↗
45. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain10.1093/jnci/djn216 ↗
46. Koźmiński, P., Halik, P.K., Chesori, R., and Gniazdowska, E. (2021). Common Shortcomings in Study on Radiopharmaceutical Design Research: A Case Study of 99mTc-Labelled Methotrexate. Molecules, 26.10.3390/molecules26195862 ↗
47. Practical considerations for navigating the regulatory landscape of non-clinical studies for clinical translation of radiopharmaceuticals10.1186/s41181-022-00168-x ↗
48. Radiopharmaceuticals Regulations: Current Scenario and the Way Forward
49. Position paper to facilitate patient access to radiopharmaceuticals: Considerations for a suitable pharmaceutical regulatory framework10.1186/s41181-023-00230-2 ↗