Login Register Cart 0
Generic placeholder image

Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

A Novel Dual-labeled Peptide for Multimodal Imaging of EGFR with L858R Mutation

Author(s): Myoung Hyoun Kim, Seul-Gi Kim and Dae-Weung Kim*

Volume 17, Issue 2, 2024

Published on: 17 October, 2023

Page: [174 - 183] Pages: 10

DOI: 10.2174/0118744710249198231002055810

Price: $65

Abstract

Background: The development of molecular imaging agents targeting epidermal growth factor receptor (EGFR) with L858R mutation may help with the selection of non-small cell lung carcinoma (NSCLCL) patients who may benefit from EFGR tyrosine kinase inhibitor (TKI) therapy.

Objective: In this study, we developed 99mTc STHHYYP-GHEG-ECGK-tetramethylrhodamine (STHHYYP-ECGK-TAMRA) to target EGFR with L858R mutation in NSCLC tumors and verified its probability as a molecular imaging agent.

Methods: Fmoc solid-phase peptide synthesis was used to synthesize STHHYYP-ECGKTAMRA. 99mTc labelled STHHYYP-ECGK-TAMRA was prepared. Gamma imaging, fluorescent imaging and biodistribution were performed in murine models bearing NCI-H1975 and NCI-H1650 tumors.

Results: The binding affinity value (Kd) of 99mTc STHHYYP-ECGK-TAMRA was estimated to be 130.6 ± 29.2 nM in NCI-H1975 cells. The gamma camera images showed a substantial uptake of 99mTc STHHYYP-ECGK-TAMRA in the NCI-H1975 tumor. The % injected dose/gram of the NCI-H1975 tumor tissue was 2.77 ± 0.70 and 3.48 ± 1.01 at 1 and 3 h, respectively.

Conclusion: Specific binding of 99mTc STHHYYP-ECGK-TAMRA to L858R-mutated EGFRpositive NCI-H1975 cells and tumors was demonstrated in in vivo and in vitro studies. The results suggest that 99mTc STHHYYP-ECGK-TAMRA is a good candidate agent for dualmodality imaging targeting EGFR with L858R mutation.

Keywords: EGFR, 99mTc, L858R mutation, multimodal imaging, lung cancer, peptide, SPECT.

« Previous Next »
Graphical Abstract

[1]
Yarden Y. The EGFR family and its ligands in human cancer. Eur J Cancer 2001; 37 (Suppl. 4): 3-8.
[http://dx.doi.org/10.1016/S0959-8049(01)00230-1] [PMID: 11597398]
[2]
Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 2003; 21(20): 3798-807.
[http://dx.doi.org/10.1200/JCO.2003.11.069] [PMID: 12953099]
[3]
Mok T, Wu YL, Lee JS, et al. Detection and dynamic changes of EGFR mutations from circulating tumor DNA as a predictor of survival outcomes in nsclc patients treated with first-line intercalated erlotinib and chemotherapy. Clin Cancer Res 2015; 21(14): 3196-203.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2594] [PMID: 25829397]
[4]
Tan DSW, Yom SS, Tsao MS, et al. The international association for the study of lung cancer consensus statement on optimizing management of EGFR mutation–positive non–small cell lung cancer: Status in 2016. J Thorac Oncol 2016; 11(7): 946-63.
[http://dx.doi.org/10.1016/j.jtho.2016.05.008] [PMID: 27229180]
[5]
Jackman D, Pao W, Riely GJ, et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010; 28(2): 357-60.
[http://dx.doi.org/10.1200/JCO.2009.24.7049] [PMID: 19949011]
[6]
Peled N, Roisman LC, Miron B, et al. Subclonal therapy by two EGFR TKIs guided by sequential plasma cell-free DNA in EGFR -mutated lung cancer. J Thorac Oncol 2017; 12(7): e81-4.
[http://dx.doi.org/10.1016/j.jtho.2017.02.023] [PMID: 28286242]
[7]
Zhang J, Späth SS, Marjani SL, Zhang W, Pan X. Characterization of cancer genomic heterogeneity by next-generation sequencing advances precision medicine in cancer treatment. Precis Clin Med 2018; 1(1): 29-48.
[http://dx.doi.org/10.1093/pcmedi/pby007] [PMID: 30687561]
[8]
Huang S, Han Y, Chen M, et al. Radiosynthesis and biological evaluation of 18F-labeled 4-anilinoquinazoline derivative (18FFEA-Erlotinib) as a potential EGFR PET agent. Bioorg Med Chem Lett 2018; 28(6): 1143-8.
[http://dx.doi.org/10.1016/j.bmcl.2017.08.066] [PMID: 29486966]
[9]
Yeh HH, Ogawa K, Balatoni J, et al. Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT. Proc Natl Acad Sci USA 2011; 108(4): 1603-8.
[http://dx.doi.org/10.1073/pnas.1010744108] [PMID: 21220318]
[10]
Tavakoli F, Ganjalikhany MR. Structure-based inhibitory peptide design targeting peptide-substrate binding site in EGFR tyrosine kinase. PLoS One 2019; 14(5): e0217031.
[http://dx.doi.org/10.1371/journal.pone.0217031] [PMID: 31116768]
[11]
King R, Surfraz MBU, Finucane C, Biagini SCG, Blower PJ, Mather SJ. 99m Tc-hynic-gastrin peptides: Assisted coordination of 99m Tc by amino acid side chains results in improved performance both in vitro and in vivo. J Nucl Med 2009; 50(4): 591-8.
[http://dx.doi.org/10.2967/jnumed.108.058289] [PMID: 19289435]
[12]
Kim MH, Kim SG, Kim DW. A novel dual-labeled small peptide as a multimodal imaging agent for targeting wild-type EGFR in tumors. PLoS One 2022; 17(2): e0263474.
[http://dx.doi.org/10.1371/journal.pone.0263474] [PMID: 35120180]
[13]
Kaye J, Hayward M. Soft tissue uptake on 99mTc methylene diphosphonate bone scan imaging: Pictorial review. Australas Radiol 2002; 46(1): 13-21.
[http://dx.doi.org/10.1046/j.1440-1673.2001.00989.x] [PMID: 11966582]
[14]
Shiau CJ, Babwah JP, da Cunha Santos G, et al. Sample features associated with success rates in population-based EGFR mutation testing. J Thorac Oncol 2014; 9(7): 947-56.
[http://dx.doi.org/10.1097/JTO.0000000000000196] [PMID: 24922009]
[15]
Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352(8): 786-92.
[http://dx.doi.org/10.1056/NEJMoa044238] [PMID: 15728811]
[16]
Chang S, Shim HS, Kim TJ, et al. Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group. J Pathol Transl Med 2021; 55(3): 181-91.
[http://dx.doi.org/10.4132/jptm.2021.03.23] [PMID: 33966368]
[17]
Xia N, An J, Jiang Q, Li M, Tan J, Hu C. Analysis of EGFR, EML4-ALK, KRAS, and c-MET mutations in Chinese lung adenocarcinoma patients. Exp Lung Res 2013; 39(8): 328-35.
[http://dx.doi.org/10.3109/01902148.2013.819535] [PMID: 23919423]
[18]
Vignot S, Besse B, André F, Spano JP, Soria JC. Discrepancies between primary tumor and metastasis: A literature review on clinically established biomarkers. Crit Rev Oncol Hematol 2012; 84(3): 301-13.
[http://dx.doi.org/10.1016/j.critrevonc.2012.05.002] [PMID: 22710198]
[19]
Guo L, Chen Z, Xu C, et al. Intratumoral heterogeneity of EGFR-activating mutations in advanced NSCLC patients at the single-cell level. BMC Cancer 2019; 19(1): 369.
[http://dx.doi.org/10.1186/s12885-019-5555-y] [PMID: 31014278]
[20]
Chen W, Shen B, Sun X. Analysis of progress and challenges of egfr-targeted molecular imaging in cancer with a focus on affibody molecules. Mol Imaging 2019; 18.
[http://dx.doi.org/10.1177/1536012118823473] [PMID: 30799684]
[21]
Du B, Wang S, Cui Y, Liu G, Li X, Li Y. Can 18 F-FDG PET/CT predict EGFR status in patients with non-small cell lung cancer? A systematic review and meta-analysis. BMJ Open 2021; 11(6): e044313.
[http://dx.doi.org/10.1136/bmjopen-2020-044313] [PMID: 34103313]
[22]
Yeh SHH, Lin CF, Kong FL, et al. Molecular imaging of nonsmall cell lung carcinomas expressing active mutant EGFR kinase using PET with [(124)i]-morpholino-IPQA. BioMed Res Int 2013; 2013: 1-10.
[http://dx.doi.org/10.1155/2013/549359] [PMID: 23956990]
[23]
Memon AA, Jakobsen S, Dagnaes-Hansen F, Sorensen BS, Keiding S, Nexo E. Positron emission tomography (PET) imaging with [11C]-labeled erlotinib: a micro-PET study on mice with lung tumor xenografts. Cancer Res 2009; 69(3): 873-8.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-3118] [PMID: 19155297]
[24]
Su H, Seimbille Y, Ferl GZ, et al. Evaluation of [18F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors. Eur J Nucl Med Mol Imaging 2008; 35(6): 1089-99.
[http://dx.doi.org/10.1007/s00259-007-0636-6] [PMID: 18239919]
[25]
Wang H, Yu J, Yang G, et al. Further characterization of the epidermal growth factor receptor ligand 11C-PD153035. Chin Med J (Engl) 2007; 120(11): 960-4.
[http://dx.doi.org/10.1097/00029330-200706010-00004] [PMID: 17624262]
[26]
Fawwaz M, Mishiro K, Nishii R, et al. A radiobrominated tyrosine kinase inhibitor for EGFR with L858R/T790M mutations in lung carcinoma. Pharmaceuticals (Basel) 2021; 14(3): 256.
[http://dx.doi.org/10.3390/ph14030256] [PMID: 33809064]
[27]
Sun X, Xiao Z, Chen G, et al. A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management. Sci Transl Med 2018; 10(431): eaan8840.
[http://dx.doi.org/10.1126/scitranslmed.aan8840] [PMID: 29515002]
[28]
Liljegren Sundberg Å, Gedda L, Orlova A, et al. [177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma. Cancer Biother Radiopharm 2004; 19(2): 195-204.
[http://dx.doi.org/10.1089/108497804323071977] [PMID: 15186600]
[29]
Shamni O, Grievink H, Itamar B, Mishani E, Abourbeh G. Development of a fluorinated analogue of erlotinib for PET imaging of EGFR mutation–positive NSCLC. Mol Imaging Biol 2019; 21(4): 696-704.
[http://dx.doi.org/10.1007/s11307-018-1286-8] [PMID: 30377939]
[30]
Orbay H, Hong H, Zhang Y, Cai W. PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow. Angiogenesis 2013; 16(2): 279-87.
[http://dx.doi.org/10.1007/s10456-012-9319-4] [PMID: 23117521]

Rights & Permissions Print Cite
Article Metrics
19
2
© 2024 Bentham Science Publishers | Privacy Policy