EGFR突變陽性肺癌分子探針的PET顯像研究進展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

謝佳峻 ¹ , 徐維國 ¹ , 陳正國 ^1,3 , 吳春燕 ^1,3 ,  朱靜 ^1,2

1. ;
2. ;
3. ;

Corresponding?author：

朱靜, Email: zhujing_1126@126.com

Keywords：

DOI：

10.7507/1671-6205.202501040

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Citation： 謝佳峻, 徐維國, 陳正國, 吳春燕, 朱靜. EGFR突變陽性肺癌分子探針的PET顯像研究進展. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(12): 902-908. doi: 10.7507/1671-6205.202501040 Copy

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	Jokhadze N, Das A, Dizon DS. Global cancer statistics: A healthy population relies on population health. CA Cancer J Clin, 2024, 74(3): 224-226.
3.	Li S, Choi YL, Gong Z, et al. Comprehensive Characterization of Oncogenic Drivers in Asian Lung Adenocarcinoma. J Thorac Oncol, 2016, 11(12): 2129-2140.
4.	Zheng D, Wang R, Ye T, et al. MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer. Oncotarget, 2016, 7(27): 41691-41702.
5.	Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer, 2007, 7(3): 169-181.
6.	Roskoski R Jr. Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. Pharmacol Res, 2019, 139: 395-411.
7.	Vecchione L, Jacobs B, Normanno N, et al. EGFR-targeted therapy. Exp Cell Res, 2011, 317(19): 2765-71.
8.	Bahce I, Yaqub M, Smit EF, et al. Personalizing NSCLC therapy by characterizing tumors using TKI-PET and immuno-PET. Lung Cancer, 2017, 107: 1-13.
9.	Kawaguchi T, Koh Y, Ando M, et al. Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study. J Clin Oncol, 2016, 34(19): 2247-57.
10.	Suda K, Rivard CJ, Mitsudomi T, et al. Overcoming resistance to EGFR tyrosine kinase inhibitors in lung cancer, focusing on non-T790M mechanisms. Expert Rev Anticancer Ther, 2017, 17(9): 779-786.
11.	Engelman JA, J?nne PA. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res, 2008, 14(10): 2895-9.
12.	Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med, 2005, 2(3): e73.
13.	Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med, 2017, 376(7): 629-640.
14.	To C, Jang J, Chen T, et al. Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov, 2019, 9(7): 926-943.
15.	Pirker R, Herth FJ, Kerr KM, et al. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop. J Thorac Oncol, 2010, 5(10): 1706-1713.
16.	Aggarwal C, Rolfo CD, Oxnard GR, et al. Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice. Nat Rev Clin Oncol, 2021, 18(1): 56-62.
17.	de Bruin EC, McGranahan N, Mitter R, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science, 2014, 346(6206): 251-256.
18.	Zhang J, Fujimoto J, Zhang J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science, 2014, 346(6206): 256-259.
19.	Maute RL, Gordon SR, Mayer AT, et al. Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc Natl Acad Sci U S A, 2015, 112(47): E6506-514.
20.	Niemeijer AN, Leung D, Huisman MC, et al. Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nat Commun, 2018, 9(1): 4664.
21.	Carney B, Kossatz S, Lok BH, et al. Target engagement imaging of PARP inhibitors in small-cell lung cancer. Nat Commun, 2018, 9(1): 176.
22.	Memon AA, Jakobsen S, Dagnaes-Hansen F, et al. Positron emission tomography (PET) imaging with [11C]-labeled erlotinib: a micro-PET study on mice with lung tumor xenografts. Cancer Res, 2009, 69(3): 873-878.
23.	Bahce I, Yaqub M, Errami H, et al. Effects of erlotinib therapy on [(11)C]erlotinib uptake in EGFR mutated, advanced NSCLC. EJNMMI Res. 2016, 6(1): 10.
24.	Abourbeh G, Itamar B, Salnikov O, et al. Identifying erlotinib-sensitive non-small cell lung carcinoma tumors in mice using [(11)C]erlotinib PET. EJNMMI Res, 2015, 5: 4.
25.	Stewart DJ, Erasmus JJ. Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. J Thorac Oncol, 2011, 6(7): 1149-51.
26.	Bahce I, Smit EF, Lubberink M, et al. Development of [(11)C]erlotinib positron emission tomography for in vivo evaluation of EGF receptor mutational status. Clin Cancer Res, 2013, 19(1): 183-193.
27.	Jain A, Kameswaran M, Pandey U, et al. (68)Ga labeled Erlotinib: A novel PET probe for imaging EGFR over-expressing tumors. Bioorg Med Chem Lett, 2017, 27(19): 4552-4557.
28.	Huang S, Han Y, Chen M, et al. Radiosynthesis and biological evaluation of (18)F-labeled 4-anilinoquinazoline derivative ((18)F-FEA-Erlotinib) as a potential EGFR PET agent. Bioorg Med Chem Lett, 2018, 28(6): 1143-1148.
29.	Wang JQ, Gao M, Miller KD, et al. Synthesis of [11C]Iressa as a new potential PET cancer imaging agent for epidermal growth factor receptor tyrosine kinase. Bioorg Med Chem Lett, 2006, 16(15): 4102-4106.
30.	Su H, Seimbille Y, Ferl GZ, et al. Evaluation of [(18)F]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): 1089-1099.
31.	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.
32.	Lu X, Wang C, Li X, et al. Synthesis and preliminary evaluation of (18)F-icotinib for EGFR-targeted PET imaging of lung cancer. Bioorg Med Chem, 2019, 27(3): 545-551.
33.	Slobbe P, Windhorst AD, Stigter-van Walsum M, et al. Development of [18F]afatinib as new TKI-PET tracer for EGFR positive tumors. Nucl Med Biol, 2014, 41(9): 749-757.
34.	Slobbe P,Windhorst AD, Stigter-van Walsum M, et al.A comparative PET imaging study with the reversible and irreversible EGFR tyrosine kinase inhibitors [(11)C]erlotinib and [(18)F]afatinib in lung cancer-bearing mice.EJNMMI Res,2015,5:14.
35.	van de Stadt EA, Yaqub M, Lammertsma AA, et al. Quantification of [(18)F]afatinib using PET/CT in NSCLC patients: a feasibility study. EJNMMI Res. 2020 Aug 17;10(1): 97.
36.	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 U S A. 2011, 108(4): 1603-1608.
37.	Ortu G, Ben-David I, Rozen Y, et al. Labeled EGFr-TK irreversible inhibitor (ML03): in vitro and in vivo properties, potential as PET biomarker for cancer and feasibility as anticancer drug. Int J Cancer, 2002, 101(4): 360-370.
38.	Ben-David I, Rozen Y, Ortu G, et al. Radiosynthesis of ML03, a novel positron emission tomography biomarker for targeting epidermal growth factor receptor via the labeling synthon: [11C]acryloyl chloride. Appl Radiat Isot, 2003, 58(2): 209-217.
39.	Gelovani JG. Molecular imaging of epidermal growth factor receptor expression-activity at the kinase level in tumors with positron emission tomography. Cancer Metastasis Rev, 2008, 27(4): 645-653.
40.	Abourbeh G, Dissoki S, Jacobson O, et al. Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing tumors. Nucl Med Biol, 2007, 34(1): 55-70.
41.	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.
42.	Fawwaz M, Mishiro K, Nishii R, et al. Synthesis and Fundamental Evaluation of Radioiodinated Rociletinib (CO-1686) as a Probe to Lung Cancer with L858R/T790M Mutations of Epidermal Growth Factor Receptor (EGFR). Molecules. 2020, 25(12): 2914.
43.	Ballard P, Yates JW, Yang Z, et al. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity. Clin Cancer Res, 2016, 22(20): 5130-5140.
44.	Varrone A, Varn?s K, Jucaite A, et al. A PET study in healthy subjects of brain exposure of (11)C-labelled osimertinib - A drug intended for treatment of brain metastases in non-small cell lung cancer. J Cereb Blood Flow Metab, 2020, 40(4): 799-807.
45.	Cheng H, Bai L, Zhang X, et al. (68)Ga labeled Olmutinib: Design, synthesis, and evaluation of a novel PET EGFR probe. Bioorg Chem, 2024, 153: 107987.
46.	H?gn?sbacka AA, Poot AJ, Plisson C, et al. Synthesis and preclinical evaluation of [(11)C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor. EJNMMI Res. 2024 Feb 16;14(1): 19.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. Jokhadze N, Das A, Dizon DS. Global cancer statistics: A healthy population relies on population health. CA Cancer J Clin, 2024, 74(3): 224-226.
3. Li S, Choi YL, Gong Z, et al. Comprehensive Characterization of Oncogenic Drivers in Asian Lung Adenocarcinoma. J Thorac Oncol, 2016, 11(12): 2129-2140.
4. Zheng D, Wang R, Ye T, et al. MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer. Oncotarget, 2016, 7(27): 41691-41702.
5. Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer, 2007, 7(3): 169-181.
6. Roskoski R Jr. Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. Pharmacol Res, 2019, 139: 395-411.
7. Vecchione L, Jacobs B, Normanno N, et al. EGFR-targeted therapy. Exp Cell Res, 2011, 317(19): 2765-71.
8. Bahce I, Yaqub M, Smit EF, et al. Personalizing NSCLC therapy by characterizing tumors using TKI-PET and immuno-PET. Lung Cancer, 2017, 107: 1-13.
9. Kawaguchi T, Koh Y, Ando M, et al. Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study. J Clin Oncol, 2016, 34(19): 2247-57.
10. Suda K, Rivard CJ, Mitsudomi T, et al. Overcoming resistance to EGFR tyrosine kinase inhibitors in lung cancer, focusing on non-T790M mechanisms. Expert Rev Anticancer Ther, 2017, 17(9): 779-786.
11. Engelman JA, J?nne PA. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res, 2008, 14(10): 2895-9.
12. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med, 2005, 2(3): e73.
13. Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med, 2017, 376(7): 629-640.
14. To C, Jang J, Chen T, et al. Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov, 2019, 9(7): 926-943.
15. Pirker R, Herth FJ, Kerr KM, et al. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop. J Thorac Oncol, 2010, 5(10): 1706-1713.
16. Aggarwal C, Rolfo CD, Oxnard GR, et al. Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice. Nat Rev Clin Oncol, 2021, 18(1): 56-62.
17. de Bruin EC, McGranahan N, Mitter R, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science, 2014, 346(6206): 251-256.
18. Zhang J, Fujimoto J, Zhang J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science, 2014, 346(6206): 256-259.
19. Maute RL, Gordon SR, Mayer AT, et al. Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc Natl Acad Sci U S A, 2015, 112(47): E6506-514.
20. Niemeijer AN, Leung D, Huisman MC, et al. Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nat Commun, 2018, 9(1): 4664.
21. Carney B, Kossatz S, Lok BH, et al. Target engagement imaging of PARP inhibitors in small-cell lung cancer. Nat Commun, 2018, 9(1): 176.
22. Memon AA, Jakobsen S, Dagnaes-Hansen F, et al. Positron emission tomography (PET) imaging with [11C]-labeled erlotinib: a micro-PET study on mice with lung tumor xenografts. Cancer Res, 2009, 69(3): 873-878.
23. Bahce I, Yaqub M, Errami H, et al. Effects of erlotinib therapy on [(11)C]erlotinib uptake in EGFR mutated, advanced NSCLC. EJNMMI Res. 2016, 6(1): 10.
24. Abourbeh G, Itamar B, Salnikov O, et al. Identifying erlotinib-sensitive non-small cell lung carcinoma tumors in mice using [(11)C]erlotinib PET. EJNMMI Res, 2015, 5: 4.
25. Stewart DJ, Erasmus JJ. Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. J Thorac Oncol, 2011, 6(7): 1149-51.
26. Bahce I, Smit EF, Lubberink M, et al. Development of [(11)C]erlotinib positron emission tomography for in vivo evaluation of EGF receptor mutational status. Clin Cancer Res, 2013, 19(1): 183-193.
27. Jain A, Kameswaran M, Pandey U, et al. (68)Ga labeled Erlotinib: A novel PET probe for imaging EGFR over-expressing tumors. Bioorg Med Chem Lett, 2017, 27(19): 4552-4557.
28. Huang S, Han Y, Chen M, et al. Radiosynthesis and biological evaluation of (18)F-labeled 4-anilinoquinazoline derivative ((18)F-FEA-Erlotinib) as a potential EGFR PET agent. Bioorg Med Chem Lett, 2018, 28(6): 1143-1148.
29. Wang JQ, Gao M, Miller KD, et al. Synthesis of [11C]Iressa as a new potential PET cancer imaging agent for epidermal growth factor receptor tyrosine kinase. Bioorg Med Chem Lett, 2006, 16(15): 4102-4106.
30. Su H, Seimbille Y, Ferl GZ, et al. Evaluation of [(18)F]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): 1089-1099.
31. 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.
32. Lu X, Wang C, Li X, et al. Synthesis and preliminary evaluation of (18)F-icotinib for EGFR-targeted PET imaging of lung cancer. Bioorg Med Chem, 2019, 27(3): 545-551.
33. Slobbe P, Windhorst AD, Stigter-van Walsum M, et al. Development of [18F]afatinib as new TKI-PET tracer for EGFR positive tumors. Nucl Med Biol, 2014, 41(9): 749-757.
34. Slobbe P,Windhorst AD, Stigter-van Walsum M, et al.A comparative PET imaging study with the reversible and irreversible EGFR tyrosine kinase inhibitors [(11)C]erlotinib and [(18)F]afatinib in lung cancer-bearing mice.EJNMMI Res,2015,5:14.
35. van de Stadt EA, Yaqub M, Lammertsma AA, et al. Quantification of [(18)F]afatinib using PET/CT in NSCLC patients: a feasibility study. EJNMMI Res. 2020 Aug 17;10(1): 97.
36. 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 U S A. 2011, 108(4): 1603-1608.
37. Ortu G, Ben-David I, Rozen Y, et al. Labeled EGFr-TK irreversible inhibitor (ML03): in vitro and in vivo properties, potential as PET biomarker for cancer and feasibility as anticancer drug. Int J Cancer, 2002, 101(4): 360-370.
38. Ben-David I, Rozen Y, Ortu G, et al. Radiosynthesis of ML03, a novel positron emission tomography biomarker for targeting epidermal growth factor receptor via the labeling synthon: [11C]acryloyl chloride. Appl Radiat Isot, 2003, 58(2): 209-217.
39. Gelovani JG. Molecular imaging of epidermal growth factor receptor expression-activity at the kinase level in tumors with positron emission tomography. Cancer Metastasis Rev, 2008, 27(4): 645-653.
40. Abourbeh G, Dissoki S, Jacobson O, et al. Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing tumors. Nucl Med Biol, 2007, 34(1): 55-70.
41. 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.
42. Fawwaz M, Mishiro K, Nishii R, et al. Synthesis and Fundamental Evaluation of Radioiodinated Rociletinib (CO-1686) as a Probe to Lung Cancer with L858R/T790M Mutations of Epidermal Growth Factor Receptor (EGFR). Molecules. 2020, 25(12): 2914.
43. Ballard P, Yates JW, Yang Z, et al. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity. Clin Cancer Res, 2016, 22(20): 5130-5140.
44. Varrone A, Varn?s K, Jucaite A, et al. A PET study in healthy subjects of brain exposure of (11)C-labelled osimertinib - A drug intended for treatment of brain metastases in non-small cell lung cancer. J Cereb Blood Flow Metab, 2020, 40(4): 799-807.
45. Cheng H, Bai L, Zhang X, et al. (68)Ga labeled Olmutinib: Design, synthesis, and evaluation of a novel PET EGFR probe. Bioorg Chem, 2024, 153: 107987.
46. H?gn?sbacka AA, Poot AJ, Plisson C, et al. Synthesis and preclinical evaluation of [(11)C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor. EJNMMI Res. 2024 Feb 16;14(1): 19.

Previous Article
低氧負荷在評估阻塞性睡眠呼吸暫停的應用

Chinese Journal of Respiratory and Critical Care Medicine

EGFR突變陽性肺癌分子探針的PET顯像研究進展

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Format

Content