Neoadjuvant Therapies Do Not Reduce Epidermal Growth Factor Receptor (EGFR) Expression or EGFR-Targeted Fluorescence in a Murine Model of Soft-Tissue Sarcomas.
ABY-029
Fluorescence
Fluorescence imaging
Neoadjuvant therapy
Soft-tissue sarcoma
Journal
Molecular imaging and biology
ISSN: 1860-2002
Titre abrégé: Mol Imaging Biol
Pays: United States
ID NLM: 101125610
Informations de publication
Date de publication:
27 Dec 2023
27 Dec 2023
Historique:
received:
15
08
2023
accepted:
01
12
2023
revised:
01
11
2023
medline:
28
12
2023
pubmed:
28
12
2023
entrez:
27
12
2023
Statut:
aheadofprint
Résumé
ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for fluorescence-guided surgery of sarcomas. To date, studies using ABY-029 have occurred in tumors naïve to chemotherapy (CTx) and radiation therapy (RTx), although these neoadjuvant therapies are frequently used for sarcoma treatment in humans. The goal of this study was to evaluate the impact of CTx and RTx on tumor EGFR expression and ABY-029 fluorescence of human soft-tissue sarcoma xenografts in a murine model. Immunodeficient mice (n = 98) were divided into five sarcoma xenograft groups and three treatment groups - CTx only, RTx only, and CTx followed by RTx, plus controls. Four hours post-injection of ABY-029, animals were sacrificed followed by immediate fluorescence imaging of ex vivo adipose, muscle, nerve, and tumor tissues. Histological hematoxylin and eosin staining confirmed tumor type, and immunohistochemistry staining determined EGFR, cluster of differentiation 31 (CD31), and smooth muscle actin (SMA) expression levels. Correlation analysis (Pearson's correlation coefficients, r) and linear regression (unstandardized coefficient estimates, B) were used to determine statistical relationships in molecular expression and tissue fluorescence between xenografts and treatment groups. Neoadjuvant therapies had no broad impact on EGFR expression (|B|≤ 7.0, p ≥ 0.4) or on mean tissue fluorescence (any tissue type, (|B|≤ 2329.0, p ≥ 0.1). Mean tumor fluorescence was significantly related to EGFR expression (r = 0.26, p = 0.01), as expected. Results suggest that ABY-029 as an EGFR-targeted, fluorescent probe is not negatively impacted by neoadjuvant soft-tissue sarcoma therapies, although validation in humans is required.
Identifiants
pubmed: 38151580
doi: 10.1007/s11307-023-01884-9
pii: 10.1007/s11307-023-01884-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIBIB NIH HHS
ID : K23 EB026507
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA167413
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.
Références
Fletcher CDM, Bridge JA, Hogendoorn PCW, et al (eds) (2013) WHO classification of tumours of soft tissue and bone. 4th edn., vol. 5. Lyon, IARC Press
Pasquali S, Gronchi A (2017) Neoadjuvant chemotherapy in soft tissue sarcomas: Latest evidence and clinical implications. Ther Adv Med Oncol 9:415–429. https://doi.org/10.1177/1758834017705588
doi: 10.1177/1758834017705588
pubmed: 28607580
pmcid: 5455882
Bowden L, Booher RJ, Peabody TD, Mindell ER (2004) The classic: The principles and technique of resection of soft parts for sarcoma. Clin Orthop Relat Res 1976–2007:426
Kawaguchi N, Ahmed AR, Matsumoto S et al (2004) The concept of curative margin in surgery for bone and soft tissue sarcoma. Clin Orthop Relat Res 419:165–172. https://doi.org/10.1097/00003086-200402000-00027
O’Donnell PW, Griffin AM, Eward WC et al (2014) The effect of the setting of a positive surgical margin in soft tissue sarcoma. Cancer 120:2866–2875. https://doi.org/10.1002/cncr.28793
doi: 10.1002/cncr.28793
pubmed: 24894656
Endo M, Lin PP (2018) Surgical margins in the management of extremity soft tissue sarcoma. Chin Clin Oncol 7:37. https://doi.org/10.21037/cco.2018.08.10
Pisters PW, Leung DH, Woodruff J et al (1996) Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14:1679–1689. https://doi.org/10.1200/JCO.1996.14.5.1679
doi: 10.1200/JCO.1996.14.5.1679
pubmed: 8622088
Stojadinovic A, Leung DHY, Hoos A et al (2002) Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas. Ann Surg 235:424–434. https://doi.org/10.1097/00000658-200203000-00015
doi: 10.1097/00000658-200203000-00015
pubmed: 11882765
pmcid: 1422449
Potter BK, Hwang PF, Forsberg JA et al (2013) Impact of margin status and local recurrence on soft-tissue sarcoma outcomes. J Bone Joint Surg Am 95:e151. https://doi.org/10.2106/JBJS.L.01149
doi: 10.2106/JBJS.L.01149
pubmed: 24132366
Abarca T, Gao Y, Monga V et al (2018) Improved survival for extremity soft tissue sarcoma treated in high-volume facilities. J Surg Oncol 117:1479–1486. https://doi.org/10.1002/jso.25052
doi: 10.1002/jso.25052
pubmed: 29633281
pmcid: 6322682
Gundle KR, Kafchinski L, Gupta S et al (2018) Analysis of margin classification Systems for Assessing the risk of local recurrence after soft tissue sarcoma resection. JCO 36:704–709. https://doi.org/10.1200/JCO.2017.74.6941
doi: 10.1200/JCO.2017.74.6941
Stummer W, Novotny A, Stepp H et al (2000) Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: A prospective study in 52 consecutive patients. J Neurosurg 93:1003–1013. https://doi.org/10.3171/jns.2000.93.6.1003
doi: 10.3171/jns.2000.93.6.1003
pubmed: 11117842
Stummer W, Pichlmeier U, Meinel T et al (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401. https://doi.org/10.1016/S1470-2045(06)70665-9
doi: 10.1016/S1470-2045(06)70665-9
pubmed: 16648043
Hadjipanayis CG, Stummer W (2019) 5-ALA and FDA approval for glioma surgery. J Neurooncol 141:479–486. https://doi.org/10.1007/s11060-019-03098-y
doi: 10.1007/s11060-019-03098-y
pubmed: 30644008
pmcid: 6445645
Mito JK, Ferrer JM, Brigman BE et al (2012) Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging. Cancer 118:5320–5330. https://doi.org/10.1002/cncr.27458
doi: 10.1002/cncr.27458
pubmed: 22437667
Cuneo KC, Mito JK, Javid MP et al (2013) Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents. Int J Radiat Oncol Biol Phys 86:136–142. https://doi.org/10.1016/j.ijrobp.2012.12.007
doi: 10.1016/j.ijrobp.2012.12.007
pubmed: 23391816
pmcid: 3923491
Samkoe KS, Gunn JR, Marra K et al (2017) Toxicity and pharmacokinetic profile for single-dose injection of ABY-029: A fluorescent anti-EGFR synthetic affibody molecule for human use. Mol Imaging Biol 19:512–521. https://doi.org/10.1007/s11307-016-1033-y
doi: 10.1007/s11307-016-1033-y
pubmed: 27909986
pmcid: 5648591
Samkoe KS, Sardar HS, Bates BD et al (2019) Preclinical imaging of epidermal growth factor receptor with ABY-029 in soft-tissue sarcoma for fluorescence-guided surgery and tumor detection. J Surg Oncol 119:1077–1086. https://doi.org/10.1002/jso.25468
doi: 10.1002/jso.25468
pubmed: 30950072
pmcid: 6529257
Sardar HS, Zai Q, Xu X et al (2020) Dual-agent fluorescent labeling of soft-tissue sarcomas improves the contrast based upon targeting both interstitial and cellular components of the tumor milieu. J Surg Oncol 122:1711–1720. https://doi.org/10.1002/jso.26190
doi: 10.1002/jso.26190
pubmed: 32885452
pmcid: 8287542
Streeter SS, Hebert KA, Bateman LM et al (2023) Current and future applications of fluorescence guidance in orthopaedic surgery. Mol Imaging Biol 25:46–57. https://doi.org/10.1007/s11307-022-01789-z
doi: 10.1007/s11307-022-01789-z
pubmed: 36447084
Sato O, Wada T, Kawai A et al (2005) Expression of epidermal growth factor receptor, ERBB2 and KIT in adult soft tissue sarcomas: A clinicopathologic study of 281 cases. Cancer 103:1881–1890. https://doi.org/10.1002/cncr.20986
doi: 10.1002/cncr.20986
pubmed: 15772959
Yang J-L, Hannan MT, Russell PJ, Crowe PJ (2006) Expression of HER1/EGFR protein in human soft tissue sarcomas. Eur J Surg Oncol 32:466–468. https://doi.org/10.1016/j.ejso.2006.01.012
doi: 10.1016/j.ejso.2006.01.012
pubmed: 16524687
Keizman D, Issakov J, Meller I et al (2009) Expression and significance of EGFR in malignant peripheral nerve sheath tumor. J Neurooncol 94:383–388. https://doi.org/10.1007/s11060-009-9862-z
doi: 10.1007/s11060-009-9862-z
pubmed: 19330289
Teng H-W, Wang H-W, Chen W-M et al (2011) Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma. J Surg Oncol 103:773–781. https://doi.org/10.1002/jso.21852
doi: 10.1002/jso.21852
pubmed: 21240992
Yang J-L, Gupta RD, Goldstein D, Crowe PJ (2017) Significance of phosphorylated epidermal growth factor receptor and its signal transducers in human soft tissue sarcoma. Int J Mol Sci 18. https://doi.org/10.3390/ijms18061159
Braun AC, de Mello CAL, Corassa M et al (2018) EGFR expression in circulating tumor cells from high-grade metastatic soft tissue sarcomas. Cancer Biol Ther 19:454–460. https://doi.org/10.1080/15384047.2018.1433498
doi: 10.1080/15384047.2018.1433498
pubmed: 29394136
pmcid: 5927672
Norberg SM, Movva S (2015) Role of genetic and molecular profiling in sarcomas. Curr Treat Options Oncol 16:24. https://doi.org/10.1007/s11864-015-0339-3
doi: 10.1007/s11864-015-0339-3
pubmed: 25939540
Mariño-Enríquez A, Bovée JVMG (2016) Molecular pathogenesis and diagnostic, prognostic and predictive molecular markers in sarcoma. Surg Pathol Clin 9:457–473. https://doi.org/10.1016/j.path.2016.04.009
doi: 10.1016/j.path.2016.04.009
pubmed: 27523972
pmcid: 4988391
Grünewald TG, Alonso M, Avnet S et al (2020) Sarcoma treatment in the era of molecular medicine. EMBO Mol Med 12:e11131. https://doi.org/10.15252/emmm.201911131
Salerno KE, Alektiar KM, Baldini EH et al (2021) Radiation therapy for treatment of soft tissue sarcoma in adults: Executive summary of an ASTRO clinical practice guideline. Pract Radiat Oncol 11:339–351. https://doi.org/10.1016/j.prro.2021.04.005
doi: 10.1016/j.prro.2021.04.005
pubmed: 34326023
Murakami T, DeLong J, Eilber FC et al (2016) Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model. Oncotarget 7:12783–12790. https://doi.org/10.18632/oncotarget.7226
Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661. https://doi.org/10.1096/fj.07-9574LSF
doi: 10.1096/fj.07-9574LSF
pubmed: 17942826
Schindelin J, Arganda-Carreras I, Frise E et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682. https://doi.org/10.1038/nmeth.2019
doi: 10.1038/nmeth.2019
pubmed: 22743772
Ferreira T, Miura K, Chef B, Eglinger J (2015) Scripts: BAR 1.1.6 (Version 1.1.6). Zenodo. https://doi.org/10.5281/ZENODO.28838
Zhou Q, van den Berg NS, Kang W et al (2022) Factors for differential outcome across cancers in clinical molecular-targeted fluorescence imaging. J Nucl Med 63(11):1693–1700. https://doi.org/10.2967/jnumed.121.263674
doi: 10.2967/jnumed.121.263674
pubmed: 35332092
pmcid: 9635681
Peter RU, Beetz A, Ried C et al (1993) Increased expression of the epidermal growth factor receptor in human epidermal keratinocytes after exposure to ionizing radiation. Radiat Res 136:65–70
doi: 10.2307/3578641
pubmed: 8210340
Park C-M, Park M-J, Kwak H-J et al (2006) Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways. Cancer Res 66:8511–8519. https://doi.org/10.1158/0008-5472.CAN-05-4340
doi: 10.1158/0008-5472.CAN-05-4340
pubmed: 16951163
de Almeida VH, de Melo AC, Meira DD et al (2017) Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer. Braz J Med Biol Res 51:e6822. https://doi.org/10.1590/1414-431X20176822
doi: 10.1590/1414-431X20176822
pubmed: 29160417
pmcid: 5685065
Song X, Shao Y, Jiang T et al (2018) Radiotherapy upregulates programmed death Ligand-1 through the pathways downstream of epidermal growth factor receptor in glioma. EBioMedicine 28:105–113. https://doi.org/10.1016/j.ebiom.2018.01.027
doi: 10.1016/j.ebiom.2018.01.027
pubmed: 29396299
pmcid: 5835577
Pisters PWT, Patel SR, Prieto VG et al (2004) Phase I trial of preoperative doxorubicin-based concurrent chemoradiation and surgical resection for localized extremity and body wall soft tissue sarcomas. J Clin Oncol 22:3375–3380. https://doi.org/10.1200/JCO.2004.01.040
doi: 10.1200/JCO.2004.01.040
pubmed: 15310783
Mack LA, Crowe PJ, Yang JL et al (2005) Preoperative chemoradiotherapy (modified Eilber protocol) provides maximum local control and minimal morbidity in patients with soft tissue sarcoma. Ann Surg Oncol 12:646–653. https://doi.org/10.1245/ASO.2005.03.064
doi: 10.1245/ASO.2005.03.064
pubmed: 15965732