Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
received:
27
05
2024
accepted:
30
09
2024
revised:
11
09
2024
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
15
10
2024
Statut:
aheadofprint
Résumé
The primary goal of surgery in HNSCC is the complete resection of tumor cells with maximum preservation of normal tissue. The membrane Hsp70-targeting fluorescence labelled peptide TPP-IRDye800 represents a promising tool for real-time intraoperative tumor visualization, enabling the detection of true tumor margins, critical isles of high-grade dysplasia and LN metastases. Membrane Hsp70 (mHsp70) expression on HNSCC cell lines and primary HNSCC was determined by flow cytometry and fluorescence microscopy using FITC-conjugated mAb cmHsp70.1 and TPP. TPP-IRDye800 was sprayed on freshly resected tumor material of immunohistochemically confirmed HNSCC and LN metastases for tumor imaging. TBRs were compared using TPP-IRDye800 and Cetuximab-IRDye680, recognizing EGFR. mHsp70 expressing HNSCC cells specifically bind and internalize TPP in vitro. The TBR (2.56 ± 0.39) and AUC [0.98 CI, 0.95-1.00 vs. 0.91 CI, 0.85-0.97] of TPP-IRDye800 on primary HNSCC was significantly higher than Cetuximab-IRDye680 (1.61 ± 0.39) (p = 0.0068) and TPP-IRDye800 provided a superior tumor delineation. Fluorescence imaging showed higher AUC values than a visual inspection by surgeons [0.97 CI, 0.94-1.00 vs. 0.92 CI, 0.88-0.97] (p = 0.048). LN metastases could be visualized using TPP-IRDye800. Real-time tissue delineation was confirmed using the clinically applied KARL-STORZ imaging system. TPP-IRDye800 is a promising fluorescence imaging probe for HNSCC.
Sections du résumé
BACKGROUND
BACKGROUND
The primary goal of surgery in HNSCC is the complete resection of tumor cells with maximum preservation of normal tissue. The membrane Hsp70-targeting fluorescence labelled peptide TPP-IRDye800 represents a promising tool for real-time intraoperative tumor visualization, enabling the detection of true tumor margins, critical isles of high-grade dysplasia and LN metastases.
METHODS
METHODS
Membrane Hsp70 (mHsp70) expression on HNSCC cell lines and primary HNSCC was determined by flow cytometry and fluorescence microscopy using FITC-conjugated mAb cmHsp70.1 and TPP. TPP-IRDye800 was sprayed on freshly resected tumor material of immunohistochemically confirmed HNSCC and LN metastases for tumor imaging. TBRs were compared using TPP-IRDye800 and Cetuximab-IRDye680, recognizing EGFR.
RESULTS
RESULTS
mHsp70 expressing HNSCC cells specifically bind and internalize TPP in vitro. The TBR (2.56 ± 0.39) and AUC [0.98 CI, 0.95-1.00 vs. 0.91 CI, 0.85-0.97] of TPP-IRDye800 on primary HNSCC was significantly higher than Cetuximab-IRDye680 (1.61 ± 0.39) (p = 0.0068) and TPP-IRDye800 provided a superior tumor delineation. Fluorescence imaging showed higher AUC values than a visual inspection by surgeons [0.97 CI, 0.94-1.00 vs. 0.92 CI, 0.88-0.97] (p = 0.048). LN metastases could be visualized using TPP-IRDye800. Real-time tissue delineation was confirmed using the clinically applied KARL-STORZ imaging system.
CONCLUSION
CONCLUSIONS
TPP-IRDye800 is a promising fluorescence imaging probe for HNSCC.
Identifiants
pubmed: 39406917
doi: 10.1038/s41416-024-02872-8
pii: 10.1038/s41416-024-02872-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Eldeeb H, Macmillan C, Elwell C, Hammod A. The effect of the surgical margins on the outcome of patients with head and neck squamous cell carcinoma: single institution experience. Cancer Biol Med. 2012;9:29–33.
pubmed: 23691451
pmcid: 3643636
Hamman J, Howe CL, Borgstrom M, Baker A, Wang SJ, Bearelly S. Impact of Close Margins in Head and Neck Mucosal Squamous Cell Carcinoma: A Systematic Review. Laryngoscope. 2022;132:307–21.
pubmed: 34143492
doi: 10.1002/lary.29690
Voskuil FJ, De Jongh SJ, Hooghiemstra WTR, Linssen MD, Steinkamp PJ, De Visscher SAHJ, et al. Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study. Theranostics. 2020;10:3994–4005.
pubmed: 32226534
pmcid: 7086353
doi: 10.7150/thno.43227
Smits RWH, Koljenović S, Hardillo JA, Ten Hove I, Meeuwis CA, Sewnaik A, et al. Resection margins in oral cancer surgery: Room for improvement. Head Neck. 2016;38:E2197–E2203.
pubmed: 25899524
doi: 10.1002/hed.24075
Sutton DN, Brown JS, Rogers SN, Vaughan ED, Woolgar JA. The prognostic implications of the surgical margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2003;32:30–34.
pubmed: 12653229
doi: 10.1054/ijom.2002.0313
Lee YJ, Krishnan G, Nishio N, Berg NS, Lu G, Martin BA, et al. Intraoperative Fluorescence‐Guided Surgery in Head and Neck Squamous Cell Carcinoma. Laryngoscope. 2021;131:529–34.
pubmed: 33593036
doi: 10.1002/lary.28822
Schouw HM, Huisman LA, Janssen YF, Slart RHJA, Borra RJH, Willemsen ATM, et al. Targeted optical fluorescence imaging: a meta-narrative review and future perspectives. Eur J Nucl Med Mol Imaging. 2021;48:4272–92.
pubmed: 34633509
pmcid: 8566445
doi: 10.1007/s00259-021-05504-y
Fang H-Y, Stangl S, Marcazzan S, Carvalho MJB, Baumeister T, Anand A, et al. Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus. Eur J Nucl Med Mol Imaging. 2022;49:2049–63.
pubmed: 34882260
doi: 10.1007/s00259-021-05582-y
Ferrarini M, Heltai S, Zocchi MR, Rugarli C. Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer. 1992;51:613–9.
pubmed: 1601523
doi: 10.1002/ijc.2910510418
Kleinjung T, Arndt O, Feldmann HJ, Bockmühl U, Gehrmann M, Zilch T, et al. Heat shock protein 70 (Hsp70) membrane expression on head-and-neck cancer biopsy-a target for natural killer (NK) cells. Int J Radiat Oncol Biol Phys. 2003;57:820–6.
pubmed: 14529789
doi: 10.1016/S0360-3016(03)00629-1
Multhoff G, Botzler C, Wiesnet M, Müller E, Meier T, Wilmanns W, et al. A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int J Cancer. 1995;61:272–9.
pubmed: 7705958
doi: 10.1002/ijc.2910610222
Gehrmann M, Liebisch G, Schmitz G, Anderson R, Steinem C, De Maio A, et al. Tumor-specific Hsp70 plasma membrane localization is enabled by the glycosphingolipid Gb3. PLoS One. 2008;3:e1925.
pubmed: 18382692
pmcid: 2271151
doi: 10.1371/journal.pone.0001925
Stangl S, Gehrmann M, Dressel R, Alves F, Dullin C, Themelis G, et al. In vivo imaging of CT26 mouse tumours by using cmHsp70.1 monoclonal antibody. J Cell Mol Med. 2011;15:874–87.
pubmed: 20406322
doi: 10.1111/j.1582-4934.2010.01067.x
Stangl S, Varga J, Freysoldt B, Trajkovic-Arsic M, Siveke JT, Greten FR, et al. Selective In Vivo Imaging of Syngeneic, Spontaneous, and Xenograft Tumors Using a Novel Tumor Cell–Specific Hsp70 Peptide-Based Probe. Cancer Res. 2014;74:6903–12.
pubmed: 25300920
doi: 10.1158/0008-5472.CAN-14-0413
Stangl S, Gehrmann M, Riegger J, Kuhs K, Riederer I, Sievert W, et al. Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc Natl Acad Sci. 2011;108:733–8.
pubmed: 21187371
doi: 10.1073/pnas.1016065108
Gehrmann M, Stangl S, Foulds GA, Oellinger R, Breuninger S, Rad R, et al. Tumor Imaging and Targeting Potential of an Hsp70-Derived 14-Mer Peptide. PLoS ONE. 2014;9:e105344.
pubmed: 25165986
pmcid: 4148261
doi: 10.1371/journal.pone.0105344
Chames P, Van Regenmortel M, Weiss E, Baty D. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol. 2009;157:220–33.
pubmed: 19459844
pmcid: 2697811
doi: 10.1111/j.1476-5381.2009.00190.x
Kondo E, Iioka H, Saito K. Tumor‐homing peptide and its utility for advanced cancer medicine. Cancer Sci. 2021;112:2118–25.
pubmed: 33793015
pmcid: 8177760
doi: 10.1111/cas.14909
Kondo E, Saito K, Tashiro Y, Kamide K, Uno S, Furuya T, et al. Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems. Nat Commun. 2012;3:951.
pubmed: 22805558
doi: 10.1038/ncomms1952
Gabriels RY, van Heijst LE, Hooghiemstra WTR, van der Waaij AM, Kats-Ugurlu G, Karrenbeld A, et al. Detection of early esophageal neoplastic Barrett lesions with quantified fluorescence molecular endoscopy using cetuximab-800CW. J Nucl Med. 2023. jnumed.122.264656
Abramoff M, Magalhães P, Ram SJ. Image Processing with ImageJ. Biophotonics Int. 2003;11:36–42.
RCoreTeam. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/ . 2023.
Gwet KL _irrCAC: Computing Chance-Corrected Agreement Coefficients (CAC)_. R package version 1.0, https://CRAN.R-project.org/package=irrCAC . 2019.
Stangl S, Tei L, De Rose F, Reder S, Martinelli J, Sievert W, et al. Preclinical Evaluation of the Hsp70 Peptide Tracer TPP-PEG24-DFO[89Zr] for Tumor-Specific PET/CT Imaging. Cancer Res. 2018;78:6268–81.
pubmed: 30228173
doi: 10.1158/0008-5472.CAN-18-0707
Liao J, Lowthert LA, Ghori N, Omary MB. The 70-kDa Heat Shock Proteins Associate with Glandular Intermediate Filaments in an ATP-dependent Manner. J Biol Chem. 1995;270:915–22.
pubmed: 7529764
doi: 10.1074/jbc.270.2.915
Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C. Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol. 2007;81:15–27.
pubmed: 16931602
doi: 10.1189/jlb.0306167
Landis JR, Koch GG. The Measurement of Observer Agreement for Categorical Data. Biometrics. 1977;33:159.
pubmed: 843571
doi: 10.2307/2529310
Wu C, Gleysteen J, Teraphongphom NT, Li Y, Rosenthal E. In-vivo optical imaging in head and neck oncology: basic principles, clinical applications and future directions. Int J Oral Sci. 2018;10:10.
pubmed: 29555901
pmcid: 5944254
doi: 10.1038/s41368-018-0011-4
Hantschel M, Pfister K, Jordan A, Scholz R, Andreesen R, Schmitz G, et al. Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients. Cell Stress Chaperones. 2000;5:438–42.
pubmed: 11189449
pmcid: 312874
doi: 10.1379/1466-1268(2000)005<0438:HPMEOP>2.0.CO;2
Thomas CM. Phase II Panitumumab-IRDye800 in Head & Neck Cancer ClinicalTrials.gov: Thomas, Carissa M 2020 [Available from: https://clinicaltrials.gov/ct2/show/NCT04511078 .
Gao RW, Teraphongphom N, de Boer E, van den Berg NS, Divi V, Kaplan MJ, et al. Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Theranostics. 2018;8:2488–95.
pubmed: 29721094
pmcid: 5928904
doi: 10.7150/thno.24487
Kalyankrishna S, Grandis JR. Epidermal Growth Factor Receptor Biology in Head and Neck Cancer. J Clin Oncol. 2006;24:2666–72.
pubmed: 16763281
doi: 10.1200/JCO.2005.04.8306
Wee P, Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers (Basel). 2017;9:52.
pubmed: 28513565
doi: 10.3390/cancers9050052
Licitra L, Perrone F, Tamborini E, Bertola L, Ghirelli C, Negri T, et al. Role of EGFR family receptors in proliferation of squamous carcinoma cells induced by wound healing fluids of head and neck cancer patients. Ann Oncol. 2011;22:1886–93.
pubmed: 21343382
doi: 10.1093/annonc/mdq756
Braakhuis BJ, Brakenhoff RH, Leemans CR. Second field tumors: a new opportunity for cancer prevention? Oncologist. 2005;10:493–500.
pubmed: 16079316
doi: 10.1634/theoncologist.10-7-493
Slaughter DP, Southwick HW, Smejkal W. Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer. 1953;6:963–8.
pubmed: 13094644
doi: 10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q
Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, et al. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res. 1996;56:2488–92.
pubmed: 8653682
Kamat MS, Rai BD, Puranik RS, Datar UV. Immunoexpression of p53 in histologically negative surgical margins adjacent to oral squamous cell carcinoma: A preliminary study. J Oral Maxillofac Pathol. 2020;24:184.
pubmed: 32508474
pmcid: 7269284
doi: 10.4103/jomfp.JOMFP_288_19
Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia - A systematic review and meta-analysis. Head Neck. 2009;31:1600–9.
pubmed: 19455705
doi: 10.1002/hed.21131
Mahmood U. Optical Molecular Imaging Approaches in Colorectal Cancer. Gastroenterology. 2010;138:419–22.
pubmed: 20026448
doi: 10.1053/j.gastro.2009.12.014
Mizushima T, Ohnishi S, Shimizu Y. Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: A pilot study. Engl: BioMed Cent. 2016;16:411.
Devgan L, Bhat S, Aylward S, Spence RJ. Modalities for the assessment of burn wound depth. J Burns Wounds. 2006;5:e2.
pubmed: 16921415
pmcid: 1687143
Rosenthal EL, Warram JM, de Boer E, Chung TK, Korb ML, Brandwein-Gensler M, et al. Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer. Clin Cancer Res. 2015;21:3658–66.
pubmed: 25904751
pmcid: 4909371
doi: 10.1158/1078-0432.CCR-14-3284
Albakova Z, Armeev GA, Kanevskiy LM, Kovalenko EI, Sapozhnikov AM. HSP70 Multi-Functionality in Cancer. Cells. 2020;9:587.
pubmed: 32121660
pmcid: 7140411
doi: 10.3390/cells9030587
Murakami N, Kühnel A, Schmid TE, Ilicic K, Stangl S, Braun IS, et al. Role of membrane Hsp70 in radiation sensitivity of tumor cells. Radiat Oncol. 2015;10:149.
pubmed: 26197988
pmcid: 4511458
doi: 10.1186/s13014-015-0461-1
Gehrmann M, Radons J, Molls M, Multhoff G. The therapeutic implications of clinically applied modifiers of heat shock protein 70 (Hsp70) expression by tumor cells. Cell Stress Chaperones. 2008;13:1–10.
pubmed: 18347936
pmcid: 2666213
doi: 10.1007/s12192-007-0006-0
Xanthopoulos A, Samt AK, Guder C, Taylor N, Roberts E, Herf H, et al. Hsp70-A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers. Biomedicines. 2023;11:2276.
pubmed: 37626772
pmcid: 10452093
doi: 10.3390/biomedicines11082276
Werner C, Stangl S, Salvermoser L, Schwab M, Shevtsov M, Xanthopoulos A, et al. Hsp70 in Liquid Biopsies-A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer. Cancers (Basel). 2021;13:3706.
pubmed: 34359606
doi: 10.3390/cancers13153706
Gunther S, Ostheimer C, Stangl S, Specht HM, Mozes P, Jesinghaus M, et al. Correlation of Hsp70 Serum Levels with Gross Tumor Volume and Composition of Lymphocyte Subpopulations in Patients with Squamous Cell and Adeno Non-Small Cell Lung Cancer. Front Immunol. 2015;6:556.
pubmed: 26579130
pmcid: 4629690
doi: 10.3389/fimmu.2015.00556