Quantifizierung von Glukosemetabolismus und Hypoxie mittels PET bei Kopf-Hals-Tumoren

Zusammenfassung

Der vorliegende Artikel beschäftigt sich mit der Bedeutung der FDG- und der Hypoxie-PET bei Kopf-Hals-Tumoren. Dabei liegt der Fokus auf den verschiedenen Quantifizierungsmöglichkeiten und deren Wertigkeit für die klinische Routine und Forschung. Die FDG-PET erfordert in der klinischen Routine nicht zwingend eine quantitative Analyse. Demgegenüber ist die ausschließlich qualitative Auswertung der Hypoxie-PET durch den im Vergleich zum FDG deutlich niedrigeren Kontrast, den alle Hypoxietracer gemein haben, erschwert.

Dem Nachteil des niedrigeren Kontrastes steht hier die strikt eindimensionale Aufnahme bzw. das Verweilen des Hypoxie-Tracers im hypoxischen Gewebe gegenüber, ein eindeutiger Vorteil im Vergleich zum Hochkontrast-Tracer FDG, dessen Aufnahme in Tumorzellen multifaktoriell ist.

Es gibt eine Vielzahl quantitativer Parameter, die weit über den scheinbar omnipräsenten, aber keinesfalls unumstrittenen maximalen Standardized uptake value (SUV_max) hinausgehen. Deren Erfordernis und ihr Einfluss auf die klinische Routinediagnostik werden dargestellt und kritisch abgewogen.

Abstract

The present article deals with the role of FDG- and hypoxia-PET in head and neck cancer. The focus lays on the multitudinously different methods of quantification and their valence in clinical routine and research. FDG PET does not necessarily require a quantitative analysis. However, hypoxia PET imaging typically suffers from a low contrast compared to FDG which hampers pure qualitative analysis.

Hypoxia tracers advantageously show a strict one-dimensional uptake / retention, while the accumulation in tumor cells of the high-contrast tracer FDG is driven by several factors.

There is a variety of further quantitative parameters beside the apparently omnipresent but debatable maximum standardized uptake value (SUV_max). Their influence on clinical routine diagnostics will be presented and critically considered.

Schlüsselwörter

PET - Quantifizierung - Kopf-Hals-Tumore - FDG - F-MISO - Hypoxie

Keywords

PET - quantification - HNSCC - FDG - F-MISO - hypoxia

• Literatur

• 1 Manca G, Vanzi E, Rubello D. et al. (18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications. Eur J Nucl Med Mol Imaging 2016; 43: 1360-1375
• 2 Grunnert M, Prasad V. PET-basierte Bestrahlungsplanung. Der Nuklearmediziner 2020; 43: 112-128
• 3 Kohler A, Löck S, Appold S. et al. Comparison of subjective evaluation versus objective algorithm in the interpretation of follow-up FDG-PET/CT scans after radiochemotherapy in head and neck cancer patients. Nuklearmedizin 2019; 58: 93-100
• 4 Boellaard R, O’Doherty MJ, Weber WA. et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 2010; 37: 181-200
• 5 Thie JA. Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med 2004; 45: 1431-1434
• 6 Janmahasatian S, Duffull SB, Ash S. et al. Quantification of lean bodyweight. Clin Pharmacokinet 2005; 44: 1051-1065
• 7 Halsne T, Müller EG, Spiten A-E. et al. The Effect of New Formulas for Lean Body Mass on Lean-Body-Mass – Normalized SUV in Oncologic ¹⁸F-FDG PET/CT. J Nucl Med Technol 2018; 46: 253-259
• 8 Boellaard R, Delgado-Bolton R, Oyen WJG. et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging 2015; 42: 328-354
• 9 Cheson BD, Fisher RI, Barrington SF. et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32: 3059-3068
• 10 Itti E, Meignan M, Berriolo-Riedinger A. et al. An international confirmatory study of the prognostic value of early PET/CT in diffuse large B-cell lymphoma: comparison between Deauville criteria and ΔSUVmax. Eur J Nucl Med Mol Imaging 2013; 40: 1312-1320
• 11 Boellaard R. Standards for PET image acquisition and quantitative data analysis. J Nucl Med 2009; 50 (Suppl. 01) 11S-20S
• 12 Boellaard R, Krak NC, Hoekstra OS. et al. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med 2004; 45: 1519-1527
• 13 Keyes JW. SUV: standard uptake or silly useless value?. J Nucl Med 1995; 36: 1836-1839
• 14 Wahl RL, Jacene H, Kasamon Y. et al. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med 2009; 50 (Suppl. 01) 122S-50S
• 15 Geets X, Lee JA, Bol A. et al. A gradient-based method for segmenting FDG-PET images: methodology and validation. Eur J Nucl Med Mol Imaging 2007; 34: 1427-1438
• 16 van Dalen JA, Hoffmann AL, Dicken V. et al. A novel iterative method for lesion delineation and volumetric quantification with FDG PET. Nucl Med Commun 2007; 28: 485-493
• 17 Hatt M, Lamare F, Boussion N. et al. Fuzzy hidden Markov chains segmentation for volume determination and quantitation in PET. Phys Med Biol 2007; 52: 3467-3491
• 18 Erdi YE, Mawlawi O, Larson SM. et al. Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding. Cancer 1997; 80: 2505-2509
• 19 Nestle U, Kremp S, Schaefer-Schuler A. et al. Comparison of different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-Small cell lung cancer. J Nucl Med 2005; 46: 1342-1348
• 20 Black QC, Grills IS, Kestin LL. et al. Defining a radiotherapy target with positron emission tomography. Int J Radiat Oncol 2004; 60: 1272-1282
• 21 Visser EP, Boerman OC, Oyen WJG. SUV: from silly useless value to smart uptake value. J Nucl Med 2010; 51: 173-175
• 22 Larson SM, Erdi Y, Akhurst T. et al. Tumor Treatment Response Based on Visual and Quantitative Changes in Global Tumor Glycolysis Using PET-FDG Imaging. The Visual Response Score and the Change in Total Lesion Glycolysis. Clin Positron Imaging 1999; 2: 159-171
• 23 Mertens J, Dobbeleir A, Ham H. et al. Standardized added metabolic activity (SAM): a partial volume independent marker of total lesion glycolysis in liver metastases. Eur J Nucl Med Mol Imaging 2012; 39: 1441-1448
• 24 Tylski P, Stute S, Grotus N. et al. Comparative assessment of methods for estimating tumor volume and standardized uptake value in (18)F-FDG PET. J Nucl Med 2010; 51: 268-276
• 25 Chen CH, Muzic RF, Nelson AD. et al. Simultaneous recovery of size and radioactivity concentration of small spheroids with PET data. J Nucl Med 1999; 40: 118-130
• 26 Boktor RR, Walker G, Stacey R. et al. Reference range for intrapatient variability in blood-pool and liver SUV for 18F-FDG PET. J Nucl Med 2013; 54: 677-682
• 27 Hasenclever D, Kurch L, Mauz-Körholz C. et al. qPET – a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma. Eur J Nucl Med Mol Imaging 2014; 41: 1301-1308
• 28 Annunziata S, Cuccaro A, Calcagni ML. et al. Interim FDG-PET/CT in Hodgkin lymphoma: the prognostic role of the ratio between target lesion and liver SUVmax (rPET). Ann Nucl Med 2016; 30: 588-592
• 29 van den Hoff J, Oehme L, Schramm G. et al. The PET-derived tumor-to-blood standard uptake ratio (SUR) is superior to tumor SUV as a surrogate parameter of the metabolic rate of FDG. EJNMMI Res 2013; 3: 77
• 30 Shin S, Pak K, Kim IJ. et al. Prognostic Value of Tumor-to-Blood Standardized Uptake Ratio in Patients with Resectable Non-Small-Cell Lung Cancer. Nucl Med Mol Imaging (2010) 2017; 51: 233-239
• 31 Hofheinz F, Li Y, Steffen IG. et al. Confirmation of the prognostic value of pretherapeutic tumor SUR and MTV in patients with esophageal squamous cell carcinoma. Eur J Nucl Med Mol Imaging 2019; 46: 1485-1494
• 32 van den Bosch S, Dijkema T, Philippens MEP. et al. Tumor to cervical spinal cord standardized uptake ratio (SUR) improves the reproducibility of 18F-FDG-PET based tumor segmentation in head and neck squamous cell carcinoma in a multicenter setting. Radiother Oncol 2019; 130: 39-45
• 33 Marcus C, Ciarallo A, Tahari AK. et al. Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes. J Nucl Med 2014; 55: 1411-1416
• 34 Veit-Haibach P, Luczak C, Wanke I. et al. TNM staging with FDG-PET/CT in patients with primary head and neck cancer. Eur J Nucl Med Mol Imaging 2007; 34: 1953-1962
• 35 Roh J-L, Yeo N-K, Kim JS. et al. Utility of 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography and positron emission tomography/computed tomography imaging in the preoperative staging of head and neck squamous cell carcinoma. Oral Oncol 2007; 43: 887-893
• 36 Rusthoven KE, Koshy M, Paulino AC. The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer 2004; 101: 2641-2649
• 37 Goel R, Moore W, Sumer B. et al. Clinical Practice in PET/CT for the Management of Head and Neck Squamous Cell Cancer. AJR Am J Roentgenol 2017; 209: 289-303
• 38 Szyszko TA, Cook GJR. PET/CT and PET/MRI in head and neck malignancy. Clin Radiol 2018; 73: 60-69
• 39 Castaldi P, Leccisotti L, Bussu F. et al. Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma. Acta Otorhinolaryngol Ital 2013; 33: 1-8
• 40 Allal AS, Slosman DO, Kebdani T. et al. Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18f]fluoro-2-deoxy-d-glucose. Int J Radiat Oncol 2004; 59: 1295-1300
• 41 Schwartz DL, Rajendran J, Yueh B. et al. FDG-PET Prediction of Head and Neck Squamous Cell Cancer Outcomes. Arch Otolaryngol Neck Surg 2004; 130: 1361
• 42 Higashi K, Clavo AC, Wahl RL. Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. J Nucl Med 1993; 34: 414-419
• 43 Gupta T, Chatterjee A, Rangarajan V. et al. Evaluation of quantitative imaging parameters in head and neck squamous cell carcinoma. Q J Nucl Med Mol Imaging 2019;
• 44 Sager S, Asa S, Yilmaz M. et al. Prognostic significance and predictive performance of volume-based parameters of F-18 FDG PET/CT in squamous cell head and neck cancers. J Cancer Res Ther 2014; 10: 922-926
• 45 Mamelle G, Pampurik J, Luboinski B. et al. Lymph node prognostic factors in head and neck squamous cell carcinomas. Am J Surg 1994; 168: 494-498
• 46 Snow GB, Annyas AA, van Slooten EA. et al. Prognostic factors of neck node metastasis. Clin Otolaryngol Allied Sci 1982; 7: 185-192
• 47 Lowe VJ, Duan F, Subramaniam RM. et al. Multicenter Trial of [18F]fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging of Head and Neck Cancer and Negative Predictive Value and Surgical Impact in the N0 Neck: Results From ACRIN 6685. J Clin Oncol 2019; 37: 1704-1712
• 48 Schwartz DL, Ford E, Rajendran J. et al. FDG-PET/CT imaging for preradiotherapy staging of head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2005; 61: 129-136
• 49 Gordin A, Golz A, Keidar Z. et al. The Role of FDG-PET/CT Imaging in Head and Neck Malignant Conditions: Impact on Diagnostic Accuracy and Patient Care. Otolaryngol Neck Surg 2007; 137: 130-137
• 50 de Bree R, Deurloo EE, Snow GB. et al. Screening for distant metastases in patients with head and neck cancer. Laryngoscope 2000; 110: 397-401
• 51 Xu GZ, Guan DJ, He ZY. (18)FDG-PET/CT for detecting distant metastases and second primary cancers in patients with head and neck cancer. A meta-analysis. Oral Oncol 2011; 47: 560-565
• 52 Chung MK, Jeong HS, Park SG. et al. Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer. Clin Cancer Res 2009; 15: 5861-5868
• 53 Chang K-P, Tsang N-M, Liao C-T. et al. Prognostic significance of 18F-FDG PET parameters and plasma Epstein-Barr virus DNA load in patients with nasopharyngeal carcinoma. J Nucl Med 2012; 53: 21-28
• 54 Haerle SK, Schmid DT, Ahmad N. et al. The value of (18)F-FDG PET/CT for the detection of distant metastases in high-risk patients with head and neck squamous cell carcinoma. Oral Oncol 2011; 47: 653-659
• 55 Scott AM, Gunawardana DH, Bartholomeusz D. et al. PET changes management and improves prognostic stratification in patients with head and neck cancer: results of a multicenter prospective study. J Nucl Med 2008; 49: 1593-1600
• 56 Gupta T, Jain S, Agarwal JP. et al. Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation. Radiother Oncol 2010; 97: 194-199
• 57 Hentschel M, Appold S, Schreiber A. et al. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer. Eur J Nucl Med Mol Imaging 2011; 38: 1203-1211
• 58 Schinagl DAX, Vogel WV, Hoffmann AL. et al. Comparison of Five Segmentation Tools for 18F-Fluoro-Deoxy-Glucose–Positron Emission Tomography–Based Target Volume Definition in Head and Neck Cancer. Int J Radiat Oncol 2007; 69: 1282-1289
• 59 Hentschel M, Appold S, Schreiber A. et al. Serial FDG-PET on patients with head and neck cancer: Implications for radiation therapy. Int J Radiat Biol 2009; 85: 796-804
• 60 Ong SC, Schoder H, Lee NY. et al. Clinical utility of 18F-FDG PET/CT in assessing the neck after concurrent chemoradiotherapy for Locoregional advanced head and neck cancer. J Nucl Med 2008; 49: 532-540
• 61 Isles MG, McConkey C, Mehanna HM. A systematic review and meta-analysis of the role of positron emission tomography in the follow up of head and neck squamous cell carcinoma following radiotherapy or chemoradiotherapy. Clin Otolaryngol 2008; 33: 210-222
• 62 Mehanna H, Wong WL, McConkey CC. et al. PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med 2016; 374: 1444-1454
• 63 Beichel RR, Ulrich EJ, Smith BJ. et al. FDG PET based prediction of response in head and neck cancer treatment: Assessment of new quantitative imaging features. PLoS One 2019; 14: e0215465
• 64 Beichel RR, Van Tol M, Ulrich EJ. et al. Semiautomated segmentation of head and neck cancers in 18F-FDG PET scans: A just-enough-interaction approach. Med Phys 2016; 43: 2948-2964
• 65 O’Connor JPB, Aboagye EO, Adams JE. et al. Imaging biomarker roadmap for cancer studies. Nat Rev Clin Oncol 2017; 14: 169-186
• 66 Gao S, Li S, Yang X. et al. 18FDG PET-CT for distant metastases in patients with recurrent head and neck cancer after definitive treatment. A meta-analysis. Oral Oncol 2014; 50: 163-167
• 67 de Bree R, van der Putten L, van Tinteren H. et al. Effectiveness of an (18)F-FDG-PET based strategy to optimize the diagnostic trajectory of suspected recurrent laryngeal carcinoma after radiotherapy: The RELAPS multicenter randomized trial. Radiother Oncol 2016; 118: 251-256
• 68 Ling CC, Humm J, Larson S. et al. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol 2000; 47: 551-560
• 69 Roberts HJ, Zietman AL, Efstathiou JA. Painting Dose: The ART of Radiation. Int J Radiat Oncol Biol Phys 2016; 96: 722-728
• 70 Troost EGC, Laverman P, Philippens MEP. et al. Correlation of [18F]FMISO autoradiography and pimonidazole [corrected] immunohistochemistry in human head and neck carcinoma xenografts. Eur J Nucl Med Mol Imaging 2008; 35: 1803-1811
• 71 Carlin S, Zhang H, Reese M. et al. A comparison of the imaging characteristics and microregional distribution of 4 hypoxia PET tracers. J Nucl Med 2014; 55: 515-521
• 72 Kaanders JHAM, Bussink J, van der Kogel AJ. ARCON: a novel biology-based approach in radiotherapy. Lancet Oncol 2002; 3: 728-737
• 73 Zschaeck S, Steinbach J, Troost EGC. FMISO as a Biomarker for Clinical Radiation Oncology. Recent Results Cancer Res 2016; 198: 189-201
• 74 Wack LJ, Mönnich D, van Elmpt W. et al. Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia--a simulation study. Acta Oncol 2015; 54: 1370-1377
• 75 Nehmeh SA, Lee NY, Schröder H. et al. Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer. Int J Radiat Oncol Biol Phys 2008; 70: 235-242
• 76 Lee N, Nehmeh S, Schöder H. et al. Prospective trial incorporating pre-/mid-treatment [18F]-misonidazole positron emission tomography for head-and-neck cancer patients undergoing concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys 2009; 75: 101-108
• 77 Okamoto S, Shiga T, Yasuda K. et al. High reproducibility of tumor hypoxia evaluated by 18F-fluoromisonidazole PET for head and neck cancer. J Nucl Med 2013; 54: 201-207
• 78 Abolmaali N, Haase R, Koch A. et al. Two or four hour [18F]FMISO-PET in HNSCC. Nuklearmedizin 2011; 50: 22-27
• 79 Thorwarth D, Alber M. Individualised radiotherapy on the basis of functional imaging with FMISO PET. Z Med Phys 2008; 18: 43-50
• 80 Zips D, Zöphel K, Abolmaali N. et al. Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer. Radiother Oncol 2012; 105: 21-28
• 81 Wiedenmann NE, Bucher S, Hentschel M. et al. Serial [18F]-fluoromisonidazole PET during radiochemotherapy for locally advanced head and neck cancer and its correlation with outcome. Radiother Oncol 2015; 117: 113-117
• 82 Löck S, Perrin R, Seidlitz A. et al. Residual tumour hypoxia in head-and-neck cancer patients undergoing primary radiochemotherapy, final results of a prospective trial on repeat FMISO-PET imaging. Radiother Oncol 2017; 124: 533-540
• 83 Bandurska-Luque A, Löck S, Haase R. et al. FMISO-PET-based lymph node hypoxia adds to the prognostic value of tumor only hypoxia in HNSCC patients. Radiother Oncol 2019; 130: 97-103
• 84 Zschaeck S, Haase R, Abolmaali N. et al. Spatial distribution of FMISO in head and neck squamous cell carcinomas during radio-chemotherapy and its correlation to pattern of failure. Acta Oncol 2015; 54: 1355-1363
• 85 Boeke S, Thorwarth D, Mönnich D. et al. Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer. Acta Oncol 2017; 56: 1571-1576
• 86 Thorwarth D, Eschmann S-M, Paulsen F. et al. Hypoxia dose painting by numbers: a planning study. Int J Radiat Oncol Biol Phys 2007; 68: 291-300
• 87 Welz S, Mönnich D, Pfannenberg C. et al. Prognostic value of dynamic hypoxia PET in head and neck cancer: Results from a planned interim analysis of a randomized phase II hypoxia-image guided dose escalation trial. Radiother Oncol 2017; 124: 526-532
• 88 Due AK, Vogelius IR, Aznar MC. et al. Recurrences after intensity modulated radiotherapy for head and neck squamous cell carcinoma more likely to originate from regions with high baseline [18F]-FDG uptake. Radiother Oncol 2014; 111: 360-365
• 89 Thorwarth D, Welz S, Mönnich D. et al. Prospective evaluation of a tumor control probability model based on dynamic 18F-FMISO PET for head-and-neck cancer radiotherapy. J Nucl Med 2019;