Dynamic 68Ga-DOTATOC PET/CT and static image in NET patients

Sofie Van Binnebeek; Michel Koole; Christelle Terwinghe; Kristof Baete; Bert Vanbilloen; Karine Haustermans; Paul M. Clement; Kris Bogaerts; Alfons Verbruggen; Kris Nackaerts; Eric Van Cutsem; Chris Verslype; Felix M. Mottaghy; Christophe M. Deroose

doi:10.3413/Nukmed-0742-15-05

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

Nuklearmedizin 2016; 55(03): 104-114
DOI: 10.3413/Nukmed-0742-15-05

Original article

Schattauer GmbH

Dynamic ⁶⁸Ga-DOTATOC PET/CT and static image in NET patients

Correlation of parameters during PRRTDynamische und statische 68Ga-DOTATOC-PET/CT bei Patienten mit NETKorrelation der Parameter während der PRRT

Sofie Van Binnebeek

¹Nuclear Medicine, University Hospitals Leuven and Department of Imaging & Pathology, KU Leuven

,

Michel Koole

¹Nuclear Medicine, University Hospitals Leuven and Department of Imaging & Pathology, KU Leuven

,

Christelle Terwinghe

¹Nuclear Medicine, University Hospitals Leuven and Department of Imaging & Pathology, KU Leuven

,

Kristof Baete

¹Nuclear Medicine, University Hospitals Leuven and Department of Imaging & Pathology, KU Leuven

,

Bert Vanbilloen

¹Nuclear Medicine, University Hospitals Leuven and Department of Imaging & Pathology, KU Leuven

,

Karine Haustermans

²Radiation Oncology, University Hospitals Leuven and Department of Oncology, KU Leuven

,

Paul M. Clement

³General Medical Oncology, University Hospitals Leuven and Department of Oncology, KU Leuven

,

Kris Bogaerts

⁴Department of Public Health and primary Care (I-BioStat), KU Leuven

,

Alfons Verbruggen

⁵Laboratory for Radiopharmacy, KU Leuven

,

Kris Nackaerts

⁶Pulmonology, University Hospitals Leuven

,

Eric Van Cutsem

⁷Division of Digestive Oncology, University Hospitals Leuven and Department of Oncology, KU Leuven

,

Chris Verslype

⁷Division of Digestive Oncology, University Hospitals Leuven and Department of Oncology, KU Leuven

,

Felix M. Mottaghy

⁸Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands

⁹Department of Nuclear Medicine, University Hospital Aachen, Germany

,

Christophe M. Deroose

¹Nuclear Medicine, University Hospitals Leuven and Department of Imaging & Pathology, KU Leuven

› Institutsangaben

Abstract

Summary

Purpose: To investigate the relationship between the dynamic parameters (K_i) and static image-derived parameters of ⁶⁸Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs). Patients, methods: 20 patients with metastasized NETs underwent a dynamic and static ⁶⁸Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of ⁹⁰Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static ⁶⁸Ga-DOTATOC-PET and the dynamic and static ⁶⁸Ga-DOTATOC-PET at the other time-points; SUV_max and SUV_mean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, K_i was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUV_tumour were delineated on the static scans resulting in 5 ratios (SUV_ratio). Results: SUV_max and SUV_mean of the tumoural lesions on the dynamic ⁶⁸Ga-DO-TATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUV_max, SUV_mean and K_i of the lesions showed a good linear correlation; the SUV_ratios correlated poorly with K_i. A significantly better correlation was noticed between K_i and SUV_tumour(_{max and mean}) (p < 0.0001). Conclusions: As the dynamic para meter K_i correlates best with the absolute SUV_tumour, SUV_tumour best reflects underlying SSR-levels in NETs.

Zusammenfassung

Das Ziel der Studie war das Verhältnis zwischen dem dynamischen Parameter (K_i) und statischen Parametern der ⁶⁸Ga-DOTATOC-PET zu untersuchen und den statischen Parameter zu definieren, der am besten mit der Somatostatinrezeptor (SSR) Expression von neuroendokrinen Tumoren (NET) korreliert. Patienten und Methoden: 20 Patienten mit metastasierten NET erhielten eine dynamische und statische ⁶⁸Ga-DOTATOC-PET vor der ersten PRRT und 7 und 40 Wochen nach der ersten Administration von ⁹⁰Y-DOTATOC (insgesamt wurden 4 Zyklen geplant); 175 Läsionen wurden auf den statischen und dynamischen Bildern definiert und ausgewertet. Die quantitative Analyse wurde mit der Software PMOD durchgeführt. Eine bis fünf Zielläsionen wurden pro Patient im ersten dynamischen Scan ausgewählt, mit einer VOI versehen, welche dann auf die weiteren dynamischen und statischen Scans transferiert wurde; sowohl SUV_max als auch SUV_mean wurden bestimmt. Die Input Funktion wurde aus der im Field-of-view liegenden Aorta generiert. K_i wurde mit Hilfe des Patlak-Plots berechnet. Zuletzt wurden 5 Referenzregionen für die Normalisation des SUV_tumo auf den statischen Scans bestimmt, zur Bestimmung von 5 Verhältnissen (SUV_ratio). Ergebnisse: SUV_max und SUV_mean der Tumorläsionen inden dynamischen ⁶⁸Ga-DOTATOC-PET zeigten eine sehr starke Korrelation mit den entsprechenden Parametern in den statischen Scans (R²: 0,94 bzw. 0,95). SUV_max, SUV_mean und K_i der Läsionen zeigte eine gute lineare Korrelation; die verschiedenen SUV_ratios korrelierten auf sehr niedrigem Niveau mit K_i. Eine signifikant bessere Korrelation zeigte sich zwischen K_i und SUV_{tumour(max and mean)} (p < 0.0001). Schlussfolgerung: Der dynamische Parameter K_i korreliert am besten mit dem absoluten SUV_tumour. SUV_tumour reflektiert am besten den Level der SSR-Expression in NET.

Keywords

⁶⁸Ga-DOTATOC PET - K_i - somatostatin receptor expression - PRRT - neuroendocrine tumour

Schlüsselwörter

⁶⁸Ga-DOTATOC PET - K_i - Somatostatinrezeptor-Expression - PRRT - neuroendokriner Tumor

Volltext

Referenzen

References
1 Armani C, Catalani E, Balbarini A. et al. Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages. J Leukoc Biol 2007; 81: 845-855.
2 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.
3 Buchmann I, Henze M, Engelbrecht S. et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2007; 34: 1617-1626.
4 Cascini GL, Cuccurullo V, Mansi L. The non tumour uptake of 111In-octreotide creates new clinical indications in benign diseases, but also in oncology. Q J Nucl Med Mol Imaging 2010; 54: 24-36.
5 Ferone D, Pivonello R, Kwekkeboom DJ. et al. Immunohistochemical localization and quantitative expression of somatostatin receptors in normal human spleen and thymus: Implications for the in vivo visualization during somatostatin receptor scintigraphy. J Endocrinol Invest 2012; 35: 528-534.
6 Gabriel M, Decristoforo C, Kendler D. et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007; 48: 508-518.
7 Haug AR, Auernhammer CJ, Wangler B. et al. 68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors. J Nucl Med 2010; 51: 1349-1356.
8 Henze M, Schuhmacher J, Hipp P. et al. PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med 2001; 42: 1053-1056.
9 Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S. et al. Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas. J Nucl Med 2005; 46: 763-769.
10 Hofmann M, Maecke H, Borner R. et al. Biokinetics and imaging with the somatostatin receptor PET radioligand 68Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001; 28: 1751-1757.
11 Koukouraki S, Strauss LG, Georgoulias V. et al. Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging 2006; 33: 1115-1122.
12 Kowalski J, Henze M, Schuhmacher J. et al. Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D Phe(1)-Tyr(3)-Octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors. Mol Imaging Biol 2003; 5: 42-48.
13 Meyer GJ, Macke H, Schuhmacher J. et al. 68Ga-labelled DOTA-derivatised peptide ligands. Eur J Nucl Med Mol Imaging 2004; 31: 1097-1104.
14 Modlin IM, Oberg K, Chung DC. et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9: 61-72.
15 Ohtake T, Kosaka N, Watanabe T. et al. Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. J Nucl Med 1991; 32: 1432-1438.
16 Pisarek H, Pawlikowski M, Kunert-Radek J. et al. SSTR1 and SSTR5 subtypes are the dominant forms of somatostatin receptor in neuroendocrine tumors. Folia Histochem Cytobiol 2010; 48: 142-147.
17 Putzer D, Gabriel M, Henninger B. et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med 2009; 50: 1214-1221.
18 Reubi JC, Waser B, Schaer JC. et al. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med 2001; 28: 836-846.
19 Reubi JC, Schar JC, Waser B. et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000; 27: 273-282.
20 Severi S, Nanni O, Bodei L. et al. Role of 18FDG PET/CT in patients treated with 177Lu-DOTATATE for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013; 40: 881-888.
21 Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med 1991; 32: 623-648.
22 Sundin A, Garske U, Orlefors H. Nuclear imaging of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2007; 21: 69-85.
23 Van Binnebeek S, Karges W, Mottaghy FM. Functional imaging of neuroendocrine tumors. Methods Mol Biol 2011; 727: 105-122.
24 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.
25 Weckbecker G, Lewis I, Albert R. et al. Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2003; 2: 999-1017.
26 Yap JT, Guo M, Locascio T. et al. Comparison of standardized measurement of SUVmax versus a threshold-based SUVmean in cancer response assessment using GDG-PET. J Nucl Med 2010; 51 (Suppl. 02) 1178.