RSS-Feed abonnieren
DOI: 10.3413/Nukmed-0581-13-05
Early prediction of tumour response to PRRT
The sequential change of tumour-absorbed doses during treatment with 177Lu-octreotateFrühe Prädiktion des Ansprechens auf PRRTDie sequenzielle Änderung der Tumorherddosis unter Therapie mit 177Lu-OctreotatPublikationsverlauf
received:
07. Mai 2013
accepted in revised form:
01. Juli 2013
Publikationsdatum:
12. Januar 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034924/201305/lookinside/thumbnails/10-3413-nukmed-0581-13-05_de-1.jpg)
Summary
[177Lu-DOTA0, Tyr3]-octreotate (177Lu-octreotate) in peptide receptor radionuclide therapy (PRRT) offers direct intra-therapeutic dosimetry. The aim of this study was to compare tumour and non-tumour parameters and assess intra-individual variations. Patients, methods: Retrospective analysis of 53 consecutive PRRT treatment cycles (mean activity of 7.53 ± 0.46 GBq 177Lu-octreotate, intended four cycles at intervals of 10–14 weeks, standard nephroprotection) in 27 GEP NET patients. Extended planar dosimetry with serial wholebody imaging on selected, non-superimposed tumour and non-tumour regions; liver (LM), bone (BM), and other (OM) metastases. The per-cycle variation was compared with posttreatment response (CT/MRI three months post-treatment, modified SWOG criteria). Results: Residence time in tumor lesions (133–147 h) exceeded that in kidneys (93 h). Tumour-to-kidney absorbed dose ratios ranged from 14 to 28 (LM, BM, OM). Intra-individual per-cycle dose variation was insignificant for kidneys, but significant for metastases (LM, BM, and OM; p < 0.05). The mean per-cycle decrease of tumour absorbed dose (_D/A0[%]) was linked to morphologic response after PRRT. A mean decrease of >20% was predictive of a partial or minor remission in all 11 evaluable patients, while absent significant dose reduction indicated stable or progressive disease in 4/5 patients. The dose decrease was unrelated to volume effects and also observed for BM. Conclusion: Besides confirmation of a favourable tumour-to-kidney parameter relation for 177Lu-octreotate, stepwise intra-lesional comparison seems to imply a prognostic impact of tumor dosimetry: The early per-cycle change _D/A0 between treatment cycles may predict the outcome after PRRT. Larger studies are needed to confirm this finding.
Zusammenfassung
[177Lu-DOTA0, Tyr3]-Octreotat (177Lu-octreotate) bei der Peptid-Radiorezeptortherapie (PRRT) bietet eine direkte Form der intra-therapeutischen Dosimetrie. Das Ziel der Studie war der Vergleich von Tumor- und Normal-gewebe-Parametern und die Untersuchung intra-individueller Variationen. Patienten, Methodik: Retrospektive Analyse von 53 konsekutiven PRRT-Behandlungszyklen (mottler Aktivität 7.53 ± 0.46 GBq 177Lu-octreotate, intendierte vier Zyklen in 10- bis 14-wöchigen Intervallen, Standard-Nephroprotektion) in 27 GEP-NET-Patienten. Erweiterte planare Dosimetrie mittels serieller Ganzkörperbildgebung von selektierten, nicht-überlagerten Tumorund Nichttumor-Regionen: Leber- (LM), Knochen- (BM) und anderer (OM) Metastasen. Die Zyklus-bezogene Variation wurde mit dem Therapieansprechen (CT/MRT 3 Monate post-PRRT, modifizierte SWOG Kriterien) verglichen. Ergebnisse: Die Residenzzeit der Tumorläsionen (133–147 h) übertraf die der Nieren (93 h). Die Herddosis-Ratio Tumor-zu-Niere lag zwischen 14 und 28 (LM, BM, OM). Die intra-individuelle Variation der Herddosen zwischen den Zyklen war nicht signifikant für die Nieren, aber signifikant für die Metastasen (LM, BM und OM; p < 0.05). Die mittlere Zyklus-assoziierte Abnahme der Tumor-Herddosis (_D/A0[%]) korrelierte mit dem morphologischen Ansprechen nach PRRT. Eine mittlere Abnahme von >20% war prädiktiv für eine Teilremission in den 11 auswertbaren Patienten, während eine fehlende signifikante Herddosis-Reduktion einen stabilen oder progredienten Verlauf in 4/5 Patienten vorher sagte. Die Dosisabnahme war unabhängig von Volumeneffekten und auch bei Knochenmetastasen zu beobachten. Schlussfolgerung: Neben der Bestätigung einer günstigen Relation „Tumor-zu-Niere“ verschiedener Parameter für 177Lu-octreotate zeigte der schrittweise intra-läsionale Vergleich in der Tumordosimetrie einen prädiktiven Einfluss: Die frühe Zyklus-bezogene Veränderung _D/A0 zwischen den Behandlungszyklen vermag das Ergebnis nach PRRT vorherzusagen. Größere Studien müssen diese Beobachtung bestätigen.
-
References
- 1 Baechler S, Hobbs RF, Boubaker A. et al. Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy. Med Phys 2012; 39: 6118-6128.
- 2 Breeman WA, De Jong M, Visser TJ. et al. Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur J Nucl Med Mol Imaging 2003; 30: 917-920.
- 3 Breeman WA, van der Wansem K, Bernard BF. et al. The addition of DTPA to [177Lu-DOTA0, Tyr3] octreotate prior to administration reduces rat skeleton uptake of radioactivity. Eur J Nucl Med Mol Imaging 2003; 30: 312-315.
- 4 Cremonesi M, Botta F, Di Dia A. et al. Dosimetry for treatment with radiolabelled somatostatin analogues. A review. Q J Nucl Med Mol Imaging. 2010; 54: 37-51.
- 5 Cremonesi M, Ferrari M, Bodei L. et al. Dosimetry in patients undergoing 177Lu-DOTATATE therapy with indications for 90Y-DOTATATE. Eur J Nucl Med Mol Imaging 2006; 33 (Suppl. 01) S102.
- 6 Cremonesi M, Ferrari M, Di Dia A. et al. Recent issues on dosimetry and radiobiology for peptide receptor radionuclide therapy. Q J Nucl Med Mol Imaging 2011; 55: 155-167.
- 7 Ezziddin S, Opitz M, Attassi M. et al. Impact of the Ki-67 proliferation index on response to peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2011; 38: 459-466.
- 8 Forrer F, Krenning EP, Kooij PP. et al. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA(0), Tyr(3)]octreotate. Eur J Nucl Med Mol Imaging 2009; 36: 1138-1146.
- 9 Garkavij M, Nickel M, Sjogreen-Gleisner K. et al. 177Lu-[DOTA0, Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy. Cancer 2010; 116: 1084-1092.
- 10 Garske U, Sandstrom M, Johansson S. et al. Minor changes in effective half-life during fractionated 177Lu-Octreotate therapy. Acta Oncol 2012; 51: 86-96.
- 11 Gonias S, Goldsby R, Matthay KK. et al. Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol 2009; 27: 4162-4168.
- 12 Gotthardt M. Radiogenic nephropathy. Nuklearmedizin 2010; 49 (Suppl. 01) S59-S63.
- 13 Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992; 10: 239-253.
- 14 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.
- 15 Helisch A, Forster GJ, Reber H. et al. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTAPhe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004; 31: 1386-1392.
- 16 Hindorf C, Chittenden S, Causer L, Lewington VJ, Macke HR, Flux GD. Dosimetry for 90Y-DOTATOC therapies in patients with neuroendocrine tumors. Cancer Biother Radiopharm 2007; 22: 130-135.
- 17 Kairemo K, Kangasmaki A. 4D SPECT/CT acquisition for 3D dose calculation and dose planning in 177Lu-peptide receptor radionuclide therapy: applications for clinical routine. Recent Results Cancer Res 2013; 194: 537-550.
- 18 Kwekkeboom DJ, Bakker WH, Kam BL. et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0), Tyr3]octreotate. Eur J Nucl Med Mol Imaging 2003; 30: 417-422.
- 19 Kwekkeboom DJ, Bakker WH, Kooij PP. et al. [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Eur J Nucl Med. 2001; 28: 1319-1325.
- 20 Kwekkeboom DJ, de Herder WW, Kam BL. et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26: 2124-2130.
- 21 Kwekkeboom DJ, Kam BL, van Essen M. et al. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer 2010; 17: R53-R73.
- 22 Kwekkeboom DJ, Krenning EP, Lebtahi R. et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology 2009; 90: 220-226.
- 23 Kwekkeboom DJ, Teunissen JJ, Bakker WH. et al. Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 2005; 23: 2754-2762.
- 24 Pauwels S, Barone R, Walrand S. et al. Practical dosimetry of peptide receptor radionuclide therapy with 90Y-labeled somatostatin analogs. J Nucl Med 2005; 46 (Suppl. 01) 92S-98S.
- 25 Safford SD, Coleman RE, Gockerman JP. et al. Iodine-131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocytoma and paraganglioma. Surgery 2003; 134: 956-962.
- 26 Safford SD, Coleman RE, Gockerman JP. et al. Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients. Cancer 2004; 101: 1987-1993.
- 27 Sandstrom M, Garske U, Granberg D. et al. Individualized dosimetry in patients undergoing therapy with 177Lu-DOTA-D-Phe (1)-Tyr (3)-octreotate. Eur J Nucl Med Mol Imaging 2010; 37: 212-225.
- 28 Turner JH. Defining pharmacokinetics for individual patient dosimetry in routine radiopeptide and radioimmunotherapy of cancer: Australian experience. Curr Pharm Des 2009; 15: 966-982.
- 29 Van Binnebeek S, Baete K, Terwinghe C. et al. Significant impact of transient deterioration of renal function on dosimetry in PRRT. Ann Nucl Med 2013; 27: 74-77.
- 30 Wehrmann C, Senftleben S, Zachert C. et al. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm. 2007; 22: 406-416.
- 31 Wessels BW, Dale RG, Cremonesi M. et al. Renal dosimetry. Cancer Biother Radiopharm 2010; 25: 597-599.