Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate
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Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine—allowing only approximate estimates of GFR—the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement.
Nephrotoxicity was analysed using 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with 177Lu-octreotate. The mean follow-up period was 21 months (range 12–50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by 99mTc-DTPA clearance versus serum creatinine.
The alteration in GFR differed widely among the patients (mean −2.1 ± 13.1 ml/min/m2 per year, relative yearly reduction −1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2–10 ml/min/m2 per year) and 16 patients (22 %) a significant (>10 ml/min/m2 per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m2 per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of patients. None of the investigated factors including cumulative administered activity contributed to the decline of renal function.
Serious nephrotoxicity after PRRT with 177Lu-octreotate is rare (1.3 %). However, slight renal impairment (GFR loss >2 ml/min/m2 per year) can frequently (43 %) be detected by 99mTc-DTPA clearance assessments. Cumulative administered activity of 177Lu-octreotate is not a major determinant of renal impairment in our study.
KeywordsNephrotoxicity PRRT 177Lu-octreotate NET
The authors are grateful to Professor Eric Krenning, Professor Dik Kwekkeboom and Professor Wouter A. P. Breeman (Erasmus Medical Center, Rotterdam, Netherlands) for sharing their experience in the receptor targeting field and making somatostatin receptor-mediated treatment in our institution possible. Also, we thank Professor Richard P. Baum (Department of Nuclear Medicine and PET Center, Zentralklinik Bad Berka, Germany) for his critical and constructive input in this field. The authors also are thankful to the personnel of the Nuclear Medicine Department and especially the nursing staff of the therapy ward.
Conflicts of interest
- 5.Delpassand ES, Samarghandi A, Mourtada JS, Zamanian S, Espenan GD, Sharif R, et al. Long-term survival, toxicity profile, and role of F-18 FDG PET/CT scan in patients with progressive neuroendocrine tumors following peptide receptor radionuclide therapy with high activity In-111 pentetreotide. Theranostics 2012;2(5):472–80. doi: 10.7150/thno.3739.PubMedCentralPubMedCrossRefGoogle Scholar
- 15.Cwikla JB, Sankowski A, Seklecka N, Buscombe JR, Nasierowska-Guttmejer A, Jeziorski KG, et al. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol 2010;21(4):787–94. doi: 10.1093/annonc/mdp372.PubMedCrossRefGoogle Scholar
- 19.Forrer F, Rolleman E, Bijster M, Melis M, Bernard B, Krenning EP, et al. From outside to inside? Dose-dependent renal tubular damage after high-dose peptide receptor radionuclide therapy in rats measured with in vivo (99m)Tc-DMSA-SPECT and molecular imaging. Cancer Biother Radiopharm 2007;22(1):40–9. doi: 10.1089/cbr.2006.353.PubMedCrossRefGoogle Scholar
- 24.Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, 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(3):417–22. doi: 10.1007/s00259-002-1050-8.PubMedCentralPubMedCrossRefGoogle Scholar
- 25.Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008;35(10):1847–56. doi: 10.1007/s00259-008-0778-1.PubMedCrossRefGoogle Scholar
- 28.Breeman WA, van der Wansem K, Bernard BF, van Gameren A, Erion JL, Visser TJ, 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(2):312–5. doi: 10.1007/s00259-002-1054-4.PubMedCrossRefGoogle Scholar
- 34.Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 2011;29(17):2416–23. doi: 10.1200/JCO.2010.33.7873.PubMedCrossRefGoogle Scholar