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Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    Amir Sabet, Khaled Ezziddin, Karl Reichman, Torjan Haslerud, Hojjat Ahmadzadehfar, Hans-Jürgen Biersack & Samer Ezziddin

  2. Department of Hepatology and Gastroenterology, Charité, University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany

    Ulrich-Frank Pape

  3. Department of Nuclear Medicine, University Hospital, Essen, Germany

    James Nagarajah

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  1. Amir Sabet
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Correspondence to Samer Ezziddin.

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Sabet, A., Ezziddin, K., Pape, UF. et al. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate. Eur J Nucl Med Mol Imaging 41, 505–510 (2014). https://doi.org/10.1007/s00259-013-2601-x

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