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Long-Term Follow-Up of Renal Function After Peptide Receptor Radiation Therapy with ⁹⁰Y-DOTA⁰,Tyr³-Octreotide and ¹⁷⁷Lu-DOTA⁰, Tyr³-Octreotate

¹ Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
² Service de Medecine Nucleaire, Cliniques Universitaires Saint-Luc, Universite Catholique Louvain, Brussels, Belgium
³ Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Hospital, University of South Florida, Tampa, Florida
⁴ Novartis Pharmaceuticals Corp., East Hanover, New Jersey

The kidneys are critical organs in peptide receptor radiation therapy (PRRT). Renal function loss may become apparent many years after PRRT. We analyzed the time course of decline in creatinine clearance (CLR) in patients during a follow-up of at least 18 mo after the start of PRRT with ⁹⁰Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA),Tyr³-octreotide (⁹⁰Y-DOTATOC) or ¹⁷⁷Lu-DOTA⁰,Tyr³-octreotate (¹⁷⁷Lu-DOTATATE). Methods: Twenty-eight patients with metastasized neuroendocrine tumors received 1–5 cycles of ⁹⁰Y-DOTATOC, leading to renal radiation doses of 5.9–26.9 Gy per cycle and a total of 18.3–38.7 Gy. Median follow-up was 2.9 y (range, 1.5–5.4 y), with a median of 16 measurements (range, 5–53) per patient. Thirty-seven patients with metastasized neuroendocrine tumors received 3–7 cycles of ¹⁷⁷Lu-DOTATATE, leading to renal radiation doses of 1.8–7.8 Gy per cycle and a total of 7.3–26.7 Gy. Median follow-up was 2.4 y (range, 1.7–4.0 y), with a median of 10 (range, 6–27) measurements per patient. All renal dose estimates were calculated with the MIRDOSE3 model. All patients were infused with renoprotective amino acids during the administration of the radioactive peptides. The time trend of CLR was determined by fitting a monoexponential function through the data of individual patients, yielding the decline in CLR in terms of percentage change per year. Results: The median decline in CLR was 7.3% per y in patients treated with ⁹⁰Y-DOTATOC and 3.8% per y in patients treated with ¹⁷⁷Lu-DOTATATE (P = 0.06). The time trend of decline in CLR was sustained during the follow-up period. Eleven patients had a >15% per y decline in CLR. Cumulative renal radiation dose, per-cycle renal radiation dose, age, hypertension, and diabetes are probable contributing factors to the rate of decline in CLR after PRRT. Conclusion: This study showed that the time course of CLR after PRRT was compatible with the pattern of sustained CLR loss in progressive chronic kidney disease.

Key Words: ⁹⁰Y-DOTA⁰,Tyr³-octreotide • ¹⁷⁷Lu-DOTA⁰,Tyr³-octreotate • peptide receptor radiation therapy • radiation nephropathy • chronic kidney disease

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