Poster Presentation Asia Pacific Neuroendocrine Tumour Society 2018

Renal tubular injury presenting after 177Lu-DOTATATE peptide receptor radionuclide therapy with high renal dosimetry (#108)

Kevin Lee 1 , Maciej Debowski 1 , Steven Goodman 1 , Manoj Bhatt 1 , Stuart Ramsay 1 , David Pattison 1 , Leo Francis 2 , David Wyld 3
  1. Department of Nuclear Medicine, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  2. Department of Pathology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  3. Cancer Care Services, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

177Lu-DOTATATE (LuTATE) peptide receptor radionuclide therapy (PRRT) is increasingly used and shown to have low risk of renal toxicity(2), such not seen in the prospective NETTER-1 trial (1). There is paucity of human renal studies, however rodent models of LuTATE nephrotoxicity showed damage occur at a dose-dependent fashion in the proximal tubules continuing to more distal tubules (3), and renal toxicity becoming clinically overt 100-200days afterwards(4).

We present a case of a 58 year-old Caucasian with metastatic small bowel neuroendocrine tumour, who was treated with cumulative administered dose of 33GBq of over standard 4 cycles, who developed decline in renal function from baseline GFR of 65ml/min/1.73sqm to stage 4 CKD (eGFR ranging 17-29ml/min/1.73sqm.) evident only 3-6 months after completion of LuTATE. Patient also developed progressively worsening macrocytic anaemia becoming transfusion dependent despite erythropoietin, with bone marrow aspirate showing hypocellular marrow.

Renal biopsy showed relatively acute tubular injury, predominantly in the proximal tubules, with background mild tubular atrophy, interstitial fibrosis, focal moderate arteriolosclerosis and ischaemic glomeruli (patient has history of hypertension).

We postulate that the renal tubular injury is related to PRRT, given absence of any other causes that could lead to such persistent stepwise decline in renal function, this is despite satisfactory pre-cycle eGFR that ranged between 58-83ml/min/1.73sqm, that many centres would have treated with standard cumulative dose.

We will show that  this patient’s routine post-cycle 1 renal dosimetry showed a renal absorbed dose of 12.6Gy(1.58Gy/GBq), which in retrospect is higher than our contemporaneous cohort of 50 patients with post-cycle 1 dose of 5.4+/-2.1GBq (mean +/-SD).  

We will contend that LuTATE renal dosimetry should be universally performed as more patients are being treated, so that more data can be collected from major centres and analysed to better inform a more appropriate renal dose upper limit for LuTATE.