The impact of 177Lu-octreotide therapy on 99mTc-MAG3 clearance is not predictive for late nephropathy.

Rudolf A Werner,Katharina Lückerath,Heribert Hänscheid,Michael Lassmann,Andreas K Buck,Constantin Lapa,Christina Bluemel,Ken Herrmann,Alexander Weich,Seval Beykan,Michael Scheurlen,Takahiro Higuchi

doi:10.18632/oncotarget.9775

Rudolf A Werner, Katharina Lückerath + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.9775

Copy DOI

Journal: Oncotarget	Publication Date: Jun 1, 2016
Citations: 35	License type: cc-by

Affiliation: University Hospital Würzburg

Abstract

Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq 177Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m2 before PRRT (baseline) and 221 ± 45 ml/min/1.73 m2 after a median follow-up of 370 days. The age-corrected decrease (mean: −3%, range: −27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=−0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by 99mTc-MAG3clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy.

Highlights

Recent randomized trial results of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) reporting a significant improvement of progressionfree survival will result in increasing clinical use of PPRT [1]
Kidney function is usually assessed by estimating the Glomerular Filtration Rate (GFR) from the serum creatinine (SCr) concentration such measurements are affected by confounding factors like dietary intake of creatinine [7] or presence of comorbidities like hepatic insufficiency [8] or glomerulopathy [9]
In order to correct for the normal decrease of TE rate (TER) with age, all measured TER values were normalized to the ageadjusted lower limit of the normal range (TERLoLi)

Summary

Introduction

Recent randomized trial results of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) reporting a significant improvement of progressionfree survival will result in increasing clinical use of PPRT [1]. Impairment of renal function even years after initiation of therapy, especially after treatment with 90Y conjugates, may become evident [5]. Since the kidneys represent the dose-limiting organ for PRRT, pre-therapeutic and serial measurements of kidney function using laboratory (e.g., serum creatinine (SCr)) or imaging tests are mandatory [6]. As the decline of GFR must be at least 50% to become evident in patients with initially normal function, SCr based GFR estimates (hereafter referred to as eGFR) are insensitive to early toxicity [11] and underestimate renal impairment in 12% of subjects after PRRT as compared to 99mTc-diethylenetriaminepentaacetic acid (99mTc- DTPA) clearance measurements [12]

Objectives

Methods

Results

Conclusion