Impact of co-administration of two amino acid solutions on the elimination and adverse effects of 177Lu-Dotatate


Somatostatin analogs 

population pharmacokinetic analysis 

relationship pharmacokinetic/pharmacodynamics

neuroendocrin tumor 

theranostic approach

Marie Lambertéquipe DIAD – Dose Individualisation of Anticancer Drugs

177Lu-Dotatate is a somatostatin analog prescribed to treat neuroendocrine tumours. Plasma concentrations of 177Lu-Dotatate in 83 patients were used to build a population pharmacokinetic model and estimate its pharmacokinetic parameters. Amino acid infusion is associated to decrease the nephrotoxicity of 177Lu-Dotatate. We compared the impact of two amino acid solutions (Primene® which a mixed of 20 amino-acids and Lysakare® composed of only Arginine and Lysine) on pharmacokinetics of 177Lu-Dotatate. Lysakare® does not increase the elimination of 177Lu-Dotatate on average, unlike Primene®. However, for both solutions there is an inter-individual variability in both the impact of the amino acid solution and the elimination of 177Lu-Dotatate. A relationship between 177Lu-Dotatate exposure and treatment-induced lymphopenia was also observed.

The systemic exposure of each patient could be an additional parameter to consider in the individualised management of patients treated with 177Lu-Dotatate. Population pharmacokinetic methodology may lead to a better understanding of both the efficacy and toxicity of this therapeutic modality.

These results open up a new avenue of research and offer the possibility of individually tailoring 177Lu-Dotatate administration for this indication justified by the large pharmacokinetic interindividual variability associated with a limited intrapatient variability of this radiolabeled compound.

Discover the published article

Curr Radiopharm. 2022 Feb 1.doi: 10.2174/1874471015666211228123525. Online ahead of print.
Comparison of Two Types of Amino Acid Solutions on 177Lu-Dotatate Pharmacokinetics and Pharmacodynamics in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors
Marie Lambert, Lawrence Dierickx, Séverine Brillouet, Frédéric Courbon, Etienne Chatelut

Centre de Recherches en Cancérologie de Toulouse

Toulouse Cancer Research Center (Oncopole)

Toulouse – FR

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