Comparison of Two Types of Amino Acid Solutions on ¹⁷⁷Lu-Dotatate Pharmacokinetics and Pharmacodynamics in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors

Title:Comparison of Two Types of Amino Acid Solutions on ¹⁷⁷Lu-Dotatate Pharmacokinetics and Pharmacodynamics in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors

Volume: 15 Issue: 2

Author(s): Marie Lambert, Lawrence Dierickx, Séverine Brillouet, Frédéric Courbon and Etienne Chatelut*

Affiliation:

• Department of Pharmacologie, Institut Claudius-Regaud, Institut Universitaire du Cancer Toulouse - Oncopole; CRCT, Cancer Research Center of Toulouse, Inserm U1037, Université Paul Sabatier, 1 avenue Irène Joliot-Curie F-31059 Toulouse, France

Keywords: Somatostatin analogs, population pharmacokinetics, pharmacokinetics/pharmacodynamics relationship, ¹⁷⁷Lu-Dotatate, theragnostic compound, neuroendocrine tumor.

Abstract:

Background: ¹⁷⁷Lu-Dotatate is used in the treatment of somatostatin-receptor-positive inoperable progressive gastroenteropancreatic neuroendocrine tumors. A co-infusion of amino acids (AAs) is administered to prevent renal toxicity.

Objective: This study aimed to quantify the impact of two types of AA cocktails on the pharmacokinetics and toxicity of ¹⁷⁷Lu-Dotatate.

Methods: Four injections of 7400 MBq ¹⁷⁷Lu-Dotatate were given per patient with administration of either Primene® 10% (containing a cocktail of 20 AAs with 22g of Lysine and 16.8 g of Arginine) or Lysakare® (containing 25 g of Lysine and 25 g of Arginine). Nine blood samples were collected at each cycle. Radioactivity-time data were analyzed according to a population-based model using NONMEM (version 7.4.1). Renal and hematological toxicity was evaluated after each cycle.

Results: 1,678 ¹⁷⁷Lu-Dotatate plasma concentrations versus time were analyzed from 83 consecutive patients with Primene® (n= 45 pts) or Lysakare® (n= 36 pts). Population pharmacokinetic analysis showed that Primene® significantly increased the elimination rate constant of ¹⁷⁷Lu-Dotatate as opposed to Lysakare®. Primene® also significantly lowered Lutathera® plasma exposure (AUC) by 34%, whereas Lysakare® increased AUC by 7%. There was no renal toxicity in either case. Lymphopenia significantly correlated with AUC (p=0.021) with a trend towards higher toxicity with Lysakare®.

Conclusion: Unlike Primene®, Lysakare® does not increase ¹⁷⁷Lu-Dotatate elimination. This difference is associated with a significant impact on AUC. The latter parameter has a high interpatient variability but a low intrapatient variability, which could have important clinical implications for treatment tailoring.

Cite this article as:

Lambert Marie, Dierickx Lawrence, Brillouet Séverine, Courbon Frédéric and Chatelut Etienne*, Comparison of Two Types of Amino Acid Solutions on ¹⁷⁷Lu-Dotatate Pharmacokinetics and Pharmacodynamics in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors, Current Radiopharmaceuticals 2022; 15 (2) . https://dx.doi.org/10.2174/1874471015666211228123525