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

Curr Radiopharm. 2022;15(2):164-172. doi: 10.2174/1874471015666211228123525.


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.

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

MeSH terms

  • Arginine / therapeutic use
  • Humans
  • Intestinal Neoplasms
  • Lysine / therapeutic use
  • Neuroendocrine Tumors* / radiotherapy
  • Octreotide / pharmacology
  • Organometallic Compounds*
  • Pancreatic Neoplasms
  • Positron-Emission Tomography
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Stomach Neoplasms


  • Organometallic Compounds
  • Radiopharmaceuticals
  • copper dotatate CU-64
  • Arginine
  • Lysine
  • Octreotide

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor