Pharmacokinetics and theranostic radiolabelled molecules.

Dr Lawrence Dierickx

In internal vectored radiotherapy there are currently no biomarkers to predict treatment efficacy or to identify patients at risk of early or late haematological toxicity (myelodysplasia, leukaemia). We assume that the intensity and duration of exposure to the radiotracer of normal and malignant cells plays a very important role regarding its toxicity and efficacy, respectively.  Our team has already demonstrated and validated the contribution of population pharmacokinetic (PK) methodology in analyzing the impact of co-infusion of an amino acid cocktail on the treatment of neuroendocrine tumours with a theranostic somatostatin analogue (¹⁷⁷Lu-Dotatate). We have established that there is high inter-individual variability with moderate intra-individual variability in plasma concentration during treatment with this radiotracer. The aim is to evaluate the correlation between the efficacy and toxicity of the treatment and the PK profile and to use this PK profile in the individualization of this treatment (PACLUNET). Other studies (GENEBIOLUNET, LUDOVIQUE) with the same tracer and for the same pathology are interested in intrinsic radiosensitivity via molecular biomarkers (mRna and miRna transcripts) and the combination with the parameters of the population PK analysis. Finally, PK analysis continues to be an object of study in the context of paediatric metastatic neuroblastoma (Phase 1, NEUROBLU 02).

Funding :

• GENEBIOLUNET: ARI2017;
• LUDOVIQUE: PRT-K submission;
• Neuroblu02: PHRC-K17-034

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