Impact of per-cycle changes in spatial and temporal pattern of dose and biokinetics in neuroblastoma patients receiving 177Lu-DOTATATE

Thesis

Recently, there has been a growth in using post-treatment dosimetry after the first treatment cycle to plan the prescription for subsequent administrations to achieve an acceptable safe dose to kidneys and therapeutic dose to tumour. This level of personalisation recognises inter-patient variability in the uptake and clearance of 177Lu-DOTATATE by the kidneys and tumours. Increasingly, studies are showing additional variation in pharmacokinetics between cycles in an individual patient which may be particularly relevant in NETs cases in paediatric cases like NBL. The central goals for this work were to characterise variability in the spatial and temporal patterns of renal and tumour biokinetics and dose during a four cycle course of 177Lu-DOTATATE and investigate relationships between these variabilities and patient response.

To accomplish this, an open-source software platform was written to facilitate calculation of per cycle pharmacokinetics of organs at risk and lesions using published clinical protocols. Subsequently, we applied these protocols on a single pretherapy Ga68-DOTATATE PET/CT and intra-therapy longitudinal SPECT/CT image sets acquired in six children with NBL after each cycle to understand the temporal change in physical dose and effective half life over a course of treatment in two anatomical and one functional region. The kinetics of radiobiological dose in the tumour was explored using parameters derived from in-vitro experiments.

The effective half life of 177Lu-DOTATATE in the tumour showed the greatest variation between cycles. Overall, the temporal and spatial variability in renal and tumour pharmacokinetics and dose showed no clear relationship with response in this small cohort. This thesis is a significant step towards further understanding intra-cycle variability during a course of treatment which may impact dosimetry based treatment planning aimed at delivering a set dose per cycle.

Authors: Malcolm, J

• DOI: 10.5287/ora-kokgmv845
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: radionuclide; lutetium; personalised; dosimetry
• Subjects: Radiation dosimetry