First-in-human quantitative [¹⁵O]H₂O PET imaging of tumour blood flow at rest and during exercise in lymphoma patients

BACKGROUND AND PURPOSE: Although exercise is recommended for cancer patients, its acute effects on tumour blood flow (TBF) have not been quantified in humans. As TBF may influence tumour progression and treatment efficacy, we assessed its circulatory responses in malignant lymphoma during exercise using dynamic PET imaging. Patient/material and methods: Eight patients with Hodgkin or non-Hodgkin lymphoma underwent thoracic [¹⁵O]H₂O positron emission tomography/computed tomography (PET/CT) at rest and during 10 min of supine cycling (Borg RPE 11-16). TBF and its heterogeneity, tumour blood volume (TBV), mean transit time (MTT), and vascular resistance were quantified in eight index and three secondary tumours. RESULTS: Baseline TBF in index tumours was high (mean 57.6 mL/dL/min; range 30.3-105.0). During exercise, TBF (mean 48.1 ± 16.1 mL/dL/min), its heterogeneity and MTT did not change significantly. However, TBV decreased (p = 0.038), and vascular resistance tended to increase (p = 0.055). TBF change correlated positively with age (r = 0.73, p = 0.04) and negatively with tumour volume (r = -0.67, p = 0.02), but not with heart rate or power output. Secondary tumours showed similar exercise responses, with lower absolute TBF (p = 0.02). INTERPRETATION: This study demonstrates the feasibility of using [¹⁵O]H₂O PET/CT to quantify TBF in lymphoma patients in real time during acute exercise. Baseline TBF is remarkably high in lymphoma tumours, and responses to acute exercise are variable, tending to decline in younger patients and larger tumours, while vascular resistance tended to increase.