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Background: Our aim was to measure the impact of two cycles of standard chemotherapy on tumoural neoangiogenesis by [18F] fluorine arginine-glycine-aspartic (RGD-K5) positron emission tomography–computed tomography (PET) on patients presenting with lymphoma. Nineteen patients at Rouen's Henri Becquerel Cancer Centre were prospectively included. Fluorodeoxyglucose (FDG) and RGD-K5 PET were performed before (C0) and after (C2) two cycles of chemotherapy. End-of-treatment FDG PET was performed for final evaluation. Maximum standardised uptake value (SUVmax), SUVmean, Metabolic Tumour Volume (MTV) and Angiogenic Tumour Volume (ATV) were measured for all lesions. RGD SUVmax and SUVmean were also analysed in 13 normal organs at C0 and C2. The patient's treatment response was considered using the Deauville score (DS) at the end of FDG PET treatment (DS 1–3 were considered responders, and 4 and 5 non-responders). Results: Eighteen patients had both C0 FDG and RGD PET. Twelve patients had both C2 FDG and RGD, completed the treatment protocol and were included in end-of-treatment analysis. No statistical difference was found in RGD uptake of normal organs before and after chemotherapy for SUVmax and SUVmean. On C0 RGD, apart from classical Hodgkin lymphoma (cHL; n = 5) and grey zone lymphoma (GZL; n = 1), other lymphoma sub-types (n = 12) had low RGD uptake (p < 0.001). Regarding FDG, there was no significant difference for SUVmax, SUVmean and MTV at C0 and C2 between patients with cHL and non-Hodgkin lymphoma (NHL). At C2 RGD, non-responders had higher SUVmax and SUVmean compared to responders (p < 0.001). There was no significant difference in RGD ATV between responders and non-responders. Conclusions: Our study showed significant higher initial RGD uptake in patients presenting with cHL and GZL compared to NHL. Non-responder also had higher post-chemotherapy RGD uptake compared to responders. Issues raised by RGD uptake, particularly in cHL, are yet to be explored and need to be confirmed in a larger population. [ABSTRACT FROM AUTHOR]