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Purpose  In this prospective exploratory study, we evaluated the feasibility of [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) PET/MRI-based chemotherapy response prediction in pancreatic ductal adenocarcinoma at two weeks upon therapy onset.    Material and methods  In a mixed cohort, seventeen patients treated with chemotherapy in neoadjuvant or palliative intent were enrolled. All patients were imaged by [ 18 F]FDG PET/MRI before and two weeks after onset of chemotherapy. Response per RECIST1.1 was then assessed at 3 months [ 18 F]FDG PET/MRI-derived parameters (MTV 50% , TLG 50% , MTV 2.5 , TLG 2.5 , SUV max , SUV peak , ADC max , ADC mean  and ADC min ) were assessed, using multiple  t -test, Man–Whitney- U  test and Fisher’s exact test for binary features.    Results  At 72 ± 43 days, twelve patients were classified as responders and five patients as non-responders. An increase in ∆MTV 50%  and ∆ADC (≥ 20% and 15%, respectively) and a decrease in ∆TLG 50%  (≤ 20%) at 2 weeks after chemotherapy onset enabled prediction of responders and non-responders, respectively. Parameter combinations (∆TLG 50%  and ∆ADC max  or ∆MTV 50%  and ∆ADC max ) further improved discrimination.    Conclusion  Multiparametric [ 18 F]FDG PET/MRI-derived parameters, in particular indicators of a change in tumor glycolysis and cellularity, may enable very early chemotherapy response prediction. Further prospective studies in larger patient cohorts are recommended to their clinical impact.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13550-021-00808-4.

[18F]FDG PET/MRI enables early chemotherapy response prediction in pancreatic ductal adenocarcinoma