(1) Background: The appearance of enlarged lymph nodes on imaging adds another layer of complexity to the differential diagnosis of disease progression versus immune response to COVID-19 vaccines. Our aim was to find an optimal timing between the vaccination and the PET-CT scan. (2) Methods: 25 cancer patients with 18F-FDG PET-CT evaluations and a history of COVID-19 vaccination between September 2021 and December 2021 were retrospectively analyzed to characterize the lymph nodes related to the time interval from COVID vaccination. (3) Results: All patients presented one or more adenopathies localized in the ipsilateral axilla (96%), ipsilateral cervical area (20%), ipsilateral retropectoral (20%) and pulmonary hilum (8%). The median value of SUVmax was 3.5 ± 0.5. There was a significant indirect correlation between SUVmax and the time passed between the vaccination and the PET CT (Pearson Correlation r = -0.54, p = 0.005). There was no significant difference (p = 0.19) in the SUVmax value in patients receiving Moderna mRNA-1273 vaccine vs. BNT162b2 mRNA Pfizer vaccine. (4) Conclusions: Lymph node enlargement is commonly seen in patients post-vaccination for COVID-19 and must be differentiated from disease progression. The data from our study strongly suggests that the minimum interval of time between an mRNA vaccine and a PET-CT should be more than six weeks.
Keywords: 18F-FDG PET-CT; COVID-19; cancer management; mRNA vaccine.