To our knowledge this is the first study assessing the PET/CT findings with different tracers after COVID-19 vaccination in cancer patients and the consequent impact on their management.
The prevalence of locoregional PET positive lymph-nodes after SARS-CoV-2 vaccine inoculation was significantly higher as compared to pre-COVID-19 era.
After recently vaccine administration reactive lymphadenopathy in the ipsilateral axillary and/or supraclavicular area is most likely to occur. Unfortunately, it represents a serious challenge in cancer patients who undergo F-18-FDG, since it might mimic disease onset, relapse, or recurrence [22–25] whereas for F-18-Choline and Ga-68 DOTATOC PET/CT scans it may constitute only an unusual finding. Our patients were referred for staging, re-staging or follow-up to PET/CT examinations with different radioligands according to their diagnostic inquiry. Incidentally, the rate of apparently positive lymph-nodes was significant in this setting. Although our findings may appear not astonishing, they deserve caution, particularly for cancer patients as recently reported by some other authors [23–25]. The correct interpretation of this secondary effect of vaccine is of primary importance to avoid unnecessary changes in patients’ management and to rule out undue biopsies as well as to differentiate them from malignancies, recurrence and/or metastases.
We focused on the importance of a correct anamnestic interview concerning recent vaccination in oncological patients undergoing diagnostics and particularly on the precise appraisal of co-recorded CT features when they go through PET/CT scans. In this study patients were invited to report about vaccine inoculation from the beginning of COVID-19 vaccination era. In addition, suspected lymph-nodes on the PET scan were reviewed on co-registered CT for malignancy . According to daily practice, nodes with aggregate positivity were further investigated by US or mdc CT, at least . This approach avoided undue further investigations for most of patients and unnecessary invasive procedures  for those supposed positive. In fact, 84% of patients suspected positive on PET scan resulted to have benign features on co-recorded CT images. In only one case imaging confirmed malignancy.
The prevalence of the abovementioned incidental findings was significant for all the tracers investigated according to their different frequency in use (see Ga-68 peptides). From a physio-pathological point of view, F-18 FDG, as glucose analogue, distributes in both cancer and inflammatory glucose-utilizing cells [16–17, 28] and, with different pathways, inflammatory cells may concentrate the F-18-Choline and Ga-68-DOTATOC [18–20].
Recently, some authors [23–25] have reported similar results but, in smaller cohorts, sometimes in form of case report, using one tracer and after adenovirus-based vaccine which is known to elicit inflammatory response . Our study was conducted collecting data from 333 consecutive patients, irrespective of the tracer used, who underwent mRNA SARS-CoV-2 vaccination and reporting on findings both in pre-COVID-19 period and thereafter in a subset of patients. Almost 50% of patients had PET/CT scan negative in this two moments confirming the incidental nature of the observations during vaccination age.
Moreover, we renew the importance of the correct interpretation of these incidental findings during metabolic imaging in cancer patients to prevent unjustified misapprehension and the temporal enlargement of diagnostic path, as well as unnecessary changes in therapy and management.
When PET positive, the uptake index (SUVmax) was significant in all the three radiotracers satisfying the method of Thomassen  and justifying the need for further caution.
Concerning the nodes’ metabolic positivity duration few information are still available. It seems that reactive processes to vaccination may last up to 70 days [30–31]. Indeed, the longer the time elapsed the lower the tracers’ uptake intensity once scans performed newly. Accordingly, in our patients the difference in SUVmax values between the radiotracers could be explained by the time elapsed from vaccination and the different pharmacodynamic characteristics as showed in table 2.
Finally, we suggest careful interpretation of PET/CT data in cancer patients who recently undergo SARS-CoV-2 vaccine (and others vaccine as well) [32–36] considering the vaccine site of injection and addressing for subsequent imaging appraisal for the ambiguous lymph-nodes to confirm or reject the diagnostic hypothesis. In doubtful cases, the biopsy remains the last useful tool.