An increased uptake of the UPP has been described in about one-third of 68Ga-DOTA-peptides PET/CT [6, 7, 16], similar to that reported with older tracers such as 111In-DTPA-octreotide [9]. This uptake has been reported to be due to pancreatic polypeptide cell hyperplasia [8, 9], a particular cell subtype known to be restricted to the uncinate process in the pancreas [17].

Kroiss et al. [14] suggested at first that UPP SUVmax could help differentiate the benign or malignant origin of this uptake with an SUVmax of 33.6 ± 14.3 for NETs and 10.5 ± 4.1 for physiological uptake. However, the physiological uptake group included patients without increased uptake of the UPP considering the reported SUVmax range (2.9 to 28.7). The difference between increased physiological UPP uptake and pathological uptake is therefore more subtle. This physiological uptake may hinder SSTR imaging interpretation.

Our study showed that the administration of cSAs was associated with decreased physiological UPP uptake in 68Ga-DOTATOC PET/CT. The mean SUVmax value was significantly lower in the UPP when patients received cSA. A recent systematic review has shown that cSAs, acting on the same target as 68Ga-DOTA-peptides, led to a decrease in healthy organ uptake [13]. Among the included studies, only the study by Jahn et al. [18] reported changes in pancreatic uptake, with a decrease of SUVmax of around 50% under cSAs. We confirmed this result with a similar decrease factor. No significant correlation was found between the delay PET--last-administration of cSA and SUVmax. As previously described by Morland et al. [13], cSAs also led to a significant decrease of hepatic SUVmax in our study. Conversely, the mean blood pool SUVmax value was significantly higher: the residual tracer concentration in the blood is probably increased by the lack of tracer uptake by healthy organs.

The hypothesis of a link between UPP uptake and the presence of diabetes mellitus quickly arose in the literature: while a negative correlation was reported by Oh et al. [19] between blood glucose levels and UPP uptake, the diabetic status seems to have no impact [10]. Similarly, we found no impact of diabetes either. Age also seemed to have no influence, as previously reported [10].

Nowadays, cSAs are particularly used in well-differentiated small intestinal (or midgut) NETs and little or not at all in other indications, explaining the over-representation of this type of tumor in the cSA-treated subgroup. Long-administration of cSAs inhibits indeed tumor growth and prolongs progression-free survival in patients with well-differentiated gastro-entero-pancreatic NETs [11, 12, 20]. However, in light of our results, the question of cSAs administration in other indications to reduce physiological uptake and improve imaging quality may arise. A single intravenous administration of short-acting cSAs 15 min prior to 68-DOTA-peptide administration may be sufficient to produce a decrease in physiological uptake [18]. The risk of altering tumor uptake with such a protocol seems to have been ruled out [13]. Although tumor uptake seems to decrease slightly during cSAs treatment, the tumor/healthy organ contrast remains increased overall [13]. The only downside might be the proximity of large vessels given the increase in blood uptake. Prospective multicentric studies will be needed.

Some limitations should be acknowledged. First, the low number of patients especially in the subgroup of patients receiving cSA treatment, could lead to a lack of power, particularly regarding the role of diabetes mellitus. We did not consider blood glucose levels, as they were not measured in routine for this type of examination.