Normal organ [68Ga]DOTATOC uptake during PRRT: challenging the assumption of stable background shaped by cold somatostatin analogues treatment

Purpose: To characterize longitudinal changes in normal-organ [68Ga]DOTATOC uptake through sequential PET/CT during [177Lu]DOTATATE PRRT in patients with small intestine neuroendocrine tumors (SiNET) and to relate these changes to the somatostatin-analogue (SSA) regimen, early PET response after two PRRT cycles, and 1-year outcome. Methods: Thirty-four patients who underwent [68Ga]DOTATOC PET/CT before PRRT (PET-baseline), after two cycles (PET-interim), and at treatment completion (PET-end) were retrospectively included. At study entry, all patients received long-acting SSA, which was discontinued during PRRT. The mean SSA-to-scan intervals were 22.1 ± 9.4 days (baseline), 125.9 ± 19.7 days (interim), and 326.2 ± 26.9 days (end). SUVmax was measured in 11 organs. Wilcoxon test with Bonferroni correction was used for group comparisons, Pearson for correlations, and two-sided Mann–Whitney U test for subgroup analyses. Results: The most significant, consistent changes occurred in the liver and spleen, both of which significantly increased from PET-baseline to PET-interim and further to PET-end (liver: +61%, spleen: +103%, p < 0.01) and evolved in parallel (r = 0.64–0.71). Hepatic uptake continued to rise through the end of PRRT and remained elevated long after the last SSA injection. At interim, liver SUVmax was higher in early PET responders than in non-responders and in patients who later progressed at one year; the spleen showed a similar pattern. These findings suggest an SSA-timing–sensitive background drift superimposed on treatment effects. Conclusion: Normal organ [68Ga]DOTATOC uptake during PRRT is dynamic and influenced by SSA regimen and scan timing. Liver and spleen are unreliable as stable references, underscoring the need for harmonized PET timing and explicit reporting of SSA-to-scan intervals.