Peptide receptor radiotherapy (PRRT) with ¹⁷⁷Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. Radiological response utilized response evaluation criteria in solid tumors 1.1 and toxicity was graded according to common terminology criteria for adverse events version 4. Median 4 (range 3–11) 7.4 GBq cycles of ¹⁷⁷Lu-DOTATATE were administered as first-line therapy (n = 13) or because of progressive disease (n = 9). Partial response (PR) was achieved in two and stable disease (SD) in 20 patients. The median overall survival (OS) was 49.6 (range 8.2–139) months and median progression-free survival (PFS) was 21.6 (range 6.7–138) months. Scintigraphic response >50% was achieved in 9/19 (47%) patients. Biochemical response (>50% decrease) of chromogranin A was found in 6/15 (40%) patients and of catecholamines in 3/12 (25%) patients. Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). No hematological or kidney toxicity grade 3–4 was registered. ¹⁷⁷Lu-DOTATATE therapy was associated with favorable outcome and low toxicity. High Ki-67 (≥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.

Pheochromocytomas (PCC) and paragangliomas (PGL) may be difficult to diagnose because of vague and uncharacteristic symptoms and equivocal biochemical and radiological findings. This was a retrospective cohort study in 102 patients undergoing ¹¹C-hydroxy-ephedrine (¹¹C-HED)-PET/CT because of symptoms and/or biochemistry suspicious for PCC/PGL and/or with radiologically equivocal adrenal incidentalomas. Correlations utilized CT/MRI, clinical, biochemical, surgical, histopathological and follow-up data. ¹¹C-HED-PET/CT correctly identified 19 patients with PCC and six with PGL, missed one PCC, attained one false positive result (nodular hyperplasia) and correctly excluded PCC/PGL in 75 patients. Sensitivity, specificity, positive and negative predictive values of ¹¹C-HED-PET/CT for PCC/PGL diagnosis was 96%, 99%, 96% and 99%, respectively. In 41 patients who underwent surgical resection and for whom correlation to histopathology was available, the corresponding figures were 96%, 93%, 96% and 93%, respectively. Tumor ¹¹C-HED-uptake measurements (standardized uptake value, tumor-to-normal-adrenal ratio) were unrelated to symptoms of catecholamine excess (p > 0.05) and to systolic blood pressure (p > 0.05). In PCC/PGL patients, norepinephrine and systolic blood pressure increased in parallel (R² = 0.22, p = 0.016). ¹¹C-HED-PET/CT was found to be an accurate tool to diagnose and rule out PCC/PGL in complex clinical scenarios and for the characterization of equivocal adrenal incidentalomas. PET measurements of tumor ¹¹C-HED uptake were not helpful for tumor characterization.

Aims/hypothesis: Compromised pancreatic sympathetic innervation has been suggested as a factor involved in both immune-mediated beta cell destruction and endocrine dysregulation of pancreatic islets. To further explore these intriguing findings, new techniques for in vivo assessment of pancreatic innervation are required. This is a retrospective study that aimed to investigate whether the noradrenaline (norepinephrine) analogue ¹¹C-hydroxy ephedrine (¹¹C-HED) could be used for quantitative positron emission tomography (PET) imaging of the sympathetic innervation of the human pancreas. Methods: In 25 individuals with type 2 diabetes and 64 individuals without diabetes, all of whom had previously undergone ¹¹C-HED-PET/CT because of pheochromocytoma or paraganglioma (or suspicion thereof), the ¹¹C-HED standardised uptake value (SUV_mean), ¹¹C-HED specific binding index (SBI), pancreatic functional volume (FV, in ml), functional neuronal volume (FNV, calculated as SUV_mean × FV), specific binding index with functional volume (SBI FV, calculated as SBI × FV) and attenuation on CT (HU) were investigated in the entire pancreas, and additionally in six separate anatomical pancreatic regions. Results: Generally, ¹¹C-HED uptake in the pancreas was high, with marked individual variation, suggesting variability in sympathetic innervation. Moreover, pancreatic CT attenuation (HU) (p<0.001), ¹¹C-HED SBI (p=0.0049) and SBI FV (p=0.0142) were lower in individuals with type 2 diabetes than in individuals without diabetes, whereas ¹¹C-HED SUV_mean (p=0.15), FV (p=0.73) and FNV (p=0.30) were similar. Conclusions/interpretation: We demonstrate the feasibility of using ¹¹C-HED-PET for non-invasive assessment of pancreatic sympathetic innervation in humans. These findings warrant further prospective evaluation, especially in individuals with theoretical defects in pancreatic sympathetic innervation, such as those with type 1 diabetes. Graphical