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Introduction: The demonstration of type 2 somatostatin receptors (SSTRs) in small-cell lung cancer (SCLC) represents the rationale for the use of positron emission tomography/computed tomography (PET/CT) to determine SSTR expression, and select patients suitable for peptide radioreceptor radionuclide therapy (PRRT) in extensive-disease stage (ED) SCLC., Methods: We evaluated 24 ED-SCLC patients with radiolabeled SST-analog PET/CT. Lesions at PET/CT scan were semiquantitatively scored (from 0 to 3+) and compared with contrast-enhanced CT findings. Patients scored as 3+ were admitted to PRRT after dosimetric evaluation. Average injected activity/cycle was 2.6 GBq (yttrium-PRRT) or 6.0 GBq (lutetium-PRRT). PRRT efficacy was clinically and radiologically assessed., Results: PET/CT was negative in four of 24 patients, whereas in the remaining 20 cases uptake was scored as 1+ in seven of 20, 2+ in one of 20, and 3+ in 12 of 20. Primary tumor lesions showed uptake in 16 of 24 patients. Uptake in metastatic lesions was observed in four of four adrenals, two of five brain, 12 of 16 bone, three of eight liver, and 17 of 20 lymph node lesions. Of the 12 patients eligible for PRRT, 11 were eventually treated and four of 11 patients received multiple PRRT administrations. Dosimetry resulted in a BED for kidney of 7.5 Gy (range, 4-21); bone marrow provisional dosage was 0.43 Gy (range, 0.1-1.7). Hematological PRRT toxicity occurred in three of 11 patients. No clinical or objective responses were observed with disease progression occurring approximately 48 days (range, 9-32) after PRRT., Conclusion: Radiolabeled SST-analog PET/CT demonstrated enhanced SSTR expression in 50% of cases. Nevertheless, PRRT in ED-SCLC was ineffective, suggesting the need to anticipate or combine PRRT in a multimodality approach.