DOTATATE PET and Poorly Differentiated Extrapulmonary NEC: JNM | June 2026

• Somatostatin receptor (SSTR) imaging with ⁶⁸Ga-DOTATATE PET is a cornerstone for well-differentiated neuroendocrine tumours, but its role in poorly differentiated neuroendocrine carcinoma (NEC) has remained uncertain.
• Previous retrospective studies suggested that up to 40% of NECs might demonstrate strong somatostatin receptor expression, raising interest in peptide receptor radionuclide therapy (PRRT) for these patients.
• This prospective study was designed to provide a more accurate assessment by evaluating an unselected cohort of metastatic extrapulmonary NEC patients.
• Thirty patients with metastatic extrapulmonary NEC underwent ⁶⁸Ga-DOTATATE PET, and most also underwent ¹⁸F-FDG PET.
• Primary tumour sites included pancreas, colorectum, uterus, and cancers of unknown primary origin.
• Histologies included both small-cell and large-cell neuroendocrine carcinoma.
• The key finding was that uniform, high-level somatostatin receptor expression was uncommon.
• Only 13% of patients demonstrated strong, homogeneous DOTATATE uptake consistent with high SSTR expression.
• The vast majority of tumors showed either:

Absent SSTR expression

Patchy/heterogeneous receptor expression

Predominantly FDG-avid biology

• These findings suggest that most poorly differentiated NECs retain aggressive glycolytic behaviour rather than the receptor-rich phenotype typically seen in well-differentiated NETs.
• The study challenges previous reports that may have overestimated SSTR positivity because of selection bias or inclusion of tumours with lower Ki-67 indices.
• Clinically, this means that routine DOTATATE PET scanning is unlikely to identify large numbers of poorly differentiated NEC patients suitable for PRRT.
• However, a small subset of NEC patients may still demonstrate strong receptor expression and could remain candidates for receptor-targeted therapies.
• Dual-tracer imaging with FDG PET and DOTATATE PET may be particularly useful when considering individualised treatment strategies.
• The findings reinforce the biological distinction between well-differentiated NETs and poorly differentiated NECs.

Bottom line: Strong and uniform somatostatin receptor expression is present in only a small minority of patients with metastatic extrapulmonary poorly differentiated NEC. Most NECs remain predominantly FDG-avid tumours, limiting the routine applicability of DOTATATE-based imaging and PRRT in this population.