Gastroenteropancreatic neuroendocrine
neoplasms (GEP NENs) are rare
cancers consisting of
neuroendocrine carcinomas (NECs) and
neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for studying GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated
tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of six mice developed
tumors (NEC913 and NEC1452). Over 80% of NEC913 and NEC1452
tumor cells stained positive for Ki67. NEC913 PDX
tumors expressed neuroendocrine markers such as
chromogranin A (CgA),
synaptophysin (SYP), and
somatostatin receptor-2 (SSTR2), whereas NEC1452 PDX
tumors did not express SSTR2. Exome sequencing revealed loss of TP53 and RB1 in both NEC
tumors. To demonstrate an application of these novel NEC PDX models for SSTR2-targeted
peptide imaging, the NEC913 and NEC1452 cells were bilaterally injected into mice. Near infrared-labelled
octreotide was administered and the fluorescent signal was specifically observed for the NEC913 SSTR2 positive
tumors. These 2 GEP NEC PDX models serve as a valuable resource for GEP NEN
therapy testing.