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Updated: Sep 26, 2025
The Establishment and Utilization of Patient Derived Xenograft Models of Central Nervous System Metastasis
Published on: May 7, 2021
Establishment of Novel Neuroendocrine Carcinoma Patient-Derived Xenograft Models for Receptor Peptide-Targeted
Catherine G Tran1, Luis C Borbon1, Jacqueline L Mudd2
1Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Abstract:
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.
Insights
Researchers developed new patient-derived xenograft (PDX) models for gastroenteropancreatic neuroendocrine neoplasms (GEP NENs). These models, NEC913 and NEC1452, are crucial for advancing imaging and treatment strategies for these rare cancers.
Area of Science:
- Oncology
- Translational Research
- Cancer Biology
Background:
- Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare, with increasing incidence.
- Limited availability of preclinical models hinders the development of novel imaging and treatments for GEP NENs.
Purpose of the Study:
- To establish patient-derived xenograft (PDX) models for GEP neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs).
- To characterize these novel PDX models for their utility in preclinical research and therapeutic development.
Main Methods:
- Tumor cells from cryopreserved GEP NECs and NETs were used to create PDX models in immunocompromised mice.
- Tumor characteristics, including Ki67 proliferation index, neuroendocrine marker expression (CgA, SYP, SSTR2), and genetic mutations (TP53, RB1), were analyzed.
- SSTR2-targeted peptide imaging using near-infrared-labeled octreotide was performed on the established PDX models.
Main Results:
- Two GEP NEC PDX models, NEC913 and NEC1452, were successfully established.
- Both models showed high Ki67 proliferation (>80%).
- NEC913 PDX tumors expressed SSTR2, CgA, and SYP, while NEC1452 PDX tumors expressed CgA and SYP but lacked SSTR2. Both harbored TP53 and RB1 loss.
- SSTR2-targeted imaging successfully detected the NEC913 tumors.
Conclusions:
- The developed NEC913 and NEC1452 PDX models represent valuable preclinical tools for GEP NEN research.
- These models facilitate the testing of novel imaging agents and therapeutic strategies, particularly for SSTR2-expressing GEP NENs.
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