# Advances in Molecular Imaging for Neuroendocrine Neoplasms

## TL;DR

This review discusses how molecular imaging, especially PET/CT, is crucial for diagnosing and managing neuroendocrine neoplasms, which are diverse and challenging to treat.

## Contribution

The paper evaluates current and emerging imaging techniques and radiopharmaceuticals for neuroendocrine neoplasms to improve diagnosis and treatment.

## Key findings

- PET/CT using somatostatin receptor-targeted radiopharmaceuticals is the standard for diagnosing most neuroendocrine neoplasms.
- FDG-PET is used for tumors with low somatostatin receptor expression to assess disease aggressiveness.
- Dual-tracer imaging and new radiopharmaceuticals are being developed to address the heterogeneity of these tumors.

## Abstract

In the past two decades, molecular imaging techniques, particularly PET/CT, have become the cornerstone modality for the diagnosis and staging of neuroendocrine neoplasms (NENs). These are a heterogenous and diverse group of neoplasms estimated to account for approximately 3–4 cases per 100,000 in the United States, but vary significantly around the world and by age demographics. Despite the diversity of these neoplasms, the vast majority express the somatostatin receptor (SSTR), which is why radiopharmaceuticals targeting somatostatin receptors have become the most commonly used ones for the diagnosis and staging of NENs. NENs that express low levels of the SSTR generally have poorer progressions and can be imaged with other radiopharmaceuticals, such as F-18-labeled fluorodeoxyglucose (FDG), to assess disease heterogeneity as well as the relative aggressiveness of the disease.

Neuroendocrine neoplasms (NENs) represent a heterogenous group of tumors with significant inter- and intra-patient variability. Once considered to be rare, neuroendocrine neoplasms are being increasingly recognized through the advent of advanced diagnostic techniques, which may be contributing to the significant increase in the incidence and detection rate of these tumors. NENs can be classified into well differentiated and poorly differentiated neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs). The proliferation rate of NETs can vary from Ki-67 1–55%. In addition, the SSTR expression can vary significantly. Because of this high “heterogeneity”, their detection and characterization have become essential to disease management, leading to dual-tracer imaging, most commonly with FDG- and SSTR-targeted PET/CT. Because of the complexity of the disease, the optimal treatment of patients depends on a combination of imaging, serological biomarkers, and clinical information. There remains a significant portion of patients who do not respond as anticipated, and the management of their disease remains challenging with current techniques, necessitating the refinement of our technologies and the development of new ones. In addition to new biological targets, improved peptide vector targeting for the somatostatin receptor needs further development. This review aims to evaluate the existing imaging techniques utilized in the diagnosis, assessment, and treatment of NENs, as well as the emerging radiopharmaceuticals and technologies, which will expand our imaging repertoire as well as our management options.