Neuroendocrine tumours (NETs) are a unique group of cancers that often require specialised imaging techniques for accurate diagnosis and monitoring. Unlike many other cancers, which can be detected using standard radiological imaging such as computed tomography (CT) or magnetic resonance imaging (MRI), NETs often require functional imaging to visualise their activity at the molecular level.
This is where nuclear medicine plays a critical role. Nuclear medicine imaging is not just about detecting the physical presence of a tumour—it also allows doctors to see how the tumour functions, including whether it expresses somatostatin receptors (SSTRs) or has a high metabolic rate. These insights are essential for staging the disease, selecting appropriate treatments, and monitoring response to therapy.
In this article, we explore the key nuclear medicine techniques used in NET diagnosis, their advantages over traditional imaging, and emerging advancements in this field.
Neuroendocrine Cancer Australia (NECA), is dedicated to assisting individuals diagnosed with NETs and their loved ones. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients can engage with NECA’s comprehensive support and information by calling the NET nurse line.
What is nuclear medicine?
Nuclear medicine is a specialised branch of medical imaging that uses radioactive tracers (radiopharmaceuticals) to diagnose diseases. Unlike standard imaging, which focuses on anatomy and structure, nuclear medicine provides information about how tissues and organs function.
In cancer diagnosis, nuclear medicine is particularly valuable because it allows doctors to:
- Detect tumours based on their metabolic or receptor activity.
- Identify metastases that may not be visible on CT or MRI scans.
- Assess how a tumour responds to treatment.
How it differs from standard radiological imaging
| Feature | Standard radiology (CT/MRI) | Nuclear medicine (PET/SPECT) |
| Focus | Physical structure of tumours | Functional activity of tumours |
| Best for | Assessing tumour size, shape, and spread | Identifying active tumour cells and receptor expression |
| Contrast use | Uses iodine or gadolinium contrast | Uses radioactive tracers |
| Limitations | May miss small, slow-growing NETs | Requires specialised tracers and imaging equipment |
Nuclear medicine plays an essential role in NET diagnosis because these tumours can be small, slow-growing, or spread widely, making them difficult to detect with conventional scans.
Why nuclear medicine is important in NETs
NETs often have somatostatin receptors (SSTRs), which allows them to be targeted using specific radiotracers in nuclear imaging. This enables:
- More precise tumour detection than traditional imaging.
- Better differentiation between benign and malignant NETs.
- A clearer picture of the tumour’s biological behaviour.
Detecting both primary and metastatic disease
One of the biggest challenges in NET diagnosis is that tumours often spread before symptoms appear. Nuclear medicine scans help:
- Find the primary tumour site, which may be hidden in the digestive tract, pancreas, or lungs.
- Identify distant metastases, especially in the bones, liver, and lymph nodes.
- Guide treatment decisions, such as whether a patient is eligible for peptide receptor radionuclide therapy (PRRT).
By providing a whole-body view of NET activity, nuclear medicine scans offer a comprehensive assessment of the disease.
Key nuclear medicine scans for NET diagnosis
Gallium-68 DOTATATE PET/CT
Gallium-68 DOTATATE PET/CT is the gold standard for imaging well-differentiated NETs. It works by:
- Using Gallium-68, a radioactive tracer, that binds to somatostatin receptors (SSTRs) on NET cells.
- Emitting signals that are detected by the PET scanner, creating detailed images of the tumour’s location and extent.
- Combining with CT imaging to provide both functional and anatomical information in a single scan.
Advantages in sensitivity and accuracy
- Superior detection of small and early-stage NETs.
- More accurate staging of the disease compared to CT or MRI.
- Essential for determining eligibility for PRRT.
Gallium-68 PET/CT has largely replaced older imaging techniques, offering higher resolution and better accuracy.
FDG PET/CT
While Gallium-68 PET is effective for low and intermediate-grade NETs, high-grade, poorly differentiated neuroendocrine carcinomas (NECs) often do not express somatostatin receptors. Instead, they have high glucose metabolism, which makes fluorodeoxyglucose (FDG) PET/CT a better choice.
FDG PET/CT works by:
- Detecting tumours with increased glucose uptake, which is a hallmark of aggressive cancers.
- Identifying highly proliferative NETs that may not be visible on Gallium-68 PET.
- Providing information on tumour aggression and treatment response.
Complementary role with Gallium-68 imaging
For some patients, both Gallium-68 PET and FDG PET may be needed to fully assess tumour behaviour. This dual imaging approach helps determine:
- Whether PRRT is suitable (if SSTR expression is present).
- How aggressive the tumour is, guiding chemotherapy decisions.
In some cases, individuals may have tumours with multiple different grades, making combined imaging particularly valuable for treatment planning.
Octreotide Scans (SRS)
Before the introduction of Gallium-68 PET/CT, Octreotide scans (Somatostatin Receptor Scintigraphy – SRS) were the main imaging method for NETs. They involve:
- Injecting a radiolabelled somatostatin analogue (Indium-111 Octreotide).
- Taking images over 24–48 hours to track tumour uptake.
Comparison to newer techniques
- Lower sensitivity – Less effective at detecting small tumours.
- Longer imaging time – Requires multiple scans over two days.
- Still useful in some cases where Gallium-68 PET is unavailable.
Most centres now prefer Gallium-68 PET/CT due to its greater accuracy and faster imaging time.
Selecting the right nuclear medicine scan
Here’s a cheat sheet on how to select the right nuclear medicine scan for NET diagnosis and treatment.
How tumour grade and location influence imaging choices
- Well-differentiated NETs → Gallium-68 PET/CT
- Poorly differentiated NECs → FDG PET/CT
- Unclear cases or limited access to PET scans → Octreotide scans (SRS)
- When tumour grade is unknown or multiple grades are suspected →
- A combination of Gallium-68 and FDG PET/CT can provide a more complete picture for diagnosis and treatment planning
Combining nuclear medicine with other diagnostic tools
- CT/MRI for anatomical details.
- Biopsy and histopathology for tumour grading.
- Blood and urine markers (CgA, 5-HIAA) for biochemical confirmation.
Role in staging and treatment planning
Imaging plays a crucial role in determining the extent of disease in patients with neuroendocrine tumours, helping to assess whether surgery is a viable option for tumour removal. It also identifies patients eligible for peptide receptor radionuclide therapy (PRRT) by evaluating somatostatin receptor (SSTR) expression and provides insight into lymph node and liver involvement for more effective treatment planning.
Ongoing imaging is equally important for monitoring response to therapies over time. By comparing scans taken before and after treatment, clinicians can track tumour shrinkage or progression, detect new metastases, and observe changes in tumour activity, allowing for timely adjustments to care.
Advancements in nuclear medicine for NETs
Advancements in nuclear medicine are opening new possibilities for the diagnosis and treatment of neuroendocrine tumours (NETs).
Among the most promising developments is the introduction of new tracers like Copper-64 DOTATATE, which offers a longer half-life than the commonly used Gallium-68, allowing for more flexible imaging schedules and potentially improved diagnostic accuracy.
Alpha-emitting radiopharmaceuticals are also gaining attention for their ability to more precisely target NET cells, which may lead to better treatment outcomes and reduced damage to surrounding healthy tissue.
Looking ahead, the future of personalised imaging for NETs is set to benefit from rapid technological progress. Artificial intelligence is playing an increasingly important role in enhancing imaging interpretation, making it easier to detect tumours that might otherwise be missed.
At the same time, researchers are focusing on developing more tailored tracers designed to match the unique biological characteristics of different NET subtypes, offering a more individualised approach to patient care.
Access to nuclear medicine in NET Care
Access to Gallium-68 PET/CT and PRRT may be limited in some regions, requiring referral to NET specialist centres.
Early referral to a NET expert ensures the right imaging is used, improving diagnosis and treatment success.
Further information and support for people diagnosed with NETs is available by calling the NECAÂ NET nurse line
SOURCES
Role of Nuclear Medicine in NET Diagnosis
- Nuclear Medicine Imaging of Neuroendocrine Tumours
https://pmc.ncbi.nlm.nih.gov/articles/PMC4952131/ - Nuclear Medicine Techniques for the Imaging and Treatment of Neuroendocrine Tumours
https://erc.bioscientifica.com/view/journals/erc/18/S1/S27.xml - Types of PET/CT Scans for Neuroendocrine Tumors
https://netrf.org/old-for-patients/nets-info/diagnostic-tests-for-neuroendocrine-cancer/imaging/ - Nuclear Imaging of Neuroendocrine Tumors
https://pmc.ncbi.nlm.nih.gov/articles/PMC7700750/ - Neuroendocrine Tumors – SNMMI
https://snmmi.org/Patients/Patients/Cancer/Neuroendocrine-Tumors.aspx - Neuroendocrine Tumor Diagnosis and Management
https://ajronline.org/doi/10.2214/AJR.18.1988 - Nuclear Medicine Role in Neuroendocrine Tumors
https://isotopia-global.com/nuclear-medicine-role-in-neuroendocrine-tumors/ - What is Peptide Receptor Radionuclide Therapy (PRRT) for NETs?
https://netrf.org/old-for-patients/nets-info/net-treatment/nuclear-medicine/
