Background
In my online patient group, there is constant discussion about the meaning of both pictures and words on scan reports. The one that seems to cause the most confusion is PET scans, mainly somatostatin receptor (SSTR) PETs such as Ga68 and Cu64 variants. Worth adding that it’s the addition of a nuclear tracer that makes PETs seem different. Generally speaking, the PET hardware is essentially the same. Most have a built-in CT scan, much less frequently an MRI scan.
Confusion is often triggered by healthcare system processes where the patient receives the report before the appointment to discuss the results with the referring physician. Cue anxiety because the average patient reader does not understand and certain words cause them to worry, often unnecessary worry. The patient then becomes impatient and will take to patient online groups to try to decode the report. Given this is such a specialist subject far beyond the understanding of most patients, this can often lead to even worse confusion and anxiety. One positive though, it can help the patient formulate questions for the expert who will discuss the scan report with them at some point. Some healthcare systems are bound by law to produce these on patient accessible online information so this problem in patient groups is here to stay. In patient groups, a heavy dose of moderation is often required when these are posted.
As a general principle, it should be noted that not all Neuroendocrine Cancer patients will express somatostatin receptors, or at least not sufficiently and not uniformly across all their tumours. The latter is important e.g. Lung NET is one example where recent studies found that around half of metastatic patients lacked uniform SSTR expression and were thus suboptimal candidates for SSTR-targeted therapy. Furthermore, some patients may need SSTR PET in combination with FDG PET/CT to assess tumour heterogeneity, especially in G2 and G3 NETs, offering a personalised management of their tumour burden (in terms of surveillance and treatment choices).
In this blog post (which I will update as time goes on), I wanted to initially focus on a number of frequently confusing areas, and these will be sectioned below. These include:
1. CT vs PET
2. Measuring tumours
3. Uptake pitfalls
4. PET Colours
5. SUV readings
The aim of this post is not a technical briefing on scans, something the author thinks is not an exact science. This post is just to help you formulate questions for your specialists or perhaps even put your mind at rest until you meet your doctor. It may even calm your fear of certain parts of the report you can see before your doctor has explained it to you!
1. CT vs PET
Scientists and physicians will often describe scan types in a grouping called conventional imaging (CI) for CT, MRI etc. PETs are sometimes called ‘functional imaging’ (not to be confused with functional tumours, different contexts). Sometimes a PET is also known as molecular imaging, and this is the wording now being pushed as the textbook nomenclature to use. Most PET/CT will use a PET tracer but not a CT tracer as the latter provides the anatomical view to help the PET display better. There is the potential to use both PET tracer and CT tracer but it’s not routine.
As above, a PET scan normally has a built-in CT, but much less frequently a built-in MRI is used. The efficacy of this approach is well documented as combining (or fusing) the anatomical view of the CT with the molecular view of the PET provides a richer picture.
To put that into context, the 3 imaging pictures below from left to right, the left is PET only, right is CT only. The centre picture is the fused CT and PET picture and allows the radiologist and other specialists to pin down locations of uptake more accurately than on PET only. This is one of the reasons why you are told to lie still on a PET/CT.
One of the reasons I include this section is firstly a lack of understanding of the purpose of the CT (or MRI) element of PET scans. I have heard patients say their tumours could not be found on CT but were found on PET but in those circumstances, while that can often happen with benign issues, tumours being obscured, or tumours lacking somatostatin receptors, it is always useful to double-check the PET/CT output. Even without a CT tracer being used with my own SSTR PET/CT, I asked my own Oncologist to show me something from my recent PET/CT on CT only and it was there.
2. Measuring tumours
When you look at scans, the tumours (or abnormalities/lesions) can be quite difficult to measure, after all it’s just a ‘glow’ on a screen, not the actual tumour. The glow might be brighter on different machines and trying to get the size to the nearest millimetre (mm) is pretty arbitrary. Different human interpretation can produce different sizes from the same scan. Different scans (even the same type) can also provide differences in interpretation.
As above, the SSTR PETs come with a CT or less frequently, an MRI. The pictures in section 1 above show why this is a really important part of the overall picture and emphasises the importance of conventional imaging as standalone surveillance regimes, but even within SSTR PET imaging they are so important.
People in my group get pretty excited when they see change in size but they also get pretty anxious when they see that size increase. I learned a long time ago that lesion measurements by a mm here and there is nothing to worry about. But I wanted to introduce this issue here because the type of ‘glow’ provided by SSTR PET can often make the tumours seem much larger due to their level of ‘avidity’. The picture below will cover the same tumours on both SSTR PET and CT from the same SSTR PET/CT. Thankful to Dr Thor for another nugget.
3. Uptake Pitfalls
Not everything that lights up on a scan is cancer or NET (chant it 3 times!)
This phenomenon is well-known and well-documented. There’s a perception among patients that anything with uptake is abnormal. However, this is not always true and can cause unnecessary alarm and concern. I’m going to refer to the output from someone who I believe is a leading authority on this subject.
One of the challenges with modern scanning equipment and techniques is the ability to correctly interpret the results – in my opinion, this is almost as important as the efficiency of the machines and radionuclides. This requirement has been acknowledged in many articles and I particularly like this technical paper from a very experienced nuclear medicine physician Professor Michael Hofman from the Centre for Cancer Imaging at the Peter MacCallum Cancer in Melbourne. I had a chat with Professor Hofman who added that this is a very sensitive scan, so often picks up “new” disease, which isn’t really new, just never identifiable on standard imaging. However, there’s an excellent section on pitfalls in interpretation and I’m quoting an abstract below. Although this document is mainly talking about Ga68 PET/CT for NETs, the majority of these pitfalls will generally apply to most SSTR PETs.
“Although GaTate PET/CT is a highly sensitive and specific technique for NETs, the attending physician or radiologist must be aware of various physiologic and other pathologic processes in which cellular expression of SSTR can result in interpretative error. Most of these processes demonstrate low-intensity and/or nonfocal uptake, in contrast with the focal intense abnormality encountered in NETs. Causes of interpretative pitfalls include prominent pancreatic uncinate process activity, inflammation, osteoblastic activity (degenerative bone disease, fracture, vertebral hemangioma), splenunculi or splenosis, and benign meningioma. Moderately intense uptake is also seen in the liver, salivary glands, and thyroid gland.” and “The highest-intensity physiologic uptake of GaTate is seen in the spleen, followed by the adrenal glands, kidneys, and pituitary gland”
(note “GaTate” is an Australian colloquial term for somatostatin receptor PET (SSTR PET))
This has recently been reinforced in the latest set of guidelines published in February 2023 by The Society of Nuclear Medicine and Molecular Imaging (SNMMI) SNMMI Procedure Standard/EANM Practice Guideline for SSTR PET: Imaging Neuroendocrine Tumors (click blue link to read more)
It follows that failure to interpret nuclear scans alongside the patient’s clinical history and tempered by the known behaviours of Neuroendocrine Neoplasms can sometimes result in two big issues for patients:
1. Unnecessary worry when ‘something’ shows up.
2. Something which leads to irreversible treatment when it is not required.
Short extract of interpretative pitfalls in this table:
You can see from above there is physiological uptake. Normal uptake of PET tracers occurs in many sites of the body and may cause confusion in interpretation, particularly in oncology imaging. Osteoblastic and Inflammatory conditions can also light up given concern. Finally, other tumours that can light up (many benign) and can be incidentally diagnosed, mainly Meningioma which is known to have somatostatin receptors. But PETs can also pick up malignancies unrelated to NET, these are more incidental findings rather than physiologic uptake. See section below on incidental findings.
Finally, just to point out there can also be false positives in conventional imaging.
4. PET Colours
As I understand how this works, the colours are used as a rule of thumb by nuclear radiologists BUT….. with caution. As a guide blue/green is low metabolic activity, orange/yellow is medium and red is high – a bit like a traffic light. Clearly, this is an oversimplification, but it enables radiologists to eyeball the PET image and decide if the uptake is of low, moderate or high metabolic activity, i.e. working out the type of uptake needs an experienced radiologist as physiologic uptake which is benign can sometimes show in each colour. i.e. this can be a dangerous scale to use if there isn’t a disciplined and consistent use of the threshold setting principles (an added layer of complexity).
5. SUV Readings with SSTR PET (incl use of Krenning Score)
This is one of the most confusing issues for patients who continually read SUV numbers on their scan reports. Worth reminding people that the nuclear radiologist is writing the report for the doctor who ordered the scan, it is that doctor’s job to interpret what it means. It’s a technical report and as you may have gathered from above, it’s not an exact science.
A PET scan report will also indicate SUV (standardized uptake value). While it seems obvious to believe a higher SUV indicates new, growing, or more aggressive malignancy – that is absolutely not the case. Even when the numbers increase from scan to scan, this does not necessarily mean growth or more aggressive behaviour. It’s the same the other way, low SUV numbers than your last scan does not mean regression of disease.
In SSTR PET, there are two useful applications of SUV figures.
Firstly, in general terms it can help determine if a NET patient is likely to benefit from somatostatin receptor-based therapy. SUV can herp guide and assist in the identification of tumours more likely to be NET via a suggested threshold figure. Some studies put that SUV (max) figure at around 16. Again, this is not an exact science and is not an absolute measure. Dr Hofman mentions this issue in this seminal paper above “……in contrast with the focal intense abnormality encountered in NETs”.
Krenning score
The Krenning score is a semi-quantitative method of assessing the degree of tracer uptake (introduced with octreotide scans). Some radiologists and studies suggest it is equally applicable to modern SSTR PETs and many organisations do actually use it. It helps to assess candidacy for peptide receptor radionuclide therapy (PRRT), such as lutetium-177 DOTATATE, usually with a score greater than 2. Determination of the Krenning score requires comparison to the liver and spleen (or kidney if not applicable). In order to account for false positives, interpretation should take place in the appropriate clinical context.
Relative uptake score
- 0: none
- 1: much lower than liver
- 2: slightly less than or equal to liver
- 3: greater than liver
- 4: greater than spleen
History and etymology
The notion of grading neuroendocrine tumour uptake was introduced by Eric Krenning, a Dutch physician, who led whole-body efforts into somatostatin receptor imaging
Interpreting changes in SUV numbers
Finally, quotes from nuclear radiologists who are “big hitters” on the issue of interpreting SUV numbers. I’m thankful to Josh Mailman for sparking this exchange on twitter.
Do these issues also exist with FDG PET?
Essentially yes but there could be some subtle differences. For example, interpreting SUV numbers on an FDG PET is not the same as SSTR PET.
I refer you to this link where there is a bunch of frequently asked questions (FAQ) on Understanding PETs (specifically in reference to FDG). The conversation is chaired by Arif Sheikh who has a vast experience including with NET. He is also co-chair of the Neuroendocrine Tumor Outreach Working Group in the Society of Nuclear Medicine and Molecular Imaging (SNMMI).
Click on the picture below to read the Q&A on FDG PET interpretation.
If you can see it, you can detect it
All you need to know about SSTR PET
Somatostatin Receptors
Dual SSTR/FDG PET/CT
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I have never received or had access to any of my scan reports. Should I be concerned?
Personally, I would be asking for copies. I trust my doctor but I still like to read these
I have requested copies on two occasions and on both nothing has happened. I may need to formally request copies.