SAP scintigraphy (SAP scan)


Structure of the SAP molecule
Structure of the SAP molecule, reproduced from Nature 367, 338 – 345 (27 January 1994)

In 1987 Sir Mark Pepys invented a completely new test for amyloidosis called SAP scintigraphy or SAP scanning and Professor Philip Hawkins developed it for routine clinical use. This technique shows the distribution and amount of amyloid in the organs throughout the body without the need for biopsies, which can only sample a microscopic amount of tissue from a limited number of places. SAP scanning has revolutionised understanding of the natural course of amyloidosis and its response to treatment. Unfortunately the method is complex, requires sophisticated materials, technology and equipment and is very expensive.  As a result it is only available in the National Amyloidosis Centre, where its development was funded by the UK Medical Research Council for 11 years and its routine application is now funded by the UK Department of Health. Over the last 25 years over 10,000 SAP scans have been performed in the NAC.

The basis for the test is injection of a small amount of radio-labelled SAP which homes in on amyloid deposits throughout the body. This method is:

  • safe
  • painless
  • non-invasive
  • capable of providing a whole body overview
  • a very powerful technique for diagnosis and monitoring of amyloidosis

Why is the SAP scan more informative than biopsies?

Biopsies can show microscopic traces of amyloid in small tissue samples but cannot provide a whole body overview. Such an overview is necessary and informative in evaluating patients because most patients with systemic amyloidosis have amyloid deposits in organs that have not been biopsied and/or cannot be biopsied. Yet these organs may appear to be functioning normally. So SAP scanning is the only way to obtain a full picture of the extent of disease.

How does the SAP scan work?

Serum amyloid P component (SAP) is a normal blood protein, present in everybody, which is always present in amyloid deposits, in all types of amyloidosis because it binds strongly to amyloid fibrils of all types.

In healthy people there are very small quantities of SAP and it is only present inside the bloodstream, but not in the organs. In the bodies of patients with amyloidosis, in addition to the small quantities of SAP in the blood there are large quantities of SAP coating the amyloid deposits in the organs. In the SAP scan, all of this coating shows up clearly, as if it has been highlighted, or labelled.

This is achieved using radiolabelled SAP: human SAP molecules that have a radioactive “label” attached to them.

The radiolabelled SAP:

  1. Is injected into the patient.
  2. Homes in on the amyloid deposits and coats them, just like most of the SAP already in the body.
  3. Transmits a small amount of radioactive signal.

This signal is picked up using a detector called a gamma camera. All body parts where radioactive signal is detected must contain amyloid deposits.

So a very clear picture is obtained of the location and quantity of the amyloid deposits in organs throughout the body.

Stages of the SAP scan

For the purpose of this scan the NAC laboratory has isolated and fully characterised a supply of pure human SAP suitable for injection into patients. A trace of radioactive iodine is then attached to the SAP molecules- this is called radiolabelled SAP.

Before the scan:

Patient drinking potassium iodide before a scan
Patient drinking potassium iodide before a scan

The patient drinks a small amount of potassium iodide before receiving the injection of radiolabelled SAP.  This prevents the thyroid gland from absorbing the radioactive iodine. The clinic nurse gives the potassium iodide to patients when they come for their appointments. It should be taken twice daily for 3 days. This is because residues of the radio-isotope can remain in the body for up to 48 hours. the patient is given the small bottle to go home with.  The amount of potassium in the preparation is tiny and does not cause any health problems, even in dialysis patients and patients on thyroid medication.

Injection of tracer before the scan
Injection of tracer before the scan

A small amount of radiolabelled SAP is administered by injection into the patient’s vein. it is then necessary to wait for some hours while the radiolabelled SAP spreads out inside the body and homes in on the amyloid deposits. Unless the patient has been told by a doctor to restrict fluid intake, it is advisable to drink plenty of liquid between the injection and the scan to clear any residue from the stomach and give a better picture. The patient should empty his bladder before the scan.

During the scan:

A patient undergoing SAP scan
A patient undergoing SAP scanning

The scan is performed either the day after or 2-3 hours after the injection of the radiolabelled SAP protein. The patient is scanned on an open device called a whole body gamma camera scanner. The scan takes place while lying flat, still and fully clothed for about 25 minutes on the scanner. A technician stays in the room throughout the procedure and a carer may also stay, if desired.

After the scan:

NAC doctors view the images obtained from the scanner which provide invaluable information on amyloid deposits throughout the body. The patient should continue to drink the potassium iodide twice daily for 48 hours after the scan. Repeat scans can monitor progress and detect changes in the amount of amyloid and response to treatment over months and years.

Safety considerations

The SAP scan is safe and painless. No adverse effects have been observed from more than 10,000 scans that have been performed at the NAC over the past 25 years.

The SAP injected is obtained from healthy blood donors. It is then purified, treated and tested to minimise any risk of contamination or infection.

The radiation exposure is minimised by administration of potassium iodide before, during and after the scan.

The dose of radioactivity received during a scan is very small, about the same as received from a back X-ray. To put this into perspective, a patient living in London who has 2 SAP scans per year may receive less radiation than people living in some parts of South West England, where background environmental radiation levels are a little higher than those in London.

The scanner is not an enclosed “tunnel” and there is no discomfort or danger of claustrophobia .

Importance of the SAP scan

The information gained from SAP scanning has helped patients by adding considerably to our understanding of amyloidosis. SAP scans have shown that:

  • Amyloid is distributed very differently in different forms of the disease. For example, bone marrow amyloid deposits are only present in AL amyloidosis.
  • Amyloid may occur in organs not available for biopsy, such as the spleen and adrenal glands.
  • In some forms of amyloidosis previously thought to be limited to single organs, there are in fact extensive deposits around the body.
  • There is poor correlation between quantity of amyloid in a given organ and level of organ function.
  • Amyloid is distributed unevenly within organs.
  • Amyloid deposits may progress and regress at different rates in different organs.
  • Most importantly, amyloid deposits often regress when therapy controls the underlying disease causing the amyloidosis.
  • This usually leads to improved general health.
  • These findings have led to a more vigorous approach to treatment than existed previously.

An SAP scan is usually performed the first time a patient is assessed at the NAC. Then the scan is repeated every 6 to 12 months to monitor the course of the disease and guide the need for treatment. Using the information obtained from the SAP scan the NAC doctors are able to tailor individual treatment appropriately.

Unfortunately the SAP scan is not informative about amyloidosis in hollow or moving organs such as the heart and gut. Other imaging techniques are used to detect and follow the course of amyloidosis in these areas, and SAP scanning is important to look for and follow amyloid in other organs in patients with heart or gut amyloidosis. SAP scanning is also not useful for detection of amyloid deposits in the brain due to the relatively slow penetration of SAP into the brain.

Sequential SAP scans from a patient with AL amyloidosis. In 2005 the scan showed significant deposits in the liver and spleen. The scan in 2009 showed considerable shrinkage of the deposits after a good response to treatment. In 2011 there was a relapse and the scan showed amyloid building up, this time in the kidneys.
Reproduced from: Journal of Immunological Methods 384;Issues 1-2, 2012, 92-102