A Doctor's Guide to Nuclear Medicine

Barry E Chatterton MBBS FRACP DDU
Senior Director, Nuclear Medicine, Royal Adelaide Hospital

Definitions:

Nuclear Medicine is a medical speciality that uses the nuclear properties of elements (mainly radioactive but occasionally stable) in diagnosis or therapy of diseases. The most visible component of this is in the use of gamma-ray emitting radioisotopes to produce images (scans). There is also extensive use of in-vivo non-imaging diagnostic methods (eg breath tests) which use either stable or radioactive elements, a declining use of in-vitro diagnostic tests (eg radioimmunoassay), and use of elements decaying with gamma, beta and alpha radiation producing higher radiation doses as therapeutic agents

Because many of these radionuclides are delivered to their intended site by linking them to complex organic or biological molecules, and because of the change in the emotion generated by the word “Nuclear” in the 60 years of the specialty’s existence, the term “Molecular Imaging” is becoming more widespread in journals and special society titles.

Background.

Nuclear Medicine relies on the “tracer” principle, where the distribution of a substance depends on physical or chemical processes. The tracer material is itself, or is labelled with a radioactive material. The combination is usually referred to as a radiopharmaceutical. The most commonly used radioactive material used in conventional nuclear medicine is technetium 99m (99mTc), the chemistry of which allows its attachment to many molecules, allowing, in turn, concentration in multiple organs or processes (eg bone, heart, liver, kidney, lung etc). It has an ideal g-ray energy for imaging, a half life long enough to allow preparations to last a working day, but short enough to minimise patient radiation exposure (typically similar to an X-ray of the corresponding region) by decaying to negligible amounts shortly after the end of the diagnostic process. For diagnostic (not therapeutic) doses of radiopharmaceuticals in the patient, there is no need for the surgeon to delay operating, as the radiation dose arising from the patient will be negligible.

Radioactivity is a property of the nucleus of the element in which the ratio of protons and neutrons in the element is such that an adjustment has to be made for the nucleus to be at the lowest energy state. This can be done by the release of an alpha particle (2 protons and 2 neutrons, a heavy, charged particle, which gives a large radiation dose, and travels less than a millimetre within soft tissue, and cannot be detected from outside the intact body. Alpha () emitters are therefore of potential use in therapy, but are of little use in diagnostic applications. Many heavy or natural radioisotopes (Uranium, Radium) are alpha emitters. Beta (ß) emission occurs from many of the frequently used radionuclides, and accompanies the transmutation of a neutron to a proton (ß-) from radioactive isotopes produced in a nuclear reactor, or positrons (ß+) from isotopes produced in cyclotrons. These latter tracers are more usually used in positron emission tomography (PET). ß- travel several mm in tissue, again causing a radiation dose to tissue, but not readily detected at the surface.

The radiotherapeutic effects of many radionuclides (eg 131Iodine) are caused by their ß emissions.

Gamma () rays are electromagnetic waves physically undisguisable from X-rays and pass relatively freely through tissue, and causing least radiation effect of these radiations. As they will exit the body and are relatively easily detected, they are of most use in non-invasive imaging using gamma cameras.

The time-activity relationship of uptake or transit of tracer in or through an organ may be determined with dynamic studies (eg gastric emptying). Nuclear medicine particularly lends itself to quantitative studies. Frequently, the distribution of tracer in the process of interest at one time point “static image” is all that is required (eg presence or absence of a tumour). Computed Tomography is very commonly performed in nuclear medicine. This is commonly performed with conventional tracers SPECT, Single Photon Emission Computed Tomography, or PET, Positron Emission (computed) Tomography. When looking at nuclear images, it should be remembered that they are not “shadows” but images of radioactive organs. The display, therefore is as if the observer were “viewing” “luminous” organs, and therefore in an anterior image, the patient’s left is on the observer’s right, but from posterior right is on right.

Diagnostic nuclear medicine interacts with many medical specialties.

Most frequently, the radiopharmaceutical will either localise in the organ of interest, and so diagnosis is based on disturbance in the anatomy or dynamics of the organ, or it will localise in the pathological process of interest (eg cancer, infection).

The following topics are arranged in organ systems preceded by the relevant radiopharmaceutical

Bone

Radiopharmaceutical: Tc99m bisphosphonate (adsorbed to actively mineralising bone)
Uptake: local blood flow, mass of bone, and metabolic activity

Infection.

Flow/metabolism increased within hours (before x-ray changes). Other imaging may show soft-tissue changes of oedema early. Each of 3 phase study (dynamic blood flow: 0-1min, blood pool showing tissue hyperaemia;1-2min, and delayed images; 2-3hr after injection) showing increased activity in the bone (not adjacent soft tissue). In acute oedema and tamponade, perfusion may be compromised (cold scan)- indication for urgent decompression. Bone may remodel and show increased uptake for an extended period after any insult, therefore less valuable for the follow-up of osteomyelitis or diagnosis after trauma (surgery). Other tracers, which localise in inflammatory tissue (67Gallium or labelled leucocytes), are likely to be more specific (Fig 1). Fig 1 - click to enlarge and view caption (37kb)

Fracture.

Fig 2 - click to enlarge and view caption (14.5kb) On occasion, the fracture line is not easily seen on X-ray in association with undisplaced bone (including athletic stress fractures or osteoporotic insufficiency fractures). Three phase techniques will see local metabolic response in a matter of hours in the young, or 2-3 days in the elderly (Fig 2).
The bone scan will show soft tissue involvement in conditions such as tendonitis (fig 2b).
Fig 2b - click to view with caption (6kb)
 

Avascularity.

Avascularity - either post trauma (femoral neck) or spontaneous (Legg-Perthe's disease - Fig 3). Is seen early as absent uptake, but later as increased uptake as revascularization and remodelling occurs. (MRI marrow signal is often abnormal early) Post traumatic heterotopic calcification may be seen before significant x-ray abnormalities, and its progress monitored. Fig 3 - click to enlarge and view caption (51.2kb)
 

Tumours.

Primary or metastatic malignancies usually have bony remodelling at periphery - increased uptake. MRI shows soft-tissue component, particularly in primary. Some benign lesions show increased uptake on the bone scan, (eg the classically painful and difficult to diagnose osteoid osteoma is very “hot” on the bone scan).

Fig 4 - click to enlarge Malignant lesions are seldom “cold” (Fig 4), and bone scanning is performed very frequently to diagnose or monitor metastatic disease. Both lytic and sclerotic metastases are “hot” on the bone scan (Fig 5) except multiple myeloma, which may have normal bone scan appearances.
The whole body bone scan is sensitive in screening the whole skeleton for metastases (although the yield may be low in early stage of most malignancies and not routinely indicated). Other commonly occurring pathologies (eg vertebral crush fractures, arthritis) will also give an abnormal scan, but accuracy of the reporter is often enhanced by experience and pattern recognition. Directed Plain X-ray, CT and MRI add specificity. The whole body scan is useful in following progression or therapy of established metastatic disease. Awareness of the “flare” phenomenon (increased visualisation of previously invisible, but successfully treated healing metastases)is needed. Fig 5 - click to enlarge and view caption (23kb)
 

Paraneoplastic phenomena, such as hypertrophic pulmonary osteoarthropathy, or the results of malignant hypercalcemia (lung, stomach and increased bone uptake), may also manifest on the bone scan.

Urinary Tract.

Radiopharmaceuticals:
99m
Tc-DTPA - cleared by glomerular filtration
99mTc-MAG3 - cleared by glomerular filtration and tubular excretion - more useful if renal function is impaired or in children.
99m
Tc-DMSA - accumulates in renal tubules, gives map of functioning renal tissue, useful in cortical masses or scarring.

Function.

Relative renal function dictates the uptake or clearance of radiopharmaceuticals in the kidney in proportion to local renal function, and therefore their relative contribution to renal function may be derived from the scan. Global GFR (total renal function) can calibrate this by measuring plasma clearance of activity. Follow up and surgical decisions may then be made on quantitative data.

Renal artery stenosis.

May be recognised by its effect on the inflow into and subsequent reduced function of the affected kidney. This is enhanced by prior administration of Angiotensin Converting Enzyme inhibitor (Fig 6). The technique is useful for screening, but also monitoring the effect of revascularisation surgery. Functional results of renal artery stenosis are shown by changes in size or function, rather than the anatomical lesions shown by conventional imaging, which may not be associated with significant functional change. Fig 6 - click to enlarge and view caption (17kb)
 

Infection.

Fig 7 - click to enlarge and view caption (26kb) Particularly in paediatric patients, localised functional disturbance in renal parenchyma with prognostic significance (often a prelude to scarring in children with reflux) may be demonstrated with 99mTc-DMSA scanning (Fig 7) and prompt decisions regarding intervention. Reflux in children may be assessed by direct (activity introduced into the bladder via catheter) or indirect (99mTc MAG3 excreted by kidney) cystography. This has a radiation dose advantage on the x-ray techniques.

Obstruction.

Dilated renal collecting systems may not be “obstructed” (normal function, good prognosis) Interventional decisions may be assisted by the diuretic renogram which uses a rapidly cleared radiopharmaceutical to fill, then “stress” the dilated system with diuretic. The dilated, but not obstructed system, clears promptly (typically half –clearance time < 13min. See Fig 8 and movie 1). The differential renal function is also important to confirm loss if present. Fig 8 - click to enlarge and view caption (38kb)
 

Transplant.

In the early post-operative period, perfusion to the transplant may be determined. Acute tubular necrosis is usual and rapid fading of filtered tracer will occur without excretion. Urinary leaks or obstruction may also be diagnosed and differentiated from lymphocele. Later, serial studies may be used to monitor rejection.

Testicular imaging.

This test for torsion has been superseded by Doppler ultrasound (although rapid surgery without investigations may give the best chance of testicular survival).

GI imaging

Radiopharmaceuticals:
99m-
Tc colloid (reticulo-endothelial function)
99m-Tc red cells (acute GI bleeding, hepatic haemangiomata)
99m-
Tc heat-damaged red cells (splenunculi)
99m-Tc-IDA derivative (excreted in bile)
Na99m-TcO4 (Meckel’s Diverticulum)
99m-Tc –colloid or 111In labelled leucocytes (inflammatory bowel disease)
Labelled anti-CEA antibodies (colon cancer)

GI Motility.

Radiopharmaceuticals:
labelled foodstuffs, (liquid, solid, fats, proteins, carbohydrates or fibre) usually labelled with 99mTechnetium, 111Indium and 67Gallium.

Liver masses.

Fig 9 - click to enlarge and view caption (48kb) The traditional colloid liver scan (depending on phagocytosis of particles in liver Kupffer cells and splenic sinusoids) is obsolete other than for confirming focal nodular hyperplasia (Fig 9). Depending on the radiopharmaceutical, masses may have more uptake (“hot”) or less (“cold” Fig 10) than the surrounding liver, or be invisible. For some common patterns see table 1. Haemangiomata are common and have typical appearances on ultrasound and CT scans (biopsy being unhelpful and contraindicated). If atypical, and if not thrombosed, they may be shown to slowly fill their vascular spaces if scanned with labelled red cells (Fig 11). For these and most lesions, a diameter of >1.5cm is needed for confidence. SPECT improves the contrast. Very few other lesions (vascular haemangiosarcomata) show similar activity. Fig 10 - click to enlarge and view caption (33kb) Fig 11 - click to enlarge and view caption (44.5kb)
 

Table 1

 

Colloid

Red Cells

IDA derivatives

Octreotide

MIBG

Labelled anti-CEA antibody

FDG

Hepatocellular carcinoma

-

-

-

+/-

-

-

++

Adenoma

-

-

+/-

-

-

-

+

Haemangioma

-

++

-

-

-

-

-

Focal nodular hyperplasia

+

+

+

+

-

-

+

Metastasis

-

-

-

++*

+/-

++ (colorectal)

++*

Cyst

-

-

-

-

-

-

-

Neuroendocrine tumour

-

-

-

++*

+/-

-

+/-

Splenic tissue (splenuculus)

++

++ (heat-damaged)

-

+

-

-

-

Biliary function.

99mTc IDA –derivatives are useful in assessing biliary tract disease. Visualisation of the gall bladder an hour after injection (enhanced by 2mg iv morphine to cause sphincter of Oddi contraction if indicated) virtually excludes acute cholecystitis (Fig 12). Quantitative studies may be useful in patients in whom biliary dyskinesia is a problem (gall-bladder ejection fraction following fatty meal or iv cholecystokinin is normally >40%). Post-traumatic and post surgical biliary leaks are readily assessed (Fig 13, movie 2). Following liver transplantation. Scanning after administration of a 99mTc IDA derivative can demonstrate adequacy of perfusion, uptake by liver parenchyma, excretory function and patency of biliary channels. Serial imaging is particularly useful. Fig 13 - click to enlarge and view caption (37.6kb) Fig 12 - click to enlarge and view caption (16kb)

Spleen.

Fig 14 - click to enlarge and view caption (43.7kb) Autologous red cells labelled with 99mTc and damaged by heating to 49°C for 20 minutes are taken up very avidly by splenic tissue Following relapse of conditions treated by splenectomy, (spherocytosis, ITP), regenerating splenic rests or splenunculi are often to blame. This is the procedure of choice to localise these splenic rests (Fig 14).
 

Apart from the exclusion of splenic infarction (wedge–shaped defects often in an enlarged spleen), most indications for splenic colloid imaging are obsolete. It has no part to play in trauma.

Radionuclide tests lend themselves to quantitation, and assessment of GI motility is an ideal indication Pharyngeal clearance studies are seldom performed, but may be useful indications for oesophageal clearance studies include anatomical (stricture, hiatus hernia but not suspected malignancy) neuromuscular (spasm, achalasia) or reflux. Quantitative oesophageal clearance (Fig 15) studies often displayed as functional images where the vertical position of the radionuclide is plotted against time, which gives a image of the clearance of activity from the oesophagus. Slowing of transit, sites of hold-up, or reflux are easily demonstrated. Fig 15 - click to enlarge and view caption (48.9kb)
 
Fig 16 - click to enlarge and view caption (34.2kb) Movie 3b: Antral peristalsis (192kb movie) Movie 3a: Gastric emptying - (529kb movie) Radionuclide gastric emptying is the “gold standard” in gastric emptying assessment. It is often useful simultaneously follow the emptying of both solid and liquid components of a meal (Fig 16). Indications include the assessment of possible gastroparesis, unexplained nausea and vomiting, reflux and after surgery.

Bowel.

Fig 17 - click to enlarge and view caption (53kb)Small bowel transit (most simply mouth-caecum transit time) is readily studied by radionuclide techniques, although the indications for this are limited. Colonic transit studies are much more frequently performed in the assessment of constipation, giving a readily quantifiable assessment of bowel transit, and the site of hold-up. The agent of choice is 67Gallium citrate because of its half-life. Daily scans are performed, with the centroid of activity plotted, and the rate of clearance measured. Obstructed defaecation is readily distinguished from more generalised motility disturbances (fig 17).

Haemorrhage.

In obscure anaemia, the faecal excretion of 57Cr autologous red cells gives precision of better than 1ml/day (the same technique can measure menstrual loss if this is a differential). This has no localising ability.

If the bleeding is acute and rapid, then localisation of the bleeding site is feasible. Autologous erythrocytes are labelled with 99mTc and reinjected. Bleeding rates of 0.5-1 ml/ min should be identifiable in the GI tract. It is important that images are taken serially (at short intervals of no more than a few minutes movie 4) to localise the bleeding (Fig 18) If the patient is imaged only several hours after beginning, then the extravasated activity will have moved distally, and redundantly confirm that the patient was bleeding. In the paediatric or young adult population, if Meckel’s diverticulum is considered then Na99mTc04 may be used. It is taken up by excretory epithelium, (particularly gastric mucosa) and will localise within a few minutes in native and ectopic gastric mucosa, adjacent to which is the ulcer causing bleeding. Fig 18 - click to enlarge and view caption (30.2kb)
 

Inflammatory bowel disease.

May be difficult to assess in activity or extent by conventional techniques. Leucocytes (mixed or granulocytes) localise at sites of active bowel inflammation and are shed into the lumen. Imaging (fig 20) and counting excreta can both localise and score disease activity.

Non imaging nuclear techniques may be used in the investigation of absorption: The Schilling test (vitamin B12) is affected both by gastric (intrinsic factor) or terminal ileal (specific receptors) disease, either medical or post surgical.

Note: From 30-Jun-2009 Schillings tests will be unavailable due to cessation of manufacturing of radiolabelled vitamin B12

Breath testing for malabsorption of fat (triglycerides, triolein) is also well established.

 99mTc-monoclonal antibody (CEA_Scan) has been shown to be useful in the localisation of recurrent and metastatic colon cancer. It is less accurate than 18FDG PET.

Fig 20 - click to enlarge and view caption (42.2kb)

Inflammation and infection22,23

Radiopharmaceuticals:
67
Gallium citrate (non-specific)
99mTc-colloid
99mTc-Exametazime
111In-oxine labelled leucocytes
99mTc-antileucocyte antibodies
99mTc-labelled immunoglobulins
Fig 21 - click to enlarge and view caption (46.2kb) These share many pathophysiological pathways, and no absolutely specific agent exists. Nevertheless, labelled granulocytes in particular appear to accumulate in areas of acute inflammation, and help localise this if there is acute leucocytic infiltration. Chronic inflammation (infection) is less likely to have leucocytic infiltration, and therefore labelled leucocytes may not reveal these. Particular use has been made in determining infection in “violated” bone, and inflammatory bowel disease, but the technique is useful in localising acute inflammation anywhere Abscesses are readily seen (Fig 21), and acute appendicitis is readily visualised (fig 22), although anatomical imaging is usually used first. Pyrexia of unknown origin without suspected focal sepsis has a poor yield with these investigations. Fig 22 - click to enlarge and view caption (33.4kb)
 

Endocrinology.

Radiopharmaceuticals:
Na99mTc04
131I (thyroid)
123I MIBG (Meta-iodo-benzyl-guanidine, adrenal medulla)
131
I cholesterol (adrenal cortex)
99m
Tc-Sestamibi (MIBI) (parathyroid)
99m Tc DMSA(V)(Medullary carcinoma thyroid)
111
In Octreotide (nuroendocrine tumours)

Thyroid.

Fig 23 - click to enlarge and view caption (18.2kb) Nuclear techniques remain relevant in the assessment of thyroid structure and function. Although ultrasound and fine needle aspiration are most frequently used to determine the nature of palpable nodules, assessment of global thyroid uptake (most conveniently with Na99mTc04 may give useful information about the function of nodules). Malignancy is less common in functioning than “cold” nodules (fig 23), and prior to surgery for hyperthyroidism, the exclusion of an autonomously functioning “hot” thyroid nodule, or the lack of uptake in viral or drug induced thyroiditis may be worthwhile (fig 24). Whole body iodine scanning (most usually 131I) is indicated in the follow up of follicular and papillary thyroid cancer after radionuclide ablative treatment (Fig 25). Medullary thyroid cancer arises from a different cell line and is not iodine avid. Despite these thyroid cancers having less uptake than normal thyroid, they have far more uptake than other tissues, and will concentrate radioiodine for diagnostic or therapeutic purposes. Use in recurrence of thyroid cancer tends to be complementary to thyroglobulin assay. Fig 24 - click to enlarge and view caption (37.4kb)Fig 25 - click to enlarge and view caption (37.4kb)
 

Parathyroid.

Fig 26 - click to enlarge and view caption (29.1kb) Although open surgery is very effective in locating and treating hyperparathyroidism, it may fail in 5-10% of operations. Minimally invasive parathyroid surgery is also becoming more common. Both of these are indications for pr-operative parathyroid imaging. The sensitivity of CT, MR, ultrasound and MIBI scanning is similar (70%-90%) The nuclear scan is particularly useful in demonstrating mediastinal lesions and in the post –surgical situation, where conventional imaging is difficult because of scarring. Both the thyroid and parathyroid will take up the current agent of choice, MIBI but the parathyroid lacks the P-Glycoprotein mechanism which clears sestamibi from the thyroid, hence parathyroid tissue retains activity for several hours. Some thyroid nodules also lose this mechanism, and therefore they may be a differential diagnosis for focal uptake in the neck (Fig 26).

Adrenal cortex.

131I or 75Se cholesterol is incorporated into the biochemical pathway manufacturing steroids in the adrenal cortex. In selected cases these tracers will confirm the function of a known mass, or localise a functioning lesion suspected biochemically. Availability of these tracers is limited.

Neuroendocrine tumours.

Fig 27 - click to enlarge and view caption (43.4kb) MIBG-usually labelled with 123I is a catecholamine precursor, which is taken up in phaeochromocytoma (faintly in normal adrenal medulla and adrenergic nerve endings), and some other malignancies (eg carcinoid, neuroblastoma). It may be used in the confirmation of the nature of incidentally found lesions, as well as detecting those in hypertensive patients with appropriately abnormal biochemistry (Fig 27). Functioning metastases are also localisable.
 
Octreotide (a somatostatin analogue usually labelled with 111In) is frequently taken up in primary and metastatic carcinoid tumours (Fig 28) and other neuroendocrine tumours such as gastrinomas and pituitary neoplasms. Fig 28 - click to enlarge and view caption (14.3kb)
 

Other tumour localising agents.

Radiopharmaceuticals:
99mTc-MIBI
201Tl
67Ga
99mTcDMSA(V)
Fig 29 - click to enlarge and view caption (31.5kb)

Many radiopharmaceuticals will localise within tumours as a result of their intrinsic biodistribution. 99mTc-MIBI is initially distributed by blood flow and metabolic activity. It has been shown to be useful in the diagnosis of primary and recurrent breast cancer, particularly in mammographically dense breasts (Fig 29). The technique is not sensitive enough for local staging. Uptake has also been shown in sarcomata and lung cancers. 99mTcDMSA(V) is also a non-specific tumour scanning agent, shown to be useful in medullary thyroid cancer (Fig 30), and may detect recurrences indicated by calcitonin increases. 201Thallium whole body scans may detect iodine non-avid metastatic thyroid malignancy, sarcomas and brain tumours. Nevertheless it is likely that 18FDG PET scanning is of equal or better utility in most of these indications.

Fig 30 - click to enlarge and view caption (11.4kb)

Lymphoscintigraphy

Radiopharmaceuticals:
99m
Tc antimony colloid
99mTc sulphur colloid
99mTc nanocolloid
Fig 31 - click to enlarge and view caption (52kb) Soluble or fine colloidal materials injected interstitially will be taken up into lymphatic vessels and subsequently particulate material will be taken up into draining lymph nodes, mimicking the presumed behaviour of micrometastases.
 
Sentinel lymph nodes are nodes receiving direct drainage from the tumour, and are regarded as those most likely to be involved with (micro) metastases and predictive of the status of the entire nodal basin. The technique has found most use in cutaneous melanoma (Fig 31) and breast tumour (Fig 32), although head and neck (movie 5), vulval and internal cancers (injected endoscopically) have been studied by this technique. When staging the axilla in breast cancer, many studies have shown concordance between the sentinel node and axillary status of better than 95%. Localisation of lymph nodes is best performed with a combination of radioactive tracers and blue dyes. Fig 32 - click to enlarge and view caption (30.4kb)
 

Pulmonary embolism

Radiopharmaceuticals:
99mTc-MAA
99mTc-aerosol
Pulmonary embolism is a frequent post operative complication, and confirmation has important therapeutic implications. The ventilation-perfusion (V/Q) scan has been a mainstay of diagnosis for many years, and continues to have a very high predictive value with normal or scans with mismatch (Fig 33). Its specificity is reduced if there are chest-x-ray abnormalities, and in this situation, CT pulmonary angiography will likely give more information, but has a number of contra-indications. Fig 33 - click to enlarge and view caption (32.9kb)
 

Therapy.

Radiopharmaceuticals:
131
I
131I MIBG
90Y Octreotide
153Sm EDTMP
89Sr
131I-antibodies

Differentiated thyroid malignancy was the original condition treated by radioisotopes, which remain a mainstay of treatment. Metastatic disease is treated by at least two doses of radioiodine (131I). The first dose is needed to ablate the normal thyroid, rests which remain no matter how extensive the surgery. The metastases are usually less avid than normal thyroid tissue. Scanning should be performed after therapeutic doses, as sensitivity for thyroid metastases (Fig 25) is greater. The patient should have an elevated TSH at the time of iodine administration (cease thyroid hormone therapy or administer synthetic TSH).

For hyperthyroidism as an alternative to medical or surgical therapy, the larger the dose of radioiodine administered, the more rapidly control is reached. Ultimately most patients will become hypothyroid. Debate continues regarding the role of radioiodine in the therapy of multinodular goitre.

Neuro-endocrine tumours, may be treated with 131I-MIBG (particularly phaeochromocytoma and neuroblastoma. Octreotide derivatives labelled with 111In, 90Y or other radionuclides have shown some effectiveness in avid tumours. 32P is a therapeutic alternative to reduce the re-accumulation of malignant pleural effusion or ascites.

Metastatic disease in the liver is supplied mainly by the hepatic artery (predominant portal flow for normal liver), therefore radiopharmaceuticals which will embolise a capillary circulation will preferentially localise in metastatic disease after injection into the hepatic artery. 90Y labelled ceramic microspheres (SIR-Spheres), Fig 34 have has some success in this indication (movie 6), and similarly 131I-labelled lipiodol in hepatocellular carcinoma. Painful bony metastases will localise other bone-seeking radiopharmaceuticals using the same mechanism as bone-scanning agents. 153Sm EDTMP and 89Sr have been shown to be useful in palliation. Labelled monoclonal antibodies are effective in treating certain lymphomas and specific antibodies are being developed for other indications. Fig 34 - click to enlarge and view caption (14.4kb)

Cardiology

Radiopharmaceuticals:
Perfusion scanning
201Thallous chloride
99mTc Sestamibi
99mTc tetrofosmin
Gated Blood Pool Scanning
99mTc labelled Red Cells
Myocardial infarct scanning
99mTc Imidiodiphosphate
Cardiac Shunt studies
Left-Right
99mTc labelled Red Cells
Right-Left
99mTc-MAA

Nuclear cardiology is one of the main indications for nuclear medicine studies. The major areas of study include assessment of blood flow to the heart muscle itself (perfusion scanning), the contractile function of the heart muscle, and occasionally the determination of whether a myocardial infarct has occurred recently.
If a patient has typical symptoms of angina, and intervention to improve blood-flow to the heart is planned, then generally a coronary angiogram will be performed. This is an invasive test which usually involves the passage of a catheter.

Nuclear Perfusion Scanning.

In some general departments, this may account for half the workload. Although different techniques may be used, the general principle involves the comparison of the myocardial distribution of a tracer under conditions of stress (hyperaemia) with the distribution at rest. The differences in these images might suggest :

The stressors used are typically:

Each of these stressors is associated with a small risk, and patient informed consent is important.

Radiopharmaceuticals:

Indications:

Myocardial perfusion scanning is used usually to:

The images obtained are usually tomographic (slices) displayed in a standardised orientation (not anatomical) related to the long axis of the left ventricle which is >80% of myocardial bulk. These may also be related to typical distribution of coronary artery territory, but anomalous vessels cannot be recognised on these studies. Displays may be enhanced by “bullseye” images, which display the entire myocardium in one picture of concentric slices, apex to the centre.
The images below give some examples of these.
NOTE: The usual jargon used for defects is “reperfusing” ie changes between rest and stress implying relatively ischaemic but viable tissue, and “fixed” implying myocardial scar.

Fig 35. Normal SPECT images demonstrating slice orientation, typical appearance and "bullseye" dispaly
Fig 35a - click to enlarge and view caption (188kb) Fig 35b - click to enlarge and view caption (78kb) Fig 35c - click to enlarge and view caption (20kb)

Fig 36 Normal gated images - slices and 3D

Fig 36a - click to enlarge and view caption (190kb) Fig 36b - click to enlarge and view caption (202kb)
Fig 37 - click to enlarge and view caption (67kb) Fig 38 - click to enlarge and view caption (79kb) Fig 39 - click to enlarge (79kb)
Figs 37-39: Reversible myocardial ischaemia in LAD, circumflex artery and RCA territory
Fig 40: A polar map, to quantify inferior ischaemia Fig 40 - click to enlarge and view caption (145kb)
Fig 41: Cardiomyopathy with large LV Fig 41a - click to enlarge and view caption (120kb)

Gated Blood Pool Scanning. (gated heart pool scanning)

By acquiring images synchronised with the heart beat (ECG), sufficient radioactive counts may be collected to produce an image of a typical cardiac cycle. This principle was seen above in the myocardial perfusion scanning section, where the movement of the myocardium itself was monitored. Although those images may be used to estimate an ejection fraction, this depends on a number of geometric assumptions, which may be incorrect, particularly in disease, and therefore the precision of ejection fractions obtained from perfusion scans is not high, particularly if they are to be used to monitor the progress of a patient.


If the blood (usually the red-cell component) rather than the myocardium is labelled, then the ejection fraction may be estimated from the counts ejected per cardiac cycle, rather than the geometry. This is more accurate and reproducible for the left ventricle. Focal and general movement abnormalities may also be seen.


The major indication is in the assessment of cardiac function in oncology, when cardiotoxic anthracycline chemotherapy is administered to the tolerance of the patient. Cardiac function needs to be monitored. The technique is also used in the workup before cardiac transplantation. Typical precision of LV ejection fraction (Normal 50%-80%) is 5%. Computer processing of the dynamic data is often used to produce “functional” images (figs 42b, 43b), showing the phase and amplitude of contraction so that the dynamic data may be represented on a static picture. Additional analysis of the volume time curve can also provide additional information such as peak filling rate, time to peak filling and peak ejection rate (fig 44).

This technique is most useful to determine LV function. For RV function, a “first pass” study allows the estimation in a beat-by-beat technique which removes the interference of overlying cardiac chambers.
Fig 42 - click to enlarge and view caption (276kb) Fig 42b - click to enlarge and view caption (83kb)

Fig 42:

Normal GBPS scan and curves

Fig 43 - click to enlarge and view caption (280kb) Fig 42b - click to enlarge and view caption (100kb)

Fig 43:

Low LVEF with dyskinesia and apical aneurism

 

Fig 44:

LV filling curve

Fig 44 - click to enlarge and view caption (53kb)

Myocardial infarct scanning.

Fig 45b - click to enlarge and view caption (43kb)
Several radiopharmaceuticals, most notably the bone seeking radiopharmaceutical, 99mTc imidodiphosphate, localise in recently necrotic myocardium. If the standard ECG or biochemical tests of myocardial necrosis are not helpful, an IDP scan 2 hr ± 6 days after the acute event may help confirm recent infarction.
Fig 45a - click to enlarge and view caption (43kb)
Fig 45c - click to enlarge and view caption (43kb)

Cardiac shunt studies

Confirmation of shunting from the left to the right side of the circulation (eg atrial septal defect), and quantification of this may be simply done in a study taking a few minutes. Rapid frames are taken following IV injection of tracer. Early recirculation to the lungs implies shunting of blood. The ratio of blood flow through the systemic to pulmonary circulation (QP/QS) may be calculated.

Fig 46a - click to enlarge and view caption (67kb) Fig 46b - click to enlarge and view caption (67kb) Fig 46c - click to enlarge and view caption (55kb)
Fig 46: QP/QS curve.

If the shunt is in the opposite direction (venous to arterial side, reversal in VSD, AV shunting in the lungs), then 99mTc MAA, used in lung scanning, will bypass the pulmonary circulation, and lodge in the next capillary bed (brain and kidneys in particular at rest). The proportion shunted may be easily calculated.

Fig 47: R-L shunt. Fig 47 - click to enlarge and view caption (13kb)

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