Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

310

—In cases of

201

Tl- and

99m

Tc-sestamibi, images are obtained after adminis-

tration and may be repeated at 3 hours.

—Images are then recorded in either a whole body or spot view format. In

the latter case, imaging should be performed for 5–10 min over several

areas: neck, chest spine, pelvis and proximal extremities in both the

anterior and posterior projections. For the skull, a posterior image should

be considered. For images with a whole body camera, the scan speed

should be slow, usually less than 10 cm/min, and appropriate to the count

rate.

5.7.3.7. Interpretation

Assess the size, shape and location of any areas of tracer uptake that

correspond to normal or abnormal thyroid tissue, more particularly in the

anterior neck area. Note also the tracer distribution in the residual thyroid

tissue. The study should be compared with any prior scan and correlated with

the recent thyroglobulin assay.

Activity in the gastro-intestinal tract, including the salivary and nasal

glands, and the genito-urinary tract is considered normal, while tracer locali

zation in the head and neck, liver, lungs and bones is considered to be due to

metastatic deposits or functioning thyroid remnants. Uptake in the thymus in

young patients should be recognized as normal.

BIBLIOGRAPHY TO SECTION 5.7.3

ALONSO, O., MUT, F., LAGO, G., Double-phase technetium-99m-sestamibi scanning

to evaluate nodular thyroid malignancy, J. Nucl. Med. 37 (1996) 1919–1920.

BECKER, D., et al., Procedure guideline for extended scintigraphy for differentiated

thyroid cancer: 1.0, J. Nucl. Med. 37 (1996) 1269–1271.

BLUMHARDT, R., WILLIAMS, S.C., MAY, C.C., Yearbook of Nuclear Medicine,

Radionuclides used in Thyroid Imaging: Review and Reference Notes on Nuclear

Medicine 1995–1996, Mosby (1995).

CAVALIERI, R.R., Nuclear imaging in the management of thyroid carcinoma, Thyroid

6 5 (1996) 485–492.

DIETLEIN, M., et al., Fluorine-18 fluorodeoxyglucose positron emission tomography

and iodine-131 whole body scintigraphy in the follow-up of differentiated thyroid

cancer, Eur. J. Nucl. Med. 24 (1997) 1342–1348.

5.7. NUCLEAR MEDICINE IMAGING STUDIES IN ENDOCRINOLOGY

311

GARIN, E., et al., Use of indium-111 pentetreotide somatostatin receptor scintigraphy

to detect recurrent thyroid cancer in patients with detectable iodine uptake, Eur. J. Nucl.

Med. 25 (1998) 687–694.

KOIZUMI, M., et al., Scintigraphic detection of recurrence of medullary thyroid cancer,

Ann. Nucl. Med. 9 2 (1995) 101–104.

LEAROYD, D.L., et al., Technetium-99m sestamibi scanning in recurrent medullary

thyroid carcinoma, J. Nucl. Med. 38 (1997) 227–230.

MAXON, H.R., et al., Relation between effective radiation dose and outcome of

radioiodine therapy of thyroid cancer, New Engl. J. Med. 309 (1983) 937–941.

READING, C.C., GORMAN, C.A., Thyroid imaging techniques, Clin. Lab. Med. 13

(1993) 711–724.

SISSON, J.C., Selection of the optimal scanning agent for thyroid cancer, Thyroid 7 2

(1997) 295–302.

SUNDRAM, F.X., MACK, P., Evaluation of thyroid nodules for malignancy using

99m

Tc-sestamibi, Nucl. Med. Commun. 16 8 (1995) 687–693.

UGUR, O., et al., Comparison of Tl-201, Tc-99m MIBI and I-131 imaging in the follow-

up of patients with well-differentiated thyroid carcinoma, Nucl. Med. Commun. 17

(1996) 373–377.

5.7.4. Parathyroid scintigraphy

5.7.4.1. Principle

Hyperfunctioning parathyroid tissues are primarily due to parathyroid

adenomas (85–90% of cases) and hyperplasia of several or all the parathyroid

glands (10–15%). Carcinoma of the parathyroid is extremely rare (2% of

cases). Many centres have experience with

201

Tl- and

99m

Tc-pertechnetate

subtraction scans for parathyroid scintigraphy. The rationale is based on the

fact that

201

Tl, being a potassium analogue, is taken up by all tissues with high

cellularity and vascularity, including parathyroid adenomas and hyperplastic

parathyroid glands and the thyroid gland. The

99m

Tc-pertechnetate thyroid

image would then be subtracted from the

201

Tl image. However, many other

tissues can take up

201

Tl, mimicking parathyroid adenomas (e.g. thyroid

adenomas and cervical lymph nodes). Since the average parathyroid gland is

only 40 mg in size, it is not possible to see normal parathyroids by this

technique.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

312

Recent developments have shown that

99m

Tc-sestamibi and tetrofosmin

have an advantage in detecting abnormal parathyroid glands. Sestamibi washes

out of the normal thyroid more rapidly than out of abnormal parathyroid

glands. A persistent increase in tracer localization in the delayed views would

then be construed as hyperfunctioning parathyroid glands.

There are two problems with a direct subtraction technique. Firstly, it is

not possible to normalize the two images in a rigorous enough way to know

how much of one to subtract from the other, making subtraction subjective.

Secondly, there is always some slight movement between the two images. These

problems can be addressed by using a formal translation rotation programme

(a) to superimpose the two images and (b) to compare the two images using a

change detection analysis, the result of which is a colour coded probability map

where significant differences are displayed in red (P < 0.001) or orange (P

0.01). The use of different energy radionuclides also creates a problem. This

can be avoided by using

99m

Tc-pertechnetate thyroid imaging instead of

99m

Tc-

MIBI.

5.7.4.2. Clinical indications

Parathyroid scintigraphy can be used for:

(a) Localization of parathyroid adenomas;

(b) Localization of ectopic parathyroid adenomas.

5.7.4.3. Radiopharmaceuticals

The following radiopharmaceuticals can be used for parathyroid scinti-

graphy:

(a) Thallium-201 chloride:

— Physical half-life of 73 hours;

— Photopeak due to characteristic X rays of 68–80 keV (98%);

— Emission gamma rays of 135 keV (2%) and 167 keV (8%);

— Intravenous dose of 80–120 MBq (2–3 mCi).

(b) Tc-99m pertechnetate:

Pertechnetate is taken up by the thyroid and is subtracted from the

201

image. The dose is dependent on which radionuclide (

201

Tl- or

99m

Tc-

pertechnetate) is administered first – the dose is generally within 80–400

MBq (2–10 mCi). There are many reports on the sequence of adminis

tration of radionuclides (

201

Tl- followed by

99m

Tc-pertechnetate or vice

versa), each having advantages and disadvantages. Giving

201

Tl first is

5.7. NUCLEAR MEDICINE IMAGING STUDIES IN ENDOCRINOLOGY

313

preferred as it has lower energy as well as the ability to image the

mediastinum. The patient must, however, be properly instructed to

remain immobile throughout the procedure.

with an activity of 200–800 MBq (5–20 mCi).

5.7.4.4. Equipment

A gamma camera with a high resolution collimator is needed.

5.7.4.5. Patient preparation

No special preparation is needed. However, clear instructions should be

given to the patient regarding movement, particularly in

201

Tl–

99m

Tc-pertech-

netate digital subtraction scans. Sedation is sometimes inevitable.

5.7.4.6. Procedure

The following procedure is used for parathyroid scintigraphy:

(a) Thallium-201–Tc-99m pertechnetate digital subtraction scans:

— Position the patient in the supine position with imaging done in the

anterior projection and with the patient’s head immobilized.

— Set up the gamma camera to acquire images in a dual isotope study.

Digital data are acquired in a 256 × 256 matrix.

—Inject

201

Tl intravenously. Begin to acquire images of the mediastinum

between the heart and the thyroid in the

201

Tl energy window recorded for

3–5 min not later than 2–3 min after injection. After the upper

mediastinum image has been completed, image the entire neck for 15 min

with the collimator placed closer to the patient. The thyroid is now

centred.

— Inject Tc-99m pertechnetate intravenously. After 5 minutes, image the

neck with the same total count as the 15 minute

201

Tl image. The patient’s

immobilization should be maintained.

— Process the images by serial subtraction of 10% increments of the

pertechnetate image from the thallium image until the entire thyroid is

removed.

(b) Dual-phase

99m

Tc-sestamibi

— Position the patient in the supine position with their neck extended to

include the mediastinum in the FOV.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

314

—Inject

99m

Tc-sestamibi and after 15 min start the imaging for 10 min. This is

to be repeated every 15 min for the first hour, and at 2 and 3 hours post-

injection.

5.7.4.7. Interpretation

Normal parathyroid glands are not seen scintigraphically. Abnormal

parathyroid tissue usually presents as a focal area of increased tracer

deposition, which would become increasingly intense on the delayed views.

Hyperfunctioning parathyroid glands, more particularly parathyroid

adenomas, have a slow washout in comparison with the thyroid tissues. Hyper

plastic glands, on the other hand, have a more rapid washout than adenomas,

and are not visualized in late images.

The most common cause of a solitary focus of radioactivity pertaining to

the parathyroid is an adenoma. Parathyroid adenomas are usually seen unilat

erally. The presence of two abnormal glands strongly suggests parathyroid

hyperplasia since the prevalence of double adenoma is extremely rare (around

2–4% of patients with hyperparathyroidism). Change detection analysis is able

to identify adenomas down to 100 mg and four gland hyperplasia in patients

with renal failure with 87% accuracy.

BIBLIOGRAPHY TO SECTION 5.7.4

BEIERWALTES, W.H., Endocrine imaging: Parathyroid, adrenal cortex and medulla

and other endocrine tumours, Part II, J. Nucl. Med. 32 (1991) 1627–1639.

FINE, E.J., Parathyroid imaging: Its current status and future role, Semin. Nucl. Med. 17

(1987) 350–359.

GORIS, M.L., BASSO, L.V., KEELING, C., Parathyroid imaging, J. Nucl. Med. 32

(1991) 887–889.

GREENSPAN, B.S., et al., Procedure guideline for parathyroid scintigraphy, J. Nucl.

Med. 39 (1998) 1111–1114.

ISHIBASHI, M., et al., Comparison of technetium-99m MIBI, technetium-99m tetro-

fosmin, ultrasound and MRI for localization of abnormal parathyroid glands, J. Nucl.

Med. 39 (1998) 320–324.

NORMAN, J., CHHEDA, H., Minimally invasive parathyroidectomy facilitated by

intraoperative nuclear mapping, Surgery 122 (1997) 998–1004.

5.7. NUCLEAR MEDICINE IMAGING STUDIES IN ENDOCRINOLOGY

315

PONS, F., et al., Preoperative parathyroid gland localization with Tc-99m sestamibi in

secondary hyperparathyroidism, Eur. J. Nucl. Med. 24 (1997) 1494–1498.

WILSON, M.A., et al., Parathyroid localization scans: Cost effective and reduced

incidence of postoperative hypocalcemia, J. Nucl. Med. 28 (1987) 583.

5.7.5. Adrenal medulla scintigraphy

5.7.5.1. Principle

Adrenal medulla scintigraphy is primarily indicated for the evaluation of

functioning paragangliomas. These are catecholamine-secreting tumours

(paragangliomas, in particular pheochromocytomas, neuroblastomas, ganglio

neuroblastomas and ganglioneuromas). These paraganglionic cells belong to

the amine precursor uptake and decarboxylation (APUD) system and have the

ability to store catecholamines in intracellular cytoplasmic vesicles.

Meta-iodobenzyl-guanidine (MIBG) is an analogue of guanethidine and

norepinephrine. Localization of MIBG in adrenergic tumours is thought to be

via the energy dependent active amine transport mechanism and further

storage in the cytoplasmic storage vesicles in pre-synaptic adrenergic nerves.

However, MIBG does not bind to post-synaptic receptors and does not induce

a pharmacological response. MIBG also localizes to other organs with

sufficient sympathetic innervation (heart, salivary glands, spleen and

occasionally the colon).

5.7.5.2. Clinical indications

Adrenal medulla scintigraphy is used for:

(a) Localization of adrenal pheochromocytomas and extra-adrenal paragan-

gliomas;

(b) Localization of metastatic adrenal medullary cancer secondary to

pheochromocytoma;

secondary to pheochromocytoma;

(d) Evaluation of patients with suspected neuroblastomas;

(e) Evaluation of patients with carcinoid and medullary thyroid cancer, to

determine if there is a likelihood that

131

I-MIBG therapy would be of

benefit.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

316

5.7.5.3. Radiopharmaceuticals

MIGB is available labelled with either

123

I or

131

I. Because of

unfavourable dosimetry properties,

131

I-MIBG places a high radiation burden

on the adrenal medulla. It is recommended to block thyroid uptake with iodine

administration (saturated solution of potassium iodide (SSKI) or Lugol’s

solution) and this is continued for five days. Its disadvantage lies in the

requirement for delayed imaging.

Iodine-123 MIBG, on the other hand, shows some superiority in

visualizing the adrenal glands but is usually not available. Iodine-131 MIBG is

preferred in developing countries.

The dose of

131

I-MIBG is 20–40 MBq (0.5–1.0 mCi). Excretion is via the

kidneys, with about 85% being excreted unchanged in the urine.

5.7.5.4. Equipment

A gamma camera with a high energy, parallel hole collimator for

131

I-

MIBG is required.

5.7.5.5. Patient preparation

Patient preparation consists of the following:

(a) Check the patient’s current intake of medication. All the drugs in the

following list have been shown to interfere with MIBG uptake. All of

these should be discontinued from three days before the study:

— Tricyclic antidepressants (amitriptyline and imipramine);

— Decongestants (phenylpropanolamine and pseudoephedrine – common

in nose drops and cough mixtures);

— Sympathomimetics and amphetamines;

— Reserpine;

— Antipsychotics (phenothiazines);

— Calcium channel blockers;

— Adrenergic blockers (long acting beta blockers);

— Cocaine.

(b) Administer SSKI or Lugol’s solution one day prior to the study and

continue for five days, or 60 mg potassium iodide (KI) twice daily for five

days.

5.7. NUCLEAR MEDICINE IMAGING STUDIES IN ENDOCRINOLOGY

317

5.7.5.6. Procedure

Ensure that the patient has stopped all medications known to interfere

with the uptake of

131

I-MIBG.

Check if the patient has taken SSKI, KI tablets or Lugol’s solution prior

to the study.

Slowly inject 20–40 MBq (0.5–1.0 mCi)

131

I-MIBG intravenously over

s. Higher doses have been used post-operatively to look for residual

remnant tissues.

Acquire images for 20 min obtained at 24 and 48 h post-injection. Obtain

anterior and posterior spot views of the body from the skull to the pelvis. For

pheochromocytomas, anterior and posterior views of the mid-abdomen to

include the region of the adrenal glands are most important. An image at

min will show the renal excretion, which may be misinterpreted as adrenal

activity if there is pelvic retention of tracer.

5.7.5.7. Interpretation

The adrenal glands are usually either not identified or faintly identified

with

131

I-MIBG. A normal adrenal gland is visualized with

123

I-MIBG and with

therapeutic doses of

131

I-MIBG. Pheochromocytomas usually present as

unilateral focal tracer depositions. In general, most pheochromocytomas

demonstrate a more intense uptake than the liver (80%). The sensitivity is

reported to be in the range of 85–90% with a specificity of 95–99%. Computed

tomography scans or MRI are more accurate in detecting primary tumours of

the adrenal glands but they are inferior to MIBG in the detection of extra-

adrenal tumours, which account for about 10% of lesions. For neuroblastomas,

sensitivity is about 90–95% with 95–100% specificity. In detecting bone

metastasis, MIBG is superior to bone scans for neuroblastomas, while in

pheochromocytomas a bone scan is also required. Liver metastasis is difficult to

ascertain since MIBG is normally taken up by the liver, although

123

I-MIBG

allows this distinction to be made.

BIBLIOGRAPHY TO SECTION 5.7.5

BEIERWALTES, W.H., Endocrine imaging: Parathyroid, adrenal cortex and medulla

and other endocrine tumours, Part II, J. Nucl. Med. 32 (1991) 1627–1639.

FALKE, T.H.M., SANDLER, M.P., Classification of silent adrenal masses: Time to get

practical, J. Nucl. Med. 35 (1994) 1152–1154.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

318

GROSS, M.D., et al., Scintigraphic evaluation of clinically silent adrenal masses, J. Nucl.

Med. 354 (1994) 1145–1152.

MOZLEY, P.D., et al., The efficacy of I-123 MIBG as a screening test for pheochromo-

cytoma, J. Nucl. Med. 35 (1994) 1138–1144.

TENENBAUM, F., et al., Comparison of radiolabelled ocreotide and meta-iodibenzyl-

guanidine (MIBG) scintigraphy in malignant pheochromocytoma, J. Nucl. Med. 36

(1995) 1–6.

5.8. MUSCULOSKELETAL SYSTEM

5.8.1. Introduction

This section provides guidelines for nuclear imaging of the musculo-

skeletal system using

99m

Tc-methylene-diphosphonate (MDP) or hydroxy-

ethylene diphosphonate (HEDP) in a broad spectrum of diseases of the bone,

joint, muscle and musculotendinous unit. Bone infections can additionally be

imaged using

111

In-leucocytes and

Ga. Bone scan modes include whole body

planar scintigraphy, planar spot scintigraphy, SPECT, planar pinhole scinti

graphy and pinhole SPECT.

5.8.1.1. Radiopharmaceuticals

Technetium-99m MDP is universally used for bone scintigraphy. It is a

monoenergetic emitter of 140 keV gamma rays with a physical half-life of

6.02

hours and efficiently labels phosphonates or pyrophosphates, yielding

99m

Tc-MDP and

99m

Tc-HEDP among other compounds. These have a strong

avidity for hydroxyapatite crystals in the mineral phase of the bone, especially

at sites where new bone is actively formed as in the physes of growing bones

and fractures. The diphosphonate molecule is adsorbed onto the calcium of

hydroxyapatite in bone. Following intravenous injection,

99m

Tc-diphosphonates

are rapidly distributed in the extracellular fluid space and approximately half of

the injected dose is taken up by bone, with the unfixed portion excreted into

the urine by glomerular filtration. The amount of radiopharmaceutical

accumulated in bone at 1 hour after injection is 58% with MDP, 48% with

HEDP and 47% with pyrophosphate. The blood levels of HEDP are 10% at

hour after injection and continue to fall to 6, 4 and 3% at 2, 3 and 4 hours,

respectively.

The usual dose for adults is 740–1110 MBq (20–30 mCi) injected intrave-

nously. For markedly obese adults, the administered dose may be increased to

5.8. MUSCULOSKELETAL SYSTEM

319

11–13 MBq/kg (0.3–0.35 mCi/kg). For children, the administered dose is 9–

MBq/kg (0.25–0.3 mCi/kg), with a minimum of 40–90 MBq (1.1–2.4 mCi). In

children, the administered dose can be scaled on the basis of body surface area.

Bone radiopharmaceuticals are subject to oxidation, hence care should be

taken to avoid introducing air into the multidose vial. Quality control should be

performed prior to administration of the radiopharmaceutical.

5.8.1.2. Equipment: Gamma camera system

A large FOV gamma camera is best suited for bone scintigraphy. A low

energy, high resolution collimator and a pinhole collimator are the two most

widely used collimators for bone scanning. For SPECT, a high resolution

parallel hole should be used but some systems also accept pinhole collimators.

5.8.1.3. Modes of bone scintigraphy

Scintigraphic modes for the imaging of bone, joint and musculotendinous

units include planar whole body scintigraphy, planar spot scintigraphy, three

phase planar scintigraphy, planar pinhole scintigraphy, conventional SPECT

and pinhole SPECT.

(a) Planar whole body bone scintigraphy

Planar whole body bone scintigraphy produces a pair of the anterior and

posterior images of the entire skeleton, including cranially from the skull and

caudally from the cervical spine, to the complete upper and lower extremities.

(b) Planar spot bone scintigraphy

Planar spot bone scintigraphy portrays a localized portion of the body,

usually the ROI, with most of the rest of the skeleton in additional views.

Three phase planar bone scintigraphy consists of dynamic arterial blood

flow images, static blood pool images and delayed static bone images. The

blood flow phase is obtained in sequence as the tracer is injected in a bolus.

Sixteen to 20 frames are taken, with the acquisition time per frame varying

from 2 to 4 seconds according to the site imaged. The static images of the blood

pool, one or two in number, are taken within 10 min of the injection. The

delayed planar images are taken 2–3 hours after injection. Scanning can be