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The Society of Nuclear Medicine Procedure

Guideline For Parathyroid Scintigraphy
Version 3.0, approved June 2004

Authors: Bennett S. Greenspan, MD (University of Missouri Medical Center, Columbia, MO); Manuel L. Brown, MD
(Henry Ford Hospital, Detroit, MI); Gary L. Dillehay, MD (Loyola University Medical Center, Maywood, IL); Mike
McBiles, MD (Brooke Army Medical Center, San Antonio, TX); Martin P. Sandler, MD (Vanderbilt University Medical
Center, Nashville, TN); James E. Seabold, MD (University of Iowa Hospitals and Clinics, Iowa City, IA); and James C.
Sisson, MD (University of Michigan Medical Center, Ann Arbor, MI).

I. Purpose Dual-phase or double-phase imaging refers to util-
izing 99mTc-sestamibi and acquiring early and de-
The purpose of this guideline is to assist nuclear
layed images. Dual-isotope or subtraction studies re-
medicine practitioners in recommending, performing,
fer to protocols using 2 different radiopharmaceuti-
interpreting, and reporting the results of parathyroid
cals for imaging acquisition.
imaging.

II. Background Information and Definitions III. Examples of Clinical or Research
Applications
Primary hyperparathyroidism is characterized by in-
creased synthesis and release of parathyroid hor- A. To localize hyperfunctioning parathyroid tissue
mone, which produces an elevated serum calcium (adenomas or hyperplasia) in primary hyperpara-
level and a decline in serum inorganic phosphates. thyroidism. This may be useful before surgery to
Asymptomatic patients are frequently diagnosed as a help the surgeon find the lesion, thus shortening
result of screening by automatic multichemistry pan- the time of the procedure.
els. The vast majority of cases of primary hyperpara- Although the use of preoperative localizing pro-
thyroidism (80%–85%) are the result of single or cedures, including parathyroid scintigraphy, has
multiple hyperfunctioning adenomas. Hyperplasia of been controversial, sestamibi scans have been
several or all parathyroid glands accounts for ap- shown to be accurate and to reduce the time and,
proximately 12%–15% of cases, whereas parathyroid therefore, the cost of an initial operation for hyper-
carcinomas occur in only 1%–3% of cases of hyper- parathyroidism. Selected high-surgical-risk pa-
parathyroidism. In general, parathyroid adenomas tients and those with life-threatening adenomas are
larger than 500 mg can be detected scintigraphically. especially likely to benefit from parathyroid scinti-
99m
Tc-sestamibi allows detection of hyperplastic graphy. An unequivocally positive study will aid
glands, although with less sensitivity than adenomas. the surgeon in streamlining the surgical procedure.

The Society of Nuclear Medicine (SNM) has written and approved these guidelines as an educational tool designed to promote the cost-
effective use of high-quality nuclear medicine procedures or in the conduct of research and to assist practitioners in providing appropriate care
for patients. The guidelines should not be deemed inclusive of all proper procedures nor exclusive of other procedures reasonably directed to
obtaining the same results. They are neither inflexible rules nor requirements of practice and are not intended nor should they be used to es-
tablish a legal standard of care. For these reasons, SNM cautions against the use of these guidelines in litigation in which the clinical deci-
sions of a practitioner are called into question.
The ultimate judgment about the propriety of any specific procedure or course of action must be made by the physician when considering the
circumstances presented. Thus, an approach that differs from the guidelines is not necessarily below the standard of care. A conscientious
practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in his or her reasonable judgment,
such course of action is indicated by the condition of the patient, limitations on available resources, or advances in knowledge or technology
subsequent to publication of the guidelines.
All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources,
and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achiev-
ing this objective.
Advances in medicine occur at a rapid rate. The date of a guideline should always be considered in determining its current applicability.
2 z PARATHYROID SCINTIGRAPHY

B. To localize hyperfunctioning parathyroid tissue 2. Results of physical examination, especially
(usually adenomas) in patients with persistent or palpation of the neck.
recurrent disease. Many of these patients will al- 3. Presence of concurrent thyroid disease, espe-
ready have had 1 or more surgical procedures, cially nodular thyroid disease. History of prior
making reexploration much more technically dif- thyroid or parathyroid surgery.
ficult. Also, ectopic tissue is much more prevalent 4. Recent administration of iodine-containing
in this population, and preoperative localization preparations, such as for radiographic studies
will likely increase surgical success, in part by (i.e., CT scans, intravenous urography), or
sometimes helping to direct the surgical approach. thyroid hormone, when the technique utilizing
thyroid imaging and subsequent subtraction
will be employed.
IV. Procedure
5. Results of CT, MRI, or ultrasound scans and
A. Patient Preparation other diagnostic tests.
No special patient preparation is necessary. C. Precautions
The procedure should be explained to the patient, None
because preventing patient motion during the D. Radiopharmaceuticals
study is extremely important, particularly if using 1. 201Tl-Chloride
201
dual-tracer/subtraction techniques. Patients who Tl has a physical half-life of 72 h. Its main
are unable or unwilling to remain completely im- photopeak is due to characteristic x-rays of
mobilized during the study may require sedation. mercury, which have an energy range of 69–
B. Information Pertinent to Performing the Pro- 83 keV. In addition, gamma rays are produced
cedure at 167 keV (8% abundance) and 135 keV (2%
1. Documentation of an elevated serum calcium abundance). The administered radioactivity is
and parathyroid hormone. Documented in- 75–130 MBq (2–3.5 mCi) and is given intra-
creased urinary excretion of calcium is also venously. 201Tl is taken up by both abnormal
advised when other laboratory abnormalities parathyroid tissue and thyroid tissue in pro-
are mild. portion to blood flow.

Radiation Dosimetry: Adults

Radiopharmaceuticals Administered Organ receiving the largest Effective dose ∗
activity radiation dose∗ mSv/MBq
MBq mGy/MBq (rem/mCi)
(mCi) (rad/mCi)
201
Tl-chloride 75–130 iv 0.54 0.23
Kidney
(2.0–3.5) (2.0) (0.85)
99m
Tc-pertechnetate 75–150 iv 0.062 0.013
No blocking agent Upper large intestine
(2–4) (0.23) (0.048)
99m
Tc-sestamibi 185–925 iv 0.039 0.0085
Gallbladder
(5–25) (0.14) (0.031)
123
I 7.5–20 po 1.9 0.075
15% uptake Thyroid
(0.2–0.5) (7.0) (0.28)

* International Commission on Radiological Protection. Radiation Dose to Patients from Radiopharmaceuticals. ICRP
Publication 53. London, UK: ICRP; 1988:199,264,373. International Commission on Radiological Protection. Radiation
Protection in Biomedical Research. ICRP Publication 62. New York, NY: Pergamon Press; 1993:23.
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES z 3

2. 99mTc-Pertechnetate ing problems with technetium scatter. There is
99m
Tc has a half-life of 6 h and an energy of also the advantage of being able to image the
140 keV. Pertechnetate is used for delineating mediastinum. However, the disadvantage is
the thyroid gland, because pertechnetate is the requirement for the patient to hold still for
trapped by functioning thyroid tissue. This a longer time. The advantage of administering
image is subtracted from the 201Tl or 99mTc- the 99mTc-pertechnetate first is less time for
sestamibi image, and what remains is poten- the patient to remain motionless. However,
tially a parathyroid adenoma. When utilizing there is the disadvantage of downscatter of
201
Tl, the administered radioactivity of 99mTc- 99m
Tc into the thallium window, as well as not
pertechnetate is generally 75–150 MBq (2–4 being able to image the mediastinum. These
mCi), depending on the administered radioac- studies should be acquired and stored digitally
tivity of 201Tl and which of the 2 radiophar- so that image manipulation can be performed.
maceuticals is administered first. When utiliz- Acquiring a dual-isotope image may avoid
ing 99mTc-sestamibi, the administered radioac- registration problems.
tivity of pertechnetate is generally 185–370 2. 99mTc-sestamibi studies may be performed us-
MBq (5–10 mCi), because sestamibi has a ing either the dual-phase and/or the subtrac-
higher total activity in the thyroid gland than tion techniques. If the subtraction technique is
201
Tl. used, the procedure is similar to thallium sub-
3. 99mTc-Sestamibi traction imaging. Either pertechnetate or 123I
The range of intravenously administered ra- can be given first, followed by 99mTc-
dioactivity is 185–925 MBq (5–25 mCi); the sestamibi, or sestamibi can be given first, fol-
typical dosage is 740 MBq (20 mCi). This ra- lowed by pertechnetate. (123I cannot be admin-
diopharmaceutical localizes in both parathy- istered after sestamibi, because of the long
roid tissue and functioning thyroid tissue but time needed for localization.) Overall, none of
usually washes out of normal thyroid tissue the techniques discussed here has been shown
more rapidly than out of abnormal parathyroid to be superior; however, careful selection of
tissue. (Hyperplastic parathyroid glands gen- technique on a case-by-case basis may be
erally show faster washout than most adeno- helpful. Disadvantages of 123I include its high
mas.) cost and long time required for localization.
4. 123I-Sodium Iodide Using pertechnetate or 123I as the first imaging
123
I has a half-life of 13 h and emits a photon agent, high count (10-min) images are ob-
with an energy of 159 keV. It has been used as tained 30 min or 4 h after radiopharmaceutical
a thyroid imaging agent in subtraction studies, administration, respectively. Sestamibi is then
particularly with 99mTc-sestamibi. The admin- injected, and high-count (10-min) images are
istered radioactivity, given orally, ranges from obtained 10 min after injection. If pertech-
7.5–20 MBq (200–550 µCi). netate is injected after sestamibi images are
E. Image Acquisition obtained, the patient should be immobilized
Digital data should be acquired in a 128 × 128 or for 15–30 min after the pertechnetate injec-
larger matrix. tion, and then a 10-min image is acquired. In
1. Planar images of the neck and mediastinum all cases, both sets of images are normalized
can be obtained with a gamma camera fitted to total thyroid counts and computer subtrac-
with a high-resolution collimator. Images of tion of 123I or pertechnetate images from the
the mediastinum should be obtained in all sestamibi images is obtained.
cases. Although the yield is low, the positive If a dual-phase study is performed, then a
predictive value is quite high. Mediastinal im- high-resolution parallel-hole collimator or a
ages are most helpful in cases of residual or pinhole or converging collimator can be used.
recurrent disease, where there is a much Early (10-min postinjection) and delayed
higher likelihood of ectopic tissue. Additional (1.5–2.5-h postinjection) high-count images
pinhole or converging collimator images of are obtained.
the neck may be useful. It has now become clear that SPECT imag-
When utilizing 201Tl, there is not uniform ing is useful. SPECT imaging in conjunction
agreement over which agent to administer with planar imaging provides increased sensi-
first, because there are advantages and disad- tivity and more precise anatomical localiza-
vantages for each protocol. If 201Tl is given tion. This is particularly true in detecting both
first, there is the advantage of administering primary and recurrent hyperparathyroidism
the lower energy radionuclide first and avoid- resulting from ectopic adenomas. In the medi-
4 z PARATHYROID SCINTIGRAPHY

astinum, accurate localization may assist in di- rapid washout. SPECT images may reveal lesions
recting the surgical approach, such as median not seen on planar images, especially if they are
sternotomy versus left or right thoracotomy. small.
Cine of volume-rendered images is often help- I. Reporting
ful. With large-field-of-view gamma cameras, In addition to patient demographics, the report
magnification may be of help. should include the following information:
F. Interventions 1. Indication for the study
None. 2. Procedure
G. Processing a. Radiopharmaceutical(s)
Processing with computer subtraction is only nec- i. Dosage and route of administration
essary with dual radiopharmaceutical studies. ii. If more than 1 radiopharmaceutical is
1. In 201Tl/99mTc-pertechnetate studies, computer used, the order in which they are ad-
subtraction may enhance detection of parathy- ministered and the timing of those ad-
roid adenomas. The 2 images should be nor- ministrations should be stated.
malized; that is, counts per pixel in the thyroid b. Acquisition and Display
in 1 image should equal those in the other im- i. Timing of acquisition of images.
age. There are usually more counts in the ii. Planar and/or SPECT.
pertechnetate image than the thallium image, For planar images, list projections ac-
and it may be necessary to decrease counts quired (e.g., anterior) and region im-
several fold by dividing the pertechnetate im- aged (neck, mediastinum). For SPECT,
age by a constant. The pertechnetate image is list timing of acquisition after injection
then subtracted from the thallium image. and region imaged (neck or mediasti-
However, normalization by this method can num).
be difficult as a result of heterogeneity. An al- 3. Findings
ternative method is to decrease the counts a. Time of detection of lesion (early or late
several fold by dividing the 201Tl image by a images).
constant and then using successive subtrac- b. Location (thyroid bed [upper or lower
tions until the body of the thyroid disappears. pole, and which side] or mediastinum).
Image shifting can be used to ensure optimal 4. Study limitations, confounding factors (e.g.,
registration of the 2 images. patient motion).
2. In 99mTc-sestamibi/123I or pertechnetate imag- 5. Interpretation.
ing studies, the images should be normalized J. Quality Control
similar to the technique for 201Tl/99mTc, and Gamma camera quality control will vary from
the 123I or pertechnetate image is subtracted camera to camera. Multiple spatial and energy
from the 99mTc-sestamibi image. window registration should be checked periodi-
H. Interpretation Criteria cally if dual-isotope studies are performed. For
201
Tl/99mTc images and 99mTc/123I images should further guidance in gamma camera quality con-
be inspected visually as well as evaluated with trol, refer to the Society of Nuclear Medicine Pro-
computer subtraction and/or with rapid alternating cedure Guideline for General Imaging for routine
display of images (cine). Abnormal parathyroid quality control procedures for gamma cameras.
tissue will most likely appear as an area of rela- K. Sources of Error
tively increased uptake with either 201Tl or 99mTc- 1. Patient motion.
sestamibi. Computer subtraction will probably be 2. Image misregistration.
of help in cases with equivocal visual findings. If 3. Adenomas or hyperplastic glands less than
99m
Tc-sestamibi is used without 123I or pertech- 500 mg in size are often difficult to detect.
netate (i.e., without computer subtraction), the 2 4. Ectopic adenomas can be difficult to detect;
sets of images (early and delayed) are inspected the entire neck as well as the upper and mid
visually. Abnormal parathyroid tissue will usually mediastinum to the heart should be imaged.
appear as an area of increased uptake and should 5. Lesions of the thyroid, such as adenomas and
become more prominent on the delayed images. carcinomas, may be indistinguishable from
Occasionally, parathyroid adenomas may not parathyroid adenomas.
show increased activity and may only appear as 6. Parathyroid carcinomas are also indistinguish-
tissue fullness behind the thyroid. Some adeno- able from parathyroid adenomas.
mas will show washout of tracer by 2–2.5 h and 7. Recently administered radiographic contrast
therefore may not be obvious on the delayed im- material or thyroid hormone (within the pre-
ages. Washout of tracer from adenomas may be vious 3–4 wk) will interfere with 123I and
variable. Many hyperplastic glands will show pertechnetate imaging and, therefore, will
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES z 5

compromise the use of subtraction techniques. F. Doppman JL, Skarulis MC, Chen CC, et al. Para-
This will not be a problem with dual-phase thyroid adenomas in the aortopulmonary window.
sestamibi studies. Radiology. 1996;201:456–462.
Some parathyroid adenomas wash out rap- G. Fjeld JG, Erichsen K, Pfeffer P, et al. Techne-
idly. tium-99m-tetrofosmin for parathyroid scintigra-
phy: a comparison with sestamibi. J Nucl Med.
1997;38:831–834.
V. Issues Requiring Further Clarification
H. Hindie E, Melliere D, Simon D, et al. Primary
There is now a clear consensus that imaging with hyperparathyroidism: is technetium-99m-ses
99m
Tc-sestamibi is superior to 201Tl, although 201Tl is tamibi/iodine-123 subtraction scanning the best
still in occasional use. A few investigators have util- procedure to locate enlarged glands before sur-
ized 99mTc-tetrofosmin; however, it is not yet clear if gery? J Clin Endocrinol Metab. 1995;80: 302–
this agent is as useful or accurate as 99mTc-sestamibi. 307.
There is still no consensus regarding subtraction im- I. Jeanguillaume C, Urena P, Hindie E, et al. Sec-
aging versus dual-phase imaging. There is a develop- ondary hyperparathyroidism: detection with I-
ing consensus that SPECT imaging is useful, because 123-Tc-99m-sestamibi subtraction scintigraphy
it improves sensitivity and anatomical localization. versus US. Radiology. 1998;207:207–213.
There is still controversy regarding the utility of J. Johnston LB, Carroll MJ, Britton KE, et al. The
this study as a preoperative evaluation in primary hy- accuracy of parathyroid gland localization in pri-
perthyroidism in patients who have not had prior sur- mary hyperparathyroidism using sestamibi ra-
gery. However, there are now some data that suggest dionuclide imaging. J Clin Endocrinol Metab.
that these studies may shorten the operative time and 1996;81:346–352.
reduce cost. In cases of residual or recurrent disease, K. Ishibashi M, Nishida H, Hiromatsu Y, et al.
these studies are clearly helpful. Comparison of technetium-99m-MIBI, techne-
There are now some data emerging suggesting tium-99m-tetrofosmin ultrasound and MRI for lo-
that PET imaging may be useful in imaging parathy- calization of abnormal parathyroid glands. J Nucl
roid adenomas. Med. 1998;39:320–324.
L. Majors JD, Burke GJ, Mansberger AR, et al.
Technetium Tc-99m sestamibi scan for localizing
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