Download Interpretation of Radioiodine Whole Body Scan

Interpretation of Radioiodine Whole Body Scan
June-2013
Byeong-Cheol Ahn, MD, PhD
Department of Nuclear Medicine
Kyungpook National University School of Medicine and Hospital
1.
Introduction
Radioiodine whole body scan relies on the fact that differentiated thyroid cancer is efficient at trapping
circulating radioiodine than any other tissues.1 Therefore, when I-131 is administered it accumulates in the
thyroid cancer tissues and radioiodine whole body scan plays an important role in the management of patients
with differentiated thyroid cancer. Uptake of iodine to the cancer is related to the expression of sodium iodide
symporter (NIS) which actively transports iodide in to the cancer cells. Extrathyroidal tissues, such as stomach,
salivary glands and breast, are known to have NIS expression and the organs can physiologically take up
iodine.2,3
With whole body scan with diagnostic or therapeutic doses of I-131, except the physiological
radioiodine uptake in the salivary glands, stomach, gastrointestinal and urinary tracts, lesions with radioiodine
uptake can be considered as metastatic lesion in thyroid cancer patients who underwent total thyroidectomy.
However, a variety of unusual lesions may cause false positive result on the radioiodine whole body
scan and therefore careful evaluation of an abnormal scan is imperative to manage patients with differentiated
thyroid cancer appropriately.4-7 Decision to have radioiodine treatment is mainly based on the diagnostic scan,
and misinterpretation of physiological or other causes of radioiodine uptake for metastatic thyroid cancer could
lead to the decision to perform unnecessary surgical removal or to give a high dose of I-131 which results in
fruitless radiation exposure. Therefore, correct interpretation of the diagnostic scan is critical for the proper
management.
Nuclear medicine physicians should consider a possibility of physiologic or pathologic false positive
uptake or contamination as a reason of the tracer uptake on radioiodine whole body scan.
2. Procedures for radioiodine whole body imaging
1) Patients preparation
Thyroid hormone replacement must be withheld for a sufficient time to permit an adequate rise of TSH
(>30 uIU/mL). This is at least 2 weeks for triiodothyronine (T3) and 3–4 wk for thyroxine (T4). This is also
achieved by the administration of recombinant human TSH (rhTSH, Thyrogen®, given as two injections of 0.9
mg intramuscularly on each of two consecutive days) without stopping of thyroid hormone replacement. rhTSH
must be used in patients who may not have elevation of TSH to the adequate level due to a large residual
volume of functioning thyroid tissue or pituitary abnormalities which preclude elevation of TSH. It also might
be used to prevent severe hypothyroidism related to the stopping of thyroid hormone replacement.8,9
All patients must discontinue use of iodide-containing foods or preparations, and other medications that
could potentially affect the ability of thyroid cancer tissue to accumulate iodide for a sufficient time before
radioiodine administration. A low-iodine diet is followed for 7–14 days before the radioiodine is given, as it
significantly increases the uptake of radioiodine by the well differentiated thyroid cancer tissue. Avoid or
permitted food items were summarized on table 1. Recommended time interval of drug withdrawal was
summarized on table 2. Imaging should be delayed for a period long enough to eliminate the effects of these
interfering factors. The goal of a low iodine diet and the drug withdrawal is to make a 24-hour urine iodine
output of about 50 ug.9
.
Allowed
Not-allowed
Iodized salt
Salts
Non -iodized salt
Sea salt
Rhubarb
Fruits and
Fruit or juice with red dye # 3
Fresh fruits and juices
vegetables
Canned or preserved
Seafood
Fish
None
and
sea
Shellfishs
products
Dairy
products
Paultries
and Meats
Egg
Grain
products
drinks
Seaweeds
Seaweed tableets
Agar-agar
Milk
Cheese
Yogurt
Butter
Ice cream
Chocholate
(has
content)
None
Fresh unsalted
Canned and processed
Whites of eggs
Egg yolks
Whole eggs
breads, cereal and
crackers without salt
unsalted pasta, rice,
rice
cakes,
and
popcorn
Cola,
diet
cola,
lemonade
Coffee or tea without
milk or cream
Fruit juice without red
dye#3
Fruit smoothies made
without dairy or soy
products
Beer, wine and spirits
milk
Breads, cereals or crackers
made with salt
Salted pasta, rice or popcorn
Milk, cream or drinks made
with dairy
Fruit juice and soft drinks
with red dye#3
Table 1. Food guide for a low iodine diet. Some items on the allowed list may not be low iodine in some forms
or merchandise brands. Labels must be checked to be sure that the items meet the requirements of the lowiodine diet.10,11
Type of medication
Natural synthetic thyroid hormone
Thyroxine(T4)
Triiodothyronine(T3)
Amiodarone
Multivitamine
Lugol’s solution, potassium iodide
solution (SSKI)
Topical iodine
Radiographic contrast agents
Iodinated eyedrops and antiseptics
Iodine containing expectorants and antitussives
Recommended time interval of withdrawal
10 to 14 days
3 to 4 weeks
3 to 6 months
6 weeks
6 weeks
6 weeks
3 to 6 months, depending on iodide content
6 weeks
2 to 4 weeks
Table 2. Recommended time intervals of withdrawal for drugs affecting radioiodine uptake. The time interval
can be changed by the administered doses of the medications. Amount of iodine for the drug must also be
considered.8,10,12
2) Types of radioiodine
(1) I-131
I-131 is produced in a nuclear reactor by neutron bombardment of natural tellurium (Te-127) and decays by
beta emission with a half-life of 8.02 days to Xe-133 and emits gamma emission as well. It most often (89% of
the time) expends its 971 keV of decay energy by transforming into the stable Xe-131 in two steps, with gamma
decay following rapidly after beta decay. The primary emissions of I-131 decay are beta particles with a
maximal energy of 606 keV (89% abundance, others 248–807 keV) and 364 keV gamma rays (81% abundance,
others 723 keV).
I-131 is administered orally in activities of 1–5 mCi or less, with many preferring a range of 1–2 mCi
because of data suggesting that stunning (decreased uptake of the therapy dose of I-131 by residual functioning
thyroid tissue or tumour due to cell death or dysfunction caused by the activity administered for diagnostic
imaging) is less likely at the lower activity range. However, detection of more iodine concentrating tissue has
been reported with higher dosages.9
(2) I-123
I-123 is produced in a cyclotron by proton irradiation of enriched xenon(Xe-124) in a capsule and decays
by electron capture with a half-life of 13.22 hours to Te-123 and emits gamma radiation with predominant
energies of 159 keV (the gamma ray primarily used for imaging) and 127 keV.
I-123, mainly a gamma emitter, with a high counting rate compared with I-131, provides a higher lesion-tobackground signal, thereby improving sensitivity and imaging quality. Moreover, with the same administered
activity, I-123 delivers an absorbed radiation dose that is approximately one-fifth that of I-131 to thyroid tissue,
thereby lessening the likelihood of stunning from imaging. I-123 is administered orally in activities of 0.4–5.0
mCi, which may avoid stunning.9,13
(3) I-124
I-124 is a proton-rich isotope of iodine produced in a cyclotron by numerous nuclear reactions and
decays to Te-124 with a half-life of 4.18 days. Its modes of decay are: 74.4% electron capture, 25.6% positron
emission. It emits gamma radiation with energies of 511 and 602 keV.14
I-124 is administered intravenously in activities of 0.5–2.0 mCi for detection of metastatic lesions or
assessment of radiation dose related to I-131 therapy.
Types
I-131
I-123
Advantages
 Least expensive
 Readily available
 Allows
longer
delayed image
 cheap
 No stunning
 Good image quality

I-124



Superior
image
quality
Tomographic image
Allows intermediate
delayed image
Fusion image with
CT or MR
Disadvantages
 Potential stunning
 Requirement
of
possible
radiation
safety precautions for
family and caregivers
 Limited availablity
 Expensive


Very
limited
availability
Very expensive
Table 3. Advantages and disadvantages accords to types of radioiodine.10
3) Planar, SPECT and PET imagings
(1) Planar imaging
Planar gamma camera imaging can be obtained with gamma emitting I-123 or I-131 for detection of thyroid
cancer tissue expressing NIS gene which take up iodine. Main emission energy peak of I-131 is approximately
364 keV, therefore, it requires the use of a high-energy all-purpose collimator for imaging acquisition. The peak
of the I-123 is 159 keV, which is close to the 140 keV from Tc-99m for which gamma camera design has
traditionally been optimized. I-123 can be imaged with a low-energy high-resolution collimator which is
optimized for image acquisition with the Tc-99m (140 keV). 14
With radioiodine avidity of differentiated thyroid cancer tissues, planar radioiodine whole body image
has been mainly used for the detection of metastatic thyroid cancer lesions. However, the limited resolution
planar imaging together with background activity in radioiodine images, can give false-negative results for small
lesions. Physiologic uptake of radioiodine is not always easily differentiable from pathologic uptake and it can
give false-positive results.15 Therefore, the sensitivity and specificity of planar images for diagnosis of
metastatic thyroid cancer may be limited.16
(2) SPECT (Single Photon Emission Computed Tomography) or SPECT/CT imaging
Although radioiodine whole body scan is one of excellent imaging tools for detection of thyroid cancer,
false negative results may be observed in cases with small recurrent lesions in an area of rather high background
activity or in cases with poorly differentiated cancer tissues which have low uptake ability for radioiodine (due
to dedifferentiation).17 SPECT which provides can cross-sectional scintigraphic images, has been proposed as a
way to overcome the limitations of planar imaging and it has been known to have higher sensitivity and better
contrast resolution than planar imaging.18 Radioiodine SPECT has higher performance for detecting recurrent
lesion compared to planar imaging in thyroidectomized thyroid cancer patients and furthermore it also changes
patients’ management.19
Radioiodine SPECT has excellent capability to detect thyroid cancer tissues, however, the anatomic
evaluation of lesion sites with radioiodine uptake remains difficult due to minimal background uptake of the
radioiodine. The performance of SPECT with radioiodine may be further improved by fusing SPECT and CT
images or by integrated SPECT/CT system that permits simultaneous anatomic mapping and functional
imaging.15,17 The fusion imaging modality can synergistically and significantly improve the diagnostic process
and its outcome when compared to a single diagnostic technique.20 Therefore, SPECT/CT with radioiodine can
demonstrate higher number of radioiodine uptake lesions, and more correctly can differentiate between
physiologic and pathologic uptakes, thus permit more appropriate therapeutic approach to be chosen.15 Despite
its many advantages, SPECT/CT cannot be applicable in routine use or whole body imaging due to long
scanning time and additional radiation burden, the fusion image should be selected an personalized basis who
clinically needs the imaging.16
Fig . 1. Intense cervical tracer uptake in the right side neck. SPECT/CT image shows focal uptake in right
cervical node suggesting thyroid cancer metastasis. The lesion was diagnosed as thyroid cancer metastasis by
histopathology.
Fig. 2. Multiple intense cervical tracer uptake in the neck. SPECT/CT image shows focal uptakes in both
paratracheal regions suggesting residual thyroid tissue. The lesion was diagnosed as thyroid cancer metastasis
by histopathology.
Fig. 3. Equvical lesions on radioiodine whole body scan can be clarified by additional SPECT CT acqusition.
Radioiodine whle body scan (far left side) demonstrated equivocal uptakes observed at the right lower neck and
GB fossa area on the planar image. SPECT/CT of the neck showed intense uptake at the apical segment of the
right upper lobe corresponding to the right cervical uptake observed on planar imaging. On the CT image, a tiny
pulmonary nodule was observed at the location of uptake, which was diagnosed clinically as a lung metastasis.
A, SPECT image; B, fusion image; C, CT image, arrow. SPECT/CT of the abdomen showed mild uptake at GB
(D, E, and F, arrowhead), which was a physiologic uptake.19
(3) PET (Positron Emission Tomography) or PET/CT imaging
PET detects a pairs of gamma rays produced by annihilation of positron which is introduced positron
emitting radionuclide and produce three-dimensional image. Owing to its electronic collimation, I-124 PET
gives a better efficiency and resolution than in I-123 or I-131 SPECT, therefore, it offers the best image
quality.14
Fusion imaging modality with I-124 PET and CT can improve the diagnostic efficacy when compared
to I-124 PET imaging only by the same reasons of SPECT/CT over SEPCT only. I-124 PET/CT has superiority
of better spatial resolution and faster imaging speed compared to I-123 or I-131 SPECT/CT.21 Recently PET
fused with MR is coming to the research and clinic fields, it will be positioned as state of art imaging in near
future.
4) Information pertinent to performing the radioiodine whole body scan
 Compliance with a low-iodine diet
 TSH level
 History of thyroid hormone withdrawal or utilization of recombinant human TSH
 Serum thyroglobulin and anti-thyroglobulin antibody levels
 Description of operative procedure (extent of thyroidectomy) and detailed pathologic findings
 Tumor histology, including presence or absence of capsular and/or vascular invasion and lymph node
involvement
 Results of other imaging procedures
 Physical examination findings
 History of prior I-131 treatment
 Results of prior radioiodine scintigraphy
 History of prior administration of iodinated contrast or iodine-containing drugs
 Menstrual history/pregnancy test
 Nursing/lactation history
 Surgeon performing the thyroidectomy has sufficient and ongoing expertise in performing this
procedure.
3. Radioiodine uptakes in thyroid cancer lesions on the radioiodine whole body scan
Radioiodine whole body scan based on the fact that differentiated thyroid cancer retains function of
thyroid follicular cell which has ability to trap iodine by expression of NIS and has long been used for detection
of metastatic or residual disease in patients with differentiated thyroid papillary or follicular cancer.5,22 The most
common sites of the metastasis are locally in the cervical lymph nodes, lung, bone and mediastinum.
Scintigraphy for detection of thyroid metastasis consists of obtaining images of the body, 1–3 days following
the oral ingestion of I-131, or 6 to 48 hours after I-123 (recognizing that the longer time period will require
higher dosages of I-123). Post-therapy whole body scan usually obtained 4 to 10 days later but it can be
acquired later time point.9 Generally, more lesions are demonstrated in late image that early image due to
background clearance and the higher target to background ratio, but high radioiodine dose is required to get
appropriate image quality with sufficient count rate in delayed time point imaging.
Initial radioiodine whole boy scan obtained after thyroidectomy, it is not uncommon to have intense
tracer uptake in thyroid bed due to residual thyroid remnant, which produces start artifact and precludes clear
visualization of the neck.22 Radioiodine whole body scan is not able to discriminate between residual normal
thyroid tissue and thyroid cancer. Image acquisition with pinhole collimator can better resolve in the high
intensity uptake region. Recently available SPECT/CT can provide better localization of uptake area and
visualize the lesion more sensitively.
Since medullary carcinoma and anaplastic carcinoma do not express NIS which takes up the
radioiodine, therefore, radioiodine whole body scan is not indicated for the malignancies.
Fig . 4. Intense cervical tracer uptake which makes star artifact that covers possible lesions in the neck. Intense
diffuse tracer uptake was noted at both lung fields. Chest CT scan shows multiple nodules suggesting thyroid
cancer metastasis.
Fig . 5. Radioiodine uptakes suggesting metastasis of thyroid cancer were noted in cerebellum, ribs, pelvis, spine
and lung. Radiological studies revealed corresponding results to the findings on the radioiodine whole body scan.
Fig. 6. Uptake of radioiodine in metastatic lung lesions. Intense diffuse tracer uptake was noted at both lung
fields. Chest PA and CT scan show corresponding miliary pattern of thyroid cancer metastasis.
Fig. 7. Uptake of radioiodine in metastatic lung lesions and possible metastatic neck nodes. Intense focal tracer
uptakes at both lung fields and focal uptake in thyroid bed were noted in 1st posttherapy whole body scan (left).
Chest CT scan shows corresponding metastatic lesions of thyroid cancer (bottom). Physiologic thymic uptake
and single focal uptake at left side neck were seen on 2nd posttherapy whole body scan (right).
4. Physiologic radioiodine uptake on radioiodine whole body scan
Following thyroid ablation, physiologic activity is expected in salivary glands, stomach, breast, oropharynx,
nasopharynx, oesophagus, gastrointestinal tract, and genitourinary tract.23 Physiologic radioiodine accumulation
is related to expression of NIS, metabolism related or retention of excreted iodide related.4,24 Uptake of
radioiodine in thyroid tissue, salivary gland, stomach, lacrimal sac, nasolacrimal duct and choroid plexus is
related to NIS expression in cells of the organs.25 Ectopic thyroid tissues are found by a variety of embryological
maldevelopment of thyroid gland, such as lingual thyroid (by failure of migration), thyroglossal duct (by
functioning thyroid tissue in migration route) and meditational thyroid gland (by excessive migration). Other
abnormal migration may produce widely divergent ectopic thyroid tissue in many organs, such as, liver,
oesophagus, trachea, etc. In addition, normal thyroid tissue can be in ovary (Struma ovarii. It can be classified as
uptake in pathologic lesion.).6 Ectopic gastric mucosa can be located in small bowel (Meckel's diverticulum) or
terminal oesophagus(Barrett's oesophagus).13 The ectopic thyroid and gastric mucosal tissues are able to take up
radioiodine.
Uptake of iodine in the liver after radioiodine administration is related to metabolism of radioiodinated
thyroglobulin and thyroid hormones in the organ. The gall bladder also may occasionally be depicted with
biliary excretion of the radioiodine.5,6 Simultaneous hepatobiliary scan with Tc-99m DISIA or mebrofenin is
useful for characterizing the gall bladder uptake. Tracer accumulation in oropharynx, nasopharynx and
oesophagus is related to retention of salivary excretion of administered radioiodine. Visualization of oesophagus
is extremely common and vertical linear uptake in the thorax which removed by drinking water is characteristics
of oesophageal uptake by swallowing of radioactive saliva. The oesophageal activity may also arise from gastric
reflux.5 Image acquisition after a drink of water is able to distinguish the activity from meditational node
metastasis by same washout characteristic used in oesophageal activity by saliva swallowing.6
Urinary or gastrointestinal anomalies can be responsible for false positive radioiodine uptake.13
Visualization of kidney and bladder after radioiodine administration is possible and it is known to be related to
urinary excretion of radioiodine into the urinary collecting system. Administered radioiodine is excreted mainly
by the urinary system, therefore, all dilations, diverticuli, and fistulae of the kidney, ureter, and bladder may
produce radioiodine retention.6 Location of the renal pelvis of ectopic, horseshoe and transplanted kidneys are
not usual and radioiodine at the pelvis may lead misinterpretation. In fact, the renal pelvis and ureter are usually
not visualized due to the rapid transit time of the radioiodine.26 Simultaneous renal scan with Tc-99m DTPA or
MAG3 is useful for characterizing the urinary tract uptakes.6 Although the incidence is very uncommon, renal
cysts are known to produce radioiodine uptake. Proposed mechanisms for the renal cyst uptake are
communication between the cyst and the urinary tract and radioiodine secretion by the lining epithelium of the
cyst.6
Tracer accumulation in the colon is very common. Incomplete absorption of the oral radioiodine
administration is not considered for the reason of colonic activity due to no colonic activity in early images.
Tracer accumulation is probably due to transport of radioiodine into the intestine from the mesenteric circulation
and biliary excretion of metabolites of radioiodinated thyroglobulin. 27 Appropriate use of laxatives can be a
simple remedy for the activity.6
Lactating mammary gland expresses NIS, therefore, lactating breast shows intense radioiodine uptake
which might persist for months after cessation of lactation. Mild to moderate uptake is also seen in non-lactating
breast tissue, can be asymmetrical, presumably owing to the same mechanism that operates in lactation.6,28
Uptake of radioiodine can occur in a residual normal thymus or thymic hyperplasia and suggested
mechanisms for the uptake are expression of NIS in thymic tissues and iodine concentration by the Hassal’s
bodies present in the thymic tissue, which resemble the follicular cells of the thyroid. Thymic radioiodine uptake
is more common in young patients compared to old patients. Even though the incidence is very rare, an
intrathymic ectopic thyroid tissue or thyroid cancer metastases to the thymus can be possible as the cause.
(Mello, Flamini et al. 2009)
Fig 8. Physiologic uptakes of radioiodine in the whole body; A - planar scintigraphy, B - SPECT/CT.
Radioiodine uptakes in nasal secretion (1), parotid gland (2), dental prosthesis (3), remnant thyroglossal duct (4),
remnant thyroid tissue (5), liver (6), and colon (7) are observed. The Hybrid SPECT/CT imaging helps
recognize the exact localization of the radioiodine uptakes.18
Fig. 9. Physiologic uptake of radioiodine in nasal cavity, so called "hot nose". Intense tracer uptake was noted at
thyroid bed area (due to residual thyroid tissue), breast and salivary gland (by NIS expression of the glands).
Fig. 10. Physiologic uptake of radioiodine in residual thyroid tissue. Intense tracer uptake was noted at thyroid
bed area due to residual thyroid tissue.
Fig. 11. Physiologic uptake of radioiodine in residual thyroid tissue. Intense tracer uptake was noted at midline
of the upper neck due to residual thyroid tissue in thyroglossal duct. Mild tracer uptake of salivary gland (by
NIS expression of the glands) was also noted.
Fig. 12. Physiologic uptake of radioiodine in both parotid and submandibular salivary glands. Intense activity in
oral and nasal cavities (by saliva and nasal secretion) was also noted.
Fig. 13. Physiologic uptake of radioiodine in the breast. Diffuse and moderate radioactivity in the breast was
noted. There also noted physiologic tracer uptake in thyroid bed (suggesting remnant thyroid tissue which has
NIS expression), salivary glands (by NIS expression of the glands), stomach (by NIS expression of the glands),
bowel (by secretion of radioiodine into intestine or biliary excretion of metabolites of radioiodinated proteins),
and urinary bladder (by urine activity).
Fig. 14. Physiologic uptake of radioiodine in the breast. Intense tracer accumulation was noted in both breasts.
There also noted physiologic tracer uptake in thyroid bed (suggesting remnant thyroid tissue which has NIS
expression).
Fig. 15. Physiologic uptake of radioiodine in the breast. Focal tracer uptake in the breast was noted. SPECT/CT
revealed accurate location of breast uptake. There also noted physiologic intense tracer uptake in thyroid bed
(suggesting remnant thyroid tissue which has NIS expression) and mild tracer uptake in the liver (by metabolism
of radioiodinated thyroglobulin and thyroid hormones).
Fig. 16. Physiologic uptake of radioiodine in the oesophagus. Vertical linear radioactivity in the chest was noted
by stagnation of swallowed saliva containing radioiodine. There also noted physiologic tracer uptake in thyroid
bed area (by residual thyroid tissue) and salivary glands (by NIS expression of the glands).
Fig. 17. Physiologic uptake of radioiodine in brochogenic cyst. Focal tracer uptake was found at lower mid
thorax. SPECT and CT image revealed paraverteral mass lesion. The lesion was histopathologically diagnosed
as brochogenic cyst.
Fig. 18. Physiologic uptake of radioiodine in the gall bladder. Intense tracer accumulation was noted at GB fossa
area at whole body scan and SPECT/CT revealed accurate localization of the uptake. There also noted
physiologic tracer uptake in thyroid bed area by residual thyroid tissue.
Fig. 19. Physiologic uptake of radioiodine in the thymus. Diffuse and mild radioactivity in the mid-thorax was
noted. There also noted physiologic tracer uptake in salivary glands (by NIS expression of the glands) and oral
cavity (by saliva containing radioiodine).
Fig. 20. Physiologic uptake of radioiodine in the thymus. Diffuse and mild radioactivity in the mid-thorax was
noted. There also noted focal tracer uptake in both lung field by lung metastases.
Fig. 21. Physiologic uptake of radioiodine in stomach. Intense tracer uptake was noted at right upper quadrant
due to stomach uptake of the tracer. There also noted tracer uptake in oral cavity (radioactivity of secreted
saliva), salivary gland (by NIS expression of the glands), thyroid bed (suggesting remnant thyroid tissue which
has NIS expression) and urinary bladder (by urine activity).
Fig. 22. Focal radioiodine uptake was noted at center of the abdomen. The uptake might be related to ectopic
gastric mucosa in the Meckel’s diverticulum. There also noted tracer uptake in stomach(by NIS expression of
gastric mucosa), oral cavity (radioactivity of secreted saliva), and salivary gland (by NIS expression of the
glands).
Fig. 23. Physiologic uptake of radioiodine in the lacrimal sac. The uptake is known to be related to active iodine
transport by the NIS expression at the lining epithelium of the sac. There also noted intense the tracer
accumulation in thyroid bed (by remnant tissue of the thyroid which has NIS expression) and oral cavity (by
radioactivity of secreted saliva) and minimal tracer uptake in the salivary glands (by NIS expression of the
glands).
Fig. 24. Physiologic uptake of radioiodine in the liver. The uptake is known to be related to metabolism of
radioiodinated thyroglobulin and thyroid hormone in the liver. There also noted intense the tracer accumulation
in thyroid bed (by remnant tissue of the thyroid).
Fig. 25. Physiologic uptake of radioiodine in the urinary bladder. Intense tracer uptake was noted at suprapubic
area by radioactive urine in the bladder. There noted tracer uptake in the salivary glands (by NIS expression of
the glands) and perineal area due to urine contamination.
Fig. 26. Physiologic uptake of radioiodine in the simple cyst of right kidney. Focal tracer uptake was noted at
right side abdomen. Proposed mechanisms are communication between the cyst and the urinary tract and
radioiodine secretion by the lining epithelium of the cyst. There noted intense tracer uptake in the thyroid bed
area (by remnant tissue of the gland) and mild tracer uptake in salivary gland (by NIS expression of the
glands).29
Fig. 27. Physiologic uptake of radioiodine in the simple cyst of right kidney. Focal tracer uptake was noted at
right side abdomen. Proposed mechanisms are communication between the cyst and the urinary tract and
radioiodine secretion by the lining epithelium of the cyst. There noted diffuse tracer uptake in the liver (by
metabolism of radioiodinated thyroglobulin and thyroid hormones).
(A)
(B)
Fig. 28. Physiologic uptake of radioiodine in the colon. Intense tracer uptake was noted at colon. The suggested
mechanisms for the uptake are transportation of radioiodine into the intestine from the mesenteric circulation
and biliary excretion of metabolites of radioiodinated thyroglobulin or thyroid hormones. There also noted tracer
uptake in (A) oral cavity (by radioactivity of secreted saliva), (B) salivary glands (by NIS expression of the
glands) and stomach (by NIS expression of gastric mucosa).
5. Pathologic lesions might show false positive radioiodine uptake on the radioiodine whole body scan
A variety of pathologic lesions producing false positive radioiodine whole body scan has been reported and,
in contrary to the physiologic uptakes which usually do not create diagnostic confusion, they might be tricky
enough leading to some patients undergoing unnecessary fruitless invasive surgical or high dose radioiodine
treatment.7
Not uncommon pathologic lesions showing radioiodine uptake are cystic, inflammatory, non-thyroidal
neoplstic diseases. Cystic lesions in variable organs can accumulate radioiodine and mechanism of the uptake is
passive diffusion of the tracer into the cysts. Radioiodine accumulation in ovarian, breast, pleuropericardial
cysts has been reported.6 Effusion of pleural, pericardial and peritoneal cavities also can have radioiodine uptake
by the same mechanism.6
A variety of inflammatory and infectious disease can have radioiodine accumulation by increased blood flow
which delivers increased levels of radioiodine to the site, and enhanced permeability of the capillary which
increases diffusion of the tracer to the extracellular water space.6 Radioiodine accumulation in bronchiectasis,
pulmonary aspergilloma, skin wound, arthritis, paranasal sinusitis, skin infection, myocardial infarction and
dacryocystitis has been reported.4,6
Even though only in a minority of such lesions accumulate the tracer, a variety of non-thyroidal neoplasms
have been also known to take up radioiodine. The suggested mechanisms are i) tumour expression of NIS which
actively accumulates the tracer, ii) increased vascularity and enhanced capillary permeability which might be
secondary to the inflammatory response associated with the neoplasm.6,7 Radioiodine accumulation in breast
cancer, gastric adenocarcinoma, bronchial adenocarcinoma, bronchial squamous carcinoma, salivary
adenocarcinoma, teratoma, ovarian adenocarcinoma, meningioma has been reported.6
Fortunately, false positive uptake on radioiodine whole body scan can be interpreted with serum
thyroglobulin value, which is very sensitive marker for residual or recurrent thyroid cancer. Therefore, the false
positive uptake usually does not incur diagnostic dilemma in experienced practitioners. Clinical features and
other imaging studies can also help to distinguish the false positive pathologic lesions from true positive
metastatic thyroid cancer lesions.4,7
Fig. 29. Pathologic uptake of radioiodine in the bronchectatic lesions of both lungs. There noted intense tracer
uptake in the thyroid bed area (by remnant tissue of the gland).
Fig. 30. Pathologic uptake of radioiodine in the pulmonary fugus ball. There noted tracer uptake in the thyroid
bed area (by remnant tissue of the gland) and liver (by metabolism of radioiodinated thyroglobulin and thyroid
hormones).
Fig. 31. Pathologic uptake of radioiodine in a skin wound. There noted tracer uptake in the left lower leg where
the skin wound is located. There also noted tracer uptake in salivary gland (by NIS expression of the glands),
thyroid bed (by remnant tissue of the gland) and liver (by metabolism of radioiodinated thyroglobulin and
thyroid hormones).
6. Contaminations by physiological secretions can mimic metastatic lesion on the radioiodine whole body
scan
External contamination by physiological or pathological body secretions or excretions that causes
positive radioiodine uptake and mimics metastatic involvement of differentiated thyroid cancer.24 Sweat, breast
milk, urine, vomitus, and nasal, tracheobronchial, lacrimal, salivary secretions and faeces contain radioiodine
and their contamination to the hair, skin or clothes can be misinterpreted as metastasis of thyroid cancer.6 Any
focus of radioiodine uptake for which cannot be explained by physiological or pathological causation must be
also suspected as arising from contamination by the secretions.
Fortunately, the contaminations are usually easily recognized by their pattern and image acquisition
after removing the contamination with decontaminating procedures with taking the stained clothes off. However,
unusual patterns of contamination might occur and suspicion of uptake lesions as contamination would be
difficult. Patients' peculiar physical characteristics or odd habits produce extraordinary contamination patterns.
Uptake in the scalp or wig has been reported in patient with excessive sweating, and contamination of wig was
reported in patient with a bizarre habit of styling hair with sputum.24 False positive scan by contamination can
be kept to a minimum by careful preparation of patients, such as image acquisition in a clean gown after taking
shower.
Contaminations are almost always superficial,5 therefore, the use of lateral and/or oblique views to give
a third dimension to the scan may help to identify the contamination. Furthermore, SPECT image alone or
SPECT image fused with anatomical image, which provides detailed information about the anatomic location of
radiotracer uptake sites, can be the best way to correct cognition of contamination as the reason of the uptakes.
Fig. 32. Cases with contaminations at hair and scalp. Case with unilateral hair contamination by saliva and cases
with uni- or bilateral scalp contamination by perspiration were demonstrated.
Fig. 33. Contamination at right posterior chest wall by excessive perspiration. There also noted intense tracer
accumulation in thyroid bed (by remnant tissue of the thyroid and oedema of cervical soft tissue).
Fig. 34. Contamination at skin of right upper arm. There also noted intense tracer accumulation in rectum and
moderate tracer accumulation in descending colon and liver.
Fig. 35. Vanishing contaminations after cleansing at right forearm, both thighs and right foot. There also noted
intense tracer accumulation in thyroid bed area and colon and moderate tracer accumulation in the liver.
Fig. 36. Contamination at right shoulder by saliva were abolished in additional images obtained 4 days later.
There also noted intense tracer accumulations in thyroid bed area by residual thyroid tissue.
Fig. 37. Diffuse skin contamination by excessive perspiration and genital area by radioactive urine were
vanished after taking shower. There also noted intense tracer accumulations in thyroid bed area suggesting
lymph nodes metastasis.
Sites of uptake
Mechamism
radioiodine uptake
of
thyroid bed
Active
radioiodine
uptake by expression of
the NIS
Physiologic
Residual thyroid
tissue
Ectopic normal
thyroid tissues
Salivary gland
Lingual thyroid
mediatinal thyroid
Intratracheal thyroid
Paracardiac thyroid
Intraheaptic thyroid
Parotid
and
submandibular
salivary
glands
Lacrimal
sac/nasolacrimal
duct
Lacrimal gland*
By excreted or
swallowed saiva
Oral cavity
Oesophagus
Oesophageal diverticulum
Oesophageal stricture or
scarring
Achalasia
By
secretion
Nose "hot nose"
By
urine
nasal
excreted
Renal pelvis
Ureter
Urinary bladder
Urinary tract diverticulum
Urinary tract fistula
Renal cyst*
Choroid plexus
Brain
Thymic uptake
Thymus
Gastric mucosa
Stomach
Gastric duplication cyst
Meckel‘s diverticulum
Barrett esophagus
By
excreted
gastric secretion
Esophageal uptake
Bowel uptake
Metabolism of
radioiodinated
proteins
Liver
Biliary tract
Gall bladder
Bowels
Breast
Breast,
lactating
especially
Active
radioiodine
uptake by expression of
the NIS
Active
radioiodine
uptake by expression of
the NIS
Active
radioiodine
uptake by expression of
the NIS
*controversial
Focal
accumulated
saliva with radioiodine
activity
from
the
salivary glands
Focal accumulated nasal
secretion
with
radioiodine
Accumulated
urine
radioiodine
activity
excreted by the kidneys
* Active radioiodine
uptake by expression of
the NIS can be another
mechanism
Active
radioiodine
uptake by expression of
the NIS
Expression of NIS in
thymic tissues and/or
iodine concentration by
the Hassal’s bodies
Active
radioiodine
uptake by expression of
NIS
Gastroesophagel reflux
Translocation
of
excreted
gastric
secretion into bowel
Metabolism
of
radioiodinated thyroid
hormones
or
thyroglobulin and their
excretion
into
gall
bladder and bowels via
the biliary tract
Active
radioiodine
uptake by expression of
Colon
Diffuse and/or focal (any
part of colon)
the NIS
Transport of radioiodine
into the intestine from
the
mesenteric
circulation and biliary
excretion of metabolites
of
radioiodinated
thyroglobulin.
Pathologic
Heterotopic
thyroid tissues
Struma ovarii
Active
radioiodine
uptake by expression of
the NIS
Inflammations
Assicated
with/without
infection
Pericarditis
Skin burn
Dental disease
Arthritis
Cholecystitis
Folliculitis
Paranasal sinusitis
Dacryocystitis
Bronchiectasis
Fungal infection (eg,
aspergilloma)
Pleural and pericardial
effusions
Incrased
perfusion,
vasodilation, enhanced
capillary permeability
by the inflammation
Cystic lesions
Bronchogenic cyst
Renal cyst*
Unknown mechanism,
but most likely due to
expression of the NIS
* Communication with
the urinary tract can be
another
possible
mechanism
Non-thyroidal
neoplasms
Gastric adenocarcinoma
Salivary adenocarcinoma
Lung adenocarcinoma
Ovarian cystadenoma
Fibroadenoma
Meningioma
Nurilemoma
Teratoma
Active
radioiodine
uptake by the NIS of the
tumor and/or incresed
blood
flow
and
enhanced
capillary
permeability in the
tumor
Trauma
Biopsy site
Tracheostomy site
Incrased
perfusion,
vasodilation, enhanced
capillary permeability
by the tissue trauma
Skin of any part of the
body, hair, wig, cloth, etc
Contamination
by
physiological
or
pathological
body
secretions or excretions
Contaminations
Tear
Saliva
Sweat
Vomitus
Breast milk
Urine
Feces
Table 4. Causes of radioiodine uptake not related to thyroid cancer on the whole body scan. However, there are
cases having focal radioiodine uptakes which cannot be explained by physiological and pathological
mechanisms.
Fig. 38. Schematic presentation for locations of physiologic uptake and possible contamination sources on
radioiodine whole body scan.
Summary
Radioiodine whole body scan relies on the fact that differentiated thyroid cancer is efficient at
trapping circulating radioiodine than any other tissues, therefore, when I-131 is administered it accumulates in
the thyroid cancer tissues. Whole body scan obtained with administration of diagnostic or therapeutic dose of
radioiodine have definite role in the management of patients with well differentiated thyroid cancer after total
thyroidectomy. Except the physiological radioiodine uptake in the salivary glands, stomach, gastrointestinal and
urinary tracts, lesions with radioiodine uptake can be considered as metastatic lesion in thyroid cancer patients
who underwent total thyroidectomy. However, a variety of unusual lesions may also cause false positive result
on the radioiodine whole body scan and therefore careful evaluation of an abnormal scan is imperative to
manage patients with differentiated thyroid cancer appropriately. Accurate interpretation of the scan requires a
thorough knowledge and understanding of potential confounding factors for uptakes on the scan and recognition
of the variable causes of false positive uptake will provide correct prognostic inferences and prevent
inappropriate therapeutic interventions. In addition, cause of radioiodine uptake on the scan always evaluated in
conjunction with serum thyroglobulin and clinico-radiological results in order to lessen the chance of incorrect
conclusion about the uptakes. Nuclear medicine physicians should consider a possibility of physiologic or
pathologic false positive uptake or contamination as a reason of the tracer uptake on radioiodine whole body
scan.
Suggested readings
1. Oh JR, Ahn BC (2012) False-positive uptake on radioiodine whole-body scintigraphy: physiologic and
pathologic variants unrelated to thyroid cancer. Am J Nucl Med Mol Imaging. 2:362-85
2. Ahn BC (2012) Sodium iodide symporter for nuclear molecular imaging and gene therapy: from bedside to
bench and back. 2:392-402
2. Carlisle MR, Lu C, McDougall IR (2003) The interpretation of 131I scans in the evaluation of thyroid cancer,
with an emphasis on false positive findings. Nucl Med Commun 24:715-735
2. Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E (2008)
Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 35:19411959
3. Mitchell G, Pratt BE, Vini L, McCready VR, Harmer CL (2000) False positive
131
I whole body scans in
thyroid cancer. Br J Radiol 73:627-635
4. Shapiro B, Rufini V, Jarwan A, Geatti O, Kearfott KJ, Fig LM, Kirkwood ID, Gross MD (2000) Artifacts,
anatomical and physiological variants, and unrelated diseases that might cause false-positive whole-body 131I
scans in patients with thyroid cancer. Semin Nucl Med 30:115-132
5. Silberstein EB, Alavi A, Balon HR, Becker D, Charkes ND, Clarke SEM, Divgi CR, Donohoe KJ, Delbeke
D, Goldsmith SJ, Meier DA, Sarkar SD, Waxman AD (2006) Society of Nuclear Medicine Procedure
Guideline for Scintigraphy for Differentiated Papillary and Follicular Thyroid Cancer. On webisite of
Society of Nuclear Medicine
6. Silberstein EB, Alavi A, Balon HR, Becker DV, Brill DR, Clarke SEM, Divgi C, Goldsmith SJ, Lull RJ,
Meier DA, Royal HD, Siegel JA, Waxman AD (2005) Society of Nuclear Medicine Procedure Guideline for
Therapy of Thyroid Disease with Iodine-131 (Sodium Iodide) Version 2.0. On webisite of Society of
Nuclear Medicine
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Day 6 (22 Jun.)
X. Special Lectures (3 hrs) arranged by ARCCNM
Moderated by Henry Bom, M.D., Ph.D., Professor, Department of Nuclear Medicine,
Chonnam National University Hospital, Gwangju, Korea
9:00 ~ 10:00 Introduction to ARCCNM (1 hr)
by Henry Bom, M.D., Ph.D., Professor, Department of Nuclear Medicine, Chonnam
National University Hospital, Gwangju, Korea
10:00 ~ 12:00 Group discussion for Education and Training (2 hr)
by Henry Bom, M.D., Ph.D., Professor, Department of Nuclear Medicine, Chonnam
National University Hospital, Gwangju, Korea
12:00
Adjourn