Tc-99m MIBI Scintigraphy In Follow-up Of Post-therapy Differentiated Thyroid Carcinoma (DTC).

FULL PAPER

Tc-99m MIBI SCINTIGRAPHY IN FOLLOW-UP OF
POST-THERAPY DIFFERENTIATED THYROID
CARCINOMA (DTC)

Yudistiro R, Kartamihardja AHS, and Masjhur JS
Department of Nuclear Medicine,
School of Medicine Universitas Padjadjaran, Dr. Hasan Sadikin
Hospital, Bandung, Indonesia.

POSTER PRESENTATION
4 International Conference on Radiopharmaceutical Therapy
New World Hotel, Ho Chi Minh City, Vietnam
28 Nov – 2 Dec 2011
th

Tc-99m MIBI SCINTIGRAPHY IN FOLLOW-UP OF POSTTHERAPY DIFFERENTIATED THYROID CARCINOMA
(DTC)
Yudistiro R, Kartamihardja AHS, and Masjhur JS
Department of Nuclear Medicine,

School of Medicine Universitas Padjadjaran, Dr. Hasan Sadikin Hospital,
Bandung, Indonesia.
Abstract
Background. Long terms follow-up should be performed in post-therapy DTC

patients by measuring serum thyroglobulin (Tg-off) and Thyroglobulin-antigen
antibody (AbTg) level in stimulating TSH level every 6-12 months. NaI-131
scintigraphy is done to detect location of remnant thyroid and/or metastases.1
NaI-131 scintigraphy has several disadvantages, such as patient’s discomforts
and stunning effect.

99m

Tc-methoxyisobuthyisonitrile (MIBI) is routinely used

as tumor seeking agent; the advantages of 99mTc-MIBI scintigraphy in follow-up
of post-therapy DTC patients is still controversy. Diagnostic performance of
imaging can be measured by image resolution which is resulted from uptake
ratio.
Objective. To evaluate the uptake ratio and diagnostic value of


99m

Tc-MIBI and

NaI-131 scintigraphy using Tg-off level as gold standard.
Methods.

99m

Tc-MIBI and NaI-131 scintigraphy were done in 56 patients post-

total thyroidectomy and radiothyroablation with NaI-131 who underwent follow
up. Maximum counts activity was analyzed from region of interest (ROI) of
lesion and background to measure uptake ratio. Background ROI was made in
thigh projections.

Conclusion. 99mTc-MIBI scintigraphy is not better than NaI-131 scintigraphy by

using Tg-off as gold standard. NaI-131 scintigraphy is still the best methood in

follow-up of post-therapy DTC patients.

Keywords: Tc-99m MIBI, NaI-131, Thyroglobulin, Differentiated Thyroid
Carcinoma

Introduction
Long terms follow-up should be performed in post-therapy DTC patients
by measuring serum thyroglobulin (Tg-off) and Thyroglobulin-antigen antibody
(AbTg) level in stimulating TSH level every 6-12 months. The aim of this long
terms follw-up is to early detect of remnant malignancy, relapse and far
metastases, and monitoring of thyroid stimulating hormone (TSH) suppression.
American Thyroid Association 2009 Guidance recommend the use of
thyroglobulin-off (Tg-off) serum level as indicator and anti thyroglobulin
antibody (Tg-Ab) as validator of Tg-off.1,2
NaI-131 scintigraphy is done to detect location of remnant normal thyroid
and/or metastases with high specificity.3 NaI-131 scintigraphy has several
disadvantages, such as patient’s discomforts due to they have to stop thyroid
hormone substitution in order to reach TSH stimulation condition at least 10
times of normal limits. In this hypothyroidism condition, patient will suffer due
to decrease metabolic activity. Stunning effect is also the other disadvantage of

using NaI-131 as diagnostic agent, particularly it is done with high dose and
duration between diagnostic test and time of treatment is very close. NaI-131
scintigraphy should be done at 24 and 48 hours post administration of NaI-131,
so the procedure is take long time.4

Some studies found discordance between Tg-off serum level result and
NaI-131 scintigraphy in post radioiodine ablation patient with DTC. High Tgoff serum level with negative NaI-131 scintigraphy was found in 10-15% of
patient with DTC after radioiodine ablation, and on the other hand positive NaI131 scintigraphy with low Tg-off serum level were found even less.4,5
New and non-invasive imaging modalities is a challenge to replace NaI131 as diagnostic modality to detect and localize malignancy after radioiodine
ablation

without

stopping

TSH

substitution

and


suppression.
201

Tl, 99mTc-

Radiopharmaceuticals could be used for this imaging modality are
tetrofosmin, 99mTc-MIBI, 111In-octreotide, 123I and 18F-FDG.4,6,7
99m

Tc-methoxyisobuthyisonitrile (MIBI) is a cationic lipophilic. It will be

accumulated in mitochondria following intravenous injection. 8

99m

Tc-MIBI has

been used as a routine tumor seeking agent, since it can be accumulated in
malignant cell, such as nasopharynx, lung, parathyroid, breast cancer, multiple

myolema and ostegenic sarcoma.9-14 The advantages of

99m

Tc-MIBI

scintigraphy in follow-up of post-therapy DTC patients is still controversy. The
aim of this study was to evaluate the uptake ratio and diagnostic value of

99m

Tc-

MIBI and NaI-131 scintigraphy using Tg-off level as gold standard.

Material and methods
Subjects were patient with DTC who came to Departement of Nuclear
Medicine Dr. Hasan Sadikin General Hospital for following up after radioiodine
ablation. Subject should be under TSH stimulation with TSH serum level >
30uIU/ml as an obligatory for Tg-off level test and NaI-131 scintigraphy.


Measurement of Tg-off serum level and TSH using dual high affinity
monoclonal antibody method in immunoradiometric assay (IRMA), and
radioimmuno assay is use for Tg-Ab serum level.
99m

Tc-MIBI scintigraphy was done 15 minutes and 4 hours after

intravenous incjetion of 10-15 mCi (370-555 MBq) of radiopharmaceutical.
Total body image was taken by using gamma camera with low energy high
resolution, energy setting in 140 KeV, matrix size 256x256, 3.0 zooming and
window width 20%.
NaI-131 scintigraphy was done after 4-6 weeks without TSH suppression
or TSH serum level > 30 mIU/ml. NaI-131 image was taken 24-48 hours after
oral administration of 2 mCi (74%) NaI-131 by using gamma camera with high
energy collimator, energy setting in 364 KeV, matrix size 256x256, 3.0
zooming and window width 20%.
Uptake ratio from both images was calculated from radioactivity counts
taken from region of interest (ROI) of the target and background.


Statistic analysis
Statistic analysis was used SPSS program for windows version 13.0 with
degree of confidence interval 95% and significance if p value < 0.05. Bivariate
analysis was used to evaluate the different uptake between 99mTc-MIBI and NaI131 by using non-parametric test from Wilcoxon test. Diagnostic test was used
to determine sensitivity, specificity, PPV, NPV and accuracy.

Results
This study was involving 56 subjects consist of 10 (17.9%) male and 46
(82.1%) female, aged range 13-75 years old (X= 44.2 +14.8). Histopathological
finding was 46 (82.1%) papillary, 9 (16.1) follicular and 1 (1.8%) Hurtle cell.
Positive Tg-off serum level was found in 15 (26.8%) and negative 41 (73.2%).
Positive Tg-Ab level was found in 25 (44.6%) and negative in 31 (55.4%).
Positive

99m

Tc-MIBI Scintigraphy was found in 13 (23.2%) and negative in 43

(76.8%). Positive Na-I 131 scintigraphy wa found in 18 (32.1%) and negarive in
38 (67.9). Median and ranged uptake ratio of


99m

Tc-MIBI and Na-I 131 were

2.03 (1.8-3.2) and 1.67 (0.2-2.5) respectively. Wilcoxon-test with confidence
interval 95% showed there was no significance different between

99m

Tc-MIBI

and Na-I 131 uptake ratio with p value =0.068.
The results showed 7 (46.7%) out 13 subject with positive

99m

Tc-MIBI

Scintigraphy were postive Tg-off serum level. and 35 (85.4%) out of 43 subject

with negative

99m

Tc-MIBI Scintigraphy were negative Tg-off serum level as

well. McNemar –test with confidence interval 95% showed that there was no
significance different between

99m

Tc-MIBI Scintigraphy and Tg-off in

validation of following up DTC patients after radioiodine ablation with p value
=0.791. Sensitivity, specificity, PPV, NPV and accuracy of

99m

Tc-MIBI


Scintigraphy for following up patient with DTC after radioiodine ablation were
46.7%, 85.4%, 53.8%, 81.4% and 75% respectively. The results showed 12
(80%) out 18 subject with positive Na-I 131 scintigraphy were postive Tg-off
serum level, and 35 (85.4%) out of 38 subject with negative Na-I 131
scintigraphy were negative Tg-off serum level as well. McNemar–test with
confidence interval 95% showed that there was no significance different

between Na-I 131 scintigraphy and Tg-off in validation of following up DTC
patients after radioiodine ablation with p value =0.508. Sensitivity, specificity,
PPV, NPV and accuracy of Na-I 131 scintigraphy for following up patient with
DTC after radioiodine ablation were 80.0%, 85.4%, 66.7%, 92.1% and 83.9%
respectively. (table 1)
Tabel 1. Diagnostic value of 99m Tc-MIBI Scintigraphy and Na-I 131 scintigraphy.

Thyroglobulin
Variable
99m

Positive

Negative Sensitivity

Tc-MIBI Scintigraphy

Positive

7

6

Negative

8

35

NaI-131 Scintigraphy
Positive
Negative

A

Diagnostic Value

12

6

3

35

Specificity

PPV

NPV

Accuracy

46.7 %

85.4 %

53.8 %

81.4 %

75 %

80.0 %

85.4 %

66.7 % 92.1 %

83.9 %

B

FIGURE 1. Tc-99m MIBI scintigraphy in 53 years old male with positive Tg-off
and negative AbTg showed pathological uptake (arrow) in thyroid bed (A), while in
NaI-131 there is no pathological uptake in thyroid bed (B)

A

B

FIGURE 2. Tc-99m MIBI scintigraphy in 33 years old female with negative Tg-off
and positive AbTg showed pathological uptake (arrow) in thyroid bed (A), while in
NaI-131 there is no pathological uptake in thyroid bed (B)  False positive may be
due to inflammation or muscle activity.

Discussion
99m

Tc-MIBI has been using as tumor seeking agent in many studies. This

radiopharmaceutical can be use to detect malignancy in solitary thyroid
nodule.15 This study showed there is no significance different uptake ratio
between 99mTc-MIBI Scintigraphy and NaI-131 scintigraphy, but median uptake
of 99mTc-MIBI Scintigraphy was higher compared to NaI-131 scintigraphy. This
differences could be due to difference gamma ray energy level of

99m

Tc-MIBI

more ideal for gamma camera detector compared to NaI-131.
Sensitivity and specificity of both modalities were similar to other studies.
The sensitivity and specificity of

99m

Tc-MIBI Scintigraphy were 36-100% and

89-94% respectively, while NaI-131 scintigraphy were 47-84% and 96-99%
respectively.10 Low sensitivity of 99mTc-MIBI Scintigraphy could be due to high
backgroud uptake of

99m

Tc-MIBI. ROI of background was taken from soft

tissue (sceletal muscle) which is consist a lot of mitochondria, while NaI-131 is

not taken up by sceletal muscle. The other reason of low sensitivity of

99m

Tc-

MIBI Scintigraphy due to metabolic and blood flow degradation, and cell
membrane disorder of thyroid cell after radioiodine ablation. On the othe hand
the

sensitivity

of

NaI-131

scintigraphy

was

higher

due

to

this

radiopharmaceutical will be taken by both normal thyroid tissue and thyroid
cancer.10
This study showed 8 subjects with positive Tg-off serum level, but
negative on

99m

Tc-MIBI Scintigraphy considered as false negative. False

negative result of

99m

Tc-MIBI Scintigraphy could be due to the size of cancer

too small (microcarcinoma) to be detected with gamma camera with spatial
resulution >0.5 cm.16 False positive result of

99m

Tc-MIBI Scintigraphy was

observed in 6 subjects could be due to high uptake in sceletal muscle. It is
recommended not to do physical exercise to whom

99m

Tc-MIBI Scintigraphy

procedure will be applied.
False negative result in NaI-131 scintigraphy could be due to uptake
mechanism disorder, dedifferentiated tumor cell, and microcarcinoma. False
positive results of NaI-131 scintigraphy could be due to normal uptake of
choroidal flexus, salivary gland, gastric mucous, and urinary tract.4
In this study 25 subject with postive Tg-Ab showed 16 subjects with
negative Tg-off and 9 positive. Four out of 16 subjects showed positive

99m

Tc-

MIBI Scintigraphy and 1 subject showed positive NaI-131 scintigraphy. In 8 out
of 9 subject showed positive NaI-131 scintigraphy. Positive

99m

Tc-MIBI

Scintigraphy was observed in all subject with positive Tg-off and positive TgAb. This results showed that

99m

Tc-MIBI Scintigraphy has capability to detect

more remnant thyroid cancer in all subject with postive Tg-Ab.

The advantage of

99m

Tc-MIBI Scintigraphy was the procedure could be

done in TSH suppresion and no stunning effect. The patient could continue to
take thyroid hormone substitution.

Conclusion
The conclusion of this study were 99mTc-MIBI scintigraphy was not better
procedure than NaI-131 scintigraphy as following up patients with DTC after
radioiodine ablation by using Tg-off as gold standard. NaI-131 scintigraphy is
still the method of choice in follow-up patients with DTC after radioiodine
ablation.

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