FULL PAPER
T
c-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
thInternational Conference on Radiopharmaceutical Therapy
New World Hotel, Ho Chi Minh City, Vietnam
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.
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. 99mTc-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 99mTc-MIBI and
NaI-131 scintigraphy using Tg-off level as gold standard.
Methods. 99mTc-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
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
scintigraphyshould be done at 24 and 48 hours post administration of NaI-131,
Some studies found discordance between Tg-off serum level result and
NaI-131 scintigraphy in post radioiodine ablation patient with DTC. High
Tg-off 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
NaI-131 scintigraphy with low Tg-off serum level were found even less.4,5
New and non-invasive imaging modalities is a challenge to replace
NaI-131 as diagnostic modality to detect and localize malignancy after radioiodine
ablation without stopping TSH substitution and suppression.
Radiopharmaceuticals could be used for this imaging modality are 201Tl, 99m
Tc-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 99mTc-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 99mTc-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 >
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
NaI-131 by using non-parametric test from Wilcoxon test. Diagnostic test was used
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 99mTc-MIBI
Scintigraphy were postive Tg-off serum level. and 35 (85.4%) out of 43 subject
with negative 99mTc-MIBI Scintigraphy were negative Tg-off serum level as
well. McNemar –test with confidence interval 95% showed that there was no
significance different between 99mTc-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 99mTc-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
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.
Variable
Thyroglobulin Diagnostic Value
Positive Negative Sensitivity Specificity PPV NPV Accuracy
99m
Tc-MIBI Scintigraphy 46.7 % 85.4 % 53.8 % 81.4 % 75 %
Positive 7 6
Negative 8 35
NaI-131 Scintigraphy 80.0 % 85.4 % 66.7 % 92.1 % 83.9 %
Positive 12 6
Negative 3 35
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)
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 99mTc-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 99mTc-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 99mTc-MIBI. ROI of background was taken from soft
tissue (sceletal muscle) which is consist a lot of mitochondria, while NaI-131 is
A
B
FIGURE 2. Tc-99m MIBI scintigraphy in 33 years old female with negative Tg-off
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 99mTc-MIBI Scintigraphy considered as false negative. False
negative result of 99mTc-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 99mTc-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 99mTc-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 99mTc-MIBI
Scintigraphy was observed in all subject with positive off and positive
Tg-Ab. This results showed that 99mTc-MIBI Scintigraphy has capability to detect
The advantage of 99mTc-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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