Is Brown Adipose Tissue Visualization Reliable on 99mTc-Methoxyisobutylisonitrile Diagnostic SPECT Scintigraphy?

Abstract The 99mTc-MIBI has been used with great value as a diagnostic technique in patients with primary hyperparathyroidism. False-positive scans may occur due to misinterpretation of the physiologic distribution of the 99mTc-MIBI. Reviewing consecutive SPECT scans, we evaluated this possibility and assessed how frequently brown adipose tissue (BAT) is seen on 99mTc-MIBI scintigraphy. Here, we retrospectively reviewed scans of consecutive patients who were evaluated for parathyroid adenomas from March 2015 to June 2015, using dual-phase (early and delayed) planar imaging and SPECT. We identified 60 patients (48 female and 12 male; mean age, 52.25 ± 15.20 years; range, 22–86 years). We detected the presence of 99mTc-MIBI uptake in BAT in 20 of 60 patients (33.33%) in the neck. Although the patients with 99mTc-MIBI uptake in BAT were younger (mean age, 48.85 ± 15.27 years, range, 26–73 years) than the patients with no 99mTc-MIBI uptake (mean age, 53.95 ± 15.07 years, range, 22–86 years), this difference was not statistically significant (P = 0.224). The percentage of female patients with BAT detection was higher (17/48 patients; 37.5%) than that of the male population (3/12 patients; 25%), this difference was not also statistically significant (P = 0.85). In patient population referred to 99mTc MIBI scintigraphy of the parathyroid glands, uptake of 99mTc-MIBI in BAT should not be misinterpreted with 99mTc-MIBI-avid-tumors. Fused SPECT/CT images (not SPECT-only) are necessary to distinguish BAT from bone, muscle, thyroid, myocardium, parathyroids, and other structures in the neck and chest.


INTRODUCTION
T hallium-201 ( 201 Tl) scintigraphy was the first radionuclide diagnostic method widely used in the 1980s for hyperfunctioning parathyroid localization. 1 For parathyroid localization 99m Tc scintigram which is taken up only by the thyroid was digitally subtracted from the 201 Tl scintigram which is taken up by both the thyroid and parathyroid glands. 2 In 1989, Coakley et al 3 used 99m Tc-methoxyisobutylisonitrile ( 99m Tc-MIBI) for parathyroid scintigraphy. Thallium superseded by the novel radionuclide because of several advantages such as higher energy (that makes it ideal for gamma camera imaging), better dosimetry and higher sensitivity. 4,5 The subtraction of thyroid images obtained with 123 I or 99m Tc from those obtained with 99m Tc-MIBI is a variation of this method. 6,7 Taillefer et al 8 found that 99m Tc-MIBI washes out more rapidly from thyroid gland than from hyperfunctioning parathyroid glands, so they suggested the use of a single-isotope dual-phase (early and delayed) scintigraphic method. 99m Tc tetrofosmin also has been used for parathyroid imaging, but the experiential data for this technique are scarce. 1 In some adults, brown adipose tissue (BAT) is metabolically active and can cause false-positive scans due to misinterpretation of the physiologic distribution of the 99m Tc MIBI. Previously, BAT has been detected by some nuclear imaging methods such as single-photon imaging using 123 I-metaiodobenzylguanidine, 9,10 and by PET using 18 F-FDG 11,12 or 99m Tc-tetrofosmin 13 in humans. Assessment of the visualized body during a 99m Tc MIBI scintigraphy of the heart or parathyroid glands is essential to exclude incidental tumoral uptake, which may be 99m Tc-MIBI-avid. As we know, there has been some new evidence of 1,14,15 99m Tc-MIBI uptake into BAT in humans so, reviewing consecutive SPECT scans we evaluated this possibility and assessed how frequently BAT is seen on 99m Tc-MIBI scintigraphy.

Patient Population
Here we retrospectively reviewed scans of consecutive patients who were evaluated for parathyroid adenomas from March 2015 to June 2015, using dual-phase (early and delayed) planar imaging and SPECT. We identified 60 patients (48 female and 12 male; mean age, 52.25 AE 15.20 years, range, 22-86 years). As the study was retrospective and also anonymous, ethical approval was not necessary.

Imaging Protocol and Analysis
All patients were injected intravenously with 740 to 925 MBq of 99m Tc-MIBI. We used a commercially available sestamibi kit (AEOI, Tehran, Iran) and according to the manufacturer's instructions, it was labeled and quality controlled.

Imaging
At 20, 120, and 180 min after injection, 10-min anterior planar images were acquired in a 128 Â 128 matrix, with a 20% window centered around the 140-keV photopeak, using a lowenergy, high-resolution parallel collimator. SPECT images of the neck and chest were obtained using a rotating, calibrated General Electric Infinia Hawkeye 4 scintillation dual-head gamma camera(Fairfield , Connecticut, United States) equipped with a low energy high resolution parallel hole collimator immediately after planar imaging (at approximately 20 min).

RESULTS
We detected the presence of 99m Tc-MIBI uptake in BAT in 20 of 60 patients (33.33%) in the neck (Figures 1 and 2). When BAT was visualized, it was detected on both early and delayed scans. Although the patients with 99m Tc-MIBI uptake in BAT were younger (mean age, 48.85 AE 15.27 years, range, 26-73 years) than the patients with no 99m Tc-MIBI uptake (mean age, 53.95 AE 15.07 years, range, 22-86 years), this difference was not statistically significant (P ¼ 0.224). The percentage of female patients with BAT detection was higher (17/48 patients; 37.5%) than that of the male population (3/12 patients; 25%), this difference was not also statistically significant (P ¼ 0.85).

DISCUSSION
After intravenous injection of 99m Tc-MIBI, this cationic radiotracer, which is also lipophilic, is distributed by blood flow in the body, cross the cellular membrane by passive transport, and become concentrated in the mitochondria. 16 As hyperplastic parathyroid glands and parathyroid adenomas contain oxyphil cells laden with mitochondria, they can be visualized in 99m Tc-MIBI scintigraphy. 1 Concentration of radiotracer is generally noticed in the infusion administered vein and it should not be mistaken with abnormal findings. 1 Pioneer 99m Tc-MIBI usage as a radiotracer was limited to myocardial scintigraphy but became expanded due to considerable concentration in different type of tumors. Although normal parathyroid glands have no uptake, normal concentration of 99m Tc-MIBI is visualized in many tissues such as the thyroid gland, parotid and submandibular salivary glands, heart, and liver. Occasionally mild generalized uptake in the bone marrow and thymic uptake in young patients is visualized. Secondary to radiotracer secretion from the salivary glands, consideration of oral cavity accumulation in nonsevere degree is probable. 1 99m Tc-MIBI uptake also may be seen in BAT, metabolically active tissue, and should not be misinterpreted with disease, such as abnormal uptake in tumors, thyroid cancer, lymph nodes, parathyroid adenomas, or muscle. 17 Despite reports of 99m Tc-MIBI uptake in BAT in rats, 18,19 only a few data exist in the literature demonstrating 99m Tc-MIBI uptake in BAT in a human, using SPECT (or SPECT/CT). 14,15 BAT is depicted by abundant vasculature and high mitochondrial metabolic activity and plays an important role in thermoregulation. Although additional studies are needed to understand the precise mechanism of 99m Tc-MIBI uptake in BAT but it is likely related to relatively high regional blood flow, possibly even more than to increased mitochondrial density and function. 14,[18][19][20] The frequency of BAT visualization in our study (SPECT-only) is very high in comparison with the frequency reported in studies with SPECT-CT in adults (33.33% for SPECT vs 6.3% for SPECT-CT). A higher frequency of BAT visualization with SPECT in this study might be related to the fact that no CT was obtained to ascertain that the tracer accumulation definitely is in BAT. In accordance with previous study 21 that showed the importance of fused single-photon emission computed tomography (SPECT)/ computed tomography (CT) images in radionuclide scintigraphy, BAT also could be clearly distinguished from bone, muscle, myocardium, thyroid, parathyroids, and other structures in the neck and chest (CT image of the expected region had to show fat tissue density and SPECT-only images of the patients had to show BAT in the same region).

CONCLUSION
In patient population referred to 99m Tc MIBI scintigraphy of the parathyroid glands, uptake of 99m Tc-MIBI in BAT should not be misinterpreted with 99m Tc-MIBI-avid-tumors. Fused SPECT/CT images (not SPECT-only) are necessary to distinguish BAT from bone, muscle, thyroid, myocardium, parathyroids, and other structures in the neck and chest.