**2. Salivary gland scintigraphy**

#### **2.1. Mechanism of uptake**

Salivary glands secrete saliva. The parotid, submandibular, and sublingual glands are called the "major salivary glands." Salivary epithelial cells have a sodium/iodide symporter (NIS), which takes up univalent anions such as Cl− and I− and concentrates them (**Figure 1**). The concentrated anion is secreted into saliva. Administered 99mTcO4− (**Figure 2**) is taken up by the salivary glands through NIS, similar to Cl−. Thus, intravenously administered 99mTcO4− accumulates mainly in the parotid and submandibular glands and is excreted into saliva [1]. After the accumulation of the radionuclide, loading of citric acid, such as lemon juice, stimulates the secretion of saliva, which indicates salivary gland function. Salivary gland scintigraphy is useful for differentiating salivary gland tumors because Warthin's tumors and oncocytomas, which are benign, retain 99mTcO4−.

#### **2.2. Testing procedure**

Because salivary gland function is affected by food intake, 1 hour of fasting is needed before testing.

For the kinetic analysis of salivary gland function, 185–370 MBq (5–10 mCi) of 99mTcO4− is intravenously administered. A dynamic scan (anteroposterior view) is performed at 5-minute intervals for 30 minutes. The thyroid gland should be included in the area. Citric acid (e.g., lemon juice) is instilled into the oral cavity 20 minutes after the intravenous injection to stimulate the secretion of saliva. The regions of interest are set at the bilateral parotid and submandibular glands, and at background regions to generate time-activity curves (TAC). The TAC is used to determine the function of individual salivary gland. For the diagnosis of tumors and morphology of salivary glands, the intravenously administered dose is 370–740 MBq, and the anteroposterior and lateral images are obtained 10–15 minutes after intravenous administration (**Figure 3**). When the assessment of the tumor is difficult due to the physiologic uptake in

**Figure 2.** Structural formula of 99mTcO4−. 99mTcO4− is incorporated into the salivary glands through NIS, similar to

Approach to Diagnosis of Salivary Gland Disease from Nuclear Medicine Images

http://dx.doi.org/10.5772/intechopen.70622

91

the normal salivary glands, washout by stimulating the secretion of saliva is useful.

salivary glands and the procedure is easier than that of sialography.

Salivary gland scintigraphy provides information about the morphology and function of the

The uptake in the bilateral parotid and submandibular glands begins less than 1 minute after intravenous administration of the radionuclide and increases over time. The uptake in the parotid glands is equal to or greater than that in the submandibular glands. The sublingual glands are not visible, though the reason is unknown. After the stimulation of saliva secretion, the uptake rapidly declines in all four glands and subsequently rises again. The percentage

**2.3. Imaging evaluation**

*2.3.2. Dynamic scans and TAC*

*2.3.1. Normal images*

Cl−.

**Figure 1.** Iodide uptake mechanism of sodium/iodide symporter. Sodium/iodide symporter transports two sodium ions and one iodide ion into the cytoplasm together.

**Figure 2.** Structural formula of 99mTcO4−. 99mTcO4− is incorporated into the salivary glands through NIS, similar to Cl−.

For the kinetic analysis of salivary gland function, 185–370 MBq (5–10 mCi) of 99mTcO4− is intravenously administered. A dynamic scan (anteroposterior view) is performed at 5-minute intervals for 30 minutes. The thyroid gland should be included in the area. Citric acid (e.g., lemon juice) is instilled into the oral cavity 20 minutes after the intravenous injection to stimulate the secretion of saliva. The regions of interest are set at the bilateral parotid and submandibular glands, and at background regions to generate time-activity curves (TAC). The TAC is used to determine the function of individual salivary gland. For the diagnosis of tumors and morphology of salivary glands, the intravenously administered dose is 370–740 MBq, and the anteroposterior and lateral images are obtained 10–15 minutes after intravenous administration (**Figure 3**). When the assessment of the tumor is difficult due to the physiologic uptake in the normal salivary glands, washout by stimulating the secretion of saliva is useful.

#### **2.3. Imaging evaluation**

#### *2.3.1. Normal images*

**2. Salivary gland scintigraphy**

90 Salivary Glands - New Approaches in Diagnostics and Treatment

oncocytomas, which are benign, retain 99mTcO4−.

Salivary glands secrete saliva. The parotid, submandibular, and sublingual glands are called the "major salivary glands." Salivary epithelial cells have a sodium/iodide symporter (NIS), which takes up univalent anions such as Cl− and I− and concentrates them (**Figure 1**). The concentrated anion is secreted into saliva. Administered 99mTcO4− (**Figure 2**) is taken up by the salivary glands through NIS, similar to Cl−. Thus, intravenously administered 99mTcO4− accumulates mainly in the parotid and submandibular glands and is excreted into saliva [1]. After the accumulation of the radionuclide, loading of citric acid, such as lemon juice, stimulates the secretion of saliva, which indicates salivary gland function. Salivary gland scintigraphy is useful for differentiating salivary gland tumors because Warthin's tumors and

Because salivary gland function is affected by food intake, 1 hour of fasting is needed before

**Figure 1.** Iodide uptake mechanism of sodium/iodide symporter. Sodium/iodide symporter transports two sodium ions

**2.1. Mechanism of uptake**

**2.2. Testing procedure**

and one iodide ion into the cytoplasm together.

testing.

Salivary gland scintigraphy provides information about the morphology and function of the salivary glands and the procedure is easier than that of sialography.

#### *2.3.2. Dynamic scans and TAC*

The uptake in the bilateral parotid and submandibular glands begins less than 1 minute after intravenous administration of the radionuclide and increases over time. The uptake in the parotid glands is equal to or greater than that in the submandibular glands. The sublingual glands are not visible, though the reason is unknown. After the stimulation of saliva secretion, the uptake rapidly declines in all four glands and subsequently rises again. The percentage

**Figure 3.** Static images in normal case. The radionuclide uptake of the parotid and submandibular glands is equal to or lower than that of the normal thyroid gland.

solid component of these tumors and is not eliminated after the stimulation of saliva secretion. However, the uptake may be reduced in Warthin's tumor mainly with a cystic component. The diagnostic accuracy of salivary gland scintigraphy for Warthin's tumors and oncocytomas is around 90%, but these cannot be differentiated in salivary gland scintigraphy. Because Warthin's tumors develop bilaterally in 5–20% of cases, the contralateral parotid gland should be carefully evaluated. Meanwhile, because 99mTcO4− is not taken up by pleomorphic adenomas or parotid gland cancer (defect images), salivary gland scintigraphy is useful for differ-

**Figure 4.** TAC of the normal salivary gland. After intravenous administration of the radionuclide, uptake in the parotid and submandibular glands increases over time. At 20 minutes after administration, saliva secretion is stimulated. Counts

Approach to Diagnosis of Salivary Gland Disease from Nuclear Medicine Images

http://dx.doi.org/10.5772/intechopen.70622

93

The indications for kinetic analysis of salivary gland function include Sjögren's syndrome, acute/chronic sialadenitis, and facial/glossopharyngeal nerve palsy. Salivary gland function is assessed based on dynamic images and TAC. In general, chronic sialadenitis shows a decreased uptake while acute sialadenitis shows an increased uptake; acute/chronic sialadenitis shows a reduced or no response to stimulation of saliva secretion. Uptake in salivary glands is barely evident in patients with severe Sjögren's syndrome (**Figures 6** and **7**). The severity of the reduction in washout after the stimulation of saliva secretion well correlates with the results of the Saxon test. Thus, kinetic analysis reflects the severity of Sjögren's syndrome,

entiation [2].

**2.5. Kinetic analysis of salivary gland function**

in the salivary glands rapidly decline and then gradually increase again.

allowing an objective assessment of salivary gland function [3].

of washout is calculated using the counts at the maximum uptake and those at the minimum uptake seen after the stimulation of saliva secretion in each gland. The washout (%) is 50% or higher in the normal salivary gland (**Figure 4**).

#### *2.3.3. Static images*

The radionuclide uptake of the parotid and submandibular glands are equal to or lower than that of the normal thyroid gland, and mild uptake appears in the nasal and oral cavities. On the lateral view, the parotid gland is clearly shown, but the submandibular gland overlaps with the contralateral submandibular gland.

#### **2.4. Diagnosis of salivary gland tumors**

Warthin's tumors and oncocytomas are derived from the epithelial cells of excretory ducts and do not communicate via excretory ducts (**Figure 5**). Thus, 99mTcO4− is taken up by the Approach to Diagnosis of Salivary Gland Disease from Nuclear Medicine Images http://dx.doi.org/10.5772/intechopen.70622 93

**Figure 4.** TAC of the normal salivary gland. After intravenous administration of the radionuclide, uptake in the parotid and submandibular glands increases over time. At 20 minutes after administration, saliva secretion is stimulated. Counts in the salivary glands rapidly decline and then gradually increase again.

solid component of these tumors and is not eliminated after the stimulation of saliva secretion. However, the uptake may be reduced in Warthin's tumor mainly with a cystic component. The diagnostic accuracy of salivary gland scintigraphy for Warthin's tumors and oncocytomas is around 90%, but these cannot be differentiated in salivary gland scintigraphy. Because Warthin's tumors develop bilaterally in 5–20% of cases, the contralateral parotid gland should be carefully evaluated. Meanwhile, because 99mTcO4− is not taken up by pleomorphic adenomas or parotid gland cancer (defect images), salivary gland scintigraphy is useful for differentiation [2].

#### **2.5. Kinetic analysis of salivary gland function**

of washout is calculated using the counts at the maximum uptake and those at the minimum uptake seen after the stimulation of saliva secretion in each gland. The washout (%) is 50% or

**Figure 3.** Static images in normal case. The radionuclide uptake of the parotid and submandibular glands is equal to or

The radionuclide uptake of the parotid and submandibular glands are equal to or lower than that of the normal thyroid gland, and mild uptake appears in the nasal and oral cavities. On the lateral view, the parotid gland is clearly shown, but the submandibular gland overlaps

Warthin's tumors and oncocytomas are derived from the epithelial cells of excretory ducts and do not communicate via excretory ducts (**Figure 5**). Thus, 99mTcO4− is taken up by the

higher in the normal salivary gland (**Figure 4**).

92 Salivary Glands - New Approaches in Diagnostics and Treatment

lower than that of the normal thyroid gland.

with the contralateral submandibular gland.

**2.4. Diagnosis of salivary gland tumors**

*2.3.3. Static images*

The indications for kinetic analysis of salivary gland function include Sjögren's syndrome, acute/chronic sialadenitis, and facial/glossopharyngeal nerve palsy. Salivary gland function is assessed based on dynamic images and TAC. In general, chronic sialadenitis shows a decreased uptake while acute sialadenitis shows an increased uptake; acute/chronic sialadenitis shows a reduced or no response to stimulation of saliva secretion. Uptake in salivary glands is barely evident in patients with severe Sjögren's syndrome (**Figures 6** and **7**). The severity of the reduction in washout after the stimulation of saliva secretion well correlates with the results of the Saxon test. Thus, kinetic analysis reflects the severity of Sjögren's syndrome, allowing an objective assessment of salivary gland function [3].

**Figure 5.** Warthin's tumor. On the image 20 minutes after administration, the radionuclide is taken up by the right parotid gland. After the stimulation of saliva secretion, the radionuclide remains in the right parotid tumor. The diagnosis was Warthin's tumor.

**3. Scintigraphy of inflammation (67Ga scintigraphy)**

stimulation of saliva secretion 20 minutes after administration. TAC is useful for assessment.

**3.2. Testing procedure and imaging evaluation**

67Ga administered intravenously binds to transferrin, a serum protein, and is transported into cells through transferrin receptors. The carbon atom of citrate stabilizes the bond between 67Ga and transferrin. Transferrin receptors that bind to 67Ga distributed in lysosomes and cytoplasm are often present in tumor and inflammatory cells, which show intense

**Figure 7.** TAC of the Sjögren's syndrome. All four salivary glands show decreased uptake and a poor response to

Approach to Diagnosis of Salivary Gland Disease from Nuclear Medicine Images

http://dx.doi.org/10.5772/intechopen.70622

95

67Ga is intravenously administered at a dose of 185–555 MBq. Imaging is performed 48–72 hours after intravenous administration to visualize the distribution of the radionuclide. 67Ga is excreted from the kidney and intestinal tract within 24 hours after administration and is mainly excreted by the liver. Intense uptake of 67Ga is noted in the liver, bone, and spleen 48–72 hours after administration. 67Ga is known to be taken up by inflammation and tumors; however, the sensitivity of 67Ga scintigraphy is low for malignant tumors, while the negative predictive value is high. Thus, a negative finding of focal uptake is likely to represent a benign lesion or low-grade tumor. Focal uptake in the parotid gland on 67Ga scintigraphy is useful for the supplemental diagnosis of Warthin's tumor. Meanwhile, with increased diffuse bilateral uptake, differential diagnosis includes sarcoidosis (**Figure 8**),

**3.1. Mechanism of uptake**

uptake of 67Ga.

**Figure 6.** Sjögren's syndrome. All four salivary glands show decreased uptake.

Approach to Diagnosis of Salivary Gland Disease from Nuclear Medicine Images http://dx.doi.org/10.5772/intechopen.70622 95

**Figure 7.** TAC of the Sjögren's syndrome. All four salivary glands show decreased uptake and a poor response to stimulation of saliva secretion 20 minutes after administration. TAC is useful for assessment.
