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

### **3.1. Mechanism of uptake**

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

diagnosis was Warthin's tumor.

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**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

> 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 uptake of 67Ga.

#### **3.2. Testing procedure and imaging evaluation**

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**),

is taken up by cells via glucose transporters and phosphorylated; however, unlike glucose, FDG remains in cells after phosphorylation. In general, glucose transporters and glucose metabolism are increased in tumor cells, leading to an increased uptake of FDG (**Figure 9**). The widespread use of PET combined with computed tomography (PET/CT) has increased the diagnostic accuracy by compensating for PET disadvantages, including poor spatial resolution and lack of anatomic information. Moreover, PET combined with magnetic resonance

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Fasting is required for 4 hours before testing and intake of liquids with sugar content is prohibited. FDG (**Figure 10**) is intravenously administered at a dose of 185–444 MBq (5–12 mCi). Imaging is performed 60–90 minutes after administration to visualize distribution. The accumulation is visually and semi-quantitatively assessed using the standardized uptake value

**Figure 9.** Mechanism of FDG uptake. Like glucose, FDG is taken up by cells via glucose transporters and phosphorylated;

**Figure 10.** The chemical structure of FDG. The chemical structure of FDG is identical to that of 18F (one of the hydroxy

(SUV), which is the ratio of uptake to the injected dose per unit body weight.

imaging (PET/MRI) has recently emerged.

however, unlike glucose, FDG remains in cells after phosphorylation.

groups of glucose that is replaced by a positron-emitting radionuclide).

**4.2. Testing procedure**

**Figure 8.** 67Ga scintigraphy. Upper column, normal image; lower column, sarcoidosis. Uptake is noted in the bilateral parotid glands (arrow), and mediastinal/hilar lymph nodes (arrowhead).

IgG4-related disease, Sjögren's syndrome, and Mikulicz disease. In recent years, 67Ga scintigraphy for tumor diagnosis has been increasingly replaced by FDG-PET, as described below.

#### **4. PET**

#### **4.1. Mechanism of uptake**

FDG-PET is a critical modality for determining the localization, focal lesions, and staging of many malignant tumors, as well as for their follow-up observation. It is also essential for the clinical management of salivary tumors [4–8]. Like glucose, fluorodeoxyglucose (FDG) is taken up by cells via glucose transporters and phosphorylated; however, unlike glucose, FDG remains in cells after phosphorylation. In general, glucose transporters and glucose metabolism are increased in tumor cells, leading to an increased uptake of FDG (**Figure 9**). The widespread use of PET combined with computed tomography (PET/CT) has increased the diagnostic accuracy by compensating for PET disadvantages, including poor spatial resolution and lack of anatomic information. Moreover, PET combined with magnetic resonance imaging (PET/MRI) has recently emerged.

#### **4.2. Testing procedure**

IgG4-related disease, Sjögren's syndrome, and Mikulicz disease. In recent years, 67Ga scintigraphy for tumor diagnosis has been increasingly replaced by FDG-PET, as described

**Figure 8.** 67Ga scintigraphy. Upper column, normal image; lower column, sarcoidosis. Uptake is noted in the bilateral

parotid glands (arrow), and mediastinal/hilar lymph nodes (arrowhead).

96 Salivary Glands - New Approaches in Diagnostics and Treatment

FDG-PET is a critical modality for determining the localization, focal lesions, and staging of many malignant tumors, as well as for their follow-up observation. It is also essential for the clinical management of salivary tumors [4–8]. Like glucose, fluorodeoxyglucose (FDG)

below.

**4. PET**

**4.1. Mechanism of uptake**

Fasting is required for 4 hours before testing and intake of liquids with sugar content is prohibited. FDG (**Figure 10**) is intravenously administered at a dose of 185–444 MBq (5–12 mCi). Imaging is performed 60–90 minutes after administration to visualize distribution. The accumulation is visually and semi-quantitatively assessed using the standardized uptake value (SUV), which is the ratio of uptake to the injected dose per unit body weight.

**Figure 9.** Mechanism of FDG uptake. Like glucose, FDG is taken up by cells via glucose transporters and phosphorylated; however, unlike glucose, FDG remains in cells after phosphorylation.

**Figure 10.** The chemical structure of FDG. The chemical structure of FDG is identical to that of 18F (one of the hydroxy groups of glucose that is replaced by a positron-emitting radionuclide).

#### **4.3. Normal uptake**

In the head and neck areas, many structures show physiologic uptake, including salivary glands, nasal and sinonasal mucosa, extraocular muscles, and lymphoid tissue. Because artifacts due to dentures are also often seen, information on CT or MRI images is useful [8].

uptake. Some studies have reported that the differentiation of benign from malignant salivary tumors is possible with the use of indices such as dual-time-point (DTP) imaging and tumor

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The sensitivity of PET/CT is approximately 80% for the detection of preoperative primary lesions (**Figure 12**), but the accuracy for staging may vary. In particular, FDG-PET images

Sialadenitis may show diffuse, increased uptake. However, some cases may show unilateral uptake due to the distribution of inflammation and may be difficult to differentiate from a tumor. FDG-PET, which provides information about systemic metabolism, is very useful for detecting primary or recurrent lesions for the determination of treatment strategy in cases with highly-malignant tumors requiring aggressive treatment. FDG-PET aids in detection of local involvement, regional lymph node metastasis, distant metastasis, and dissemination for the clinical staging and restaging. It is also useful in the detection of an incidental

**Figure 12.** (a). PET MIP image. (b). PET/CT fusion image. (c). T1-weighted MRI using gadolinium-based contrast (GdT1) image. Very strong uptake of FDG (SUVmax: 15.8, arrow) is seen in the region corresponding to the left parotid tumor on the MRI image. Uptake is seen in the region of the right internal jugular lymph nodes (SUVmax: 10.2, arrow head).

Parotid cancer or cervical lymph node metastasis is suspected.

often show false-positive results for the diagnosis of cervical lymph nodes.

volume, in addition to SUVmax [4, 5].

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

Some lesions are difficult to differentiate from normal structures, postoperative changes, and inflammatory changes on CT or MRI images alone. However, those lesions can be diagnosed through the combined use of FDG-PET [4, 5, 7]. FDG-PET for medical evaluation or staging of a malignant tumor may incidentally reveal a salivary gland tumor [7, 9].

The differentiation of benign from malignant parotid tumors is difficult based on the results of FDG uptake alone. Moreover, the differentiation of benign from malignant salivary tumors is often difficult based on the comparison of the results of SUVmax alone. A malignant tumor tends to show more intense FDG uptake than a benign tumor; however, benign tumors, such as Warthin's tumor and pleomorphic adenoma (**Figure 11**) [10–12], also show high FDG

**Figure 11.** Warthin's tumor. (a). PET MIP image. (b). PET/CT fusion image. (c). T1-weighted MRI image. FDG is strongly taken up by the tumor (SUVmax: 9.4) in the right parotid gland. MRI also provides many findings consistent with malignancy. Salivary gland scintigraphy is useful for differentiation.

uptake. Some studies have reported that the differentiation of benign from malignant salivary tumors is possible with the use of indices such as dual-time-point (DTP) imaging and tumor volume, in addition to SUVmax [4, 5].

**4.3. Normal uptake**

**4.4. Diagnosis of salivary gland tumors**

98 Salivary Glands - New Approaches in Diagnostics and Treatment

In the head and neck areas, many structures show physiologic uptake, including salivary glands, nasal and sinonasal mucosa, extraocular muscles, and lymphoid tissue. Because artifacts due to dentures are also often seen, information on CT or MRI images is useful [8].

Some lesions are difficult to differentiate from normal structures, postoperative changes, and inflammatory changes on CT or MRI images alone. However, those lesions can be diagnosed through the combined use of FDG-PET [4, 5, 7]. FDG-PET for medical evaluation or staging of

The differentiation of benign from malignant parotid tumors is difficult based on the results of FDG uptake alone. Moreover, the differentiation of benign from malignant salivary tumors is often difficult based on the comparison of the results of SUVmax alone. A malignant tumor tends to show more intense FDG uptake than a benign tumor; however, benign tumors, such as Warthin's tumor and pleomorphic adenoma (**Figure 11**) [10–12], also show high FDG

**Figure 11.** Warthin's tumor. (a). PET MIP image. (b). PET/CT fusion image. (c). T1-weighted MRI image. FDG is strongly taken up by the tumor (SUVmax: 9.4) in the right parotid gland. MRI also provides many findings consistent with

malignancy. Salivary gland scintigraphy is useful for differentiation.

a malignant tumor may incidentally reveal a salivary gland tumor [7, 9].

The sensitivity of PET/CT is approximately 80% for the detection of preoperative primary lesions (**Figure 12**), but the accuracy for staging may vary. In particular, FDG-PET images often show false-positive results for the diagnosis of cervical lymph nodes.

Sialadenitis may show diffuse, increased uptake. However, some cases may show unilateral uptake due to the distribution of inflammation and may be difficult to differentiate from a tumor.

FDG-PET, which provides information about systemic metabolism, is very useful for detecting primary or recurrent lesions for the determination of treatment strategy in cases with highly-malignant tumors requiring aggressive treatment. FDG-PET aids in detection of local involvement, regional lymph node metastasis, distant metastasis, and dissemination for the clinical staging and restaging. It is also useful in the detection of an incidental

**Figure 12.** (a). PET MIP image. (b). PET/CT fusion image. (c). T1-weighted MRI using gadolinium-based contrast (GdT1) image. Very strong uptake of FDG (SUVmax: 15.8, arrow) is seen in the region corresponding to the left parotid tumor on the MRI image. Uptake is seen in the region of the right internal jugular lymph nodes (SUVmax: 10.2, arrow head). Parotid cancer or cervical lymph node metastasis is suspected.

cancer. Therefore, this imaging modality is essential before the initiation of treatment and for patient follow-up [4, 5, 13–15].

evidence is limited, the advantages of radionuclide scanning should be determined. For RAI therapy, attention should be paid to adverse reactions. Coordination among healthcare providers including nurses, radiological technologists, and doctors of all departments involved

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in treatment is important for achieving effective outcomes.

This work was supported by JSPS KAKENHI Grant Number 16K20745.

Michihiro Nakayama\*, Atsutaka Okizaki, Kaori Nakajima and Koji Takahashi

[1] Pilbrow W, et al. Salivary gland scintigraphy–A suitable substitute for sialography? The

[2] Miyake H, et al. Warthin's tumor of parotid gland on Tc-99m pertechnetate scintigraphy with lemon juice stimulation: Tc-99m uptake, size, and pathologic correlation. European

[3] Shizukuishi K, et al. Gland scintigraphy in patients with Sjogren's syndrome. Annals of

[4] Jeong HS, et al. Role of 18 F-FDG PET/CT in management of high-grade salivary gland

[5] Nakayama M, et al. Dual-time-point F-18 FDG PET/CT imaging for differentiating the lymph nodes between malignant lymphoma and benign lesions. Annals of Nuclear

[6] Hadiprodjo D, et al. Parotid gland tumors: Preliminary data for the value of FDG PET/CT diagnostic parameters. AJR. American Journal of Roentgenology. 2012;**198**:W185-W190

[7] Wang HC, et al. Efficacy of conventional whole-body 18F-FDG PET/CT in the incidental

findings of parotid masses. Annals of Nuclear Medicine. 2010;**24**:571-577

\*Address all correspondence to: m-naka@asahikawa-med.ac.jp Department of Radiology, Asahikawa Medical University, Japan

British Journal of Radiology. 1990;**63**:190-196

malignancies. Nuclear-Medizin. 2007;**48**:1237-1244

Medicine. 2013;**27**:163-169. DOI: 10.1007/s12149-012-0669-1

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**Acknowledgements**

**Author details**

**References**
