Comparison between squamous cell carcinoma and inflammatory diseases of the oral and maxillofacial region using gallium-67 scintigraphy with computed tomography and magnetic resonance imaging.

PURPOSE: This study aimed to compare squamous cell carcinoma (SCC) with inflammatory diseases of the oral and maxillofacial region using gallium 67 (67Ga) scintigraphy with computed tomography (CT) and magnetic resonance imaging (MRI).
MATERIAL AND METHODS: Seventy patients with SCC and 15 patients with inflammatory diseases of the oral and maxillofacial region underwent 67Ga scintigraphy with CT and MRI. A comparison between imaging features of 67Ga scintigraphy, CT, and MRI and lesions was performed with the Pearson's chi-squared test.
RESULTS: 67Ga scintigraphy was positive for 25 of 39 patients with SCC positive on CT and/or MRI (64.1%) and for 13 of 15 patients with inflammatory diseases positive on CT and/or MRI (86.7%). The detection of inflammatory diseases with 67Ga scintigraphy was higher than that of SCC (p = 0.104).
CONCLUSIONS: This study compared SCC with inflammatory diseases of the oral and maxillofacial region using 67Ga scintigraphy with CT and MRI. 67Ga scintigraphy is an effective technique for detection of inflammatory diseases of the oral and maxillofacial region.

Introduction

Gallium 67 (67Ga) scintigraphy is a useful adjunct tool for differentiation of malignant tumours from benign tumours or inflammatory disease in the oral and maxillofacial region [1]. 67Ga scintigraphy is an effective technique for the evaluation of head and neck squamous cell carcinoma (SCC), especially tumour recurrence and distant metastases [2]. Furthermore, 67Ga single-photon emission tomography (SPECT) substantially increases confidence in the diagnosis of head and neck tumours when computed tomography (CT) and/or magnetic resonance imaging (MRI) do not permit differentiation between benign and malignant disease [3]. However, in recent years, positron emission tomography (PET) using the radiolabelled glucose analogue 18F-fluorodeoxyglucose (FDG) has shown potential to detect distant metastases [4-7].

Apart from SCC, some authors have reported that 67Ga scintigraphy is useful in the differentiation of malignant lymphoma [8], sarcoidosis [9-11], and other inflammatory diseases [12,13]. However, to the best of our knowledge, 67Ga scintigraphy with multimodal imaging, such as CT and MRI, for the comparison of SCC and inflammatory diseases of the oral and maxillofacial region has not been reported in the literature. The aim of this study was to compare SCC with inflammatory diseases of the oral and maxillofacial region using 67Ga scintigraphy with CT and MRI.

Material and methods

Patients

The Ethics Committee of our institution approved this retrospective study. After providing written, informed consent, 85 patients (44 male, 41 female; range age 25-95 years, mean age 67.0 years; 70 patients with SCC, 15 patients with inflammatory diseases) underwent 67Ga scintigraphy with CT and MRI at our university hospital from July 2013 to February 2018. The histopathological diagnoses were obtained by surgery or biopsy in all cases.

Image acquisition

CT imaging was performed with a 16-multidetector CT scanner (Aquilion TSX-101A; Canon Medical Systems, Otawara, Japan) using the oral and maxillofacial protocol at our hospital: tube voltage, 120 kV; tube current, 150 mAs; field of view, 240 × 240 mm; rotation time, 0.50 sec. The protocol consisted of axial acquisition (0.50 mm) with axial, coronal, and sagittal multiplanar reformation (MPR) images. The patients received contrast-enhanced CT (CECT) with non-ionic iodine for head and neck lesions. One non-ionic contrast media was used: Iohexol 300 mgI/ml (Omunipaque 300 Syringe, Daiichi-Sankyo, Tokyo, Japan). Contrast medium was administered as an injection of 100 ml at a rate of 2.0 ml/s (Autoenhance A-250, Nemoto-Kyorindo, Tokyo, Japan).

The MR images (1.5 Tesla MR unit; EXCELART Vantage MRT-2003; Toshiba Medical Systems, Otawara, Japan) with a head coil included unenhanced axial T1-[repetition time (TR) 660 ms, echo time (TE) 12 ms], T2-weighted imaging (TR 4000 ms, TE 120 ms), short TI inversion recovery images (TR 2500 ms, TE 15 ms, TI 190 ms), as well as coronal T1-weighted and T2-weighted imaging. After an injection of contrast medium (gadobutrol; Gadovist 1.0 mol/l Syringe, Bayer, Osaka, Japan; 0.1 ml/kg), axial and coronal T1-weighted images (TR 660 ms, TE 12 ms) were acquired.

67Ga scintigraphy was obtained with an SNC-5100R (Shimadzu, Kyoto, Japan) and a Scintipack 24000 (Shimadzu) with a 512 × 512 matrix at 72 hours after the injection; images were recorded on the computer at 6 min/frame. The radiopharmaceutical used in this study was 67Ga-citrate (Gallium Citrate-Ga67 Injection, FUJIFILM RI Pharma, Tokyo, Japan). Each patient was administered the agent at 185 MBq with a rapid intravenous injection. The stored data were displayed on a screen for analysis.

Image analysis

For patients with SCC and inflammatory diseases of the oral and maxillofacial region, imaging features of 67Ga scintigraphy, CT, and MRI were independently analysed by two oral and maxillofacial radiologists. Regarding 67Ga scintigraphy, images of the lesions were classified into two groups: positive, where the intensity of 67Ga in the lesion area was higher than that in the surrounding normal area, and negative, where the intensity of 67Ga in the lesion area was the same as in the surrounding normal area. Any discrepancies of the imaging evaluation were resolved by consensus of the two oral and maxillofacial radiologists.

Statistical analysis

The comparison between imaging features of 67Ga scintigraphy, CT, and MRI and lesions was performed with the Pearson’s chi-squared test. These analyses were performed with the statistical package IBM SPSS Statistics, version 24 (IBM Japan, Tokyo, Japan). A P value lower than 0.05 was considered statistically significant.

Results

Regarding cellulitis of the submandibular region (Figure 1), 67Ga scintigraphy showed increased uptake. Axial contrast-enhanced CT (CECT) image showed a mass-like lesion with heterogeneous enhancement. On MRI, axial T1-weighted image (T1WI) revealed homogeneous low-signal intensity. Post-contrast T1WI showed heterogeneous enhancement. Short TI inversion recovery (STIR) revealed heterogeneous high-signal intensity. Regarding neck metastases of SCC (Figures 2, 3), 67Ga scintigraphy showed increased uptake. Axial CECT image showed rim enhancement. On MRI, axial T1WI revealed homogeneous low-signal intensity. Post-contrast T1WI showed rim enhancement. STIR revealed heterogeneous high-signal intensity. Furthermore, regarding sialadenitis of the submandibular gland (Figure 2) and parotid gland (Figure 3), 67Ga scintigraphy showed increased uptake. Axial CECT image showed enhancement. On MRI, axial T1WI revealed homogeneous low-signal intensity. Post-contrast T1WI showed enhancement. STIR revealed heterogeneous high-signal intensity.

Figure 1

Cellulitis of the right side of the submandibular region in a 78-year-old male. 67Ga scintigraphy shows increased uptake in the submandibular region (arrow) (A, B). Axial contrast-enhanced CT image shows a mass-like lesion with heterogeneous enhancement in the submandibular region (arrow) (C). On MRI, axial T1-weighted image (T1WI) revealed homogeneous low-signal intensity (arrow) (D). Post-contrast T1WI showed heterogeneous enhancement (arrow) (E). Short TI inversion recovery (STIR) revealed heterogeneous high-signal intensity in the submandibular region (arrow) (F)

Figure 2

Squamous cell carcinoma of the left side of the tongue in a 39-year-old male. 67Ga scintigraphy shows increased uptake in the submandibular region (arrow) (A, B). Axial contrast-enhanced CT image shows a submandibular lymph node with rim enhancement (arrow) and submandibular gland with enhancement (arrowheads) (C). On MRI, axial T1WI revealed a submandibular lymph node (arrow) and submandibular gland (arrowheads) with homogeneous low-signal intensity (D). Post-contrast T1WI showed a submandibular lymph node with rim enhancement (arrow) and submandibular gland with enhancement (arrowheads) (E). STIR revealed a submandibular lymph node (arrow) and submandibular gland (arrowheads) with heterogeneous high-signal intensity (F)

Figure 3

Squamous cell carcinoma of the right side of the tongue in a 70-year-old female. 67Ga scintigraphy shows increased uptake in the submandibular region (arrow) and buccal region (arrowheads) (A-C). Axial contrast-enhanced CT image shows a submandibular lymph node with rim enhancement (arrow) (D). Axial contrast-enhanced CT image shows a parotid gland with heterogeneous enhancement (arrowheads) (E). On MRI, axial STIR revealed parotid gland with heterogeneous high-signal intensity (arrowheads) (F)

Table 1 shows the comparison between SCC and inflammatory diseases of the oral and maxillofacial region using 67Ga scintigraphy with CT and MRI. 67Ga scintigraphy was positive for 25 of 39 patients with SCC positive on CT and/or MRI (64.1%), and for 13 of 15 patients with inflammatory diseases positive on CT and/or MRI (86.7%). The detection of inflammatory diseases with 67Ga scintigraphy was higher than that of SCC (p = 0.104).

Table 1

Comparison between squamous cell carcinoma and inflammatory diseases of the oral and maxillofacial region using gallium-67 scintigraphy with CT and MRI

Lesions positive (number of cases)	Scintigraphy negative CT and/or MRI negative	Scintigraphy negative CT and/or MRI positive	Scintigraphy CT and/or MRI positive*
Inflammatory diseases (15)	0	2 (13.3%)	13 (86.7%)
Osteoradionecrosis (7)	0	2 (28.6%)	5 (71.4%)
Cellulitis (4)	0	0 (0%)	4 (100%)
Medication-related osteonecrosis of the jaw (MRONJ) (3)	0	0 (0%)	3 (100%)
Actinomycosis (1)	0	0 (0%)	1 (100%)
Squamous cell carcinoma (70)	31	14 (35.9%)	25 (64.1%)
Tongue (28)	18	8 (80.0%)	2 (20.0%)
Buccal mucosa (8)	5	1 (33.3%)	2 (66.7%)
Maxilla (8)	2	0 (0%)	6 (100%)
Mandible (6)	2	0 (0%)	4 (100%)
Floor of mouth (3)	3	0	0
Lip (3)	1	1 (50.0%)	1 (50.0%)
Neck metastases (13)	0	4 (30.8%)	9 (69.2%)
Distant metastases (lung: 1)	0	0 (0%)	1 (100%)

Inflammatory diseases (86.7%) vs. squamous cell carcinoma (64.1%) (p = 0.104)

Discussion

67Ga scintigraphy has been widely used to detect various malignant neoplasms, such as SCC [1,3] and malignant lymphoma [8] of the head and neck. In our study, 67Ga scintigraphy was positive for 25 of 39 patients with SCC positive on CT and/or MRI (64.1%). Regarding the mechanism of gallium-67 accumulation in tumours, Tsan et al. [14] showed that 67Ga was delivered to the tumour through capillaries with increased permeability, and 67Ga binding proteins might also contribute to the accumulation and retention of 67Ga in tumours. In this study, 67Ga scintigraphy was positive for two of 10 patients with tongue SCC positive on CT and/or MRI (20.0%). We consider that the size of tumours is also a factor of the degree of 67Ga accumulation in lesions. However, in recent years, 18F-FDG PET/CT is crucial for determining treatment strategy because it helps to avoid incorrect staging and also provides an accurate assessment of treatment response [4,6].

In this study, 67Ga scintigraphy was positive for 13 of 15 patients with inflammatory diseases positive on CT and/or MRI (86.7%). Li et al. [1] indicated that 67Ga scintigraphy was positive for two of 11 patients who had chronic inflammatory lesions (1/4 parotitis, 1/5 submaxillaritis and 0/2 lymphadenitis) (18.2%). Tsan et al. [14] showed that some tumours may be taken up by inflammatory cells when they are present. Furthermore, Keijsers et al. [9] showed imaging of the inflammatory activity of sarcoidosis, namely overall sensitivity to detect active sarcoidosis, was 88% for 67Ga imaging. Ishii et al. [10] showed that 67Ga scintigraphy was useful in differentiating between sarcoidosis and IgG4-related disease. Tsai et al. [13] suggested that the kidney uptake index from the absolute quantitative renal 67Ga scintigraphy may be a useful parameter for evaluating the disease activity in lupus nephritis. In this study, the detection of inflammatory diseases with 67Ga scintigraphy was higher than that of SCC (p = 0.104). Consequently, the authors consider that 67Ga scintigraphy was more useful for inflammatory diseases of the oral and maxillofacial region than SCC. Furthermore, we recommend 67Ga scintigraphy with multimodal imaging, such as CT and MRI, for detection of SCC and inflammatory diseases of the oral and maxillofacial region.

There were several limitations of this study. The sample was relatively small. Therefore, further research is necessary to validate these results.

Conclusions

This study compared SCC with inflammatory diseases of the oral and maxillofacial region using 67Ga scintigraphy with CT and MRI. 67Ga scintigraphy is an effective technique for detection of inflammatory diseases of the oral and maxillofacial region.