Ann Nucl Med (2013) 27:423–430 DOI 10.1007/s12149-013-0701-0

ORIGINAL ARTICLE

Clinical significance of 18F-a-methyl tyrosine PET/CT for the detection of bone marrow invasion in patients with oral squamous cell carcinoma: comparison with 18F-FDG PET/CT and MRI Mai Kim • Tetsuya Higuchi • Yukiko Arisaka • Arifudin Achmad • Azusa Tokue • Hideyuki Tominaga • Go Miyashita • Hidetaka Miyazaki Akihide Negishi • Satoshi Yokoo • Yoshito Tsushima

•

Received: 17 December 2012 / Accepted: 6 February 2013 / Published online: 24 February 2013 Ó The Japanese Society of Nuclear Medicine 2013

Abstract Objective L-3-[18F]-fluoro-a-methyl tyrosine (18F-FAMT) is an amino acid tracer for positron emission tomography/ computed tomography (PET/CT) which specifically transported into cancer cells by L-type amino acid transporter 1 (LAT1). LAT1 overexpression in tumors is significantly correlated with cell proliferation and angiogenesis. 18F-FAMT PET/CT, fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT and magnetic resonance imaging (MRI) were compared for their diagnostic performance in the detection of bone marrow invasion in patients with oral squamous cell carcinoma (OSCC). Methods Twenty-seven patients with OSCC on the upper or lower alveolar ridge underwent staging by MRI, 18 F-FDG PET/CT and 18F-FAMT PET/CT studies before surgery. Post-surgical pathologic examination was used as the standard to determine the final diagnoses. The possibility of bone marrow invasion on MRI, 18F-FDG PET/CT and 18F-FAMT PET/CT were usually graded retrospectively into five-point score. Sensitivity, specificity,

accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated according to the obtained scores. Results As the sensitivity of 18F-FDG PET/CT was highest (100 %) among that of MRI (95 %) and 18F-FAMT PET/CT (90 %), the specificity of 18F-FAMT PET/CT was highest (85.7 %) among that of MRI (57 %) and 18F-FDG PET/CT (14.3 %). The size of pathological tumor was accorded with that detected by 18F-FAMT PET/CT and was smaller than that detected by 18F-FDG PET/CT (P \ 0.01). Significant difference was not found between 18F-FAMT PET tumor volume and pathological tumor volume. Conclusions 18F-FAMT PET/CT was useful and more specific than MRI or 18F-FDG PET/CT in the detection of bone marrow invasion of OSCC and may contribute to minimize the extent of resection in oral surgery patient.

M. Kim (&)  G. Miyashita  H. Miyazaki  A. Negishi  S. Yokoo Department of Stomatology and Maxillofacial Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan e-mail: [email protected]

Introduction

T. Higuchi  Y. Arisaka  A. Achmad  A. Tokue  Y. Tsushima Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Showa-machi 3-39-22, Maebashi, Gunma 371-8511, Japan H. Tominaga Department of Molecular Imaging, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Keywords Oral squamous cell carcinoma (OSCC)  L-3-[18F]-fluoro-a-methyl tyrosine (18F-FAMT)  18 F-FDG  PET/CT  MRI

Oral cancer contributes 2 % of all diagnosed cancers worldwide and responsible for more than eight million deaths (2 % from all cancer deaths) [1]. The prevalence is more common in the developing countries [2]. More than 90 % of oral cavity cancers were oral squamous cell carcinoma (OSCC) originating in the mucosal linings [3]. Detection of oral cancer is possible by simple inspection and palpation in the advanced stages; however, extent of disease including local invasion and distant metastasis should be evaluated by the imaging modalities [4].

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Oral cancer in the early stage is usually curable, and that in the advance stage needs radical surgery involving the removal of the oral cavity organs or mandible. In the advanced stage, radical surgery such as removal of the oral cavity organs or mandible segmentectomy is commonly inevitable. Therefore, accurate initial diagnosis with assessment of local involvement is important to minimize the surgical extent and maintain the patient’s quality of life. Evaluation of local invasion and distant metastasis is also important to choose the correct therapeutic approach [4]. However, the anatomical structures of the head and neck region are complicated, and making a precise diagnosis of tumor invasion may occasionally is difficult by conventional diagnostic modalities such as CT and MRI. Fluorine-18-fluorodeoxyglucose (18F-FDG) is the most common PET radiotracer for the differential diagnosis, tumor characterization and staging of malignant tumors in oral cancers, and known for its high sensitivity for oral malignancy [5]. However, the uptake of 18F-FDG is not specific for the accurate tumor identification by accumulating the benign tumor or inflammatory lesions identified false positive area for the tumor invasion [6]. To improve the low specificity of 18F-FDG PET/CT for the diagnosis of malignant tumor, novel PET tracers such as 3-deoxy-3[18F]-fluorothymidine and amino acid tracers have been evaluated [7, 8]. We have a long history developed L-3[18F]-fluoro-a-methyl tyrosine (18F-FAMT), an amino acid tracer for PET [9–12]. 18F-FAMT is transported into cancer cells by L-type amino acid transporter 1 (LAT1) which is overexpressed only in malignant tumors, resulting in high specificity of PET images of 18F-FAMT for malignant tumors [13]. The clinical usefulness of 18F-FAMT-PET has been shown for the diagnosis of various types of malignant tumors such as brain tumor and lung cancer [6, 9]. In case of bone marrow invasion, an extensive operation involving segmental mandibulectomy and bone reconstruction are necessary to provide an adequate clear bony margin [14, 15]. When a tumor invades the maxillary marrow spaces, greater resection margin and extensive reconstruction may be required [16]. In this study, we evaluated the diagnostic performance of 18F-FAMT PET/CT by comparison with MRI and 18 F-FDG PET/CT in detecting bone marrow invasion involving both maxilla and mandible in patients with OSCC. We also evaluated the accuracy of 18F-FAMT PET in determining the tumor volume using PET volume computerised assisted reporting (PET-VCAR) software.

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who were referred for surgery to our department during the period from April 2008 to March 2011. All patients underwent surgery within 4 weeks after the MRI, 18F-FDG PET/CT and 18F-FAMT PET/CT. All patients agreed to participate in the study and gave written informed consent. The study protocol was approved by the institutional review board. Histopathology The surgical specimens were fixed in 10 % formalin solution and decalcified for 24 h. Specimens were underwent histological staining and soft tissue was removed for evaluation of bone invasion. In the presence of gross bone invasion, a representative 5-mm section of the bone–tumor interface was prepared. In the absence of gross invasion, two sections (5 mm each) were taken from the site with the deepest tumor invasion. All sections were H&E stained in 5 lm thickness and reviewed by a single pathologist who was aware of the clinical staging. MRI MRI was performed on a 1.5-T unit (Symphony; Siemens Medical Systems, Erlangen, Germany) equipped with a body total imaging matrix array coil. T2- and T1-weighted fast/turbo spin–echo sequences were applied in the axial plane. Post gadolinium contrast-enhanced T1-weighted fast/turbo spin–echo sequences with fat saturation were applied in the axial, coronal, and sagittal planes at 4-mm slice thickness. All data were archived in DICOM format and transferred to a stand-alone workstation for processing. All of the imaging analysis was performed on a picture archiving and communication system (PACS) workstation (Centricity 1.0; GE Healthcare, Milwaukee, WI, USA). Tumor invasion into the bone marrow was diagnosed by replacement of the marrow fat of the involved mandible or maxilla by contiguous tumors with abnormal hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and definite contrast enhancement. Bone erosion was considered to be present, if there was any irregular bone thinning while bone destruction was diagnosed in the presence of complete cortical bone loss. MR image distortions or artifacts close to the maxilla or mandible were carefully recorded. Synthesis of radiopharmaceuticals and PET imaging 18

Materials and methods The study included consecutive 27 patients (11 men and 16 women aged 53–90 years; mean 73.6 years) with OSCC,

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F-FAMT and 18F-FDG were produced in our cyclotron facility. FAMT was synthesized by the method developed by Sato et al. [17]. 18F-FDG and 18F-FAMT were administered intravenously at a dose of 5 MBq/kg after fasting for at least 6 h. PET study was performed 60 min after

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intravenous injection of radiopharmaceuticals using a PET/ CT scanner (Discovery STE, GE Healthcare, Milwaukee, WI, USA) with a 700-mm field of view and slice thickness of 3.27 mm. Three-dimensional data acquisition were done for 3 min per bed position followed by the image reconstruction with three-dimensional ordered subsets expectation maximization (3D-OSEM) method. Segmented attenuation correction was done by X-ray CT (140 kV, 120–240 mAs) to produce 128 9 128 matrix images. CT images were reconstructed using conventional filtered back projection method. Axial full width at half maximum (FWHM) at 1 cm from the center of FOV was 5.6 mm, and z axis FWHM at 1 cm from the center of FOV was 6.3 mm. Intrinsic system sensitivity was 8.5 cps/kBq for 3D acquisition. Patients were scanned from the thigh to the head in the arms-down position. No intravenous contrast material was given for CT scanning. A limited breathholding at normal expiration was done during the CT scan to avoid motion-induced artifacts and match co-registration of CT and PET images in the area of the diaphragm. Data analysis PET images of 18F-FAMT and 18F-FDG were interpreted by three experienced nuclear medicine physicians. The tumor was first examined visually for abnormal 18F-FDG or 18F-FAMT accumulation. For a semi-quantitative analysis of tumor 18F-FDG and 18F-FAMT uptake, loosely fitting regions of interest (ROI) covering the whole tumor were placed manually over every axial image plane, in which tumor tissue was visualized by abnormal tracer uptake. The standardized uptake value (SUV) was calculated using the following formula: SUV =

Radioactive concentration in the ROI ðMBq=gÞ ½Injected dose (MBq)/patient’s body weight (g)

Maximum SUV (SUVmax) was used for the evaluation of tumor uptake of tracers. SUVmax was defined as the peak SUV on one pixel with the highest counts within the ROI. Side-by-side image review and analysis were performed to confirm that the SUVmax was derived from the same lesions on baseline and follow-up scans. Statistical analysis Numeric data were expressed by mean ± standard deviation (SD). The diagnostic accuracies of 18F-FAMT PET/CT and 18F-FDG PET/CT were compared using a McNemar’s test. The differences between tumor pathological volume with SUV volume of 18F-FDG and 18F-FAMT were evaluated using paired Student’s t test. For all statistical

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analyses, P values of less than 0.05 were considered to be statistically significant. Image interpretation PET/CT images were reviewed by three nuclear medicine physicians (minimum 4 years experience in general nuclear medicine and 4 years in PET/CT) and three headand-neck surgeons (minimum 13 years experience), and a consensus was reached via joint reevaluation of the images. All MRI data were read by a radiologist (24 years experience), who was blinded to PET/CT findings. The readers were aware of tumor location and its origin. Qualitative evaluation of the presence of bone marrow invasion were made based on a 5-point score, in which a score of 0 indicated that bone marrow invasion was definitely absent; a score of 1, bone marrow invasion was probably absent; a score of 2, ambiguous cases characterized by cortical bone erosion in the absence of overt bone destruction; a score of 3, bone marrow invasion was probably present; and a score of 4, bone marrow invasion was definitely present; according to El-Hafez et al. [18]. A score of 2 or less was considered negative. PET volume computerised assisted reporting (PET-VCAR) Tumor volumes calculation was done using PET-VCAR (PET volume computerized assisted reporting), an automated segmentation software system installed in Advantage Workstation (GE Healthcare, Milwaukee, WI, USA) [19], which was routinely used to review PET/CT images and making reports. PET-VCAR application aids reporting by auto-segmenting the threshold PET/CT-defined volumes and then calculates it as a prediction tumor volume (in cm3). A rectangle box was placed over the ROI and adjusted in axial and coronal view to cover all the tumor entity in a 3D box. By setting and applying a cut-off value to the 3D box, the software generates an auto-contour to produce a 3D volume of interest (VOI). The SUV thresholds used were based on cut-off value of 18F-FDG and 18FFAMT PET for malignancy in OSCC from the previous reports [2, 8, 20]. In this study, we used 3.0 as the SUV threshold for 18F-FDG and 1.4 for 18F-FAMT. Finally, the functional volumes (cm3) were calculated from the summation of pixel numbers greater than SUV thresholds, which is present in 3D cube box (Fig. 1). Tumors with irregular shapes, such as spine-like formation or superficial types, or tumors with particular location such as nearby the organs with physiologic uptakes, are beyond the PET-VCAR ability to perform auto-contour. In these cases, rectangle boxes were drawn subjectively to ensure that every box contains only the

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Fig. 1 PET volume computerized assisted reporting (PET-VCAR) is an automated segmentation software system. Using irregular shaped region of interest (ROI), metabolic volume for active tumor involvement volume can be measured. a MIP image, b shaped ROI with axial image, c Shaped ROI with sagittal image

tumor entity. Instead of result in a single tumor entity, using the same cut-off values, PET-VCAR generates dissociated multiple tumor parts. These small tumor volumes were added to obtain the total tumor volume.

Results

Pathological result was positive for bone marrow invasion. Figure 2b showed another case with OSCC in the left mandible, in which the bone marrow adjacent to the primary lesion showed hypointensity on T1-weighted images, and there was also tumor uptake of 18F-FDG. However, 18 F-FAMT PET/CT showed no uptake. Pathological result was negative for bone marrow invasion.

General characteristics

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Twenty-seven patients with OSCC were enrolled (Table 1), with the most common clinical tumor status among them were T2 (29.6 %) and T4 (29.6 %). Histopathological examination revealed the presence of marrow invasion in 74.1 % (20/27) of patients. Twenty-one patients had metalrelated artifacts. The presence of metal artifacts did not affect the performance of PET/CT. In one patient, initial diagnosis from biopsy specimen was squamous cell carcinoma, but finally after operative resection, diagnosis of carcinoma in situ has been confirmed.

Mean pathological volume of the tumors was 6.4 ± 5.9 cm3, while mean VOI of 18F-FDG and 18F-FAMT were 21.6 ± 17.3 and 10.7 ± 12.5 cm3, respectively. Seven cases were analyzed without PET-VCAR due to their complex or extreme tumor shape. Both PET images of 18F-FDG and 18F-FAMT showed bigger tumor volume than that obtained from pathological specimen. 18F-FDG PET volume was significantly bigger than 18F-FAMT PET tumor volume (P \ 0.01) and pathological tumor volume (P \ 0.01). In addition, 18F-FAMT PET tumor volume showed no significant difference with pathological tumor volume (Fig. 3a). Linear relationships with high correlation were observed between pathological tumor volumes with that obtained from both 18F-FDG PET images (r = 0.69, P \ 0.01) and 18 F-FAMT PET images (r = 0.65, P \ 0.01) (Fig. 3b1, b2). Even though tumor volumes obtained from 18F-FDG PET images have higher correlation with pathological tumor volume, we should consider that this study also include tumors with the big size and correlation study strongly affected by the extreme values. In oral oncology, it is important to pay attention to the small tumors rather than the large tumors due to its impacts on the surgery decision (segmentectomy or not). As we can see in the Fig. 3b1, b2,

Diagnostic performance Among those three modalities, although 18F-FDG PET/CT had the highest sensitivity (100 %), 18F-FAMT PET/CT was the most specific (85.7 %) and the most accurate (88.9 %) modality for detection of bone marrow invasion in OSCC (Table 2a). In particular, the diagnostic accuracy of 18F-FAMT PET/CT was superior to that obtained using 18 F-FDG PET/CT (P = 0.02) (Table 2b). A representative case with OSCC in the right mandible was presented in Fig. 2a. MRI showed hypointensity on T1-weighted images in the primary lesion, and there were tumor uptakes of both 18F-FDG and 18F-FAMT.

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F-FAMT PET accuracy for tumor volume assessment

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Table 1 Characteristics of the subjects Parameter

n

Total

27

%

PET-VCAR

%

F-FAMT. Tumor volume calculated by pathological examination was 4.8 cm3, confirmed that 18F-FAMT PET tumor volume was closely related with the real tumor volume.

20

Sex Male

11

40.7

9

45

Female

16

59.2

11

55

Age (years) Median

73.6

73.7

Range

53–90

53–90

Anatomical subsites Mandible

19

70.3

16

80

Maxilla

8

29.6

4

20

Clinical T-status Tis

1

3.7

1

5

T1

4

14.8

3

15

T2

8

29.6

7

35

T3 T4

6 8

22.2 29.6

5 5

25 25

N0

11

40.7

9

45

N1

3

11.1

3

15

N2

1

3.7

0

0

NX

12

44.4

8

40

M0

7

25.9

6

30

MX

20

74.1

14

70

Clinical N-status

Clinical M-status

Pathological bone marrow invasion No

7

25.9

Yes

20

74.1

3

Tumor volume (cm )

Average

SD

Pathology

6.4

5.9

18

21.6

17.3

18

10.7

12.5

F-FDG-VOI F-FAMT-VOI

Twenty patients among 27 total patients were analyzed with PETVCAR (presented in last two columns column)

SUVs of small tumors (less than 10 cm3) were distributed around the regression line on 18F-FAMT PET compared to that of 18F-FDG PET images. This suggests that correlation of PET-VCAR tumor volume with pathological tumor volume was more meaningful in 18F-FAMT PET compared to 18F-FDG PET. The smaller gradient and coefficient in linear regression equation between 18F-FAMT PET tumor volume and pathological tumor volume showed that these tumor volumes were more closely related each other than that of 18F-FDG PET tumor volumes and pathological tumor volumes. Figure 3c, d showed the PET images of OSCC in left mandible. Estimated metabolic tumor volumes by PETVCAR were 11.42 cm3 for 18F-FDG and 5.75 cm3 for

Discussion Assessment of bone marrow invasion before treatment planning of OSCC is important due to its impacts on the extent of resection and patients’ quality of life after surgery. The type of mandibular resection chosen is determined by the assumed extent of mandibular invasion. These surgical options may have a significant impact on patient’s quality of life. In segmental resection the continuity of the mandible cannot be maintained, while the mandible is kept intact in marginal resection. Previous studies have reported that imaging may play an important role in tumor invasion assessment [21, 22]. It was shown also that PET/CT may be clinically useful compared to other modalities, with varying degrees of sensitivity and specificity for PET/CT, CT, and MRI, respectively. PET/CT may be also useful in stage planning for patients with tumors close to the mandible [5]. In this study, we have evaluated the diagnostic performance of 18F-FAMT PET/CT for detection of bone marrow invasion of OSCC. While 18F-FDG may be accumulated in either tumor or inflammation [23], 18F-FAMT, an amino acid analogue, has been reported to be accumulated in tumor cells solely via an amino acid transport system [6]. The contrast of 18F-FAMT uptake between maxillofacial tumors and the surrounding normal structures was also higher than that of 18F-FDG, indicating the possibility of more accurate diagnosis of maxillofacial tumors by 18 F-FAMT PET/CT [20]. In our study, 18F-FAMT PET/CT had the higher specificity compared to 18F-FDG PET/CT. The oral area is naturally susceptible to inflammation particularly in bad hygiene condition, and moreover, when pain caused by tumor expansion is involved. As a result, 18F-FDG PET/CT and MRI may result in false positive finding. We suspected that 18F-FAMT PET/CT may complement the role of MRI and 18F-FDG PET/CT to rule out bone marrow invasion in patients with OSCC. In therapeutic planning and monitoring, tumor volume delineation is important. Other group has reported that in 18 F-FDG PET/CT image reading, the adaptive threshold method may be of benefit when used to define the target volume before the start of radiotherapy. However, 18 F-FDG PET/CT-guided volumes delineated by automatic adaptive thresholding methods have been reported to be limited by the software sensitivity, therefore, it should only be used for dose escalation with the pretreatment imaging [19].

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Table 2 Pre- and post-operative diagnostic performance of Modality

FN

a

b

TP

TN

c

FP

d

18

F-FDG and

Sensitivity (%)

18

F-FAMT

Specificity (%)

PPVe (%)

NPVf (%)

Accuracy (%)

a Preoperative assessment of bone marrow invasion MRI

1

19

4

3

95.0

57.0

86.3

80.0

85.1

18

0

20

1

6

100.0

14.3

76.9

100.0

77.8

18

2

18

6

1

90.0

85.7

94.0

85.7

88.9

F-FDG F-FAMT

18

b Diagnostic accuracy of 18

F-FAMT (?) 18 F-FAMT (-) a

18

F-FDG (?)

18

F-FDG and

19 7

F-FDG (-)

P value

g

18

F-FAMT in PET/CT for detection of bone marrow invasion 0 1

0.0233

False negative

b

True positive

c

True negative

d

False positive

e

Positive predictive value

f

Negative predictive value

g

McNemar’s test; P values \0.05

Fig. 2 a A 63-year-old man with the diagnosis of squamous cell carcinoma of the right mandible. Axial 18F-FDG PET/CT image of the tumor showed intense 18F-FDG uptake (SUVmax = 12.4) situated beyond the periosteum of mandible. Axial 18F-FAMT PET/CT image in the corresponding plane showed narrower but intense 18F-FAMT uptake (SUVmax = 4.6) within the mandible. Contrast-enhanced axial T1-weighted and T2-weighted MR images showed right lower gum cancer with abnormal signal intensity in the right mandibular bone marrow, suggestive of bone marrow invasion. The invasion score was 4 for MRI, 18F-FDG and 18F-FAMT. Pathological result was positive for bone marrow invasion. b A 68-year-old man with the diagnosis of squamous cell carcinoma of the left mandible. Axial 18F-FDG PET/

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CT image of the tumor showed intense 18F-FDG uptake (SUVmax = 10.6) beyond the periosteum of the mandible. Axial 18F-FAMT PET/ CT image in the corresponding plane that showed narrower and weak 18 F-FAMT uptake (SUVmax = 1.7). The invasion score was 4 in 18 F-FDG and 2 in 18F-FAMT by consensus. Contrast-enhanced axial T1-weighted and T2-weighted MR images showed left lower gum cancer with abnormal signal intensity in the right mandible, suggestive of bone marrow invasion. Pathological result was negative for bone marrow invasion. In summary, the findings of MRI and 18 F-FDG PET/CT were false positive and only 18F-FAMT PET/CT revealed true negative finding

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Fig. 3 Tumor volumes prediction calculated by PET-VCAR. The tumor volume distribution of 18F-FAMT VOIs was similar to that of pathological specimen (a). Estimated pathological tumor volumes for 18 F-FAMT and 18F-FDG VOIs were shown in b1 and b2. In a 71 year-old man with the diagnosis of squamous cell carcinoma of the left mandible, axial 18F-FDG PET/CT image of the tumor showed a large and intense 18F-FDG uptake (SUVmax = 28.6) beyond the

periosteum of the left mandible (c), and axial 18F-FAMT PET image in the corresponding plane showed slightly increased 18F-FAMT uptake (SUVmax = 4.6) located within the left mandible (d). Estimated metabolic tumor volumes using PET-VCAR were 11.42 cm3 for 18F-FDG and 5.75 cm3 for 18F-FAMT. Final volume of tumor in the left mandible confirmed by histopathological examination was 4.80 cm3, closer to that of estimated by 18F-FAMT

Another limitation is the software ability to produce a single tumor entity in irregular tumors and tumors located nearby any physiologic uptake. Therefore, the correct volume evaluations of thin and very superficial tumors or very big tumor might be difficult. For example, in our case, we found one irregular tumor with a spine-like formation. There were totally seven cases that were excluded from PET-VCAR analysis (four maxilla cases and three mandible cases) in which the correct volume evaluation was difficult. In these patients, PET-VCAR produced multiple dissociated small tumor parts. Invasion extension in maxilla was more difficult to be evaluated, probably due to the porous structure of maxilla compared to mandible, which allowed the tumor to spread deeper and also resulting in irregular shape. Therefore, we suspected that difficult cases may be more common in maxilla [17, 22]. PET/CT is highly sensitive and specific in identification and delineation of tumor involvement in various diseases. To better define and delineate the tumor extent and its

relationship to the adjacent radiosensitive vital structures and to improve the therapeutic index, integration of functional imaging with PET/CT into the radiotherapy planning process is necessary [23, 24]. In head and neck cancer, 21 % of patients exhibited a finding on 18F-FDG PET suggestive of a distant metastasis or second primary carcinoma [25]. Therefore, superior sensitivity of 18F-FDG PET compared to any other modalities is undoubtedly useful [25, 26]. However, functional imaging with 18F-FDG tracer only is limited by its low specificity, which in turn, results in false positive [26]. The complementary use of 18F-FAMT PET/CT after 18F-FDG PET/CT may increase both the sensitivity and specificity not only in ruling out the ‘false’ tumor, but also in tumor delineation. In our study, the tumor volume obtained from 18F-FAMT PET represented the real tumor volume compared to 18F-FDG PET, suggesting that 18F-FAMT PET had a potential to provide a more appropriate tumor volume evaluation in preoperative resection of maxilla and mandible.

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Conclusion Although the sensitivity was not superior compared to 18 F-FDG PET/CT and MRI, 18F-FAMT PET/CT has shown the highest specificity for detection of bone marrow invasion in patients with OSCC. It was suggested that more accurate diagnosis and delineation of bone marrow invasion becomes possible using this new PET tracer. As a result, it could help optimize the amount of tumor removed by increasing the precision of tumor border, consequently the extent of resection in oral surgery could be minimized and patient’s quality of life could be maintained. Conflict of interest

None.

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