Diagnostic performance of a computer-assisted diagnostic system: sensitivity of BONENAVI for bone scintigraphy in patients with disseminated skeletal metastasis is not so high.

PURPOSE: Bone scintigraphy (BS) of disseminated skeletal metastasis is sometimes misinterpreted as normal. The use of computer-assisted diagnosis (CAD) may resolve this problem. We investigated the performance of a CAD system, BONENAVI, in the diagnosis of disseminated skeletal metastasis. METHODS: Cases of disseminated skeletal metastasis were selected from a BS log. These patients' BSs were analyzed by BONENAVI to obtain an artificial neural network (ANN) and bone scan index (BSI). Clinical features (type of primary cancer, CT type, and BS type) were compared with the BONENAVI (ANN and BSI) results. The BS findings (diffuse increased axial skeleton uptake, inhomogeneity of uptake, proximal extremity contrast, and degree of renal uptake) and ANN or BSI were evaluated. Then, negative ANN patients were presented. RESULTS: Fifty-four patients were diagnosed as having disseminated skeletal metastasis. Regarding the primary cancers, 12 had prostate cancer, 16 gastric cancers, 16 breast cancers, and 10 miscellaneous cancers. Total sensitivity of ANN (≥ 0.5) was 76% (41/54). ANN values correlated with the BS type among clinical features. Diffuse increased axial skeleton uptake was mostly correlated with ANN of the BS findings. CONCLUSION: The BONENAVI CAD system was partially helpful in diagnosing disseminated skeletal metastasis, but the sensitivity of BONENAVI was not sufficient and underestimated the disseminated skeletal metastasis. Further improvement of this CAD system is necessary to improve the detectability of disseminated skeletal metastasis.

Clinical and Biological Significance of PD-L1 Expression Within the Tumor Microenvironment of Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Programmed death-ligand 1 (PD-L1) expression in tumor cells is regulated by a close interrelation between tumor and stromal cells within the tumor microenvironment. Our aim was to evaluate the clinical and biological significance of PD-L1 expression in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: PD-L1, cluster of differentiation (CD)4, CD8, and forkhead box P3 (FOXP3) expression in tumor tissues obtained from 77 patients with OSCC was evaluated by immunohistochemical staining, and then analyzed for associations with clinical and biological factors. RESULTS: Among the clinicopathological factors tested, only vascular invasion showed a trend toward lower PD-L1 expression (p=0.05). Metabolic tumor volume (MTV), and total lesion glycolysis (TLG) significantly positively correlated with PD-L1 expression (MTV, p=0.04; TLG, p=0.03). In patients with OSCC with high PD-L1 expression, those whose tumors had abundant infiltrating CD4+ T-cells showed a longer progression-free survival than those with low CD4+ T-cell infiltration (p=0.0452). CONCLUSION: As regulation of PD-L1 expression is complex, its evaluation combined with other markers may be useful to determine clinical applications of PD-L1 expression.

Prognostic value of metabolic tumor volume of pretreatment 18F-FAMT PET/CT in non-small cell lung Cancer.

BACKGROUND: This study aimed to determine the prognostic value of positron emission tomography (PET) metabolic parameters-namely metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion retention (TLR)-on fluorine-18 (18F) fluorodeoxyglucose (FDG) and L- [3-18F]-α-methyltyrosine (18F-FAMT) PET/CT in patients with non-small-cell lung cancer (NSCLC). METHODS: The study group comprised 112 NSCLC patients who underwent 18F-FDG and 18F-FAMT PET/CT prior to any therapy. The MTV, TLG, TLR, and maximum standardized uptake value (SUVmax) of the primary tumors were determined. Automatic MTV measurement was performed using PET volume computer assisted reading software. (GE Healthcare). Cox proportional hazards models were built to assess the prognostic value of MTV, TLG (for 18F-FDG), TLR (for 18F-FAMT), SUVmax, T stage, N stage, M stage, clinical stage, age, sex, tumor histological subtype, and treatment method (surgery or other therapy) on overall survival (OS). RESULTS: Higher TNM, higher clinical stage, inoperable status, and higher values for all PET parameters (both 18F-FAMT and 18F-FDG PET) were significantly associated (P < 0.05) with shorter OS. Multivariate analysis revealed that a higher MTV of 18F-FAMT (hazard ratio [HR]: 2.88, CI: 1.63-5.09, P < 0.01) and advanced clinical stage (HR: 5.36, CI: 1.88-15.34, P < 0.01) were significant predictors of shorter OS. CONCLUSIONS: MTV of 18F-FAMT is of prognostic value for OS in NSCLC cases and can help guide decision-making during patient management.

Correlation of tumor-related immunity with 18F-FDG-PET in pulmonary squamous-cell carcinoma.

OBJECTIVES: 2-Deoxy-2-[fluorine-18] fluoro-d-glucose with positron emission tomography (18F-FDG-PET) is a clinically useful tool for cancer evaluation. 18F-FDG accumulation in tumor cells is known to be correlated with the presence of glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1α (HIF-1α). Although anti-programmed death-1 (PD-1) antibody treatments have been approved, no suitable predictor of significant responders has been identified. Based on the existing information, we investigated the relationship between tumor immunity (including PD-L1) and 18F-FDG uptake in patients with surgically resected pulmonary squamous-cell carcinoma (SQC). MATERIALS AND METHODS: This study included 167 patients (153 men and 14 women) with SQC who underwent 18F-FDG PET. Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and 18F-FDG uptake was analyzed. Student's t-test, the χ2 test, non-parametric Spearman's rank test and the Kaplan-Meier method were used to show associations between variables. RESULTS: The rate of positive PD-L1 expression was 79% (132/167), and PD-L1 expression was significantly associated with GLUT1 (P < 0.01), HIF-1α (P < 10-4), and CD8 (P < 1 × 10-3) expression. The SUVmax of 18F-FDG was significantly correlated with PD-L1 (P = 0.02) and GLUT1 (P < 0.01) expression. Multivariate analysis demonstrated that advanced stage, elevated PD-L1 expression, and elevated SUVmax were independent prognostic factors for predicting poor OS. Among patients with a high SUVmax, multivariate analysis confirmed that advanced stage and high PD-L1 expression were independent prognostic factors for poor OS; however, there was no significant difference among patients with a low SUVmax. CONCLUSION: High SUVmax on 18F-FDG-PET is associated with PD-L1 expression but is an independent prognostic factor for OS in our population of surgically resected pulmonary squamous-cell carcinoma.

Metabolic activity by 18F-FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC.

BACKGROUND: Nivolumab, an anti-programmed death-1 (PD-1) antibody, is administered in patients with previously treated non-small cell lung cancer. However, little is known about the established biomarker predicting the efficacy of nivolumab. Here, we conducted a preliminary study to investigate whether 18F-FDG-PET/CT could predict the therapeutic response of nivolumab at the early phase. METHODS: Twenty-four patients were enrolled in this study. 18F-FDG-PET/CT was carried out before and 1 month after nivolumab therapy. SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were calculated. Immunohistochemical analysis of PD-L1 expression and tumour-infiltrating lymphocytes was conducted. RESULTS: Among all patients, a partial metabolic response to nivolumab was observed in 29% on SUVmax, 25% on MTV, and 33% on TLG, whereas seven (29%) patients achieved a partial response (PR) based on RECIST v1.1. The predictive probability of PR (100% vs. 29%, p = 0.021) and progressive disease (100% vs. 22.2%, p = 0.002) at 1 month after nivolumab initiation was significantly higher in 18F-FDG on PET/CT than in CT scans. Multivariate analysis confirmed that 18F-FDG uptake after administration of nivolumab was an independent prognostic factor. PD-L1 expression and nivolumab plasma concentration could not precisely predict the early therapeutic efficacy of nivolumab. CONCLUSION: Metabolic response by 18F-FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.

Diagnostic value of 18F-fluorodeoxyglucose uptake parameters to differentiate rheumatoid arthritis from other types of arthritis.

We aimed evaluate F-fluorodeoxyglucose uptake at major joints for differentiating patients with rheumatoid arthritis (RA) from those with non-RA arthritis using F-fluorodeoxyglucose (FDG)-positron emission tomography (PET).Eighteen patients with RA (13 women; age, 66.8 ±â€Š13.2 years) and 17 patients with non-RA (6 women; age, 50.8 ±â€Š12.5 years) were included. Twelve joints of each patient were examined: shoulder, elbow, wrist, hip, knee, and ankle on both sides. A visual scoring (VS) system was used; quantitative parameters such as maximum standardized uptake value (SUVmax), metabolic active volume (MAV), and total lesion glycolysis (TLG) were evaluated. Total score and value of each parameter were compared between the RA and non-RA groups.Total VS score (mean, 37.7 ±â€Š9.0 vs 21.9 ±â€Š7.2; P < .0001) and SUVmax (mean, 28.1 ±â€Š8.5 vs 17.9 ±â€Š5.8; P < .001) were significantly higher in the RA group than in the non-RA group. A significant between-group difference was also observed with respect to total MAV (608.3 ±â€Š370.7 vs 176.5 ±â€Š217.8; P < .001) and total TLG (1139.3 ±â€Š759.1 vs 289.5 ±â€Š395.4; P < .001). Receiver operating characteristic curve analysis revealed that total VS had the highest area under curve (.92), with sensitivity and specificity of 88.9% and 76.4%, respectively.Quantitative PET parameters could differentiate RA from non-RA. Total VS score, however, appears to be the best convenient qualitative tool for diagnosing RA.

Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET.

BACKGROUND: We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (18F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose (18F-FDG) PET in 38 consecutive glioma patients. The tumor to normal brain ratios (T/N ratios) were calculated, and the relationships between T/N ratio and World Health Organization tumor grade or MIB-1 labeling index were evaluated. The diagnostic values of T/N ratios were assessed using receiver operating characteristic (ROC) curve analyses to differentiate between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). RESULTS: Median T/N ratio of 18F-FAMT PET was 2.85, 4.65, and 4.09 for grade II, III, and IV gliomas, respectively, with significant differences between HGGs and LGGs (p = 0.006). Both T/N ratio (p = 0.016) and maximum standardized uptake value (p = 0.033) of 18F-FDG PET showed significant differences between HGGs and LGGs. ROC analysis yielded an optimal cut-off of 3.37 for the T/N ratio of 18F-FAMT PET to differentiate between HGGs and LGGs (sensitivity 81%, specificity 67%, accuracy 76%, area under the ROC curve 0.776). Positive predictive value was 84%, and negative predictive value was 62%. T/N ratio of 18F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of 18F-FDG PET was positively correlated (r s = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of 18F-FDG and 18F-FAMT (r s = 0.454, p = 0.004), but median T/N ratio of 18F-FAMT PET was significantly higher than that of 18F-FDG PET in all grades of glioma. CONCLUSIONS: The T/N ratio of 18F-FAMT uptake has high positive predictive value for detection of HGGs. 18F-FAMT PET had higher T/N ratio, with better tumor-normal brain contrast, compared to 18F-FDG PET in both LGGs and HGGs. Therefore, 18F-FAMT is a useful radiotracer for the preoperative visualization of gliomas.

Preoperative Evaluation of Sellar and Parasellar Macrolesions by [18F]Fluorodeoxyglucose Positron Emission Tomography.

OBJECTIVE: Various diseases can occur in the sellar and suprasellar regions. The potential of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) for the preoperative evaluation of sellar and parasellar lesions was investigated. METHODS: A total of 49 patients aged 8-82 years with sellar and parasellar macroscopic lesions (≥10 mm) underwent FDG PET. Twenty-two patients had pituitary adenomas, including 14 nonfunctioning and 8 growth hormone-secreting adenomas. Eleven patients had craniopharyngiomas, including 5 adamantinomatous and 6 squamous-papillary types. Eight patients had chordoma, 4 had meningioma, and 4 had a Rathke cleft cyst. The maximum standardized uptake value (SUVmax), and the ratio of the SUVmax in the tumor to the mean standardized uptake value in the normal cortex (T/N ratio) or in the normal white matter (T/W ratio) were calculated. The relationships between SUVmax, T/N ratio, and T/W ratio, and lesion disease were evaluated. RESULTS: Uptakes of FDG, including SUVmax, T/N ratio, and T/W ratio, were lower in chordoma and Rathke cleft cyst compared with pituitary adenoma. SUVmax, T/N ratio, and T/W ratio of nonfunctioning adenoma were significantly higher than those of growth hormone-secreting adenoma. SUVmax, T/N ratio, and T/W ratio of squamous-papillary type were significantly higher than those of the adamantinomatous type of craniopharyngioma. CONCLUSIONS: FDG PET is useful for the preoperative diagnosis of sellar and parasellar macrolesions. High uptake in nonfunctioning pituitary adenoma, and low uptake in chordoma are significant. The difference in FDG uptake dependent on the histologic subtype may be related to the specific genetics of the craniopharyngioma subtype.

Usefulness of 18F-α-Methyltyrosine PET for Therapeutic Monitoring of Patients with Advanced Lung Cancer.

BACKGROUND/AIM: L-[3-18F]-α-methyl tyrosine (18F-FAMT) positron emission tomography (PET) has a high specificity for detecting malignant lesions. However, the usefulness of therapeutic monitoring of 18F-FAMT PET against advanced human neoplasms remains unclear. Here, we evaluated 18F-FAMT PET clinical significance regarding therapy response and outcome after systemic chemotherapy in patients with advanced lung cancer, compared to 18F-FDG PET. PATIENTS AND METHODS: All patients with untreated advanced lung cancer received 18F-FAMT PET and 18F-FDG PET before and 4 weeks after one cycle of chemotherapy. Metabolic response (MR) was defined according to the PERCIST guideline. RESULTS: Ninety-five patients were eligible for analysis on both PET scans. The histological type included 87 non-small cell lung cancers and 8 small-cell lung cancers. Post-treatment maximal standardized uptake values (SUVmax) and MR on 18F-FAMT PET were correlated with tumor response. In all patients, post-treatment SUVmax of 18F-FDG and 18F-FAMT PET and MR of 18F-FAMT PET were statistically significant prognostic markers for predicting poor outcome by univariate analysis. Multivariate analysis confirmed that MR on 18F-FAMT PET was a significant independent prognostic factor. CONCLUSION: MR on 18F-FAMT PET may be a potential parameter to predict the prognosis after first-line chemotherapy in patients with advanced lung cancer.

Advantages of L-3-[(18)F] fluoro-alpha-methyl tyrosine over 2-[(18)F]-fluoro-2-deoxyglucose in detecting liver metastasis during positron emission tomography scan.

PURPOSE: We aimed to assess the usefulness of positron emission tomography (PET) using the amino acid tracer L-3-[18F] fluoro-alpha-methyl tyrosine (FAMT) in detecting metastatic liver lesions compared with 2-[18F]-fluoro-2-deoxyglucose (FDG). METHODS: We included 24 patients with liver metastases who underwent both FDG-PET/computed tomography (CT) and FAMT-PET/CT. Maximum standardized uptake value (SUVmax) and tumor-to-liver parenchymal (T/L) ratio were analyzed to evaluate the correlation between FDG and FAMT uptakes in metastatic liver lesions; adenocarcinoma (AC, n = 21), squamous cell carcinoma (SCC, n = 23), neuroendocrine tumor (NET, n = 9), and carcinoid tumor (CAR, n = 6). RESULTS: We detected 59 lesions on performing either FDG-PET or FAMT-PET. NETs had significantly lower T/L ratios for FAMT (median, 1.00; range, 0.86-1.34) compared with those for FDG (median 2.86; range 1.70-6.13, p < 0.01). CAR tumors tended to reveal lower T/L ratios for FDG (median 1.10; range 0.78-1.92) than those for FAMT (median 1.80; range 0.80-2.34). Comparison of T/L ratios of SCC and AC revealed that FAMT in the metastatic liver lesions of SCC was higher than those of AC (p < 0.05). CONCLUSION: FAMT-PET could detect metastatic liver lesions from various cancers, except NET.

Differentiation of sarcoidosis-lymphoma syndrome lesions: a case report on the use of two different positron emission tomography tracers.

BACKGROUND: Sarcoidosis-lymphoma syndrome (SLS) is a rare disease in which both entities coexist. We aimed to study the role of (18)F-fluorodeoxyglucose (FDG) and L-[3-(18)F] α-methyltyrosine (FAMT) positron emission tomography (PET)/computed tomography (CT) in differentiating between these two lesions. CASE PRESENTATION: A 54-year-old female with large liver tumors was referred to our Nuclear Medicine Department for staging using FDG PET/CT. She had a history of primary biliary cirrhosis (PBC) for 15 years and developed lung and mediastinal sarcoidosis 1 year before the liver tumors were noted. Abdominal dynamic CT revealed two well-circumscribed, peripherally-enhancing, low-density masses in the right lobe of the liver with intensive ring-form FDG uptakes at maximum standard uptake values (SUVmax) of 18.3 and 19.5, respectively. In the arterial phase, a hepatic artery was seen penetrating the tumor, a phenomenon known as "angiogram sign". Chest PET/CT findings showed irregular thickening of the bronchovascular bundles, central peribronchial shaggy consolidations in the right middle and lower lobes (SUVmax, 4.6), and mediastinal and hilar lymphadenopathies (SUVmax, 2.7). After assessment, chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) was administered for eight cycles. Follow-up imaging studies using FDG and FAMT PET/CT were performed 3 months after the last cycle of chemotherapy, which showed that the two highly FDG-avid tumors in the liver had disappeared. However, faint FDG uptake persisted in the lung consolidations (SUVmax, 6.3), and FDG uptake for the mediastinal lymphadenopathies increased (SUVmax of 5.8). In contrast, there was no significant uptake of FAMT in the liver, as well as in the lungs and the bilateral mediastinal lymphadenopathies. These discrepant uptakes between FDG and FAMT were compatible with sarcoidosis. CONCLUSION: Combination of FDG and FAMT in PET/CT studies may play an important role in the management of SLS patients, especially in differentiating between sarcoidosis and lymphoma lesions.

Evaluation of bone scan index change over time on automated calculation in bone scintigraphy.

OBJECTIVE: Bone scintigraphy (bone scan) is useful in detecting metastatic bone lesions through visual assessment of hot spots. A semi-quantitative analysis method that evaluates bone scan images has been eagerly anticipated. BONENAVI is software that enables automatic assessment of bone scan index (BSI). BSI is useful for stratifying cancer patients and monitoring their therapeutic response. The purpose of this study was to evaluate the BONENAVI reading in determining BSI and hot spots at different time intervals after radioisotope injection. METHODS: We evaluated 32 patients, including 22 males and 10 females. Ten patients had breast cancer, 20 patients had prostate cancer, and 2 had malignant pheochromocytoma. Patients were injected with 740 MBq of (99m)Tc-methylene diphosphonate and bone scintigraphy was performed at 2, 4, and 6 h after injection on each patient. The BSI and the number of hot spots were obtained from BONENAVI software. Bone scan images were also visually assessed to exclude false positives due to artifacts. Analyses were performed in all lesions, selected true lesions, segment based and cancer type based. Non-parametric statistical analyses for pairwise multiple group comparison were performed using Friedman test followed with post hoc analysis. RESULTS: The BSIs and the number of hot spots were significantly increased with time, with significant differences between each of time points (P < 0.001). Analysis of regional BSI (rBSI) and hot spot number changes of selected 15 true lesions also showed similar increase (P < 0.001). In general, the pelvic segment was the most prone to rBSI changes and the chest segment was the most prone to hot spot number changes. Visual assessment showed that BONENAVI diagnosed some typical artifacts as metastases (hot spots). CONCLUSION: BONENAVI reading of BSIs and hot spot numbers was highly affected by acquisition time. In serial or follow-up examinations (in particular, for monitoring therapeutic efficacy), acquisition time should be fixed for each patient. Cautious interpretation should be made on segments with high physiological uptake. BONENAVI reading was prone to misinterpretation of artifacts. Visual assessment is necessary to rule out this possibility.

Role of F-18 FDG PET/CT in assessing IgG4-related disease with inflammation of head and neck glands.

PURPOSE: The aim of the current study was to evaluate the utility of F-18-fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) in assessing patients diagnosed with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) with inflammation of the head and neck glands. METHODS: We reviewed the records of 17 patients (16 men and 1 woman) with IgG4-RD exhibiting inflammation of the head and neck glands (lacrimal or salivary glands; LSG) who were diagnosed by excisional biopsy of the LSG. F-18 FDG PET/CT images were retrospectively evaluated for locations of high FDG accumulation, and the maximum standardized uptake value (SUVmax) of each lesion was calculated. RESULTS: In 15 of 17 patients (88 %), FDG accumulation was observed in organs outside of the biopsied LSG. High FDG accumulation was most frequently seen in the lymph node (71 %), followed by the non-biopsied LSG (41 %). FDG accumulation was also found in other typically affected organs including the prostate and retroperitoneum (18 %), kidney and lung (12 %), and pancreas (1 %). FDG accumulation was most commonly observed in two lesions outside of the biopsied site (41 %). CONCLUSIONS: Detection of the multi-organ involvement before treatment is important for patients with IgG4-RD. F-18 FDG PET/CT is an effective tool for assessing the location of extra-LSG lesions in patients with IgG4-RD with LSG inflammation.

Effects of intratumoral inflammatory process on 18F-FDG uptake: pathologic and comparative study with 18F-fluoro-α-methyltyrosine PET/CT in oral squamous cell carcinoma.

UNLABELLED: The accurate depiction of both biologic and anatomic profiles of tumors has long been a challenge in PET imaging. An inflammation, which is innate in the carcinogenesis of oral squamous cell carcinoma (OSCC), frequently complicates the image analysis because of the limitations of (18)F-FDG and maximum standardized uptake values (SUV(max)). New PET parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as well as (18)F-fluoro-α-methyltyrosine ((18)F-FAMT), a malignancy-specific amino acid-based PET radiotracer, are considered more comprehensive in tumor image analysis. Here, we showed the substantial effects of the intratumoral inflammatory process on (18)F-FDG uptake and further study the possibility of MTV and TLG to predict both tumor biology (proliferation activity) and anatomy (pathologic tumor volume). METHODS: (18)F-FDG and (18)F-FAMT PET images from 25 OSCC patients were analyzed. SUV(max) on the tumor site was obtained. PET volume computerized-assisted reporting was used to generate a volume of interest to obtain MTV and TLG for (18)F-FDG and total lesion retention (TLR) for (18)F-FAMT. The whole tumor dissected from surgery was measured and sectioned for pathologic analysis of tumor inflammation grade and Ki-67 labeling index. RESULTS: The high SUV(max) of (18)F-FDG was related to the high inflammation grade. The SUV(max )ratio of (18)F-FDG to (18)F-FAMT was higher in inflammatory tumors (P < 0.05) whereas the corresponding value in tumors with a low inflammation grade was kept low. All (18)F-FAMT parameters were correlated with Ki-67 labeling index (P < 0.01). Pathologic tumor volume predicted from MTV of (18)F-FAMT was more accurate (R = 0.90, bias = 3.4 ± 6.42 cm(3), 95% confidence interval = 0.77-6.09 cm(3)) than that of (18)F-FDG (R = 0.77, bias = 8.1 ± 11.17 cm(3), 95% confidence interval = 3.45-12.67 cm(3)). CONCLUSION: (18)F-FDG uptake was overestimated by additional uptake related to the intratumoral inflammatory process, whereas (18)F-FAMT simply accumulated in tumors according to tumor activity as evaluated by Ki-67 labeling index in OSCC.

CSF levels of Aß1-38/Aß1-40/Aß1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease.

Primary progressive aphasia (PPA) is a cognitive syndrome characterized by progressive and isolated language impairments due to neurodegenerative diseases. Recently, an international group of experts published a Consensus Classification of the three PPA clinical variants (naPPA, svPPA and lvPPA). We analyzed 24 patients with PPA by cognitive functions, neuroimaging (MRI, (99 m)Tc ECD-SPECT, (11)C PiB-PET and FDG-PET) and cerebrospinal fluid (CSF) analysis (ptau-181, Aß1-42, Aß1-40 and Aß1-38), to elucidate relationships between neuroimaging studies and biochemical findings in the three PPA clinical variants. Cognitive and speech functions were measured by mini-mental state examination and standard language test of aphasia. The patients with lvPPA showed significant decreases in CSF Aß1-42 and ratios of Aß1-42/Aß1-40 and Aß1-42/Aß1-38, and significant increases in CSF ptau-181 and ratios of ptau-181/Aß1-42 and ptau-181/Aß1-38; these findings were similar to those of patients with Alzheimer's disease (AD). We observed a higher frequency of the ApoE ε4 allele in the lvPPA patients relative to the two other PPA variants. In (11)C PiB-PET of lvPPA patients, PiB positive findings were detected in cortices of frontal, temporal and parietal lobes and the posterior cingulate, where massive Aß may accumulate due to AD. Our results of AD-CSF markers including Aß1-38 and (11)C PiB-PET in the lvPPA patients demonstrate a common pathological mechanism with the occurrence of AD.

A case of multiple hepatic angiomyolipomas with high (18) F-fluorodeoxyglucose uptake.

BACKGROUND: Hepatic angiomyolipoma is a rare benign mesenchymal tumor. We report an unusual case of a patient with multiple hepatic angiomyolipomas exhibiting high (18) F-fluorodeoxyglucose (FDG) uptake. CASE PRESENTATION: A 29-year-old man with a medical history of tuberous sclerosis was admitted to our hospital for fever, vomiting, and weight loss. Abdominal dynamic computed tomography revealed faint hypervascular hepatic tumors in segments 5 (67 mm) and 6 (10 mm), with rapid washout and clear borders; however, the tumors exhibited no definite fatty density. Abdominal magnetic resonance imaging revealed that the hepatic lesions were slightly hypointense on T1-weighted imaging, slightly hyperintense on T2-weighted imaging, and hyperintense with no apparent fat component on diffusion-weighted imaging. FDG-positron emission tomography (PET) imaging revealed high maximum standardized uptake values (SUVmax) of 6.27 (Segment 5) and 3.22 (Segment 6) in the hepatic tumors. A right hepatic lobectomy was performed, and part of the middle hepatic vein was also excised. Histological examination revealed that these tumors were characterized by the background infiltration of numerous inflammatory cells, including spindle-shaped cells, and a resemblance to an inflammatory pseudotumor. Immunohistochemical evaluation revealed that the tumor stained positively for human melanoma black-45. The tumor was therefore considered an inflammatory pseudotumor-like angiomyolipoma. Although several case reports of hepatic angiomyolipoma have been described or reviewed in the literature, only 3 have exhibited high (18) F-FDG uptake on PET imaging with SUVmax ranging from 3.3-4.0. In this case, increased (18) F-FDG uptake is more likely to appear, particularly if the inflammation is predominant. CONCLUSION: Although literature regarding the role of (18) F-FDG-PET in hepatic angiomyolipoma diagnosis is limited and the diagnostic value of (18) F-FDG-PET has not yet been clearly defined, the possibility that hepatic angiomyolipoma might exhibit high (18) F-FDG uptake should be considered.

Complementary roles of tumour specific PET tracer ¹8F-FAMT to ¹8F-FDG PET/CT for the assessment of bone metastasis.

PURPOSE: The usefulness of (18)F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [(18)F]-3-fluoro-alpha-methyl tyrosine ((18)F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of (18)F-FAMT PET/CT to complement (18)F-FDG PET/CT in the evaluation of bone metastasis. METHODS: This retrospective study included 21 patients with bone metastases of various cancers who had undergone both (18)F-FDG and (18)F-FAMT PET/CT within 1 month of each other. (18)F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the (18)F-FAMT in the corresponding lesions were evaluated. RESULTS: A total of 72 (18)F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. (18)F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of (18)F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher (18)F-FAMT uptake than those of adenocarcinoma. No significant difference in (18)F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. CONCLUSION: The usefulness of (18)F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that (18)F-FAMT uptake was confirmed by (18)F-FDG uptake suggests that (18)F-FAMT PET/CT has the potential to complement (18)F-FDG PET/CT for the detection of bone metastases.

Clinical significance of ¹8F-α-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.

OBJECTIVE: L-3-[(18)F]-fluoro-α-methyl tyrosine ((18)F-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. (18)F-FAMT PET/CT, fluorine-18-fluorodeoxyglucose ((18)F-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 (18)F-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, (18)F-FDG PET/CT and (18)F-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 (18)F-FDG PET/CT was highest (100 %) among that of MRI (95 %) and (18)F-FAMT PET/CT (90 %), the specificity of (18)F-FAMT PET/CT was highest (85.7 %) among that of MRI (57 %) and (18)F-FDG PET/CT (14.3 %). The size of pathological tumor was accorded with that detected by (18)F-FAMT PET/CT and was smaller than that detected by (18)F-FDG PET/CT (P < 0.01). Significant difference was not found between (18)F-FAMT PET tumor volume and pathological tumor volume. CONCLUSIONS: (18)F-FAMT PET/CT was useful and more specific than MRI or (18)F-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.

¹8F-FAMT in patients with multiple myeloma: clinical utility compared to ¹8F-FDG.

OBJECTIVE: L-[3-(18)F]-alpha-methyltyrosine ((18)F-FAMT) is an amino-acid tracer for positron emission tomography (PET), with uptake related to overexpression of L-type amino-acid transporter 1 and proliferative activity in tumour cells. This study evaluated the diagnostic performance of (18)F-FAMT PET compared with 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET in patients with multiple myeloma (MM). METHODS: Eleven patients with MM (newly diagnosed, n = 3; relapsed after treatment, n = 8) underwent whole-body (18)F-FAMT and (18)F-FDG PET within a 2-week interval. Magnetic resonance imaging (MRI) of the spine was also performed to assess patterns of bone marrow infiltration. Tracer uptake was semi-quantitatively evaluated using maximal standardized uptake value (SUV(max)). Mean SUV was also determined for normal bone marrow and the aortic arch as mediastinal background SUV to calculate lesion-to-bone marrow (L/B) and lesion-to-mediastinum (L/M) ratios, respectively. Those values were statistically compared using Student's t test. RESULTS: In 8 patients showing focal infiltration on MRI, 34 FDG-avid bone lesions were identified, with each showing increased FAMT uptake. Mean SUV(max) and L/B ratio of FDG (3.1 ± 1.2 and 3.3 ± 1.9, respectively) were significantly higher than those of FAMT (2.0 ± 1.0 and 2.6 ± 1.1, respectively; p < 0.05 each). In contrast, the L/M ratio of FDG showed no significant difference to that of FAMT (2.2 ± 1.0 and 2.4 ± 1.2, respectively; p = 0.3). CONCLUSIONS: Clear (18)F-FAMT PET uptake was seen in most (18)F-FDG-avid lesions among patients with MM, and an equivalent semi-quantitative value was obtained using L/M ratio. Our preliminary data suggest that (18)F-FAMT PET provides a useful imaging modality for detecting active myelomatous lesions.

The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT.

OBJECTIVES: To evaluate whether there is a correlation between the differences in joint uptake of 2-[18F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the improvement of clinical findings in RA patients undergoing anti-TNF therapies. METHODS: Twenty-two patients who received anti-TNF therapies, including infliximab for 16 patients and etanercept for 6 patients, were assessed. PET with (18)F-FDG studies and clinical assessments were performed at baseline and 6 months after the initiation of therapy. The maximal standardized uptake value (SUV(max)) was used as a representative value for the assessment of the FDG uptake in the bilateral shoulder, elbow, wrist, hip, knee and ankle joints. Spearman's rank correlation test was applied to assess the correlation between the SUV and the clinical parameters. RESULTS: The ΔSUV (12 joints), the difference in the SUV(max) of the affected 12 joints before and after treatment, was positively correlated with the ΔDAS28 (r = 0.609, P = 0.003), ΔDAS28-CRP (r = 0.656, P = 0.001) and Δtender joint count (TJC) (r = 0.609, P = 0.003). There were also significantly positive correlations between ΔSUV (8 joints); the difference in the SUV(max) of the bilateral shoulder, elbow, wrist and knee joints before and after treatment and the ΔDAS28 (r = 0.642, P = 0.001), ΔDAS28-CRP (r = 0.712, P < 0.001) and ΔTJC (r = 0.608, P = 0.003), respectively. CONCLUSION: The FDG uptake observed in the inflamed RA joints may reflect disease activity. The FDG-PET response was correlated with the clinical response to the biologic treatment of RA.