Thyroglobulin immunoassay with a fully automated pretreatment process provides accurate thyroglobulin values in anti-thyroglobulin antibody positive specimens.

OBJECTIVES: Human thyroglobulin (Tg) is widely used as a tumor marker for recurrence and metastasis of differentiated thyroid cancer (DTC). Currently, serum Tg values are measured using second-generation sandwich immunoassays (2nd-IMA). However, interference by endogenous autoantibodies to thyroglobulin (TgAbs) can lead to false-negative results or falsely low Tg values. Here, we describe a new Tg assay using the immunoassay for total antigen including complex via pretreatment (iTACT) method to prevent TgAb interference and compare it with 2nd-IMA. METHODS: Tg values were evaluated by three assays: iTACT Tg, Elecsys Tg-II, which is a 2nd-IMA, and LC-MS/MS (Liquid chromatography tandem-mass spectrometry). The ratio of Tg values between each assay was then compared to the Tg value by LC-MS/MS and TgAb titer. Tg immunoreactivity was analyzed by size-exclusion chromatography. RESULTS: Correlation between iTACT Tg and LC-MS/MS using TgAb-positive specimens was good: Passing-Bablok regression with iTACT Tg = 1.084 × LC-MS/MS + 0.831. Correlation between 2nd-IMA and LC-MS/MS showed a relatively lower slope: 2nd-IMA = 0.747 × LC-MS/MS - 0.518. Thus, Tg values determined by iTACT Tg are equivalent to those of LC-MS/MS regardless of TgAb titer, whereas 2nd-IMA gave lower Tg values due to TgAb interference. Tg-TgAb complexes of various molecular weights were verified by size-exclusion chromatography. Tg values measured by 2nd-IMA fluctuated depending on the molecular weight of the Tg-TgAb complexes, whereas iTACT Tg accurately quantified Tg values regardless of the size of the Tg-TgAb complexes. CONCLUSION: Tg values in TgAb-positive specimens were accurately determined by iTACT Tg. TgAb-positive specimens contain Tg-TgAb complexes of various molecular weights that interfere with Tg value determination by 2nd-IMA, whereas iTACT Tg is unaffected by the presence of Tg-TgAb complexes.

Utility of FDG PET at the Initial Radioiodine Therapy in Differentiated Thyroid Cancer.

BACKGROUND/AIM: Differentiated thyroid cancer (DTC) has a good prognosis, except in the case of patients with radioiodine therapy (RIT)-refractory cancer. However, since DTC is essentially a slowly progressing cancer, it is usually judged to be a DTC with a poor prognosis after multiple RITs and yearly follow-up with echo, computed tomography (CT), and serum thyroglobulin values. This study investigated whether fluorodeoxyglucose-positron emission tomography/CT (FDG PET/CT) combined with initial RIT could identify early-stage patients with poor prognosis. PATIENTS AND METHODS: We evaluated 100 patients with high-risk DTC who underwent total thyroidectomy and received RIT at our institution. We analyzed the clinical outcomes of patients and 18F-FDG accumulation using univariate and multivariate Cox proportional hazards regression models. RESULTS: The 10-year overall survival (OS) was 87.9%, with no significant difference in OS between 18F-FDG accumulation at pre-total or near-total thyroidectomy (NTT) (p=0.180) and 131I accumulation at initial RIT (p=0.577). However, 18F-FDG positive patients had a significantly worse prognosis than negative patients (p=0.005) at initial RIT. CONCLUSION: 18F-FDG PET/CT plays an important role in both the diagnosis and prognostic prediction of RIT refractory disease in DTC patients. 18F-FDG PET/CT can be a useful tool particularly at the time of initial RIT since the 18F-FDG accumulation enables the screening of high-risk DTC with poor prognosis at a very early time stage.

Impact of Nuclear Factor Erythroid 2-Related Factor 2 in Hepatocellular Carcinoma: Cancer Metabolism and Immune Status.

We examined phosphorylated nuclear factor erythroid 2-related factor 2 (P-NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P-NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD-L1) expression. In this retrospective study, immunohistochemical staining of P-NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine-18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD-L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2-overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P-NRF2. Positive P-NRF2 expression was significantly associated with high alpha-fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P-NRF2 expression was an independent predictor for recurrence-free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD-L1 protein expression levels were increased through hypoxia-inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P-NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity.

Usefulness of semi-quantitative analysis in 123I metaiodobenzylguanidine SPECT/CT for the differentiation of pheochromocytoma and cortical adenoma.

OBJECTIVE: 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of pheochromocytomas (PHEOs), but some PHEOs are difficult to differentiate from cortical adenoma (CA) or normal adrenal uptake by visual evaluation alone. A new semi-quantitative analysis using 123I MIBG SPECT/CT is thus expected. Herein, we introduce the tumor-to-liver count ratio (T/L) and the tumor-to-muscle count ratio (T/M). METHODS: We examined the cases of 21 patients with PHEOs (10 males, 11 females; age 24-80, median 61 years) and 23 patients with CA (15 males and 8 females, age 30-78, median 58 years). The visual scoring based on 123I MIBG planar images (planar score) and SPECT images (SPECT score) was used as the conventional evaluation. Using 123I MIBG SPECT/CT findings, we calculated the semi-quantitative values of the count ratio using the maximum or mean count of the tumor and the liver or muscle as the reference organ (T/Lmax, T/Lmean, T/Mmax and T/Mmean). Each evaluation of the PHEOs and CAs was compared, and the diagnosing performance was evaluated based on an ROC analysis. RESULTS: The area under curve (AUC) values were as follows: the planar score, 0.833; SPECT score, 0.813; T/Lmax, 0.986; T/Lmean, 0.975; T/Mmax, 0.955; and T/Mmean, 0.933. The AUC for T/Mmax was significantly higher than those of the planar score, and SPECT score by ROC analysis (p < 0.01 each). CONCLUSION: The semi-quantitative value of 123I MIBG SPECT/CT is more useful than the conventional visual evaluation for differentiating PHEOs from CAs.

A Novel Thyroglobulin Immunoassay Using the Specimen-Pretreatment Process Improves the Accuracy of Thyroglobulin Measurements in Anti-Thyroglobulin Positive Specimens.

BACKGROUND: Recently, second-generation thyroglobulin (Tg) sandwich immunoassays have been used in clinical laboratories to measure the serum Tg levels, which is a tumor marker used to monitor postoperative patients with differentiated thyroid cancers. However, these immunoassays are often subject to Tg autoantibody (TgAb) interference. TgAb interference is inevitable for almost all Tg immunoassays, resulting in unreliable Tg measurement values of TgAb-positive samples. METHODS: To address TgAb interference, we have developed a novel immunoassay based on a fully automated chemiluminescent enzyme immunoassay system using the effective specimen-pretreatment process to inactivate TgAb in blood and evaluated its assay performance. RESULTS: The developed assay was traceable to BCR457 IRMM reference material with a limit of quantification of 0.03 ng/mL. The pretreatment process inactivated almost all TgAb in specimens and allowed accurate Tg measurements in TgAb-positive samples in which TgAb interference was observed using the immunoassays. Size-exclusion chromatography analysis of immunoreactive Tg molecule in a TgAb-positive serum verified disruption of the Tg-TgAb immune complex by the pretreatment process. Good correlation of Tg values in TgAb-negative specimens was observed between the new Tg immunoassay and the second-generation sandwich immunoassays. However, there were numerous discrepant samples on bias plots between the new Tg immunoassay and the second-generation sandwich immunoassays for TgAb-positive specimens. CONCLUSIONS: This study indicates the new Tg immunoassay with the specimen-pretreatment process is both robust and free from interference by TgAb. Thus, this novel assay is superior to second-generation sandwich immunoassays and gives accurate Tg concentrations even for TgAb-positive cases.

Impact of Metabolic Activity in Hepatocellular Carcinoma: Association With Immune Status and Vascular Formation.

We evaluated the prognostic value of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC). Their association with programmed death ligand 1 (PD-L1) expression and vascular formation was further investigated. In this retrospective study, using a database of 418 patients who had undergone 18F-FDG PET/CT before hepatic resection for HCC, immunohistochemical staining of PD-L1, clusters of differentiation (CD) 8, CD68, and CD34 was performed. Patients with a high maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT showed a significantly worse recurrence-free survival (RFS) (hazard ratio [HR]: 1.500; 95% confidence interval [CI]: 1.088-2.069; P = 0.0133) and overall survival (OS) (HR: 2.259; 95% CI: 1.276-4.000; P = 0.0052) than patients with a low SUVmax. Logistic regression analysis showed that a high SUVmax in HCC was significantly associated with PD-L1-positive expression (odds ratio: 4.407; 95% CI: 2.265-8.575; P < 0.0001). SUVmax values of HCC were associated with intratumoral CD8-positive T-cell counts (P = 0.0044) and CD68-positive macrophage counts (P = 0.0061). Stratification based on SUVmax, PD-L1 expression, and the vessels that encapsulate tumor clusters (VETC) status was also significantly associated with RFS and OS. SUVmax, VETC, and PDL1 expression were independently predictive of survival on multivariable analysis. Conclusion: Our large cohort study showed that a high SUVmax on 18F-FDG PET/CT is associated with a poor clinical outcome and PD-L1 expression in patients with HCC. Additionally, stratification of patients based on the combination of SUVmax, PD-L1 expression, and the VETC status predicts poor clinical outcome.

Obesity is a risk factor for intrahepatic cholangiocarcinoma progression associated with alterations of metabolic activity and immune status.

Body mass index (BMI) is well known to be associated with poor prognosis in several cancers. The relationship between BMI and the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC) is incompletely understood. This study investigated the relationships of BMI with clinicopathological characteristics and patient outcomes, focusing on metabolic activity and immune status. The relationship between BMI and the maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was analyzed. In addition, immunohistochemistry was performed for programmed cell death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8), and forkhead box protein P3 (Foxp3). Seventy-four patients with ICC were classified into normal weight (BMI < 25.0 kg/m2, n = 48) and obesity groups (BMI ≥ 25.0 kg/m2, n = 26), respectively. Serum carbohydrate antigen 19-9 levels were higher in the obesity group than in the normal weight group. Tumor size and the intrahepatic metastasis rate were significantly larger in the obesity group. Patients in the obesity group had significantly worse prognoses than those in the normal weight group. Moreover, BMI displayed a positive correlation with SUVmax on 18F-FDG PET/CT (n = 46, r = 0.5152). Patients with high 18F-FDG uptake had a significantly higher rate of PD-L1 expression, lower CD8 + tumor-infiltrating lymphocyte (TIL) counts, and higher Foxp3 + TIL counts. The elevated BMI might predict the outcomes of patients with ICC. Obesity might be associated with ICC progression, possibly through alterations in metabolic activity and the immune status.

123I metaiodobenzylguanidine (MIBG) uptake predicts early relapse of neuroblastoma using semi-quantitative SPECT/CT analysis.

OBJECTIVE: 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of neuroblastoma (NB). MIBG uptake is correlated with norepinephrine transporter expression; hence, it is expected that high-MIBG tumors would be more highly differentiated and have a better prognosis than those with lower expression. We have introduced a method of assessing MIBG accumulation semi-quantitatively using SPECT/CT fusion images. The purpose of this study was to evaluate the relationship of 123I MIBG uptake measured by semi-quantitative values of SPECT/CT and early relapse of NB. METHODS: We studied the cases of 11 patients (5 males and 6 females, age 5-65 months, median age 20 months) with histopathologically proven NB between April 2010 and March 2015. The early-relapse group was defined as patients who had relapsed within 3 years after the first 123I MIBG SPECT/CT exam. Other patients were classified as the delay-relapse group. Uptake of MIBG was evaluated using the count ratio of tumor and muscles. T/Mmax and T/Mmean were defined as follows: T/Mmax = max count of tumor/max count of muscle, T/Mmean = mean count of tumor/mean count of muscle. RESULTS: The average T/Mmean values of the early-relapse group and delay-relapse group were 2.65 ± 0.58 and 7.66 ± 2.68, respectively. The T/Mmean values of the early-relapse group were significantly lower than those of delay-relapse group (p < 0.05). The average T/Mmax of the early-relapse group and delay-relapse group were 8.86 ± 3.22 and 16.20 ± 1.97, respectively. There was no significant difference in T/Mmax values between the two groups. CONCLUSIONS: Low 123I MIBG uptake using semi-quantitative SPECT/CT analysis was correlated with early relapse of NB.

Diagnostic accuracy for the epileptogenic zone detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT.

OBJECTIVES: To examine the utility of FDG-PET/MRI in patients with epilepsy by comparing the diagnostic accuracy of PET/MRI and PET/CT in epileptogenic zone (EZ) detection. METHODS: This prospective study included 31 patients (17 males, 14 females) who underwent surgical resection for EZ. All patients were first scanned using FDG-PET/CT followed immediately with FDG-PET/MRI. Two series of PET plus standalone MR images were interpreted independently by five board-certified radiologists. A 4-point visual score was used to assess image quality. Sensitivities and visual scores from both PETs and standalone MRI were compared using the McNemar test with Bonferroni correction and Dunn's multiple comparisons test. RESULTS: The EZs were confirmed histopathologically via resection as hippocampal sclerosis (n = 11, 35.5%), gliosis (n = 8, 25.8%), focal cortical dysplasia (n = 6, 19.4%), and brain tumours (n = 6, 19.4%) including cavernous haemangioma (n = 3), dysembryoplastic neuroepithelial tumour (n = 1), ganglioglioma (n = 1), and polymorphous low-grade neuroepithelial tumour of the young (n = 1). The sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). The visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT, as well as standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3). CONCLUSIONS: The diagnostic accuracy for the EZ detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT. KEY POINTS: • Sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). • Visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT and standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). • Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3).

A Functional Scoring System Based on Salivary Gland Scintigraphy for Evaluating Salivary Gland Dysfunction Secondary to 131I therapy in Patients with Differentiated Thyroid Carcinoma.

INTRODUCTION: Radioiodine therapy with 131I (131I therapy) after total or near-total thyroidectomy has been established as an effective treatment for Differentiated Thyroid Carcinoma (DTC), but can induce dry mouth symptoms by salivary gland damage and impair the patients' quality of life. AIM: To propose a functional scoring system based on Salivary Gland Scintigraphy (SGS) findings that evaluates development of salivary gland dysfunction secondary to 131I therapy in patients with DTC. MATERIALS AND METHODS: This retrospective study evaluated the records of 279 DTC patients who underwent SGS after one or more round(s) of 131I therapy, using 370 MBqof 99mTc-pertechnetate. The SGS results were assessed using a novel functional scoring system in the Parotid Glands (PGs) and Submandibular Glands (SMGs) according to visual evaluations based on a three-point uptake score, Washout Rate (%WR) score after lemon-juice stimulation, and functional score. The scores were compared among pre treatment, low-dose (<10 GBq), and high-dose (>10 GBq) groups and among pre treatment, symptom-positive, and symptom-negative groups. Risk factors for dry mouth were analyzed by univariate and multivariate logistic regression analyses. RESULTS: Dry mouth symptoms developed in 15.4% of the DTC patients after 131I therapy. The three-point uptake, %WR, and functional scores in both the PG and SMG were statistically significant between low-dose and high-dose groups, and between symptom-positive and symptom-negative groups. The PG/SMG functional scores were independent risk factors for dry mouth (odds ratio, 0.03 and 0.0007 respectively). CONCLUSION: SGS-based PG and SMG functional scores were effective biomarkers to objectively evaluate salivary gland dysfunction, with the high strength of association with dry mouth symptoms.

The Efficiency of Respiratory-gated 18F-FDG PET/CT in Lung Adenocarcinoma: Amplitude-gating Versus Phase-gating Methods.

OBJECTIVES: In positron emission tomography (PET) studies, thoracic movement under free-breathing conditions is a cause of image degradation. Respiratory gating (RG) is commonly used to solve this problem. Two different methods, i.e., phase-gating (PG) and amplitude-gating (AG) PET, are available for respiratory gating. It is important to know the strengths and weaknesses of both methods when selecting an RG method for a given patient. We conducted this study to clarify whether AG or PG is preferable for measuring fluorodeoxyglucose (FDG) accumulation in lung adenocarcinoma and to investigate patient conditions which are most suitable for AG and PG methods. METHODS: A total of 31 patients (11 males, 20 females; average age: 70.1±11.6 yrs) with 44 lung lesions, diagnosed as lung adenocarcinoma between April 2012 and March 2013, were investigated. Whole-body FDG-PET/CT scan was performed with both PG and AG methods in all patients. The maximum standardized uptake value (SUVmax) of PG, AG, and the control data of these two methods were measured, and the increase ratio (IR), calculated as IR(%)= (Post - Pre)/Pre × 100, was calculated. The diameter and position of lung lesions were also analyzed. We defined an 'effective lesion' of PG (or AG) as a lesion which showed a higher IR compared to AG (or PG). 8 (25.8%). RESULTS: The average SUVmax and average IR were 8.99±7.94 and %21.4±25.6 in PG and 7.60±6.70 and %4.0±14.4 in AG, respectively. Although there was no significant difference between the average SUVmax of PG and AG (P=0.09), the average IR of PG was significantly higher than that of AG (P<0.01). The number of PG- and AG-effective lesions was 32 (72.7%) and 12 (28.3%), respectively. There was no significant difference in the average diameter or position of the lesions between the PG- and AG-effective lesions. There were 23 (74.2%) PG-effective and 8 (25.8%) AG-effective patients. No significant difference was observed in sex or age between PG- and AG-effective patients. CONCLUSION: The PG method was more effective for measuring FDG accumulation of lung lesions under free-breathing conditions in comparison with the AG method.

Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System, BONENAVI, on Bone Scintigraphy Images.

OBJECTIVES: BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN) and bone scan index (BSI) values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. METHODS: We analyzed 50 patients (36 males,14 females; age range: 87-42 yrs median age:72.5 yrs) with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer). Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic, osteolytic, and mixed components) was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based) among the three primary cancers and four types of bone metastasis. RESULTS: There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer 0.909; and lung cancer, 0.864). Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic,; 0.939 mildly osteoblastic; 0.788, mixed type; 0.991, and osteolytic. 0.969) The possibility of a lesion-based ANN value below 0.5 was %10.9 for bone metastasis in prostate cancer, %12.9 for breast cancer, and %37.2 for lung cancer. The corresponding possibility were %14.7 for osteoblastic metastases, %23.9 for mildly osteoblastic metastases, %7.14 for mixed-type metastases, and %16.0 for osteolytic metastases. CONCLUSION: The lesion-based ANN values calculated by BONENAVI can be influenced by the type of primary cancer and bone metastasis.

Metabolic Tumor Volume by 18F-FDG PET/CT Can Predict the Clinical Outcome of Primary Malignant Spine/Spinal Tumors.

BACKGROUND AND PURPOSE: Primary malignant spine/spinal tumors (PMSTs) are rare and life-threatening diseases. In this study, we demonstrated the advantage of volume-based 18F-FDG PET/CT metabolic parameter, metabolic tumor volume (MTV), for assessing the aggressiveness of PMSTs. MATERIALS AND METHODS: We retrospectively reviewed 27 patients with PMSTs and calculated SUVmax, MTV, and total lesion glycolysis (TLG) to compare their accuracy in predicting progression-free survival (PFS) and overall survival (OS) by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to compare the reliability of the metabolic parameters and various clinical factors. RESULTS: MTV exhibited greater accuracy than SUVmax or TLG. The cut-off values for PFS and OS derived from the AUC data were MTV 45 ml and 83 ml and TLG 250 SUV⁎ml and 257 SUV⁎ml, respectively. MTV above cut-off value, but not TLG, was identified as significant prognostic factor for PFS by log-lank test (p = 0.04). In addition, MTV was the only significant predictive factors for PFS and OS in the multivariate analysis. CONCLUSIONS: MTV was a more accurate predictor of PFS and OS in PMSTs compared to TLG or SUVmax and helped decision-making for guiding rational treatment options.

Association between Volumetric Analysis of Lung Metastases on F-18-fluoro-2-deoxy-D-glucose Positron Emission Tomography/Computed Tomography and Short-term Progression after I-131 Therapy for Differentiated Thyroid Carcinoma.

PURPOSE: Lung metastases (LMs) and their radioiodine uptake affect prognosis in patients with differentiated thyroid carcinoma (DTC). We herein investigate the value of metabolic tumor volume (MTV) in LMs on positron emission tomography/computed tomography (PET/CT) using 2-[F-18]-fluoro-2-deoxy-D-glucose (F-18 FDG PET/CT) in predicting short-term progression after initial I-131 therapy in DTC patients. MATERIALS AND METHODS: We retrospectively evaluated 111 DTC patients with LMs. Diagnostic CT and I-131 scintigraphy were performed within 1 week of I-131 therapy. Maximum standardized uptake value (SUVmax) and total MTV (MTVtotal) were compared between patients with I-131-positive and I-131-negative LMs and between patients with and without short-term progression. Correlation analyses were performed between F-18 FDG PET/CT parameters and thyroglobulin (TG) level, and predictive factors for short-term progression were analyzed by logistic regression and receiver operating characteristic curve analysis. RESULTS: Patients with short-term progression had significantly higher SUVmax and MTVtotal than those without. TG levels were significantly correlated with SUVmax (r = 0.21) and MTVtotal (r = 0.51) after I-131 therapy. MTVtotal showed significant association (χ2 = 16.5, odds ratio = 0.02) with short-term progression after initial I-131 therapy and had the highest predictive value of all the putative risk factors. CONCLUSIONS: MTVtotal in LMs on F-18 FDG PET/CT is an independent predictive factor with a high predictive value for short-term progression of DTC after initial I-131 therapy. It is recommended that F-18 FDG PET/CT be performed before planning therapy during the evaluation of DTC patients with LM.

Impact of patient age on the iodine/FDG "flip-flop" phenomenon in lung metastasis from thyroid cancer.

OBJECTIVES: Radioiodine therapy is an effective treatment for lung metastasis from thyroid cancer. However, cases of lung metastasis without iodine uptake are often encountered. In such cases, FDG accumulation in lung lesions is often observed. There is a reverse relationship between iodine and FDG accumulation in thyroid cancer lesions, the so-called "flip-flop" phenomenon. The aim of this study was to assess the relationship between patient age and the occurrence of the flip-flop phenomenon. METHODS: Eighty-six patients who underwent radioiodine therapy for lung metastasis were studied retrospectively (age 17-73 years; median 60 years; males:females 22:64). We compared the clinical data and imaging findings (size and FDG uptake of lung nodules) between patients with (n = 44) and without (n = 42) iodine uptake in lung metastasis. RESULTS: Significantly more young patients showed iodine accumulation in lung metastasis than old patients (p = 0.0025). Lung metastases with larger size or greater FDG uptake showed no iodine uptake more frequently with significant difference (p = 0.015 and <0.001, respectively). Among patients with FDG uptake in the lung metastasis, 57.1 % of young patients (<60 years) and 24.3 % of the old patients (≥60 years) showed iodine uptake (p = 0.0029). CONCLUSIONS: Higher patient age and lung nodules with large size or FDG accumulation are negative factors for iodine accumulation in lung metastases from thyroid cancer. In addition, our results show that young patients have a greater likelihood of iodine uptake even when FDG accumulates in lung metastasis, in contrast to old patients.

Diagnostic utility of intravoxel incoherent motion mr imaging in differentiating primary central nervous system lymphoma from glioblastoma multiforme.

PURPOSE: To evaluate the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging and 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma multiforme (GBM). MATERIALS AND METHODS: Fifty patients, 17 with PCNSL and 33 with GBM, were retrospectively studied. From the 3 Tesla IVIM data, the perfusion fraction (f) and diffusion coefficient (D) were obtained. In addition, the maximum standard uptake value (SUVmax ) was obtained from the FDG-PET data. Each of the three parameters was compared between PCNSL and GBM using Mann-Whitney U-test. The performance in discriminating between PCNSL and GBM was evaluated using receiver-operating characteristics analysis and area-under-the-curve (AUC) values for the three parameters. RESULTS: The fmax and Dmin values were significantly higher in GBM than in PCNSL (P < 0.01 and P < 0.0001, respectively). In addition, the SUVmax value was significantly lower in GBM than in PCNSL (P < 0.0005). The AUC values for fmax , Dmin , and SUVmax were 0.756, 0.905, and 0.857, respectively. The combination of the fmax and Dmin increased the diagnostic performance (AUC = 0.936) of fmax (P < 0.05), but this value was not significantly different from the values for Dmin (P = 0.30). CONCLUSION: IVIM-MR imaging noninvasively provides useful quantitative information in distinguishing between PCNSL and GBM. J. Magn. Reson. Imaging 2016;44:1256-1261.

Inflammatory Pseudotumor-like Follicular Dendritic Cell Tumor of the Spleen: Case Report and Review of the Literature.

A 74-year-old woman underwent contrast-enhanced (CE) computed tomography (CT) that revealed an enlarging splenic lesion. This splenic tumor was suspected as metastasis because the patient had been diagnosed with right breast cancer with lung and right axillary lymph node metastases 4 years earlier and had undergone surgery and hormone therapy at another hospital. T2-weighted imaging of magnetic resonance (MR) imaging demonstrated the tumor with slightly high intensity with a rim of low intensity at the margin. On dynamic contrast-enhanced (DCE)-MR imaging after intravenous administration of gadolinium diethylenetriamine pentaacetic acid, delayed enhancement was observed in the center and margin of the tumor. On positron emission tomography with 2-deoxy-2-[18F] fluoro-D-glucose (FDG) integrated with CT, the tumor showed high FDG uptake. Splenic metastasis was considered based on the imaging findings, lack of inflammation on laboratory data, and clinical course, so she underwent splenectomy. Histopathologically, the tumor was encapsulated by a fibrous structure, which was depicted as the rim at the tumor margin on T2-weighted imaging and DCE-MR imaging. Immunohistochemical study allowed the diagnosis of inflammatory pseudotumor (IPT)-like follicular dendritic cell tumor (FDCT). FDCT is a primary neoplasm of lymph nodes that shows features of follicular dendritic cell differentiation, and it is rare at the spleen. Differential diagnosis is difficult between IPT-like FDCT and similar splenic tumors, such as IPT, splenic metastases, hamartoma and hemangioma. However, in addition to the enhancement pattern within a tumor on DCE-MR imaging, detection of the capsular-like rim on MR imaging might aid the diagnosis of splenic IPT-like FDCT.

Nabothian cyst a predominant cause of false-positive iodine uptake in uterus: comparison of SPECT/CT and pelvic MRI.

PURPOSE: Many cases of unexpected radioiodine uptake have been reported, including physiological uptake in healthy tissue and in both benign and malignant nonthyroidal lesions. However, iodine uptake in the uterus has not been well assessed. In this article, we systemically analyzed iodine uptake in the uterus and identified the site in which uptake occurred. MATERIALS AND METHODS: Seventy-six female patients who underwent SPECT/CT from neck to pelvis were included in this study; 5 patients with uterine uptake received pelvic MRI. Iodine uptake in the uterus was diagnosed with SPECT/CT and compared with the findings of the MRI. Serum TSH level, administered dose of iodine-131 and number of radioiodine therapies were compared between the 2 groups with and without iodine uptake in the uterus. RESULTS: Twenty (26.3%) of 76 patients showed iodine uptake in the uterine cervix on SPECT/CT. It was difficult to distinguish the uptake in the uterus from that in the urinary bladder or rectum using only planar images. The patients with the uterine uptake were younger than those without (median age, 46.5 vs. 62, P = 0.011). There were no significant differences in serum TSH level, administered dose of iodine-131, or number of radioiodine therapies between the 2 groups. In all instances of the 5 patients who underwent pelvic MRI, iodine uptake in the uteri was located in nabothian cysts. CONCLUSION: Iodine uptake in the uterus is frequently found if pelvic SPECT/CT is performed. Nabothian cysts are a predominant cause of iodine uptake in the uterine cervix.

Diagnostic and prognostic value of pretreatment SUV in 18F-FDG/PET in breast cancer: comparison with apparent diffusion coefficient from diffusion-weighted MR imaging.

UNLABELLED: In oncology, the apparent diffusion coefficient (ADC) measured by diffusion-weighted MR imaging (DWI) and the standardized uptake value (SUV) from (18)F-FDG PET have similar clinical applications. The purpose of this study was to assess the correlation between the ADC and SUV and compare their potential in the diagnosis and prediction of prognosis in breast tumors. METHODS: Seventy-nine female patients (age range, 19-69 y; average, 49.1 y) with 83 pathologically proven breast tumors were recruited. The diagnoses consisted of 70 malignant breast tumors (65 cases of invasive ductal carcinoma, 1 of medullary carcinoma, 1 of mucinous carcinoma, 1 of squamous cell carcinoma, and 2 of micropapillary carcinoma) and 13 benign breast tumors (4 cases of fibroadenoma, 4 of mastopathy, 3 of adenosis with atypia, and 2 of benign phyllodes tumor). All patients underwent mammary gland MR imaging with DWI and (18)F-FDG PET within a 2-wk interval. The patients' ADCs and SUVs were measured within the tumor by DWI and (18)F-FDG PET, respectively. For the malignant tumors, we evaluated the relationships among ADC, SUV, histopathologic appearance, and long-term prognosis. RESULTS: A significant difference (P < 0.05) was observed in both parameters (ADC and SUV) between the benign and malignant breast tumors, and the difference was more significant when we introduced a new parameter, SUV/ADC. There was a weak inverse correlation between ADC and SUV (r = -0.36; P = 0.06) among the total tumors; however, this correlation was not significant within the group of malignant tumors. High SUV was found to correlate with larger tumor size, higher nuclear grade, and the triple-negative hormonal receptor profile. High ADC was revealed to be correlated with negative progesterone receptor and positive human epidermal growth factor receptor 2 profile. Higher SUVs also showed a correlation with poor prognosis. No correlation was seen between ADC and prognosis. CONCLUSION: Both SUV and ADC are helpful parameters in differentiating benign from malignant breast tumors. The use of SUV and ADC in combination may help in the diagnosis because of their inverse relationship. High preoperative SUV was associated with poor prognosis, but the contribution of ADC to prognosis prediction was small.

Usefulness of partial volume effect-corrected F-18 FDG PET/CT for predicting I-131 accumulation in the metastatic lymph nodes of patients with thyroid carcinoma.

PURPOSE: The purpose of this study was to evaluate the clinical usefulness of partial volume effect (PVE)-corrected F-18 FDG PET/CT for predicting I-131 accumulation in metastatic lymph nodes (mLNs) during I-131 therapy for papillary thyroid carcinoma (PTC). METHODS: Sixty-five mLNs in 31 PTC patients who underwent F-18 FDG PET/CT in an initial radioiodine therapy (RIT) were retrospectively evaluated. Of these, 25 mLNs were I-131-positive and 40 were I-131-negative. SUVmax and SUVmax with PVE correction (cSUVmax) were measured for each mLN, where PVE correction was performed utilizing a simple table lookup correction method. Then, SUVmax/cSUVmax was compared between I-131-positive and I-131-negative mLNs, including the analyses for the mLNs with small-sized (<1 cm) and weak FDG accumulation (SUVmax <3.5). The predictability for I-131 accumulation with SUVmax/cSUVmax was also compared. RESULTS: For all 65 mLNs, SUVmax/cSUVmax was significantly higher in I-131-negative than I-131-positive mLNs (p < 0.0001). Only in cSUVmax, I-131-negative mLNs were significantly higher than I-131-positive, in terms of the 30 small-sized mLNs (p = 0.0001) and 14 mLNs with weak FDG uptake (p = 0.007). The highest accuracy in predictability for I-131 accumulation was significantly better with cSUVmax (92 %) than SUVmax (62 %) (p < 0.0001). CONCLUSION: PVE-corrected F-18 FDG PET/CT is a valuable predictor of I-131 accumulation in mLNs during RIT.