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Background: The goal of this article was to investigate the feasibility of 64Cu labeling in prostate-specific membrane antigen imaging and therapy (PSMA I&T) for PSMA positron emission tomography (...

Background The purpose of this study was to evaluate both the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labeled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer. Methods PET images at 1, 24, and 48 h after 296 MBq of 64Cu-NOTA-Trastuzumab injection were obtained from seven patients with breast cancer. Both the primary tumors’ and metastatic lesions’ maximum standardized uptake value (SUVmax) was evaluated. The mean SUVmax (SUVmean) was evaluated in the other organs, including the blood pool, liver, kidney, muscle, spleen, bladder, and the lungs, as well as the bones. Moreover, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed based on feedback regarding adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration. Results 64Cu-NOTA-Trastuzumab PET images showed that the overall SUVmean values in each organ negatively correlated with time. The liver’s average SUVmean values were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 h, 24 h, and 48 h after injection, respectively. The average SUVmean blood values were measured at 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 h, 24 h, and 48 h after injection, respectively. The SUVmax of HER2-positive tumors was relatively higher than HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 h after injection, respectively). Tumor-to-background ratios were higher in the HER2-positive tumors than in the HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq). Conclusions 64Cu-NOTA-Trastuzumab showed a specific uptake at the HER2-expressing tumors, thus making it a feasible and safe monitoring tool of HER2 tumor status in patients with breast cancer. Trial registration CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr

To evaluate the biodistribution of [18F]Florastamin, a novel 18F-labelled positron emission tomography (PET) tracer for prostate-specific membrane antigen (PSMA) for the diagnosis of prostate cancer. PET was performed for five healthy controls and 10 patients with prostate cancer at 0, 10, 30, 70, and 120 mins after injecting 370 MBq of [18F]Florastamin. The maximum standardised uptake value (SUVmax) was evaluated in the primary tumour. The mean SUVmax (SUVmean) was evaluated in normal organs. Furthermore, the residence time was evaluated by assessing radioactivity in each organ. The internal radiation dosimetry was calculated using the OLINDA/EXM software. The SUVmax in primary tumours increased with time. A favourable tumour to background ratio was also observed over time. Multiple lymph nodes and bone metastases were also evaluated and showed a similar pattern to SUVmax in the primary tumour. In one patient, a tiny lymph node metastasis was identified using [18F]Florastamin PET, which was not observed using other modalities, and was histologically confirmed. The highest absorbed dose was observed in the kidney (0.062 ± 0.015 mGy/MBq), followed by the bladder (0.032 ± 0.013 mGy/MBq), liver (0.022 ± 0.006 mGy/MBq), and salivary gland (0.018 ± 0.006 mGy/MBq). The effective dose with a 370 MBq injection of [18F]Florastamin was 1.81 mSv. No adverse events related to [18F]Florastamin were reported. We identified a novel PSMA-targeted PET ligand, [18F]Florastamin, for imaging prostate cancer. [18F]Florastamin showed a high SUVmax and relatively high tumour to background ratio in both primary tumour and metastatic lesions, which suggests its high sensitivity to detect tumours without any adverse events. KCT0003924 registered at https://cris.nih.go.kr/ .

We evaluated the changes in treatment response over time after single 131I-rituximab radioimmunotherapy (RIT) according to non-Hodgkin lymphoma (NHL) types. Fifteen aggressive and 21 indolent lymphoma cases undergoing RIT were evaluated. All patients underwent 18F-FDG-PET-CT before and 5 days, 1, and 3 months after RIT. The maximum standardized uptake value (SUV) and the sum of the products of the longest perpendicular diameters of tumours (SPD) were evaluated. Treatment responses were evaluated 1 and 3 months after RIT In aggressive lymphoma, SUV decreased at 5 days after RIT but increased after that. SPD decreased at 1 month but significantly increased at 3 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) at 1 month after RIT were changed to PD at 3 months after RIT. In indolent lymphoma, the SUV decreased continuously until 1 month after RIT. The SPD significantly decreased at 1 month and tended to further decrease to 3 months. CR, PR, SD, and PD at 1 month after RIT were achieved in 0, 8, 13, and 0 cases, respectively. Among the 13 SD cases, one changed to CR, three changed to PR, and nine had not changed at 3 months after RIT. The treatment response to single RIT differed depending on NHL type. These findings suggest a need to establish an optimal treatment regimen based on NHL aggressiveness.

Purpose The aim of the present study was to obtain information about distribution, radiation dosimetry, toxicity, and pharmacokinetics of O-[18F]fluoromethyl-D-tyrosine (D-18F-FMT), an amino acid PET tracer, in patients with brain tumors. Patients and methods A total of 6 healthy controls (age = 19-25 years, 3 males and 3 females) with brain PET images and radiation dosimetry and 12 patients (median age = 60 years, 6 males and 6 females) with primary (n = 5) or metastatic brain tumor (n = 7) were enrolled. We acquired 60-minute dynamic brain PET images after injecting 370 MBq of D-18F-FMT. Time-activity curves of D-18F-FMT uptake in normal brain versus brain tumors and tumor-to-background ratio were analyzed for each PET data set. Results Normal cerebral uptake of D-18F-FMT decreased from 0 to 5 minutes after injection, but gradually increased from 10 to 60 minutes. Tumoral uptake of D-18F-FMT reached a peak before 30 minutes. Tumor-to-background ratio peaked at less than 15 minutes for 8 patients and more than 15 minutes for 4 patients. The mean effective dose was calculated to be 13.2 μSv/MBq. Conclusions Using D-18F-FMT as a PET radiotracer is safe. It can distinguish brain tumor from surrounding normal brain tissues with a high contrast. Early-time PET images of brain tumors should be acquired because the tumor-to-background ratio tended to reach a peak within 15 minutes after injection.

The purpose of this study was to validate the feasibility of contrast-enhanced transcranial Doppler sonography (CE-TCCD) in the diagnosis of Moyamoya disease (MMD). CE-TCCD data on patients with MMD were analyzed. The CE-TCCD data were classified qualitatively into four patterns by two independent investigators: normal vascular color Doppler signal (pattern 1), augmented color Doppler signal with identifiable vascular structure (pattern 2), confluent color Doppler signal filling more than two-thirds of the display frame without identifiable vascular structure (pattern 3) and confluent color Doppler signal filling full display (pattern 4). To investigate the validity, we compared the CE-TCCD data with traditional transcranial Doppler data and Suzuki grades on cerebral angiography. A total of 32 CE-TCCD studies from 16 MMD patients (male 37.5%, median age 48) were included in this study. The CE-TCCD findings were distributed across patterns 1 (n = 3), 2 (n = 12), 3 (n = 10) and 4 (n = 7) and were correlated with the Suzuki grades (p 0.005) and hemodynamic parameters. Inter-rater reliability was promising (Cronbach α = 0.883). The CE-TCCD test provides distinctive patterns in MMD, according to their stage of progression. CE-TCCD patterns seem to be a reliable and valid means for the evaluation of MMD.

The aim of this study is to assess tumor differentiation using parameters from sequential positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in patients with breast cancer. This retrospective study included 78 patients with breast cancer. All patients underwent sequential PET/CT and MRI. For fluorodeoxyglucose (FDG)-PET image analysis, the maximum standardized uptake value (SUVmax) of FDG was assessed at both 1 and 2 h and metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The kinetic analysis of dynamic contrast-enhanced MRI parameters was performed using dynamic enhancement curves. We assessed diffusion-weighted imaging (DWI)–MRI parameters regarding apparent diffusion coefficient (ADC) values. Histologic grades 1 and 2 were classified as low-grade, and grade 3 as high-grade tumor. Forty-five lesions of 78 patients were classified as histologic grade 3, while 26 and 7 lesions were grade 2 and grade 1, respectively. Patients with high-grade tumors showed significantly lower ADC-mean values than patients with low-grade tumors (0.99 ± 0.19 vs.1.12 ± 0.32, p = 0.007). With respect to SUVmax1, MTV2.5, and TLG2.5, patients with high-grade tumors showed higher values than patients with low-grade tumors: SUVmax1 (7.92 ± 4.5 vs.6.19 ± 3.05, p = 0.099), MTV2.5 (7.90 ± 9.32 vs.4.38 ± 5.10, p = 0.095), and TLG2.5 (40.83 ± 59.17 vs.19.66 ± 26.08, p = 0.082). However, other parameters did not reveal significant differences between low-grade and high-grade malignancies. In receiver-operating characteristic (ROC) curve analysis, ADC-mean values showed the highest area under the curve of 0.681 (95%CI 0.566–0.782) for assessing high-grade malignancy. Lower ADC-mean values may predict the poor differentiation of breast cancer among diverse PET–MRI functional parameters.

Background To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. Methods A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). Results A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25–34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47–24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16–30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over − 39.8% or Δ%SUV02 over − 54.1% showed worse EFS rates than others (p < 0.05). Conclusions PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

This study aimed to investigate the predictive efficacy of positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the pathological response of advanced breast cancer to neoadjuvant chemotherapy (NAC). The breast PET/MRI image deep learning model was introduced and compared with the conventional methods. PET/CT and MRI parameters were evaluated before and after the first NAC cycle in patients with advanced breast cancer [n = 56; all women; median age, 49 (range 26–66) years]. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained with the corresponding baseline values (SUV0, MTV0, and TLG0, respectively) and interim PET images (SUV1, MTV1, and TLG1, respectively). Mean apparent diffusion coefficients were obtained from baseline and interim diffusion MR images (ADC0 and ADC1, respectively). The differences between the baseline and interim parameters were measured (ΔSUV, ΔMTV, ΔTLG, and ΔADC). Subgroup analysis was performed for the HER2-negative and triple-negative groups. Datasets for convolutional neural network (CNN), assigned as training (80%) and test datasets (20%), were cropped from the baseline (PET0, MRI0) and interim (PET1, MRI1) images. Histopathologic responses were assessed using the Miller and Payne system, after three cycles of chemotherapy. Receiver operating characteristic curve analysis was used to assess the performance of the differentiating responders and non-responders. There were six responders (11%) and 50 non-responders (89%). The area under the curve (AUC) was the highest for ΔSUV at 0.805 (95% CI 0.677–0.899). The AUC was the highest for ΔSUV at 0.879 (95% CI 0.722–0.965) for the HER2-negative subtype. AUC improved following CNN application (SUV0:PET0 = 0.652:0.886, SUV1:PET1 = 0.687:0.980, and ADC1:MRI1 = 0.537:0.701), except for ADC0 (ADC0:MRI0 = 0.703:0.602). PET/MRI image deep learning model can predict pathological responses to NAC in patients with advanced breast cancer.

Background and purpose The aim of this study was to determine the diagnostic performance and safety of a new ¹⁸F-labeled amyloid tracer, ¹⁸F-FC119S. Methods This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹⁸F-FC119S PET, ¹⁸F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹⁸F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹⁸F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored. Results Visual assessments of the ¹⁸F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹⁸F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹⁸F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods. Conclusions ¹⁸F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.

The aim of this study was to assess the clinical activity and toxicity of 131I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone). Patients who had been diagnosed with advanced stage (Ann Arbor III or IV) or bulky stage II DLBCL and achieved complete or partial response after six to eight cycles of R-CHOP were enrolled. A total of 16 patients were enrolled and treated with a single dose of 131I-rituximab as consolidation therapy after the completion of six or eight cycles of R-CHOP between December 2005 and June 2011. This trial was terminated before the scheduled enrollment owing to low recruitment. Among the 16 patients who were treated with consolidative 131I-rituximab, 6 achieved complete response (CR) after three cycles of R-CHOP, and another 9 patients further achieved CR after the completion of six or eight cycles of R-CHOP. During the median follow-up period of 73 months, only four patients (25 %) experienced relapse. Two-year relapse-free survival was 88 %, and 5-year relapse-free survival was 81 %. Grade 3 or 4 treatment-related toxicity occurred in four patients and included neutropenia and thrombocytopenia. 131I-rituximab showed promising efficacy as consolidation treatment for patients with DLBCL. A future randomized phase III study to confirm our results is warranted.

This study investigates the correlation of retention index (RI) using the dual phase FDG PET/CT scan with the breast cancer biomarkers.A total of 55 patients with breast cancer underwent dual phase FDG PET/CT scans (60 and 120 min after FDG injection) before treatment. SUVmax and SUVmean of the primary breast tumors were measured, then the percent change of SUVmax and SUVmean between the two scans were calculated, and denoted as RImax and RImean, respectively. After the surgical resection of the breast tumor, the status of biomarkers (ER, PR, and HER-2) was evaluated in the postsurgical specimen.RImean was significantly higher in ER (-) (median, 16.2; IQR, 10.8-21.0) or HER-2 (+) (median, 16.1; IQR, 10.7-21.6) tumors than in ER (+) tumors (median, 9.9; IQR, 5.5-15.3) or HER-2 (-) tumors (median, 10.5; IQR, 5.5-16.1). However, there were no significant differences of SUVmax or RImax according to the ER or HER-2 status. There were no significant differences of any PET parameters between PR (+) and PR (-) tumors. Based off ROC curve analyses, RImean predicted the ER (+) tumors (AUC, 0.699; p = 0.006), and HER-2 (+) tumors (AUC, 0.674; p = 0.022), but not the PR (+) tumors. However, neither SUVmax nor RImax predicted ER (+), PR (+), or HER-2 (+) tumors.Retention index of SUVmean can reflect the ER and HER-2 status of breast cancers. Higher retention index of SUVmean might associate with lower ER expression and higher HER-2 expression.

The imaging definition of lacunar infarcts is variable, particularly regarding their size and the presence of cavitation. We investigated the changes of diameter and evolution pattern of acute lacunar infarcts, and the factors associated with the evolution pattern. Patients with acute single subcortical hemispheric or brainstem ischemic lesions of penetrating arterial territories were included. Maximal diameters on initial diffusion-weighted image (DWI) and follow-up fluid-attenuated inversion recovery image (FLAIR), which performed > 12 months after initial DWI, were semi-automatically measured. Clinical characteristics were compared according to evolution patterns on follow-up FLAIR, classified as cavitated, focal lesion without cavitation, and disappeared. Five hundred nine patients were included. Mean time to follow-up was 31.3 ± 13.7 months. Mean diameter of acute lacunar lesions decreased from 12.9 ± 4.4 to 8.5 ± 4.8 mm during follow-up. Lesions of 58.2% patients remained as cavitated, 18.3% as focal lesion without cavitation, and 23.6% disappeared. Initial NIHSS score (p = 0.005), diameter of initial lesion (p

The aim of this study was to investigate if increased serum thyroglobulin (Tg) levels after radioactive iodine (RAI) showed more therapeutic effects in patients with differentiated thyroid cancer (DTC). Data of 65 patients with DTC who underwent RAI from June 2014 to September 2016 were reviewed. Serum thyroglobulin was measured immediately before (Tg1) and 48 h (Tg2) after RAI under TSH stimulation. Differences and ratios between serum Tg measurements (DeltaTg = Tg2 − Tg1 and RatioTg = Tg2/Tg1) were calculated. The treatment response of distant metastasis was assessed using the RECIST criteria. There was no difference in the median values of Tg1 and Tg2 (2.6 [range, 0.7–1957.5] ng/mL vs. 7.4 [range, 0.7–5276.0] ng/mL, p = 0.240) in all patients (73 scans, 65 patients). In subgroup analysis, Tg levels increased slightly in patients with distant metastasis (8 scans, 7 patients) (Tg1 vs. Tg2; 48.9 [range, 2.4–1957.5] ng/mL vs. 63.2 [range, 4.4–5276.0] ng/mL, p = 0.408). Among patients with distant metastasis, one patient with a partial response to treatment had a more than 4000fold increase in Tg levels and one patient with stable disease showed a 20fold increase in Tg levels. In contrast, five patients with disease progression showed only two to eightfold increase or more than 100fold decrease in Tg levels at 48 h after RAI. However, there was a significant increase in serum Tg levels in patients without distant metastasis (65 scans, 58 patients) after RAI (Tg1 vs. Tg2; 2.0 [range, 0.7–141.9] ng/mL vs. 6.8 [range, 0.7–577.7] ng/mL, p = 0.026). A higher elevation of Tg levels after RAI may be associated with a better treatment outcome in DTC patients with distant metastasis. An increase in Tg levels after RAI may reflect the destruction of cancer and thyroid cells.

Objective: Although Iodine-125 (125I) has been widely used for in vitro studies because of its relatively long half-life (60.1 days), 125I imaging is limited because of its low energy (27 - 35 keV), even in an animal-dedicated system. In this study, imaging characteristics of 125I were assessed using a small animal-dedicated imaging system and clinical scanner. Methods: Using the Siemens Inveon and Siemens Symbia TruePoint systems, imaging characteristics such as resolution, sensitivity, and image quality were compared. Mouse high resolution (MHR-0.5), mouse general purpose (MGP-1.0), and mouse high sensitivity (MHS-2.0) collimators were used for the Inveon scanner, and low energy high-resolution (LEHR) and low energy all-purpose (LEAP) collimators were used for the Symbia TruePoint. For animal imaging, 16.8 MBq of 125I was administered to BALB/c mice intravenously, and the planar image and single-photon emission computed tomography (SPECT) were obtained using both scanners. Results: The resolution of 125I for the Inveon scanner was 3.98 mm full width at half maximum (FWHM) at a 30-mm distance with the MHR-0.5 collimator, and the value of Symbia scanner was 8.72 mm FWHM at a 30-mm distance with the LEHR collimator. The sensitivity of 125I for the Inveon scanner was 21.87 cps/MBq, and the value for the clinical scanner was 30.55 cps/MBq. The planar images of mice were successfully obtained at the level of evaluating specific binding in both scanners. Conclusion: 125I small animal imaging can be achieved with a clinical scanner. This result may enhance the utilization of 125I small animal imaging using a clinical scanner.

PURPOSE: We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC). METHODS: Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular

This research aims to investigate the potential of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET) to predict pathologic response after neoadjuvant chemotherapy (NAC) and overall survival (OS) of patients with synovial sarcoma in Korea.Twenty patients with synovial sarcoma from January 2001 to December 2011 were reviewed retrospectively. All patients underwent pre-treatment FDG PET and tumor removal. Patients were classified with the maximum SUV (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), age, sex, histologic subtype, tumor size, NAC, resection margin, and metastasis at diagnosis. Pathologic response was assessed using the French Federation of Cancer Centers system. Statistical analyses were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards regression model, and Mann-Whitney test.Nine patients (45 %) showed pathologic response, and ten patients survived. Higher SUVmax, higher MTV, higher TLG, monophasic epithelial type, and metastasis at diagnosis were significantly related to poorer OS (p = 0.047, 0.016, 0.016, 0.045, and 0.018, respectively). By multivariate analysis, metastasis at diagnosis was significantly related to poorer OS (p = 0.012/HR = 5.9, 95 % CI 1.47 to 24.1). The SUVmax, MTV, and TLG of the non-responder group were significantly higher than those of the responder group (p = 0.020, 0.020, and 0.020, respectively). There was no significant difference in size between the two groups (p = 0.062).A higher SUVmax on the pre-treatment scan, monophasic epithelial type, and metastasis at diagnosis were significantly associated with a poorer OS, and pathologic responders showed a higher SUVmax before NAC. The PET parameters can be used to predict OS and pathologic response in patients with synovial sarcomas before NAC.

This study investigates the feasibility of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) to predict the pCR (pathologic complete response) rate after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer.A total of 88 patients with locally advanced rectal cancer were retrospectively analyzed. All patients were treated with NCRT, followed by radical surgery, and (18)F-FDG PET/CT was performed before and after NCRT. For a semiquantitative assessment, a volume of interest was drawn, including the whole tumor region, and the maximum SUV (SUVmax), SUVmax normalized to liver uptake (SLR), SUVmax normalized to blood pool uptake (SBR), the metabolic tumor volume at SUV 2.0 (MTV[2.0]), SUV 2.5 (MTV[2.5]), and SUV 3.0 (MTV[3.0]) were measured. In addition, their percentage changes after NCRT were assessed. The pCR was verified through a histologic examination of postsurgical specimens. A receiver operating characteristic curve analysis was conducted to predict the pCR by using these PET parameters.The pCR was predicted in 17 patients (19 %). The values of the area under the curve (AUC) for predicting the pCR were 0.774 for SUVmax after NCRT, 0.826 for SLR after NCRT, 0.815 for SBR after NCRT, 0.724 for MTV(2.5) after NCRT, 0.729 for the percentage change in SUVmax, 0.700 for the percentage change in SLR, and 0.749 for the percentage change in MTV (2.5). Among these PET parameters, SLR after NCRT showed the highest AUC value. The optimal criterion, sensitivity, specificity, and accuracy of SLR after NCRT for predicting the pCR were ≤1.41, 88 %, 65 %, and 68 %, respectively.F-FDG PET was found to be useful for predicting the pCR after NCRT in patients with locally advanced rectal cancer. Among various PET parameters, SUVmax normalized to liver uptake after NCRT was the best predictor of the pCR.

The authors evaluated the usefulness of axillary lymph node (ALN) to primary breast tumor SUV ratio (determined by 18F-FDG PET/CT) for predicting the presence of ALN metastasis in breast cancer.One hundred thirty-six consecutive female patients with breast cancer were enrolled in this retrospective study between January 2009 and November 2012. All patients underwent surgical resection without neoadjuvant chemotherapy, and ALN metastases were histologically confirmed by ALN dissection (n = 75) or sentinel lymph node (LN) biopsy (n = 61). The maximum SUVs of FDG-avid ALNs (SUVLN) and of primary breast tumors were measured on preoperative 18F-FDG PET/CT images, and ALN to primary breast tumor SUV ratios (LN/T ratios) were calculated. In a subgroup of patients with FDG-avid ALNs, optimal cutoff values for SUVLN and LN/T ratio were determined by receiver operating characteristic curve analysis for predicting the presence of ALN metastasis. Subsequently, the diagnostic performances of visual analysis (presence of FDG-avidity), SUVLN, and LN/T ratio for the prediction of ALN metastasis were determined.In a subgroup of patients with FDG-avid ALNs (n = 65), the area under the curve and the optimal criteria of SUVLN for detecting ALN metastasis were 0.655 and greater than 2.1, and those of LN/T ratio were 0.739 and greater than 0.2, respectively. For these criteria, the sensitivity, specificity, and diagnostic accuracy of detecting ALN metastasis were 71.4%, 77.3%, and 74.3%, respectively, for visual analysis; 47.1%, 93.9%, and 69.9%, respectively, for SUVLN; and 62.9%, 92.4%, and 77.2%, respectively, for LN/T ratio in all patients. The specificity of LN/T ratio was significantly higher than that of visual analysis (P = 0.0259). Although the sensitivity of LN/T ratio was higher than that of SUVLN, it did not reach a statistical significance (P = 0.0874).The LN/T ratio better predicts the presence of ALN metastasis than visual analysis or SUVLN in breast cancer.

We evaluated the potential of sequential fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/computed tomography (CT) and MRI (PET/MRI) after one cycle of neoadjuvant chemotherapy to predict a poor histologic response in osteosarcoma. A prospective study was conducted on 30 patients with osteosarcoma treated with two cycles of neoadjuvant chemotherapy and surgery. All patients underwent PET/MRI before, after one cycle, and after the completion of neoadjuvant chemotherapy, respectively. Imaging parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor volume based on magnetic resonance (MR) images (MRV)] and their % changes were calculated on each PET/MRI data set, and histological responses were evaluated on the postsurgical specimen. A total of 17 patients (57 %) exhibited a poor histologic response after two cycles of chemotherapy. Unlike the little volumetric change in MRI, PET parameters significantly decreased after one and two cycles of chemotherapy, respectively. After one cycle of chemotherapy, SUVmax, MTV, and TLG predicted the poor responders. Among these parameters, either MTV ≥ 47 mL or TLG ≥ 190 g after one cycle of chemotherapy was significantly associated with a poor histologic response on multivariate logistic regression analysis (OR 8.98, p = 0.039). The sensitivity, specificity, and accuracy of these parameters were 71 %, 85 % and 77 %; and 71 %, 85 % and 77 %, respectively. The histologic response to neoadjuvant chemotherapy in osteosarcoma can be predicted accurately by FDG PET after one course of chemotherapy. Among PET parameters, MTV and TLG were independent predictors of the histologic response.

OBJECTIVE Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. METHODS Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. CONCLUSION Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

We evaluated the ability of metabolic and volumetric parameters measured by pretreatment 18F-FDG PET/CT to predict the survival of patients with osteosarcoma of the extremities. Methods: The records of 83 patients with American Joint Committee on Cancer stage II extremity osteosarcoma treated with surgery and chemotherapy were retrospectively reviewed. Imaging parameters (maximum standardized uptake value, metabolic tumor volume [MTV], total lesion glycolysis, and tumor volume based on MR images) were measured before treatment, and histologic responses to neoadjuvant chemotherapy were assessed by examination of postsurgical specimens. Receiver-operating-characteristic curve analyses and the Cox proportional hazards model were used to analyze whether imaging and clinicopathologic parameters could predict metastasis-free survival. Results: Of the imaging parameters, MTV at the fixed standardized uptake value threshold of 2.0 (MTV(2.0)) most accurately predicted metastasis by receiver-operating-characteristic curve analysis (area under the curve = 0.679, P = 0.011). By multivariate analysis, MTV(2.0) > 105 mL (relative risk, 3.93; 95% confidence interval, 1.55–9.92) and poor response to neoadjuvant chemotherapy (relative risk, 4.83; 95% confidence interval, 1.64–14.21) independently shortened metastasis-free survival (P = 0.004 for both parameters). The stratification of patients by the combined criteria of MTV(2.0) and histologic response predicted outcome in more detail. Conclusion: MTV is an independent predictor of metastasis in patients with osteosarcoma of the extremities. The combination of MTV and histologic response predicts survival more accurately than the chemotherapeutic response alone.

The aim of this study was to measure the apparent diffusion coefficient (ADC) value at the region with the highest FDG uptake using sequential (18)F-FDG PET and MRI, and to correlate it with the histological grade of invasive ductal carcinoma (IDC) of the breast.A retrospective study was conducted on 75 untreated patients with IDC. First, a PET/CT scan and subsequent breast MRI were done and the SUVmax of the each breast tumor was recorded. Then, a PET image and ADC map were co-registered. On the axial slice containing the pixel with SUVmax, we drew multiple circular ROIs within the tumor and measured the mean ADC value of each ROI. The average (ADC-mean) and minimum (ADC-min) of the mean ADC values for all ROIs within the tumor were calculated, respectively. Then, a circular ROI was placed at the corresponding location to the pixel with the highest SUV and the mean ADC value of the ROI was denoted as ADC-PET. We compared the averages of the ADC parameters and assessed the correlations among SUVmax and ADC parameters. ROC curve and logistic regression analyses were performed to assess the utility of ADC and SUVmax for detecting histological grade 3.ADC-min was significantly lower than the ADC-mean or ADC-PET. All of the ADC parameters showed a negative correlation with SUVmax. The area under the ROC curve for identifying histological grade 3 using ADC-PET, ADC-min, ADC-mean and SUVmax was 0.684, 0.660, 0.633 and 0.639, respectively. By multivariate analysis, ADC-PET was a significant, independent predictor of histological grade 3 (p = 0.004).We estimated the ADC value at the breast tumor region with the highest FDG uptake using sequential (18)F-FDG PET and MRI. This new ADC parameter distinguished high-grade IDC, supporting the feasibility of the combined PET-MRI system in patients with breast cancer.

124I has a complex decay scheme with high gamma energy and low positron abundance. In this study, comparative performance measurements of 124I were performed in terms of spatial resolution, sensitivity, and image quality. All measurements were performed using both 2D and 3D PET in both brain mode and whole body mode. The transverse and axial spatial resolutions at 1 cm were 5.56 and 6.07 mm for 124I, and were 4.58 and 4.77 mm and for 18F, respectively. Sensitivities were 0.5 kcps/MBq (2D) and 3.4 kcps/MBq (3D) for 124I, and 1.8 kcps/MBq (2D) and 9.8 kcps/MBq (3D) for 18F. The %contrast of 3D was higher than that of 2D in 124I. For 124I PET imaging, 3D acquisition with brain mode was highest achievable imaging acquisition mode with finer spatial resolution and higher contrast. This result will be useful for 124I PET imaging.

A single treatment of (131)I-rituximab in patients with B cell non-Hodgkin lymphoma (NHL) showed a modest rate of response (29 %) in a relatively short duration (median 2.9 months). On the basis of this result, we investigated whether repeated treatment with (131)I-rituximab could improve the response.Thirty-one patients with relapsed or refractory B cell NHL received unlabeled rituximab (70 mg) immediately prior to the administration of a therapeutic dose of (131)I-rituximab. The tumor response was evaluated 1 month later by contrast-enhanced (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. Radioimmunotherapy (RIT) was repeated at 4-week intervals.A total of 87 cycles of RIT were administered. Repeated RIT yielded twofold increases in response rate (68 %) and in median response duration (8.6 months). This protocol also induced a favorable response in patients with an aggressive histology compared to that induced by a single treatment (50 vs. 9 %, respectively, p = 0.063). The toxicities were principally hematologic with grade 4 thrombocytopenia occurring in 12 % and neutropenia occurring in 17 % of the 85 assessable cycles.Compared to a single treatment, repeated RIT with (131)I-rituximab increased the response rate and duration for patients with relapsed or refractory B cell NHL, including those with an aggressive histology.

Purpose This study evaluated the usefulness of the maximum standardized uptake value (SUVmax) as a measure of histologic response to neoadjuvant chemotherapy in patients with extremity osteosarcoma. The correlation between [18 F]FDG PET SUVmax values and histologic response to preoperative chemotherapy was also assessed prospectively using PET/MRI.

Aims: It was the aim of this paper to identify prognostic factors in patients with relapsed or refractory B-cell non-Hodgkin's lymphomas, treated by radioimmunotherapy (RIT) with radioiodinated human/murine chimeric anti-CD20 monoclonal antibody rituximab (131I-rituximab). Methods: Twenty-four patients were enrolled prospectively and were treated with unlabeled rituximab 70 mg and a therapeutic activity (median 7.3 GBq) of 131I-rituximab. Contrast-enhanced 18F-FDG PET/CT scans were performed before and after 1 month of RIT. Tumor sizes and maximum standardized uptake values (SUVmax) of scans were measured. Results: Four of the 24 patients survived. High SUVmax in a pretreatment scan was found to be related to poorer overall survival (OS) and progression-free survival (p = 0.04 and 0.02, respectively). Furthermore, a large tumor size in a pretreatment scan was associated with poorer OS but not with progression-free survival (p < 0.01 and p = 0.07, respectively). By multivariate analyses, a high SUVmax, a large tumor size in a pretreatment scan and diffuse large B-cell lymphoma histology were significantly associated with poorer OS [p = 0.04/hazard ratio (HR) = 3.54, p < 0.01/HR = 5.52, and p = 0.02/HR = 3.38, respectively). Conclusion: SUVmax and tumor size determined by a pretreatment 18F-FDG PET/CT result as significant predictors of OS in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated by RIT.

PURPOSE The aim of this retrospective study was to determine whether glucose metabolism assessed by fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) provides prognostic information independent of established prognostic factors in patients with gastric lymphoma. PATIENTS AND METHODS We reviewed the medical records of 86 patients retrospectively (men, 42; women, 44; mean age 58±13 years) with pathologically proven gastric lymphoma (34 mucosa-associated lymphoid tissue and 52 aggressive non-Hodgkin's lymphoma). They underwent F-FDG PET/CT as part of a pretreatment work-up from February 2004 to July 2012. For the analysis, patients were classified by age, sex, Musshoff stage, serum lactate dehydrogenase, International Prognostic Index score, extragastric spread, and visual intensity [visual assessment and maximum standardized uptake value (SUVmax), respectively]. The relationship between F-FDG uptake and survival was analyzed using the Kaplan-Meier method with a log-rank test and Cox's proportional-hazard regression method. RESULTS The median survival of all 86 study participants was 1117 days and the median SUV measured by PET/CT was 6.1 (range, 1.9-32.7). Patients with an SUVmax less than or equal to 5.2 survived significantly longer than patients with an SUVmax more than 5.2 (median, 1163 vs. 1004 days; P=0.003). Survival was also found to be significantly related to age (P=0.0005), histological type (P=0.004), extragastric spread (P=0.0004), International Prognostic Index score (P

Recent studies have been conducted on the relationship between fluorodeoxyglucose (FDG) uptake in F-18 FDG PET/CT and prognosis in patients with pancreatic cancer, but these studies have been carried out in small numbers of patients. The aim of this retrospective study was to determine in a large number of patients whether glucose metabolism as assessed by F-18 FDG PET/CT provides prognostic information independent of established prognostic factors in patients with pancreatic cancer.We reviewed retrospectively the medical records of 165 patients (men 105, women 60, mean age 67 ± 10 years) with a diagnosis of pancreatic cancer that had undergone F-18 FDG PET/CT as part of a pretreatment workup from January 2004 to December 2009. Subsequently, all patients underwent surgery, cyberknife, radiotherapy, and/or chemotherapy. For the analysis, patients were classified by age, demographic data, maximum standardized uptake value (SUVmax), size, location, serum level of CA19-9, type of treatment, and AJCC stage. The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier with log-Rank test and Cox's proportional-hazard regression methods.Median survival for all 165 study subjects was 290 days and median SUV by PET/CT was 5.8 (range: 0-25.1). Patients were allocated to high ( 4.1) and low (≤4.1) SUV groups, and median survivals of these patients were 229 days and 610 days, respectively, which were significantly different (p 0.0001). Furthermore, SUVmax was found to be significantly related to survival in each stage, i.e., there were 1267 days in stage I, 440 days in stage II, 299 days in stage III, and 143 days in stage IV (p 0.0001). The median survival was also found to be significantly related to tumor size (p = 0.001), site (p = 0.0298), serum level of CA19-9 (p = 0.0017), distant metastasis (p 0.0001), and type of treatment (p 0.0001). Multivariate analysis study revealed that the patients with a low SUV (p = 0.0298), a lower serum level of CA19-9 (p = 0.0071), a lower stage (p = 0.0017), and no distant metastasis (p 0.0001) had longer survivals. In addition, SUVmax values were found to have a similar hazard ratio of distant metastasis; it was well known predictor. Furthermore, SUVmax values showed a higher hazard ratio than that of other clinicopathologic predictors.The present study shows that SUVmax on F-18 FDG PET/CT can provide a prognostic information in patients with pancreatic cancer.

We determined the cytotoxic properties of cytochrome P450 4B1 (CYP4B1) activated 4-ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) in rat glioma to verify the CYP4B1/4-ipo or 2-AA system for prodrug-activating gene therapy. The cyp4B1 cDNA was cloned into pcDNA3.1/Hygro from rabbit lung total RNA (pcDNA-cyp4B1). Lentiviral vector encoding firefly luciferase (fLuc) was infected into C6 (rat glioma), and the fLuc-expressing cell was selected (C6-L). After transfection with pcDNA-cyp4B1 vector into C6-L, the single clone expressing cyp4B1 gene was selected (C6-CL). Prodrug for various concentrations of 4-ipo or 2-AA was treated for 72 h and 96 h. The cell survival rate of C6-CL was determined using MTT assay and trypan-blue dye exclusion methods. By RT-PCR analysis, fLuc and CYP4B1 expression was detected in C6-CL, but not in C6. MTT assay and trypan-blue dye exclusion showed that IC50 of C6-CL was 0.3 mM and

Introduction The goal of this study was to compare the glucose analog, 2-[ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F]-FDG), the amino acid analog, o -(2-[ 18 F]fluoroethyl)-l-tyrosine ([ 18 F]-FET) and nucleoside analog, 3′-[ 18 F]fluoro-3′-deoxythymidine ([ 18 F]-FLT) with regard to their feasibility for differentiating tumors from inflammation. Methods In Fisher rat models bearing both 9L tumor and inflammation, the biodistributions and positron emission tomography (PET) images of [ 18 F]-FDG, [ 18 F]-FET and [ 18 F]-FLT at 60 min post injection were compared. Pretreatment with thymidine phosphorylase before injection of [ 18 F]-FLT was performed. Results The tumor-to-blood (T/B) and tumor-to-muscle (T/M) ratios of [ 18 F]-FDG were significantly higher than those of [ 18 F]-FET and [ 18 F]-FLT ( P 18 F]-FDG [1.23±0.52 percent injected dose per gram of tissue (%ID/g)] in inflammation was also elevated. T/B and T/M ratios of [ 18 F]-FET (2.3±0.5 and 2.2±0.5) were higher than those of [ 18 F]-FLT (1.6±0.6 and 1.6±0.5), and inflammation uptake of those tracers was very low (0.63±0.19 and 0.27±0.16 %ID/g, respectively). [ 18 F]-FET and [ 18 F]-FLT showed higher selectivity indices (tumor-to-inflammation ratio corrected background) than [ 18 F]-FDG. In PET images, [ 18 F]-FDG was found to be accumulated in both tumor and inflammation, but [ 18 F]-FET and [ 18 F]-FLT selectively localized in tumor. Conclusion Our data confirm the result of previous studies that [ 18 F]-FET and [ 18 F]-FLT are superior to [ 18 F]-FDG in differentiating tumor from inflammation.

This pilot study was launched to explore the utility of positron emission tomography scans, at the time of diagnosis, for clinical outcomes in patients with primary extranodal non-Hodgkin's lymphoma (PENHL) in the head and neck, retrospectively.Twenty-two patients with a diffuse large B cell lymphoma (DLBCL) among those with a PENHL were included. We retrospectively evaluated the clinical outcomes of patients according to the maximum standardized 18F-fluoro-2-deoxy-glucose (18F-FDG) uptake value of the primary lesion (SUVp). The SUVp was initially analyzed as a continuous variable. The cut-off value of SUVp was obtained from receiver-operating characteristic analysis to predict event-free survival. Using this value, patients were divided into those with a low and high SUV.Seventeen patients (59%) were men and the median age was 50 years. Most primary sites were in Waldeyer's ring (73%). The SUVp ranged from 3.3 to 23.7. The international prognostic index (IPI2 vs.or=2) was associated with the SUVp (P=0.014). Patients with low SUVp showed favorable survival (P=0.015). After IPI scores were stratified, the survival difference remained significant (P=0.029).The results of this pilot investigation indicate that 18F-FDG uptake of the primary lesion may be related with survival outcomes in patients with extranodal DLBCL in the head and neck. Further studies are needed to confirm and extend these results.

Small animal positron emission tomography (PET) with 18 F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal 18 F-FDG PET. Methods To determine the impact of anesthesia on 18 F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of 18 F-FDG in various tissues were evaluated. The 18 F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results Blood glucose concentration and muscle uptake of 18 F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased 18 F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest 18 F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by 18 F-FDG image with the Iso 0.5 anesthesia. Conclusion Small animal 18 F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire 18 F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model.

Purpose: Photon beams with energy higher than 10 MV interact with metal material in the primary barriers, where lead or steel have been widely used, neutrons can be generated. Monte Carlo simulations were performed to simulate the production of photoneutrons and the neutron shielding effect. Methods: For two photon beam energies, 15 MV and 18 MV, we simulated to strike metal sheets (steel and lead), and the ambient dose equivalents were calculated at the isocenter (in the patient plane) while delivering 1 Gy to the patient. For these cases, the thickness of the neutron shielding materials (Borated polyethylene (BPE) and concrete) were simulated to reduce the patient exposure by neutron doses. Results: When 18 MV photons interact with the metal sheets in the primary barrier, the evaluated neutron doses at the isocenter inside the treatment vault were 48.7 µSv and 7.3 µSv for lead and steel, respectively. In case of 15 MV photons, the calculated neutron doses were 18.6 µSv and 0.6 µSv for lead and steel, respectively. The neutron dose delivered to the patient can be reduced to negligible levels by including a 10 cm thick sheet of BPE or 22 cm thick sheet of concrete. Conclusion: When bunker shielding is designed with a primary barrier including a metal sheet inside the wall for a high energy machine, proper neutron shielding should be constructed to avoid undesirable extra dose.

Purpose: Mediastinal staging of non-small cell lung cancer can be markedly improved by FDG-PET scan, but the problem of false staging of mediastinal nodes by PET scan in non-small cell lung cancer has not yet been overcome. The aim of this study was to identify the mechanism underlying the false staging of mediastinal nodes by FDG-PET in the case of non-small cell lung cancer. Materials and Methods: To evaluate the factors determining the FDG uptake in mediastinal nodes, FDG-PET was performed preoperatively, and mediastinal dissection with pulmonary resection was performed in 62 patients with NSCLC. GLUT-1 expression was studied by immunohistochemistry of the mediastinal nodes (n=111, true positive ＜TP＞ 31, true negative ＜TN＞ 41, false positive ＜FP＞ 27, false negative ＜FN＞ 12) using the anti-GLUT-1 antibody. The size, percentage of tumor (tumor ratio), labeling index (rate of stained tumor), staining intensity of the tumor, level of follicular hyperplasia, and staining intensity of the follicle center in the mediastinal node were also studied. Results: There was no significant difference in size among the 4 nodal groups (TP, TN, FP, FN), nor in the tumor ratio of the metastatic nodes between the TP and FN groups. The labeling index and staining intensity of the TP group were higher than those of the FN group (Mann-Whitney test, p=.001, p=.007) in the case of the metastatic nodes. The level of follicular hyperplasia of the FP group was higher than that of the TN group in the case of the non-metastatic nodes (p=.000). Conclusion: These results suggest that in mediastinal staging of non-small cell lung cancer by FDG-PET, the FN node is associated with low uptake of FDG due to low expression of GLUT-1, and that the FP node is associated with a high level of follicular hyperplasia as a result of there being a reactive change to an inflammatory and/or immune reaction. This is the first report on the mechanism underlying the false results that are sometimes obtained, and which constitute a major problem in the clinical application of FDG-PET to the mediastinal staging of non-small cell lung cancer.

The therapeutic efficacy of percutaneous transluminal coronary angioplasty is limited by the incidence of restenosis. Intracoronary irradiation has shown to be effective in restenosis control by inhibiting the neointimal proliferation. Monte Carlo simulation has been performed to calculate the dose to the vessel wall for intracoronary irradiation with a rhenium 188 solution- filled balloon for restenosis inhibition. With a 3- mm- diameter and 30- mm- long balloon, the radiation dose at 1 mm from the balloon surface was 5.3% lower when the balloon structure was included in geometric modeling of the angioplasty catheter, as compared with that obtained by ignoring the structure. The additional dose reduction due to Hexabrix 320 contrast medium added in 30% of volume ratio was 4.7%. With regard to axial dose distribution, the dose was uniform over the balloon length except near the balloon end, at which the dose was reduced by 35% at a 1- mm- deep layer in the vessel wall. With the Re- 188 solution mixed with 30% of Hexabrix 320 in volume ratio, the Re- 188 activity to be injected for delivery of 15 Gy to the 1- mm- deep layer by 1- minute irradiation was 27.3 GBq/mL. Dose estimates produced in this study should be helpful in determining the Re- 188 activity to be injected or the irradiation time for a varying situation in terms of length and diameter of the irradiated arterial segment and depth of the target layer.

Increased (18)F-fluorodeoxyglucose (FDG) uptake of brown fat on (18)F-FDG positron emission tomography (PET) originating from physiological activation is a common incidental finding and is usually located in the neck, shoulder, and supraclavicular areas. We present a case of an incidental pheochromocytoma showing diffusely increased (18)F-FDG uptake in bilateral perirenal fat tissue as well as supraclavicular and paravertebral fat tissue on (18)F-FDG PET/CT. The patient had no clinical symptoms except hypertension, and a pheochromocytoma was confirmed in a postsurgical specimen. A pheochromocytoma should be considered a cause in cases of increased (18)F-FDG uptake of perirenal brown fat.

Intratumoural injection of an unsealed beta-emitting radionuclide is a new technique for the local control of tumours that has the advantage of delivering a higher radiation dose to tumour while minimising radiation hazard to the surrounding normal tissues. In this study, therapeutic effect, morphological alterations and biological responses to the high-dose continuous irradiation delivered using this new technique were evaluated in an animal model with B16 melanoma. For evaluation of the therapeutic effect, 92 C57BL/6 mice with B16 melanoma were divided into four groups. In each group, intratumoural injections were performed when the tumour measured approximately 1 cm along its long axis. Group 1 (n=25) received 0.3 ml of normal saline, group 2 (n=15) 37 MBq of carrier-free holmium-166 in 0.3 ml saline, group 3 (n=27) 185 MBq of 166Ho in 0.3 ml saline and group 4 (n=25) 185 MBq of 166Ho in 0.5 ml saline. In addition, another 30 mice were used for morphological and biological analysis of the radiation effect. These 30 mice were injected with 185 MBq of 166Ho in 0.3 ml saline, and five were sacrificed at each of the following six time points: before injection and 1, 2, 3, 6 and 14 days post injection. Haematoxylin-eosin (HE) staining, immunohistochemical analysis for p53, p21, PCNA and cyclin D1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) staining, reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed. For visual side-by-side comparison, melanoma cells were inoculated bilaterally into the back of ten additional mice, and 185 MBq of 166Ho in 0.3 ml of saline or an equal volume of normal saline was injected separately into the bilateral tumours. Nine days after inoculation of melanoma cells, mean tumour volume reached 492.5-631.9 mm3. Tumours of the control group (group 1) showed rapid growth, and the mean tumour volume reached approximately 30 times the original volume. None of the control group lived for more than 16 days following the injection of normal saline. On the other hand, mean tumour volume of the treated groups showed a gradual decrease, and 67%-74% of the treated animals were alive when all the control animals had died. The median survival of the control group was 9 days following injection, whereas it was 29 days in group 2, 33 days in group 3 and 33 days in group 4. The survival rate of group 3 was higher than that of groups 2 and 4, but statistical significance was not observed. HE stain of the tumours demonstrated central necrosis and peripheral residual cells with progressive cytoplasmic and nuclear swelling without apoptotic features. Expression of proteins and mRNAs of p53 and bax increased until 3 days, as compared with 48 h for p21; thereafter, the expression gradually decreased. TUNEL-positive nuclei could be seen from 2 days until 2 weeks after treatment. Flow cytometry did not demonstrate an increase in apoptotic features as compared with the control animals. In conclusion, intratumoural injection of the unsealed beta-emitting radionuclide 166Ho appears to be a promising alternative radiotherapeutic modality for the local control of malignant melanoma. The main cell death mechanisms with this technique seem to be radiation-induced central necrosis and peripheral growth arrest or secondary necrosis of tumour cells, rather than apoptosis.

It is recognized that the microbeam is powerful system to understand the interaction of ionizing radiation with cells. Especially, electron microbeam system is useful to investigate the effect of low-LET radiation for cells. Electron microbeam has been developed in KIRAMS. It can irradiate the small volume in cell level by collimator and electromagnetic field and give local dose to individual cell by controlling the number of electrons. When the electron microbeam irradiates the individual cell, however, there is a possibility to change the current and intended trajectory of electron beam. Because this possibility introduces the uncertainty of dose, it is necessary to monitor the trajectory and current of electron beam. This study deals with development of real time monitoring device to confirm beam quality and to control if necessary during experiment. Consequently we designed dual monitoring device to solve various factors. And we optimize the design by simulation.

We evaluated the potential of (18)F-FDG PET/CT and diffusion-weighted imaging (DWI) to monitor the histologic response in patients with extremity osteosarcoma receiving neoadjuvant chemotherapy, using sequential PET/CT and MR imaging.We prospectively registered 28 patients with high-grade osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy and surgery. All patients underwent sequential (18)F-FDG PET/CT and MR imaging before (PET/MR1) and after neoadjuvant chemotherapy (PET/MR2). Maximum standardized uptake value (SUV), tumor volume based on MR imaging (MRV), and the mean apparent diffusion coefficient (ADC) values were measured on PET/MR1 (SUV1, MRV1, and ADC1) and PET/MR2 (SUV2, MRV2, and ADC2). The percentage changes in maximum SUV (ΔSUV), MRV (ΔMRV), and ADC (ΔADC) were calculated, and the correlations among these parameters were evaluated. After surgery, the effects of neoadjuvant chemotherapy were graded histopathologically: grades III and IV (necrosis of ≥ 90%) indicated a good response, and grades I and II (necrosis of90%) indicated a poor response. The optimum cutoff values of ΔSUV, ΔMRV, ΔADC, and their combination for predicting histologic response were assessed by single- and multi-receiver-operating-characteristic curve analysis.Twenty-seven patients were enrolled in the present study after 1 patient with inadequate acquisition of MR imaging was excluded. ΔSUV and ΔADC negatively correlated with each other (ρ = -0.593, P = 0.001), and ΔMRV did not correlate with ΔSUV or ΔADC. The cutoff value, sensitivity, specificity, and accuracy for predicting good histologic response were ≤ -52%, 67%, 87%, and 78%, respectively, for ΔSUV and13%, 83%, 73%, and 78%, respectively, for ΔADC. However, ΔMRV did not predict histologic response. Sensitivity, specificity, and accuracy were 83%, 87%, and 85%, respectively, using the combined criterion of ΔSUV ≤ -31% and ΔADC13%.In the current preliminary study, both PET/CT and DWI are useful for predicting histologic response after neoadjuvant chemotherapy in osteosarcoma. Combining PET/CT and DWI may be an effective method to predict the histologic response of patients to neoadjuvant chemotherapy.

We compared the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and (99 m)Tc-methylene diphosphonate bone scintigraphy (BS) for the detection of bone metastasis in osteosarcoma. We retrospectively reviewed 206 patients with stage II–IV osteosarcoma treated with surgery and chemotherapy as well as at least one paired PET/CT and BS scan (defined as an examination). PET/CT and BS images were interpreted separately. When analyzing the diagnostic yield of a combination of PET/CT and BS (PET/CT+BS), an examination was considered positive if either PET/CT or BS scored positive. The final diagnosis was obtained from histological findings or clinical follow-up with imaging studies for at least 6 months. Diagnostic performances of PET/CT, BS, and their combinations were calculated. Out of 833 examinations in 206 patients, 55 with 101 lesions in 38 patients were confirmed as bone metastases. The sensitivity, specificity, and diagnostic accuracy were 95, 98, and 98 %, respectively, for PET/CT; 76, 97, and 96 %, respectively, for BS; and 100, 96, and 97 %, respectively, for PET/CT+BS in an examination-based analysis. Lesion-based analysis demonstrated that the sensitivity of PET/CT+BS (100 %) was significantly higher than that of PET/CT (92 %) or BS (74 %) alone. BS detected significantly less bone metastases in the growth plate region than outside the growth plate region (22 vs. 77 %). PET/CT is more sensitive and accurate than BS for diagnosing bone metastases in osteosarcoma. The combined use of PET/CT and BS improves sensitivity.

The authors conducted a retrospective review of 234 bone scans of stomach cancer patients who had been diagnosed at the Seoul National University Hospital. In 106 of the 234 cases (45.3%), there were abnormal bone scan results, suggestive of bone metastases. The most common site of bone metastases was the spine, followed by the ribs, pelvis, femur, and skull. These sites were similar to those known for other malignant diseases. The incidence of bone metastases increased according to the duration of disease, especially within 12 months after diagnosis in patients with stage III gastric cancer. The incidence of bone metastases increased as the clinical stage increased. However, the incidence of metastases did not relate to gastric cancer pathologic type. The authors found 6 cases of "superscan" in the 234 bone scans (2.6%). The bone scan findings correlated positively with the level of serum alkaline phosphatase.

We evaluated the monoclonal antibody CEA-79.4 against carcinoembryonic antigen as an immunoscintigraphic agent for assessing the state of the bone marrow. Western blotting of human granulocyte extracts with the antibody could confirm that the binding was with the epitope of NCA-95. Immunocytochemical staining of bone marrow aspirates revealed specific uptake of this antibody by granulopoietic cells. The affinity constant was 2-9 x 10(9) L/mol. Immunoscintigraphy using 99mTc-labeled CEA-79.4 in a normal volunteer revealed high uptake in the bone marrow as compared to other organs.

Esophageal cancer is a leading cause of cancer mortality worldwide. Complete resection of esophageal cancer and adjacent malignant lymph nodes is the only potentially curative treatment. Accurate preoperative staging and assessment of therapeutic response after neoadjuvant therapy are crucial in determining the most suitable therapy and avoiding inappropriate attempts at curative surgery.

The purpose of this study was to assess the optimal gates number of each region using estimated internal motion. Internal motion has been demonstrated in lung and liver region of small animal by coated molecular sieve. We coated molecular sieve with Pluronic F-127 hydrogel for keeping the activity in the body. All PET studies were performed with a dedicated small animal PET scanner. Respiratory gating was operated the external trigger device synchronized with the list mode acquisition. The trigger signals were simultaneously reflected motion of heart and breathing. The list mode data were converted to sinogram gated 2∼16 bin. In PET image analysis for determining optimal gate number, count and SNR were measured from ROI in the target region. Horizontal and vertical FWHM were measured from line profile in each images. The motion compensation PET image for optimal gate number was confirmed by internal motion. The measured value of lung region showed high count (8.67), high SNR (3.25), and high FWHM (1.83) in 8 bin. In liver region, high count (2.09), high SNR (3.99), and high FWHM (2.23) were revealed in 9 bin. The artificial tumor evaluation study using molecular sieve is a method to assess accurately internal organ motion in the rodent. The gate number for motion correction should be set differently in accordance with the organ because motion level varies as each organ. The estimated internal motion will be a useful method for motion compensation modeling.

CEA-79 is a murine IgG2a type monoclonal antibody (MoAb) generated using purified CEA from culture supernatants of a human colon cancer cell line, LS174T. The association constant and immunoreactivity of the I-131 labeled CEA-79 ranged from 2.0 to 3.2 x 10(9) l/mole, and from 54 to 74%, respectively. The purpose of this study was to evaluate the feasibility of radioimmunoscintigraphy employing MoAb CEA-79 in patients with advanced gastrointestinal carcinomas. Two mgs of MoAb CEA-79 was labeled with 111 MBq (3 mCi) of I-131, and infused intravenously in 6 stomach cancer and 16 colon cancer patients. Out of 6 patients with stomach cancer, immunoscintigraphy was able to detect the tumors in 4 cases. However, immunoscintigraphy found out tumors in all patients with colon cancer. Moreover, 1 patient with stomach cancer and 2 patients with colon cancer showed increased uptake of MoAb in the tumor lesions despite normal serum levels of CEA. We could conclude that this antibody has a potential as a new imaging agent for the diagnosis of gastrointestinal carcinoma.