[Show abstract][Hide abstract] ABSTRACT: Development of improved tumor- targeting MRI contrast agents.•To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides.•Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images.
Biochemical and Biophysical Research Communications 11/2014; · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate whether the development of hepatocellular carcinoma (HCC) in murine models resembles tumor progression in humans, using non‑invasive molecular imaging methods. Murine HCC models were generated by treating mice with diethylnitrosamine (DEN) or by the transgenic expression of hepatitis B virus X (HBx) protein (HBx-Tg model). Tumor development was detected using 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI). The histopathological changes and expression of glucose transporter 1 (Glut1) and hexokinase 2 (HK2) were evaluated using hematoxylin and eosin and immunohistochemical staining, respectively. Tumor lesions as small as 1 mm in diameter were detected by MRI. Tumor development was monitored using 18F-FDG PET/CT at 6.5‑10 months after DEN treatment or 11‑20 months after birth of the HBx-Tg model mice. A correlation study between the 18F-FDG uptake levels and expression levels of HK2 and Glut1 in developed HCC showed a high 18F-FDG uptake in poorly differentiated HCCs that expressed high levels of HK2, in contrast to that in well-differentiated tumors. The progression of primary HCCs resembling human HCC in murine models was detected and monitored by 18F-FDG PET/CT. The correlation between tumor size and SUVmax was verified in the two HCC models. To the best of our knowledge, this is the first study to demonstrate that in vivo 18F-FDG uptake varies in HCCs according to differentiation grade in a preclinical study.
[Show abstract][Hide abstract] ABSTRACT: Two new bicyclic arginine-glycine-aspartic acid (RGD) peptides, c(RGD-ACP-K) (1a) and c(RGD-ACH-K) (1b), incorporating the aminocyclopentane (ACP) and aminocyclohexane (ACH) carboxylic acids, respectively, were synthesized by grafting the aminocycloalkane carboxylic acids onto the tetra-peptide RGDK sequence. These peptides and their conjugates with DO3A (1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid) (2a-b) exhibit high affinity toward U87MG glioblastoma cells. Their affinity is greater than that exhibited by c(RGDyK). Labeling these conjugates with radiometal (64)Cu resulted in high radiochemical yields (>97%) of the corresponding complexes, abbreviated as c(RGD-ACP-K)-DOTA-(64)Cu (3a) and c(RGD-ACH-K)-DOTA-(64)Cu (3b). Both 3a and 3b are stable for 24 h in human and mouse serums and show high tumor uptake, as observed by positron emission tomography (PET). Blocking experiments with 3a and 3b by preinjection of c(RGDyK) confirmed their target specificity and demonstrated their promise as PET radiotracers for imaging ανβ3-positive tumors.
[Show abstract][Hide abstract] ABSTRACT: Although statistical parametric mapping (SPM) analysis is widely used in neuroimaging studies, to our best knowledge, there was no application to myocardial PET data analysis. In this study, we developed the voxel based statistical analysis method for myocardial PET which provides statistical comparison results between groups in image space. PET Emission data of normal and myocardial infarction rats were acquired For the SPM analysis, a rat heart template was created. In addition, individual PET data was spatially normalized and smoothed. Two sample t-tests were performed to identify the myocardial infarct region. This developed SPM method was compared with conventional ROI methods.
Journal of Instrumentation 09/2014; 9(09):P09005. · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the potential of FDG PET/CT and MRI in predicting disease-free survival (DFS) after neoadjuvant chemotherapy (NAC) and surgery in patients with advanced breast cancer.
European journal of nuclear medicine and molecular imaging 06/2014; · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Siemens Biograph TruePoint TrueV (B-TPTV) positron emission tomography (PET) scanner performs 3D PET reconstruction using a system matrix with point spread function (PSF) modeling (called the True X reconstruction). PET resolution was dramatically improved with the True X method. In this study, we assessed the spatial resolution and image quality on a B-TPTV PET scanner. In addition, we assessed the feasibility of animal imaging with a B-TPTV PET and compared it with a microPET R4 scanner.
Spatial resolution was measured at center and at 8 cm offset from the center in transverse plane with warm background activity. True X, ordered subset expectation maximization (OSEM) without PSF modeling, and filtered back-projection (FBP) reconstruction methods were used. Percent contrast (% contrast) and percent background variability (% BV) were assessed according to NEMA NU2-2007. The recovery coefficient (RC), non-uniformity, spill-over ratio (SOR), and PET imaging of the Micro Deluxe Phantom were assessed to compare image quality of B-TPTV PET with that of the microPET R4.
When True X reconstruction was used, spatial resolution was <3.65 mm with warm background activity. % contrast and % BV with True X reconstruction were higher than those with the OSEM reconstruction algorithm without PSF modeling. In addition, the RC with True X reconstruction was higher than that with the FBP method and the OSEM without PSF modeling method on the microPET R4. The non-uniformity with True X reconstruction was higher than that with FBP and OSEM without PSF modeling on microPET R4. SOR with True X reconstruction was better than that with FBP or OSEM without PSF modeling on the microPET R4.
This study assessed the performance of the True X reconstruction. Spatial resolution with True X reconstruction was improved by 45 % and its % contrast was significantly improved compared to those with the conventional OSEM without PSF modeling reconstruction algorithm. The noise level was higher than that with the other reconstruction algorithm. Therefore, True X reconstruction should be used with caution when quantifying PET data.
Annals of Nuclear Medicine 02/2014; · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) is widely used for diagnosis and follow up assessment of radiotherapy. However, thoracic and abdominal PET suffers from false staging and incorrect quantification of the radioactive uptake of lesion(s) due to respiratory motion. Furthermore, respiratory motion-induced mismatch between a computed tomography (CT) attenuation map and PET data often leads to significant artifacts in the reconstructed PET image. To solve these problems, we propose a unified framework for respiratory-matched attenuation correction and motion compensation of respiratory-gated PET. For the attenuation correction, the proposed algorithm manipulates a 4D CT image virtually generated from two low-dose inhale and exhale CT images, rather than a real 4D CT image which significantly increases the radiation burden on a patient. It also utilizes CT-driven motion fields for motion compensation. To realize the proposed algorithm, we propose an improved region-based approach for non-rigid registration between body CT images, and we suggest a selection scheme of 3D CT images that are respiratory-matched to each respiratory-gated sinogram. In this work, the proposed algorithm was evaluated qualitatively and quantitatively by using patient datasets including lung and/or liver lesion(s). Experimental results show that the method can provide much clearer organ boundaries and more accurate lesion information than existing algorithms by utilizing two low-dose CT images.
Physics in Medicine and Biology 09/2013; 58(20):7355-7374. · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to evaluate the availability of cone-beam
computed tomography(CBCT) for gel dosimetry. The absorbed dose was
analyzed by using intensity-modulated radiation therapy(IMRT) to
irradiate several tumor shapes with a calculated dose and several tumor
acquiring images with CBCT in order to verify the possibility of reading
a dose on the polymer gel dosimeter by means of the CBCT image. The
results were compared with those obtained using magnetic resonance
imaging(MRI) and CT. The linear correlation coefficients at doses less
than 10 Gy for the polymer gel dosimeter were 0.967, 0.933 and 0.985 for
MRI, CT and CBCT, respectively. The dose profile was symmetric on the
basis of the vertical axis in a circular shape, and the uniformity was
2.50% for the MRI and 8.73% for both the CT and the CBCT. In addition,
the gradient in the MR image of the gel dosimeter irradiated in an H
shape was 109.88 while the gradients of the CT and the CBCT were 71.95
and 14.62, respectively. Based on better image quality, the present
study showed that CBCT dosimetry for IMRT could be restrictively
performed using a normoxic polymethacrylic-acid gel dosimeter.
Journal- Korean Physical Society 09/2013; 63(5):1083-1087. · 0.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET), using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) as a radioactive tracer, is a useful technique for in vivo brain imaging. However, the anatomical and physiological features of the Harderian gland limit the use of FDG-PET imaging in the mouse brain. In PET studies, this gland shows strong FDG uptake, which in turn results in distorted PET images of the frontal brain region. The purpose of this study was to assess if a simple surgical procedure to remove the Harderian gland could eliminate its influence on FDG uptake, prior to PET imaging of mice brains. Measurement of FDG uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact Harderian gland makes the frontal brain region unclear. Spatial parametric measurement analysis demonstrated that the presence of the Harderian gland could prevent accurate assessment of brain PET imaging. Bilateral Harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region, beginning at postoperative day 10. Harderian adenectomy did not cause any post operative complications during the experimental period. These findings demonstrate the benefits of performing a Harderian adenectomy prior to PET imaging of mice brains.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Annals of Nuclear Medicine 05/2013; · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: I has a complex decay scheme with high gamma energy and low positron abundance. In this study, comparative performance measurements of I 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 I, and were 4.58 and 4.77 mm and for F, respectively. Sensitivities were 0.5 kcps/MBq (2D) and 3.4 kcps/MBq (3D) for I, and 1.8 kcps/MBq (2D) and 9.8 kcps/MBq (3D) for F. The %contrast of 3D was higher than that of 2D in I. For I PET imaging, 3D acquisition with brain mode was highest achievable imaging acquisition mode with finer spatial res-olution and higher contrast. This result will be useful for I PET imaging Index Terms—Image quality, reconstruction algorithms, spatial resolution, whole-body PET.
[Show abstract][Hide abstract] ABSTRACT: Attenuation correction (AC) and scatter correction (SC) are problematic issues for animal positron emission tomography (PET). In this study, the effects of AC and SC were assessed using PET on a phantom and actual rat brain. Transmission (TX) was performed using 57Co for 15 min. After a 15 min TX scan, emission (EM) PET was performed in list mode for 1 h. To assess the effects of AC and SC, the spillover ratio (SOR) was measured using a rat-sized NEMA NU4 image-quality phantom; statistical parametric mapping (SPM) was performed to assess the effects of AC and SC in the rat brain using 18F-FDG (FDG). In addition, the binding potential (BP) was compared for 18F-FP-CIT (FP-CIT) PET. SPM was used to compare PET images to which AC and SC were applied, and BP was used for FP-CIT PET. The SORs of air and water decreased after AC and SC. SPM for FDG PET after AC showed a significant increase in FDG-measured activity in the cerebellum and occipital cortex. After AC/SC, a significant decrease in FDG-measured activity was observed in the frontal and temporal cortices. For FP-CIT PET of the rat brain, the BP decreased by 26% after AC because the FP-CIT uptake increased more in the cerebellum than in the striatum owing to AC. After AC and SC, the mean BP increased by 61%. AC and AC/SC were found to be necessary components of the artifact correction process for both FDG PET and FP-CIT PET of rat brains.
[Show abstract][Hide abstract] ABSTRACT: 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 ((131)I-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 (131)I-rituximab. Contrast-enhanced (18)F-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 (18)F-FDG PET/CT result as significant predictors of OS in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated by RIT.
[Show abstract][Hide abstract] ABSTRACT: The work describes the synthesis and in vivo application of [Gd(L)(H2O)]·xH2O, where L is a ((125)I/(127)I-RGD)- DOTA conjugate, as a tumor-targeting SPECT/MR bimodal imaging probe. Here, ((125)I/(127)I-RGD)-DOTA signifies a "cocktail mixture" of radioisotopic (1a, L = (125)I-RGD-DOTA) and natural (1b, L = (127)I-RGD-DOTA) Gd complexes. The two complexes are chemically equivalent as revealed by HPLC, and their cocktail mixture exhibits the integrin-specific tumor enhancement, demonstrating that they constitute essentially a single bimodal imaging probe. Employment of a cocktail mixture thus proves to be a sole and practical approach to overcome the sensitivity difference problem between MRI and SPECT.
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) images suffer from low spatial resolution. To improve the spatial resolution, we previously proposed a sinogram-based super-resolution (SR) algorithm for a whole-body PET scanner, by assuming space invariant blur. However, since the spatial resolution of a sinogram varies along the radial direction due to parallax error, this algorithm is not appropriate for providing a high-resolution sinogram with reduction of parallax error. In this paper, we propose a novel and efficient sinogram-based SR algorithm that is suitable even for a small animal PET scanner by using space variant blur matrices. In the algorithm, we estimate the space variant blur matrices through a Monte Carlo simulation and use them for the SR process to obtain a high-resolution sinogram. Using a Derenzo phantom and a line source, we demonstrate in a real PET scanner, microPET R4, that the proposed SR algorithm noticeably improves the spatial resolution while alleviating its space variance. By applying the proposed SR algorithm, the full width at half-maximum (FWHM) value reaches 1.2 mm at the system center and 1.63 mm with a considerable parallax error reduction at a radial position of 4 cm.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Cancer Chemotherapy and Pharmacology 01/2013; · 2.80 Impact Factor