Elevated Serum IgG4 Complicated by Pericardial Involvement with a Patchy (18)F-FDG Uptake in PET/CT: Atypical Presentation of IgG4-related Disease.

IgG4-related pericardial involvement has rarely been reported and its clinical features remain unknown. We herein report a case of a 50-year-old woman with pericarditis who presented with a fever, elevated C-reactive protein levels, elevated serum IgG4 concentrations, and thickened pericardium with a patchy (18)F-fluorodeoxyglucose (FDG) uptake. A biopsy specimen of (18)F-FDG accumulated in the mediastinal lymph nodes revealed an abundant infiltration of IgG4-bearing plasma cells without fibrosis. Moderate-dose glucocorticoids promptly resolved the physical, serological, and imaging abnormalities, thus indicating a relatively acute and reversible nature of IgG4-related pericardial involvement.

Toward in vivo imaging of heart disease using a radiolabeled single-chain Fv fragment targeting tenascin-C.

Antibodies specific to a particular target molecule can be used as analytical reagents, not only for in vitro immunoassays but also for noninvasive in vivo imaging, e.g., immunoscintigraphies. In the latter case, it is important to reduce the size of antibody molecules in order to achieve suitable in vivo "diagnostic kinetics" and generate higher-resolution images. For these purposes, single-chain Fv fragments (scFvs; M(r) < 30 kDa) have greater potential than intact immunoglobulins (~150 kDa) or Fab (or Fab') fragments (~50 kDa). Our recent observation of enhanced tenascin-C (Tnc) expression at sites of cardiac repair after myocardial infarction prompted us to develop a radiolabeled scFv against Tnc for in vivo imaging of heart disease. We cloned the genes encoding the heavy and light chain variable domains of the mouse anti-Tnc monoclonal antibody 4F10, and combined them to create a single gene. The resulting scFv-4F10 gene was expressed in E. coli cells to produce soluble scFv proteins. scFv-4F10 has an affinity for Tnc (K(a) = 3.5 × 10(7) M(-1)), similar to the Fab fragment of antibody 4F10 (K(a) = 1.3 × 10(7) M(-1)) and high enough to be of practical use. A cysteine residue was then added to the C-terminus to achieve site-specific (111)In labeling via a chelating group. The resulting (111)In-labeled scFv was administered to a rat model of acute myocardial infarction. Biodistribution and quantitative autoradiographic studies indicated higher uptake of the radioactivity at the infarcted myocardium than the noninfarcted one. Single photon emission computed tomography (SPECT) provided in vivo cardiac images that coincided with the ex vivo observations. Our results will promote advances in diagnostic strategies for heart disease.

Development and performance evaluation of the second model 256-detector row CT.

Since our initial development of the 256-detector row CT scanner (256-row CT) for four-dimensional (4D) imaging of moving organs in 2003, the results of physical performance and those in animal and human studies have suggested that this scanner may be useful in the examination of moving organs such as the heart and lungs. We have now developed a second model of the 256-row CT with improved specifications, with a scan time of 0.5 s/rotation at the highest speed and real-time reconstruction and display of dynamic 3D images (4D images). Here, we investigated the image characteristics of the new model, including spatial resolution, noise, and low-contrast detectability, as well as the dose profile and its integral in stationary phantoms. One volunteer and one patient with lung cancer were scanned, and their images were evaluated. The results show that all characteristics have been improved compared with those of the first model, with a remarkable improvement in the low-contrast detectability and slice sensitivity profile. In a contrast study, coronary arteries were clearly visualized in the normal heart without electrocardiographic gating. Movement and deformation of the tumor in the patient with lung cancer was captured in a study of a single breath cycle. The second model 256-row CT with improved characteristics may be beneficial in imaging of moving organs such as the heart and lungs, and may enable cerebral perfusion studies of the whole brain.

Preliminary study: color map of hepatocellular carcinoma using dynamic contrast-enhanced 256-detector row CT.

To distinguish hepatocellular carcinoma (HCC) from normal liver tissue, a color map was made by dynamic contrast-enhanced 256-detector row CT developed at our institute. Dynamic enhanced CT of the liver of three patients with HCC was studied. The CT has 912 (transverse) x 256 (cranio-caudal) elements, each measuring approximately 0.5 mm x 0.5mm at the center of rotation. Scanning for 10 s (1.0 s/rotation) was started 30 s after intravenous injection of contrast medium. The reconstruction increment was 0.62 mm with a time interval of 0.1s and a matrix size of 512 x 512 x 256. Color maps were generated to show the gradient of the regression line of the time-density change. Due to volume acquisition, the 3D color map can be created using continuous 10-s scanning. The densities of the HCC and liver were decreased and increased during scanning, respectively. The HCC was detected clearly in the color map as a downward-sloping region. Dynamic enhanced 256-detector row CT could be useful for detecting malignant tumors in the liver with a short scan time.

Molecular therapy of human neuroblastoma cells using Auger electrons of 111In-labeled N-myc antisense oligonucleotides.

UNLABELLED: Auger electrons can create breaks in nucleic acids, giving them possible therapeutic utility. We investigated the therapeutic effect of Auger electrons emitted by 111In-labeled phosphorothioate antisense oligonucleotides on human neuroblastoma cells in which N-myc was overexpressed. METHODS: Human SK-N-DZ neuroblastoma cells (5 x 10(6) cells) were treated with cationic reverse-phase evaporation vesicles (REVs) encapsulating 111In-labeled antisense (40 MBq/2 nmol of oligonucleotides/mumol of total phospholipids) that had an average diameter of 250 nm. Hybridization of the radiolabeled oligonucleotides with N-myc messenger RNA (mRNA), N-myc expression, and cell proliferation were investigated. The tumorigenicity of treated cells was analyzed in nude mice. Nonradiolabeled antisense, 111In-labeled sense, or empty cationic REVs were used as controls. RESULTS: 111In-Labeled antisense, which hybridized with N-myc mRNA, was detected in cells at 12 and 24 h after the initiation of treatment. Reduced N-myc expression and inhibited cell proliferation were shown in the same cells at 48 h after the completion of treatment. N-myc expression-suppressed cells produced intraperitoneal tumors in nude mice, but the average weight of the tumors was lower than that of tumors in control mice. CONCLUSION: Auger electrons emitted from 111In in close proximity to their target N-myc mRNA may prolong the time to cell proliferation in human neuroblastoma cells due to inhibition of the translation of N-myc. Auger electron therapy therefore has potential as an internally delivered molecular radiotherapy targeting the mRNA of a tumor cell.

Noise properties for three weighted Feldkamp algorithms using a 256-detecotor row CT-scanner: case study for hepatic volumetric cine imaging.

In cone-beam geometry, image quality may be degraded or artifacts may occur if the cone angle is substantially wide. This is because a cone-beam scan along a circular orbit does not collect the complete set of data required to make an exact reconstruction of all volumetric data. To increase temporal resolution and thus image quality in cone-beam geometry, Silver proposed the new half-scan algorithm (NHS-FDK), which extends Parker's weighting function (HS-FDK) by utilizing a larger range up to 2pi. Here, we evaluated these algorithms for hepatic contrast-enhanced CT in cine scan mode using a 256-detector row CT. The full-scan (FS-FDK) images show uniform distribution of the image noise and CT-number uniformity. Image noise and CT-number uniformity with HS-FDK and NHS-FDK images follow the initial projection angle. HS-FDK images therefore have more changeable higher intensity (brighter) and a lower intensity (darker) areas than respective FS-FDK and NHS-FDK images. We concluded that, considering the trade-off between image quality and temporal resolution, the NHS-FDK algorithm is useful in volumetric cine imaging for the abdomen.

Clinical potentials for dynamic contrast-enhanced hepatic volumetric cine imaging with the prototype 256-MDCT scanner.

OBJECTIVE: To achieve dynamic contrast-enhanced hepatic volumetric cine imaging, we developed a prototype 256-MDCT scanner. This study examined the feasibility of the technique for human hepatic imaging in three hepatocellular carcinoma patients. CONCLUSION: Volumetric cine imaging successfully visualized dynamic contrast enhancement of the hepatocellular carcinoma. It is helpful to evaluate the phase of contrast enhancement or for functional studies of the head, renal artery, coronary artery, and liver.

Carbon-11-methionine positron emission tomography imaging of chordoma.

OBJECTIVE: Chordoma is a rare malignant bone tumor that arises from notochord remnants. This is the first trial to investigate the utility of (11)C-methionine (MET) positron emission tomography (PET) in the imaging of chordoma before and after carbon-ion radiotherapy (CIRT). DESIGN AND PATIENTS: Fifteen patients with chordoma were investigated with MET-PET before and after CIRT and the findings analyzed visually and quantitatively. Tumor MET uptake was evaluated by tumor-to-nontumor ratio (T/N ratio). RESULTS: In 12 (80%) patients chordoma was clearly visible in the baseline MET-PET study with a mean T/N ratio of 3.3+/-1.7. The MET uptake decreased significantly to 2.3+/-1.4 after CIRT ( P<0.05). A significant reduction in tumor MET uptake of 24% was observed after CIRT. Fourteen (93%) patients showed no local recurrence after CIRT with a median follow-up time of 20 months. CONCLUSION: This study has demonstrated that MET-PET is feasible for imaging of chordoma. MET-PET could provide important tumor metabolic information for the therapeutic monitoring of chordoma after CIRT.

Changes in the pharmacokinetics of Gd-DTPA in experimental tumors after charged particle radiation: comparison with gamma-ray radiation.

We performed dynamic MRI to reveal the characteristic gadopentetate dimeglumine (Gd-DTPA) uptake in carbon-ion irradiated tumor and compare it with photon irradiation. Fibrosarcomas in C3H mice legs were irradiated with either 16 Gy of carbon ions (74 keV/mm) or an equivalent dose (30 Gy) of Cs-137 gamma-rays. Dynamic MRI was performed 1 or 6 days after irradiation when the tumors showed an initial growth delay or incipient regrowth, respectively. The enhancement pattern was visualized by mapping the maximum enhanced time (Tmax), relative signal intensity maximum (SImax), and time delay of starting enhancement (Td). Significantly larger Tmax and Td values were observed in the tumors 1 day after carbon-ion irradiation than in the nonradiated tumors (No-R) and tumors 1 day after gamma-ray irradiation. Among the selected pixels in the tumors 6 days after carbon irradiation, 77% had Tmax values of less than 120 sec, significantly more than in the No-R group. The Tmax maps for the tumors irradiated with gamma-rays showed a similar tendency to the carbon-irradiated ones, and only a significant difference was obtained between tumors 1 and 6 days after irradiation. Tmax and Td in the carbon-ion irradiated tumors were different from those in the gamma-ray-irradiated tumors. These treatment-specific kinetics may be useful in predicting the therapeutic efficacy of carbon-ion treatment.

[(11)C]methionine positron emission tomography and survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy.

PURPOSE: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patient prognosis. We evaluated whether L-[methyl-(11)C]-methionine (MET) uptake and its change after CIRT were the early survival predictors in patients with unresectable bone and soft tissue sarcomas. EXPERIMENTAL DESIGN: MET positron emission tomography was prospectively performed in 62 patients with unresectable bone and soft tissue sarcomas before and within 1 month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor:nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. RESULTS: The overall median survival time was 20 months. Patients with a baseline T/N ratio of 6 (2-year survival rate: 69.4% versus 32.3%; P = 0.01). Patients with a post-CIRT ratio of 4.4 (2-year survival rate: 63.7% versus 41.3%; P = 0.01). A significant higher survival rate was observed in patients with post-therapeutic MET uptake change of >30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%; P = 0.049). The multivariate analysis showed that both baseline and post-CIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis. CONCLUSIONS: MET uptake as measured by either baseline or post-CIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy, whereas post-therapeutic MET uptake change might have potential value for the same purpose.

Detection of lung cancer with positron coincidence gamma camera using fluorodeoxyglucose in comparison with dedicated PET.

OBJECTIVE: Dual-head gamma cameras with sodium iodide (NaI) detectors operated in coincidence mode provide a new approach for imaging with positron-labeled tracers. The purpose of this study was to evaluate the feasibility of FDG imaging with positron coincidence detection gamma camera (PCD) in detecting lung tumor in comparison with FDG imaging with the dedicated positron emission tomography (PET). METHODS AND MATERIAL: Twenty-six lesions of 13 patients with suspected lung cancer were studied with both FDG PET and FDG PCD on the same day. Pulmonary lesions were analyzed visually and semi-quantitatively using the ratio of target-to-background counts (T/B ratio). RESULTS AND CONCLUSIONS: FDG PCD and FDG PET could detect visually 21 lesions (80.8%) and 23 lesions (88.0%), respectively. The mean T/B ratio and standard deviation (S.D.) of FDG PCD was 4.6 +/- 3.9, significantly lower than that of FDG PET (11.4 +/- 6.6, P<0.001). When pulmonary lesions were no more than 2.0 cm in diameter, the sensitivity of FDG PCD was 37.5%, significantly inferior to that of FDG PET (62.5%, P<0.001). There was no statistically significant difference of the sensitivity between the FDG PCD and FDG PET in lesions of more than 2.0 cm in diameter. FDG PCD with uniform attenuation correction was clinically available in detecting lung cancer. However, the sensitivity for small lesions less than 2.0 cm was limited. The application of measured attenuation correction and scatter correction may to be needed to improve the detectability of FDG PCD, especially for detecting small lung cancer.

Detection of experimental autoimmune myocarditis in rats by 111In monoclonal antibody specific for tenascin-C.

BACKGROUND: Although the identification of inflammatory infiltrates in endomyocardial biopsy specimens is necessary for the definite diagnosis of myocarditis, the biopsy test is invasive and is not sensitive. Therefore, a new diagnostic technique for the early and noninvasive evaluation of myocarditis has been awaited. Expression of tenascin-C (TNC), one of the oligometric extracellular glycoproteins, is induced in various pathological states, including inflammation, suggesting that TNC can be a molecular marker of myocarditis. METHODS AND RESULTS: An 111In anti-TNC monoclonal antibody Fab' fragment was injected intravenously into rats with experimental autoimmune myocarditis (EAM), and the biodistribution of this radiotracer was measured. Rapid clearance of radioactivity from the blood was observed in both EAM and control rats (<1% at 6 hours after injection). Myocardial uptake of the tracer was much higher in EAM rats than in control rats (7.54-, 4.39-, and 3.51-fold at 6, 24, and 48 hours after injection, respectively). By autoradiography, high radioactivities were clearly observed in the regions indicative of inflammation in EAM rats. Single-photon emission CT imaging demonstrated the focal myocardial uptake of 111In anti-TNC Fab' in vivo. CONCLUSIONS: Radiolabeled anti-TNC Fab' may be useful for the noninvasive diagnosis of myocarditis.