Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging.
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A new dedicated PET scanner, microPET, was designed and developed at the University of California, Los Angeles, for imaging small laboratory animals. The goal was to provide a compact system with superior spatial resolution at a fraction of the cost of a clinical PET scanner. METHODS: The system uses fiberoptic readout of individually cut lutetium oxyorthosilicate (LSO) crystals to achieve high spatial resolution. Each microPET detector consists of an 8 x 8 array of 2 x 2 x 10-mm LSO scintillation crystals that are coupled to a 64-channel photomultiplier tube by optical fibers. The tomograph consists of 30 detectors in a continuous ring with a 17.2-cm diameter and fields of view (FOVs) of 11.25 cm in the transaxial direction and 1.8 cm in the axial direction. The system has eight crystal rings and no interplane septa. It operates exclusively in the three-dimensional mode and has an electronically controlled bed that is capable of wobbling with a radius of 300 microm. We describe the performance of the tomograph in terms of its spatial, energy and timing resolution, as well as its sensitivity and counting-rate performance. We also illustrate its overall imaging performance with phantom and animal studies that demonstrate the potential applications of this device to biomedical research. RESULTS: Images reconstructed with three-dimensional filtered backprojection show a spatial resolution of 1.8 mm at the center of the FOV (CFOV), which remains <2.5 mm for the central 5 cm of the transaxial FOV. The resulting volumetric resolution of the system is <8 microL. The absolute system sensitivity measured with a 0.74 MBq (20 microCi) 68Ge point source at the CFOV is 5.62 Hz/kBq. The maximum noise equivalent counting rate obtained with a 6.4-cm diameter cylinder spanning the central 56% of the FOV is 10 kcps, whereas the scatter fraction is 37% at the CFOV for an energy window of 250-650 keV and the same diameter cylinder. CONCLUSION: This is the first PET scanner to use the new scintillator LSO and uses a novel detector design to achieve high volumetric spatial resolution. The combination of imaging characteristics of this prototype system (resolution, sensitivity, counting-rate performance and scatter fraction) opens up new possibilities in the study of animal models with PET. (+info)
Crystal structure of the ffh and EF-G binding sites in the conserved domain IV of Escherichia coli 4.5S RNA.
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BACKGROUND: Bacterial signal recognition particle (SRP), consisting of 4.5S RNA and Ffh protein, plays an essential role in targeting signal-peptide-containing proteins to the secretory apparatus in the cell membrane. The 4.5S RNA increases the affinity of Ffh for signal peptides and is essential for the interaction between SRP and its receptor, protein FtsY. The 4.5S RNA also interacts with elongation factor G (EF-G) in the ribosome and this interaction is required for efficient translation. RESULTS: We have determined by multiple anomalous dispersion (MAD) with Lu(3+) the 2.7 A crystal structure of a 4.5S RNA fragment containing binding sites for both Ffh and EF-G. This fragment consists of three helices connected by a symmetric and an asymmetric internal loop. In contrast to NMR-derived structures reported previously, the symmetric loop is entirely constituted by non-canonical base pairs. These pairs continuously stack and project unusual sets of hydrogen-bond donors and acceptors into the shallow minor groove. The structure can therefore be regarded as two double helical rods hinged by the asymmetric loop that protrudes from one strand. CONCLUSIONS: Based on our crystal structure and results of chemical protection experiments reported previously, we predicted that Ffh binds to the minor groove of the symmetric loop. An identical decanucleotide sequence is found in the EF-G binding sites of both 4.5S RNA and 23S rRNA. The decanucleotide structure in the 4.5S RNA and the ribosomal protein L11-RNA complex crystals suggests how 4.5S RNA and 23S rRNA might interact with EF-G and function in translating ribosomes. (+info)
Radioimmunotherapy of a human lung cancer xenograft with monoclonal antibody RS7: evaluation of (177)Lu and comparison of its efficacy with that of (90)Y and residualizing (131)I.
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Tumor targeting and therapeutic efficacy of (177)Lu-labeled monoclonal antibody (mAb) RS7 (antiepithelial glycoprotein-1) was evaluated in a human nonsmall cell lung carcinoma xenograft model. The potential of (177)Lu-labeled RS7 was compared with that of RS7 labeled with (90)Y and a residualizing form of (131)I. METHODS: A 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) conjugate of RS7 was used for radiolabeling with (177)Lu-acetate or (88/90)Y-acetate. Biodistribution and therapy studies were conducted in nude mice with subcutaneous Calu-3 xenografts. Therapy studies were performed using the maximal tolerated doses (MTDs) of (90)Y-DOTA-RS7 (3.9 MBq [105 microCi]) and (177)Lu-DOTA-RS7 (10.2 MBq [275 microCi]) and compared with the data obtained using the MTD (13.0 MBq [350 microCi]) of a residualizing form of (131)I-RS7. RESULTS: Radiolabeling of RS7-DOTA conjugate with (177)Lu-acetate was facile. (177)Lu-DOTA-RS7 displayed biodistribution results that were nearly identical to that of the (88)Y analog in a paired-label study. The mean percentage injected doses per gram (%ID/g) for (177)Lu-RS7 and (88)Y-RS7 (in parentheses) in tumor were 38.3 %ID/g (39.1 %ID/g), 63.0 %ID/g (66.0 %ID/g), 63.0 %ID/g (65.8 %ID/g), and 34.0 %ID/g (34.9 %ID/g) on days 1, 3, 7, and 14, respectively. Elimination of established tumors, with an initial mean tumor volume of 0.24 cm(3), was shown using doses of (177)Lu-DOTA-RS7 ranging from 5.6 to 9.3 MBq (150--250 microCi) per nude mouse, with no significant difference in response rate noted between the doses in this range. Specificity of the therapeutic effect was shown in an isotype-matched control experiment, in which (177)Lu-DOTA-RS7 was markedly more effective than the (177)Lu-DOTA control antibody. A comparison of the therapeutic efficacies of (177)Lu-DOTA-RS7 and (90)Y-DOTA-RS7, using mice with established tumors with an initial mean tumor volume of 0.85 cm(3), indicated similar tumor growth inhibition and similar tumor regrowth profiles. The therapy data were similar to those obtained with residualizing (131)I-RS7 obtained at the same time. CONCLUSION: (177)Lu-RS7 is an effective radioimmunoconjugate for radioimmunotherapy. With its radiophysical properties similar to those of (131)I, coupled with its facile and stable attachment to mAb, (177)Lu promises to be an alternative to (131)I, and a complement to (90)Y, in radioimmunotherapy. (+info)
Feasibility studies in rats fed heavy metals as multiple nutrient markers.
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The nitrates of five metals (cerium, terbium, ytterbium, lutetium, and iridium) were fed to rats to determine the feasibility of their use as nonabsorbed, multiple markers for recovery, passage, and indirect apparant digestibility studies. Fecal recovery of a single oral dose was completed within 72 hours. When the salts were mixed into the diet, 48-96 hours was required to establish a steady-state concentration of markers in feces. The diurnal variation of cerium in feces was found to be considerable when it was fed twice daily as a single dose prior to each feeding. When incorporated into the diet, negligible diurnal variation in fecal concentration was noted with lutetium, and small variation was seen with other metals. In nutrient apparent digestibility studies, good agreement was generally found between direct and indirect multiple marker methods. Experiments with a daily intake marker suggest that cerium was not satisfactory as a multiple marker in which neutron activation analysis was the method of determination. (+info)
Differential metabolic patterns of iodinated versus radiometal chelated anticarcinoma single-chain Fv molecules.
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Genetically engineered single-chain Fvs (sFv) are defined as recombinant proteins composed of a variable light chain amino acid sequence of an immunoglobulin tethered to a variable heavy chain sequence by a designed peptide. Previous studies using iodine-labeled sFv, derived from the anticarcinoma monoclonal antibody CC49, showed that the 125I-sFv could efficiently target antigen-positive tumors in a human tumor xenograft model while demonstrating rapid plasma clearance and minimal uptake in normal organs. One of the issues we raised in the analysis of the iodinated sFv metabolic studies was whether similar metabolic patterns would be observed if the sFv were labeled with a radiometal. In the studies reported here, 125I-CC49 sFv and 177Lu-CC49 sFv were co-injected in mice bearing antigen-positive carcinoma xenografts. Both sFv forms showed similar tumor targeting and plasma clearance pharmacokinetics. The 177Lu-sFv, however, showed a greater uptake in liver and spleen and a much higher uptake in kidney. These studies thus demonstrate that despite their small size (M(r) 27,000), the metal-chelated sFv shows a metabolic pattern very different than that of the iodinated sFv, which is most likely due to retention of the metal by organs metabolizing the sFv. (+info)
Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.
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Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with subcutaneous renal cell cancer (RCC) tumors. METHODS: The (88/90)Y and (177)Lu labeling procedures of cG250 conjugated with cyclic diethylenetriaminepentaacetic acid anhydride (cDTPA), isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA), or 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) were characterized. Stability of the labeled conjugates in plasma at 37 degrees C was assessed. Biodistribution and therapeutic efficacy of labeled cG250 were compared in nude mice with SK-RC-52 human RCC xenografts. RESULTS: Both SCN-Bz-DTPA and DOTA were stable in vitro (<5% release of the radiolabel during 14 and 21 d of incubation) and in vivo (uptake in bone +info)
Impact of patient weight and emission scan duration on PET/CT image quality and lesion detectability.
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This study was performed to prospectively evaluate fast PET/CT imaging protocols using lutetium oxyorthosilicate (LSO) detector technology and 3-dimensional (3D) image-acquisition protocols. METHODS: Fifty-seven consecutive patients (30 male, 27 female; mean age, 58.6 +/- 15.7 y) were enrolled in the study. After intravenous injection of 7.77 MBq (0.21 mCi) of (18)F-FDG per kilogram, a standard whole-body CT study (80-110 s) and PET emission scan were acquired for 4 min/bed position in 49 patients and 3 min/bed position in 8 patients. One-minute-per-bed-position data were then extracted from the 3- or 4-min/bed position scans to reconstruct single-minute/bed position scans for each patient. Patients were subgrouped according to weight as follows: <59 kg (<130 lb; n = 15), 59-81 kg (130-179 lb; n = 33), and >or=82 kg (>or=180 lb; n = 9). Three experienced observers recorded numbers and locations of lesion by consensus and independently rated image quality as good, moderate, poor, or nondiagnostic. RESULTS: The observers analyzed 220 reconstructed whole-body PET images from 57 patients. They identified 114 lesions ranging in size from 0.7 to 7.0 cm on the 3- (n = 8) and 4-min/bed position images (n = 49). Of these, only 4 were missed on the 1-min/bed position scans, and all lesions were identified on the corresponding 2-min/bed position images. One- and 2-min/bed position image quality differed significantly from the 4-min/bed position image reference (P < 0.05). CONCLUSION: LSO PET detector technology permits fast 3D imaging protocols whereby weight-based emission scan durations ranging from 1 to 3 min/bed position provide similar lesion detectability when compared with 4-min/bed position images. (+info)
PET performance measurements for an LSO-based combined PET/CT scanner using the National Electrical Manufacturers Association NU 2-2001 standard.
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Results of performance measurements for a lutetium oxyorthosilicate (LSO)-based PET/CT scanner using new National Electrical Manufacturers Association (NEMA) NU 2-2001 standards are reported. METHODS: Performance measurements following the NU 2-2001 standards were performed on an LSO-based PET/CT scanner. In addition, issues associated with the application of the NEMA standard to LSO-based tomographs in the presence of intrinsic radiation are discussed. RESULTS: We report on some difficulties experienced in following the suggested NEMA measurement techniques and describe alternative approaches. Measurements with the new standard (as compared with NU-1994) incorporate the effects of activity outside the scanner and facilitate measurements of the entire axial field of view. Realistic clinical conditions are also simulated in image quality measurements of a torso phantom. CONCLUSION: We find that, with appropriate modifications, NU 2-2001 can be successfully applied to LSO-based scanners. (+info)