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Biomedical subjects

R E Bigler

Publications and source records attributed to R E Bigler.

16 recordsLinked to original sources

Design of a 13C (1H) RF probe for monitoring the in vivo metabolism of [1-13C]glucose in primate brain.

The design of an RF probe suitable for obtaining proton-decoupled 13C spectra from a subhuman primate brain is described. Two orthogonal saddle coils, one tuned to the resonant frequency of 13C and the other to the resonant frequency of 1H, were used to monitor the in vivo metabolism of [1-13C]glucose in rhesus monkey brain at 2.1 T. Difference spectra showed the appearance of 13C-enriched glutamate and glutamine 30 to 40 min after a bolus injection of [1-13C]glucose.

Animals

Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides.

A calculational approach is described that provides the spatially varying radiation absorbed dose, presented as isodose contours superimposed on CT images, from nonuniform and/or irregular cumulated activity distributions. CT images are read from magnetic tape and are displayed on a high-resolution color graphics display monitor. Source tissue geometries are defined on a series of contiguous CT images automatically (by an edge detection algorithm) or manually (using a trackball), thereby obtaining a three-dimensional representation of the various source volumes of activity. Dose calculations are performed using a radionuclide-specific absorbed dose point kernel in the form of a lookup table. The method described yields the spatially varying dose delivered to tumor and normal tissue volumes from a patient-specific cumulated activity distribution in a clinically implementable manner. This level of accuracy in determining normal tissue and tumor doses may prove valuable in the evaluation and implementation of radionuclides and radiolabeled compounds for therapeutic purposes.

Algorithms

Quantitative SPECT in radiation dosimetry.

Accurate and precise radiation dosimetry is critical for the successful therapeutic application of systemically administered radionuclides, including, of course, radionuclides in the form of radiolabeled antibody. This requires determination, based on discrete serial measurements, of the time-dependent concentrations and/or total amounts of radioactivity in situ in order to calculate source region cumulated activities. Based on extensive studies (with clinically realistic numbers of counts and accuracies of the order of 10%) in simple geometric phantoms, in complex anthropomorphic phantoms, in animal models, and in humans, quantitative rotating scintillation camera-based single-photon emission computed tomography (SPECT) now appears to be a practical approach to such measurements. The basis of the quantitative imaging capability of a three-dimensional imaging modality such as SPECT is the elimination in the reconstructed image of counts emanating from activity surrounding the source region. Subject to considerations such as the reconstruction algorithm, attenuation and scatter corrections, and, most importantly, statistical uncertainty, the counts in a pixel in a reconstructed image are therefore directly proportional to the actual counts emanating from the corresponding voxel in situ. Among intrinsic, pre-processing, and post-processing attenuation corrections, post-processing algorithms, the most widely used approach in current commercial SPECT systems, have proven adequate in uniformly attenuating parts of the body (eg, abdomen, pelvis), subject to accurate delineation of the body contour. Although a number of sophisticated scatter correction methods have been developed, the lack of explicit scatter correction has, in practice, not been a major impediment to reasonably accurate quantitative SPECT imaging, despite scattered radiation representing up to 50% of the counts in a large source region (eg, liver). Because of its mathematical propagation in the image reconstruction process, statistical uncertainty (ie, "noise") in SPECT is far greater than would be expected if it were distributed according to Poisson statistics, as in planar imaging. The low "single slice" sensitivity of rotating scintillation camera-based SPECT is therefore the principal limitation of practical quantitative SPECT. Accordingly, absolute quantitation of count-limited clinical images has been accomplished using a judiciously selected "non-ramp" filter function. In summary, reasonable quantitative SPECT imaging is now feasible clinically, even without sophisticated scatter corrections, at least in uniformly attenuating parts of the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans

Monoclonal antibody to an intracellular antigen images human melanoma transplants in nu/nu mice.

Mouse monoclonal antibody TA99 detects a 70-kDa pigmentation-associated glycoprotein in human melanoma cell lines. The antigen cannot be detected on the cell surface by sensitive rosetting techniques or absorption studies, nor can it be detected as a secreted product in culture fluids. Contrary to expectation, 125I-labeled TA99 specifically localized to pigmented human melanoma transplants in nu/nu mice; no localization to nonpigmented melanoma or control tumors was found. Tumor imaging was initially obscured by circulating 125I-labeled TA99 during the first 6 days after antibody injection. With clearance of 125I-labeled TA99 from the blood (half-life, 4-7 days), specific tumor images could be clearly defined by day 13. Due to the persistence of 125I-labeled TA99 at the tumor site (8.9% of the injected dose at 1 week and 4.6% at 8-10 weeks), images were obtainable for up to 10 weeks. At 8-10 weeks, the tumor/blood ratio was 10(4)-10(5), and the tumor/normal tissue ratio ranged from 10(2) to 10(5). In view of these findings, antibodies detecting intracellular antigens may have a role in tumor imaging and therapy.

Animals

Imaging studies of patients with malignant fibrous histiocytoma using C-11-alpha-aminoisobutyric acid (AIB).

Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid which is rapidly transported into viable cells by the A-type or alanine-preferring amino acid transport system, has been labeled with the short-lived, positron-emitting radionuclide carbon-11. Carbon-11 labeled AIB is currently being evaluated as a tumor imaging agent for in vivo amino acid transport studies in patients with cancer. In this study, C-11 AIB was used to image two patients with malignant fibrous histiocytoma (MFH), a pleomorphic sarcoma. Following intravenous administration of C-11 AIB, tumors in the distal femur of one patient and in the anterior chest wall of another patient were well visualized using high energy gamma scintigraphy. Since therapy may alter the accumulation of amino acids in tumor tissue, studies using C-11 AIB in patients with MFH before and after chemotherapy are in progress.

Adult

Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma.

A 29 year-old-man presenting with advanced metastatic malignant melanoma was successfully imaged using carbon-11 (11C) labeled alpha-aminoisobutyric acid (AIB), a synthetic, non-metabolized amino acid transported into viable cells by the A-type, or alanine-preferring, amino acid transport system. Tumor located in the hilum of the lung was well visualized with 11C-AIB prior to chemotherapy. A gallium image with liver subtraction using 99mTc-sulfur colloid demonstrated regions of increased activity in liver which correlated with regions of increased activity on the 11C-AIB liver image.

Adult

Evaluation of [1-11C]-alpha-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies.

Alpha-aminoisobutyric acid (AIB), or alpha-methyl alanine, is a nonmetabolized amino acid transported into cells, particularly malignant cells, predominantly by the 'A' amino acid transport system. Since it is not metabolized, [1-11C]-AIB can be used to quantify A-type amino acid transport into cells using a relatively simple compartmental model and quantitative imaging procedures (e.g. positron tomography). The tissue distribution of [1-11C]-AIB was determined in six dogs bearing spontaneous tumors, including lymphosarcoma, osteogenic sarcoma, mammary carcinoma, and adenocarcinoma. Quantitative imaging with tissue radioassay confirmation at necropsy showed poor to excellent tumor localization. However, in all cases the concentrations achieved appear adequate for amino acid transport measurement at known tumor locations. The observed low normal brain (due to blood-brain barrier exclusion) and high (relative to brain) tumor concentrations of [1-11C]-AIB suggest that this agent may prove effective for the early detection of human brain tumors.

Amino Acids

Evidence for the cerebral uptake in vivo from two pools of glucose and the role of glucose-6-phosphatase in removing excess substrate from brain.

We propose the following scheme for cerebral uptake and overall metabolism of glucose in vivo: that brain selects from two pools of glucose anomers in arterial blood, that it takes up excess glucose, that glucose enters the brain tissue as glucose-6-phosphate through the actions of mutarotase and hexokinase, that some glucose-6-phosphate becomes metabolized to CO2 and some becomes incorporated into brain carbon pools, and that excess glucose-6-phosphate leaves brain through glucose-6-phosphatase and mutarotase activities. This results from our observations in arterio-venous studies for the determination of cerebral metabolism in humans in vivo that the cerebral uptake of [14C]glucose often appeared to differ from that of unlabeled glucose. With rapidly falling arterial radioactivity, unlabeled glucose uptake was more than [14C]glucose. With rising arterial radioactivity, [14C]glucose extraction exceeded unlabeled glucose. Studies with [14C]glucose-6-phosphate suggested that glucose-6-phosphatase in brain removes excess substrate by dephosphorylation. However, when arterial [14C]glucose increased slowly, [14C]glucose uptake varied considerably and the data resembled human cerebral metabolism of glucose anomers. An experiment employing [13C]glucose and NMR provided further support for our proposed scheme.

Animals

Radiation dosimetry of 204Bi- and 206Bi-citrates.

The absorbed-radiation doses from 204Bi- and 206Bi-citrates to humans are calculated from available nuclear and biologic data in order to evaluate the relative radiation risk of these radionuclides. The calculations reveal that the radiation dose to the kidneys is reduced by a factor of 8 if 204Bi replaces 206Bi. This reduction suggests that 204Bi should be investigated further as a possible soft-tissue scanning agent.

Animals