Biomedical subjects

T E Hui

Publications and source records attributed to T E Hui.

26 records · Page 2Linked to original sources

PubMed1992

Microdistribution and microdosimetry of thorium deposited in the liver.

The distribution of thorium in the liver of a patient 36 y after injection with Thorotrast was examined with autoradiographic and scanning electron microscope backscatter image techniques. Autoradiographic examination of randomly selected histologic sections of the liver showed a total alpha activity calculated at 33.7 Bq g-1, with the highest concentration of alpha activity sequestered in subcapsular scare tissue. Subcapsular scare tissue received 4.8 cGy d-1 of alpha radiation, periportal areas were accumulating 1.4 cGy d-1, and the hepatic cord areas 0.09 cGy d-1 of alpha radiation at the time of death. The concentration of dose in periportal areas correlates with higher incidence of bile duct tumors (than hepatocellular carcinomas) found in patients exposed to Thorotrast. The backscatter technique was demonstrated as useful for identifying thorium in liver specimens.

Aged↗

PubMed1991

Biodistribution and dosimetry following infusion of antibodies labeled with large amounts of 131I.

Dosimetry and treatment planning for therapeutic infusions of radiolabeled antibodies are usually performed by extrapolation from the biodistribution of trace-labeled antibody. This extrapolation assumes that the biodistribution of high specific activity antibody will be similar to that seen with trace-labeled antibody. However, high doses of radiation result in rapid depletion of lymphoid and hematopoietic cells in lymph nodes, spleen, and marrow with replacement by blood and plasma. If radiolabeled antibody is cleared slowly from blood, this replacement may result in increased radionuclide concentrations in these tissues following infusions of antibody labeled with large amounts of radionuclide. To examine the influence of deposited radiation on the biodistribution of radiolabeled antibody, we treated mice with a constant amount of antibody that was labeled with varying amounts of 131I. Survival was determined in normal specific pathogen-free AKR/Cum mice (Thy1.2+) after infusion of anti-Thy1.1 antibody labeled with 10 to 6500 muCi of 131I, to determine an appropriate range of 131I doses for further study. The dose producing 50% lethality within 30 days following infusion of 131I-labeled antibody was 530 muCi 131I. Biodistribution, bone marrow histology, and dosimetry were subsequently determined after infusion of 500 micrograms of antibody labeled with 10, 250, 500, or 3500 muCi 131I. The amount of 131I did not influence uptake or retention of antibody in blood, liver, lung, or kidney. In contrast, infusion of antibody labeled with 250 to 3500 muCi of 131I led to a dose-related increase in the concentration of 131I in marrow, spleen, lymph node, and thymus. For example, at 96 h after infusion of antibody labeled with 500 or 3500 muCi 131I, concentrations in marrow were 3- to 4-fold higher than after infusion of trace-labeled antibody. The increase in marrow 131I concentrations was associated with depletion of cells and hemorrhage within the marrow space. As a result, estimated mean absorbed doses to marrow, lymph node, spleen, and thymus were 1.2 to 3.1 times higher than would have been predicted from the biodistribution of trace-labeled antibody. These results suggest that the biodistribution of trace-labeled antibody should be an accurate predictor of the behavior of high specific activity antibody in blood and solid organs such as liver and kidney. In contrast, radiation from antibody labeled with large amounts of radionuclide can result in an alteration of the concentration of radiolabeled antibody in rapidly responding tissues such as marrow.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque.

Despite bone marrow transplantation, many patients with advanced leukemia subsequently relapse. If an additional increment of radiation could be delivered to lymphohematopoietic tissues with relative specificity, the relapse rate may decrease without a marked increase in toxicity. We have examined the biodistribution of two 131I-labeled monoclonal antibodies reactive with the CD45 antigen in Macaca nemestrina. Three animals received 0.5 mg/kg BC8, an IgG1 of low avidity (6 x 10(7) L/mol). Three received 0.5 mg/kg AC8, an IgG2a of moderate avidity (5 x 10(8) L/mol), and two received 4.5 mg/kg AC8. Estimates of radiation absorbed dose demonstrated that these antibodies could deliver up to five times more radiation to lymph nodes, and up to 2.6 times more to bone marrow, than to lung or liver. The higher avidity AC8 antibody at 0.5 mg/kg was cleared more rapidly from blood and resulted in lower antibody uptake in lymph nodes than did BC8 at 0.5 mg/kg. Increasing the dose of AC8 to 4.5 mg/kg resulted in slower blood clearance and higher lymph node uptake. These studies suggest that radiolabeled anti-CD45 antibodies can deliver radiation with relative specificity to lymphohematopoietic tissues. This approach, in combination with marrow transplantation, may improve treatment of hematologic malignancies.

Animals↗

PubMed1991

WR2721 protection of bone marrow in 131I-labeled antibody therapy.

The use of phosphorothioate radioprotectors such as WR2721 in radioimmunotherapy is attractive because radiation delivered to tumors is usually separated in time from that delivered to the marrow and most normal organs, making protection of tumors of little consequence. However, to be effective radioprotectors must provide continuous protection against radiation of varying dose rates. To evaluate the potential of radioprotectors in radioimmunotherapy we treated normal mice with graded amounts of WR2721 in combination with an LD90/30 (26 MBq) of 131I-labeled antibody. A regimen of 15 doses of WR2721, 200 mg/kg prior to antibody infusion followed by 100 mg/kg ip every 4 h for a total of 72 h, was the maximum tolerated dosage schedule. With this schedule, treatment with radioprotectors failed to prolong survival or delay myelosuppression from the 131I-labeled antibody. In contrast, this regimen of radioprotector provided partial protection from a single treatment of 10 Gy total-body radiation given at 0.2 Gy/min. Protection 30 min after the final dose of WR2721 was greater than 3 h after the 14th dose (60 min prior to the final dose). These results suggest that the potential role of phosphorothioate radioprotectors in a radioimmunotherapy is limited because of the difficulty in achieving continuous protection with nontoxic amounts of drug and possibly because of a limited effect on low-dose-rate radiation.

Amifostine↗

PubMed1991

In vitro exposure of mammalian cells to radon: dosimetric considerations.

We have developed a model to calculate the dose to the cell nucleus in cells exposed in suspension to radon and/or radon progeny. The model addresses the influence of (1) different radiation qualities and energies in the irradiation milieu; (2) the contribution to dose from radioactivity in the medium surrounding the cell after exposure to the radon gas as well as that from excess radon progeny associated with the cell; (3) the geometry of the cell and of the radiosensitive target, the cell nucleus; (4) the intracellular localization of the radionuclides; (5) attenuation of the alpha particles by the cytoplasm; (6) the radionuclide concentrations in the medium; and (7) the length of exposure. Investigation of the influence of these various parameters was made using an irradiation system in which cells were exposed to 212Bi, which decays to stability with the emission of an alpha particle (either 6.05 or 8.78 MeV). The information from these studies was then used to develop the system further for more complex systems in which 222Rn and its progeny are present. The model takes into account the contribution of dose from different radiation sources using scintillation counts of the medium and the cells, and it is useful for calculations of dose in situations where cells are exposed in suspension culture.

Animals↗

PubMedDate not supplied

Adaptive response of human lymphocytes for the repair of radon-induced chromosomal damage.

In human lymphocytes low doses of X-rays can decrease the number of chromatid deletions induced by subsequent high doses of sparsely ionizing X-rays. Because of the concern with the carcinogenic effects of low doses of alpha-particles from radon in homes, experiments were carried out to see if low doses of X-rays could also decrease the yield of chromosomal aberrations induced by subsequent exposure to radon. Human peripheral blood lymphocytes were irradiated with low doses of X-rays (2 cGy) at 48 h of culture, exposed to radon at 72 h of culture, and analyzed for the presence of chromatid aberrations at subsequent intervals. The frequency of chromatid aberrations induced by radon alone increased with time after exposure, indicating exaggerated differences in the stage sensitivity of cell cycle stages to high-LET radiation. Furthermore, the numbers of aberrations per cell did not follow a Poisson distribution but were over dispersed, as might be expected since high-LET radiations have a high relative biological effectiveness compared with low-LET radiations. Nevertheless, lymphocytes exposed to 2 cGy of X-rays before radon exposure contained approximately one-half the number of chromatid deletions compared with lymphocytes treated with radon alone and analyzed at the same time. Thus, the putative chromosomal repair mechanism induced by low doses of sparsely ionizing radiation is also effective in reducing chromosomal aberrations induced by radon, which hitherto had been thought to be relatively independent of repair processes.

Adaptation, Physiological↗

PubMedDate not supplied

Localized beta dosimetry of 131I-labeled antibodies in follicular lymphoma.

The purpose of this study is to assess the multicellular dosimetry of 131I-labeled antibody in follicular lymphoma based on histological measurements on human tumor biopsy tissue. Photomicrographs of lymph node specimens were analyzed by first-order treatment to determine the mean values and statistical variations of the radii of follicles (260 +/- 90 microns), interfollicular distances (740 +/- 160 microns), and the number density of follicles [60 +/- 18 in a volume of (2 X 1480 microns)3]. Based on these measurements, two geometrical models were developed for localized beta dosimetry. The first, a regular cubic lattice model, assumes no variation in follicular radius of follicles and interfollicular distance. The second, a randomized distribution model, is a more complicated but more realistic representation of observed histological specimens. In this model, Monte Carlo methods were used to reconstruct the spatial distribution of follicles by simulating the distribution of the radii of follicles, interfollicular distances, and the number density of follicles. Dose calculations were performed using Berger's point kernels for absorbed-dose distribution for beta particles in water, assuming the 131I-labeled antibodies as point sources. It was assumed that the activity concentration of the labeled antibody within the follicles was ten times the activity concentration in the interfollicular spaces. The spatial distribution of localized dose was calculated for a tumor having an average dose of 40 Gy. The localized dose was found to be highly nonuniform, ranging from 20 to 90 Gy, and varying by a factor of about 2 from the average tumor dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMedDate not supplied

Factors affecting use of CR-39 surface monitor technology to estimate past exposure to indoor radon.

In an epidemiologic study investigating influences of life-style and environment on lung cancer risk, CR-39 alpha-particle detectors, identified here as surface monitors, were affixed to subjects' selected household glass, ceramic, or enameled objects to measure residual radioactivity form embedded radon (Rn) decay products. The purpose was to estimate past cumulative indoor Rn concentrations to which the object was exposed to infer past exposures of the subjects. This approach was used to supplement exposure information obtained by methods traditionally used in Rn epidemiologic studies. In addition, surface monitors were affixed to objects of selected study subjects with complete exposure information to evaluate whether surface monitors provided estimates of cumulative past residual Rn exposure comparable to estimates obtained from year-long, ambient alpha track-etch measurements in each present and previous residence. These ambient measurements were time-weighted to estimate integrated exposure of objects and were adjusted for decay and ingrowth so as to be comparable to surface monitor measurements. A regression relationship was estimated between the two estimates of cumulative RN exposure. Surface monitor measurements had a satisfactory correlation (0.63) with adjusted ambient Rn measurements for new, nonceramic objects. Although not included in the study design, factors that might affect use of the technology were also investigated. Regression relationships were compared in graduated smoking environment (as judged by the subjects) to investigate possible differential plate out of radon progeny. In addition, regression relationships for windows were compared with those for other objects to investigate whether there was a significant difference between windows and other objects. It has been suggested that windows may have a higher plate out rate because of locally increased air flow. Results suggested that surface monitor information was useful to fill time gaps in estimates of historical radon exposure data obtained by ambient measurements. Glass samples provided the best correlation. Ceramic materials sometimes provided excessively high radon estimates, probably due to glazes that contained significant uranium or thorium. Due to small sample sizes, investigations of other factors were inconclusive.

Air Pollutants, Radioactive↗