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Biomedical subjects

H B Liu

Publications and source records attributed to H B Liu.

27 records · Page 2Linked to original sources

A practical procedure for the cryopreservation of marrow cells intended for autotransplantation.

A simple and practical method of unfractionated bone marrow processing and cryopreservation was studied. The date shows that RBCs can be rapidly sedimented by methylcellulose or sodium carboxymethyl starch within 15-45 min. The cells can be cryopreserved in a mixture consisting of 5% DMSO, 6% HES and 4% Albumin prepared in a Lactated Ringer solution which is widely used, and can be simply immersed into a -80 degrees C freezer and stored in liquid nitrogen until infusion. Recovery percentages of nucleated cell, cell viability and CFU-G were similar to those cryopreserved with the conventional method. Clinical toxicity was mild in 12 infused patients. Of them 8 patients had received high dose chemotherapy +/- TBI and their peripheral WBC recovery was rapid. The recovery of WBC or Platelet (PLT) in the study group was similar to that of the control group whose marrow cells were cryopreserved in 10% DMSO. Therefore, cells cryopreserved with this method can also accelerate the hematopoietic recovery in myeloablatively treated patients.

Adolescent↗

Neutron capture therapy of the 9L rat gliosarcoma using the p-boronophenylalanine-fructose complex.

PURPOSE: Intraperitoneal (IP) injection of the solubilized fructose complex of L-p-boronophenylalanine (BPA-F) produced higher boron concentrations in a rat brain tumor model than was possible using intragastric (IG) administration of L-p-boronophenylalanine (BPA). The effectiveness of IP BPA-F was compared to IG BPA in boron neutron capture therapy irradiations of the 9L rat brain tumor model. METHODS AND MATERIALS: The time course of boron accumulation in tumor and normal tissues was determined in male F344 rats bearing either SC or intracerebral 9L gliosarcomas following a single IP injection of BPA-F. On day 14 after inoculation of intracranial tumors, rats were irradiated with single doses of either: 250 kVp X rays; the thermal neutron beam of the Brookhaven Medical Research Reactor following IG administration of BPA; or thermal neutrons following IP injection of BPA-F. Magnetic resonance imaging was used to visualize the tumor scars and to assess damage to the normal brain in long-term survivors. RESULTS: 4 h after IP injection of 1200 mg/kg of BPA-F the boron concentrations in tumor, blood, and normal brain were 89.6 +/- 7.6, 27.7 +/- 2.8 and 17.5 +/- 1.5 micrograms 10B/g, respectively. Two IG doses of BPA (750 mg/kg each, 3 h apart) produced 39 +/- 5, 12 +/- 1 and 10 +/- 1 micrograms 10B/g in tumor, blood and brain, respectively at 5 h after the second dose. Three groups of rats were treated with thermal neutrons: one following IG BPA and two groups following IP BPA-F. The total physical absorbed doses to the tumor in the three BNCT groups were 15.5 Gy (IG BPA, n = 12), 17.0 Gy (IP BPA-F, n = 8), and 31.5 Gy (IP BPA-F, n = 8), respectively. The median survival of the untreated controls was 22 days. The median survival of the rats treated with 22.5 Gy of 250 kVp X rays (n = 23) was 35 days with 20% long-term survivors. Fifty percent of the rats in the IG BPA + thermal neutrons group survived over 1 year. All rats in both groups that received IP BPA-F + thermal neutrons have survived over 8 months. Magnetic resonance imaging of the brains of the long-term boron neutron capture therapy survivors showed a scar at the site of tumor implantation in all animals. In the IP BPA-F high-dose group one rat showed evidence of edema and one rat showed a fluid-filled cyst replacing the tumor. CONCLUSION: The use of IP BPA-F has significantly improved long-term survival compared to IG BPA. The high percentage of long-term tumor control (100%, n = 16) in the intracerebral rat 9L gliosarcoma brain tumor model, together with little or no damage to the surrounding normal brain in the majority of surviving animals, demonstrate the substantial therapeutic gain produced by boron neutron capture therapy.

Animals↗

Enhancement of the epithermal neutron beam used for boron neutron capture therapy.

PURPOSE: This report describes a study to enhance the epithermal neutron beam at the Brookhaven Medical Research Reactor by increasing the epithermal neutron flux and/or reducing contamination by fast neutrons. METHODS AND MATERIALS: The beam was reevaluated using Monte Carlo calculations and flux and dose measurements in air and in an ellipsoidal head phantom at the patient irradiation port. Changes in its geometry and materials were considered, including rearranging the fuel elements in the reactor core and redesigning the moderator and the patient irradiation port. RESULTS: Calculations of the new fluxes and doses at the patient irradiation port showed that the epithermal neutron flux can be increased by 100%, while the fast neutron dose per epithermal neutron can be reduced by 38%. In 1992, some of the proposed changes were made. In June 1992, measurements were made after one additional fuel element was added to replace a graphite spacer block on the epithermal beam side of the reactor core. The results show that the epithermal neutron flux increased by 18%, as predicted by the Monte Carlo calculations. In October 1992, the fuel elements in the reactor core were rearranged by placing four new fuel elements in the first row facing the epithermal port; the intensity of the epithermal neutron beam increased by 50% and the fast neutron and gamma doses per epithermal neutron may have decreased slightly. CONCLUSION: The epithermal neutron beam at the Brookhaven Medical Research Reactor has gained a 50% increase in the epithermal neutron flux and the fast neutron and gamma doses per epithermal neutron are reduced slightly after the rearrangement of the fuel elements in the core.

Boron Neutron Capture Therapy↗

Improved apparatus for neutron capture therapy of rat brain tumors.

PURPOSE: The assembly for irradiating tumors in the rat brain at the thermal neutron beam port of the Brookhaven Medical Research Reactor was redesigned to lower the average whole-body dose from different components of concomitant radiation without changing the thermal neutron fluence at the brain tumor. METHODS AND MATERIALS: At present, the tumor-bearing rat is positioned in a rat holder that functions as a whole-body radiation shield. A 2.54 cm-thick collimator with a centered conical aperture, 6 cm diameter tapering to 2 cm diameter, is used to restrict the size of the thermal neutron field. Using the present holder and collimator as a baseline design, Monte Carlo calculations and mixed-field dosimetry were used to assess new designs. RESULTS: The computations indicate that a 0.5 cm-thick plate, made of 6Li2CO3 dispersed in polyethylene (Li-poly), instead of the existing rat holder, will reduce the whole-body radiation dose. Other computations show that a 10.16 cm-thick (4 inches) Li-poly collimator, having a centered conical aperture of 12 cm diameter tapering to 2 cm diameter, would further reduce the whole-body dose. CONCLUSION: The proposed irradiation apparatus of tumors in the rat brain, although requiring a 2.3-fold longer irradiation time, would reduce the average whole-body dose to less than half of that from the existing irradiation assembly.

Animals↗

Response of the central nervous system to boron neutron capture irradiation: evaluation using rat spinal cord model.

The response of the central nervous system to boron neutron capture irradiation, with either p-boronophenylalanine (BPA) or borocaptate sodium (BSH) as neutron capture agents, has been assessed using a rat spinal cord model. The mean latency times for the development of myelopathy after irradiation with the thermal neutron beam-alone, or in combination with BPA or BSH, were 23.7 +/- 0.3, 21.8 +/- 0.4 and 19.6 +/- 0.4 weeks, respectively. The radiation-induced lesion in the spinal cord was characterised by white matter necrosis. Due to the variations in the microdistribution of different neutron capture agents in body tissues, it was considered inappropriate to define the biological effectiveness of the high LET radiation, resulting from the 10B(n, alpha)7Li neutron capture reaction, relative to photon radiation, using the term 'relative biological effectiveness' (RBE). The term 'compound biological effectiveness' (CBE) factor was used as an alternative. ED50 values for the various irradiation modalities were calculated from probit fitted dose effect curves. Expressed as total physical absorbed doses these values were 13.6 +/- 0.4, 30.3 +/- 2.7 and 13.8 +/- 0.5 Gy after irradiation with the thermal neutron beam alone, or the thermal neutron beam in combination with BSH or BPA, respectively. The RBE of the thermal neutron beam was 1.4 +/- 0.04. The microdistribution of the two neutron capture agents played a crucial role in the determination of the overall biological effect, after thermal neutron activation. BSH, which is excluded from the CNS parenchyma by the blood brain barrier, had a low CBE factor value of 0.46 +/- 0.5. BPA, on the other hand, which crosses the blood brain barrier and distributes in the CNS parenchyma, had a higher CBE factor value of 1.33 +/- 0.16.

Absorption↗

Design of a high-flux epithermal neutron beam using 235U fission plates at the Brookhaven Medical Research Reactor.

Beams of epithermal neutrons are being used in the development of boron neutron capture therapy for cancer. This report describes a design study in which 235U fission plates and moderators are used to produce an epithermal neutron beam with higher intensity and better quality than the beam currently in use at the Brookhaven Medical Research Reactor (BMRR). Monte Carlo calculations are used to predict the neutron and gamma fluxes and absorbed doses produced by the proposed design. Neutron flux measurements at the present epithermal treatment facility (ETF) were made to verify and compare with the computed results where feasible. The calculations indicate that an epithermal neutron beam produced by a fission-plate converter could have an epithermal neutron intensity of 1.2 x 10(10) n/cm2.s and a fast neutron dose per epithermal neutron of 2.8 x 10(-11) cGy.cm2/nepi plus being forward directed. This beam would be built into the beam shutter of the ETF at the BMRR. The feasibility of remodeling the facility is discussed.

Boron Neutron Capture Therapy↗

Derivations of relative biological effectiveness for the high-let radiations produced during boron neutron capture irradiations of the 9L rat gliosarcoma in vitro and in vivo.

PURPOSE: Relative biological effectiveness (RBE) values for the high linear-energy-transfer particles produced during boron neutron capture therapy have generally been based on theoretical considerations or in vitro experiments. The purpose of this study was to independently determine RBE values for all of the boron neutron capture therapy dose components. METHODS AND MATERIALS: Clonogenic cell survival data were obtained for 9L rat gliosarcoma cells irradiated in the Brookhaven Medical Research Reactor thermal neutron beam both in vitro and as an intracerebral tumor. These data were analyzed using the linear quadratic model for cell survival to derive measured RBE values for all beam components and for a number of different boron compounds. RESULTS: In the absence of boron, the combined effects of the protons from the nitrogen capture, 14N(n,p)14C, and the fast neutron scatter, 1H(n,n')p, reactions generated RBEs of 3.7 in vitro and 3.2 in an in vivo/in vitro excision assay, compared to 250 kVp X rays using an end point of 1% cell survival. Apparent RBEs for the 10B(n,alpha)7Li reaction products were calculated from cell survival data following reactor irradiations in the presence of the amino acid p-boronophenylalanine, the sulfhydryl dodecaborate monomer or dimer, or boric acid. Apparent RBEs for the 10B(n,alpha)7Li reaction ranged from 1.2 to 9.8 depending on which boron compound was used. RBEs from the in vitro studies were consistently higher than from the in vivo/in vitro studies. Under any conditions, the apparent RBE for the 10B(n,alpha)7Li reaction with p-boronophenylalanine was higher than that with any other boron compound tested. CONCLUSIONS: Generally accepted RBE values for the fast neutron and 14N(n,p)14C reaction components of the total dose are too low. The apparent RBEs calculated for the 10B(n,alpha)7Li reaction were compound-dependent and consistent with differences in the distribution of 10B relative to glioma cell nuclei.

Animals↗

Neutron capture therapy with 235U seeds.

A combination of brachytherapy and neutron capture therapy has been evaluated using 235U metal seeds and external neutron beam irradiation. When thermal neutrons are absorbed by 235U, high-energy neutrons and gamma rays are produced and some of these deposit energy in surrounding tissue. A Monte Carlo program, using the code MCNP, has been used to evaluate two sizes of 235U seeds in a water phantom. The results of flux suppression around the seeds and dose distributions are illustrated and discussed. The results show that high doses can be delivered in a relatively short time by using 235U seeds with neutron capture therapy. This therapy with multiple needles or seeds can be envisioned as a substitute for traditional brachytherapy to give an effective killing dose.

Brachytherapy↗