Measuring partial body potassium in the legs of patients with spinal cord injury: a new approach.

Patients with acute spinal cord injury (SCI) with paralysis experience rapid and marked muscle atrophy below the level of the lesion. Muscle is lost above the lesion due to enforced bed rest associated with immobilization. Presently, there is no viable method to quantify muscle loss between the time of injury to the initiation of rehabilitation and remobilization. Furthermore, to assess the efficacy of any physical or pharmacological intervention necessitates the ability to accurately determine the impact of these treatments on muscle mass and function. Our results are presented from measurements of regional potassium (K) in the legs of persons with chronic SCI. The intracellular body K, comprising approximately 97% of the total body K, is indicative of the metabolically active cell mass, of which over 50% is located in the skeletal muscle (SM). To assess regional variations in SM mass in the legs, a partial body K (PBK) system designed for this purpose was placed on a potentially mobile cart. The SM mass measured by PBK in an able-bodied control cohort (n = 17) and in patients with chronic SCI (n = 21) was 17.6 +/- 0.86 and 11.0 +/- 0.65 kg, respectively, a difference of approximately 37.5%. However, the difference in the lean tissue mass of the legs obtained by dual-energy absorptiometry (DXA) in the same cohorts was 20.5 +/- 0.86 and 15.5 +/- 0.88 kg, respectively, or a difference of approximately 24.4%. PBK offers a novel approach to obtain regional K measurements in the legs, thus allowing the potential for early and serial assessment of muscle loss in SCI subjects during the acute and subacute periods following paralysis. The basic characteristics and performance of our PBK system and our calibration procedure are described in this preliminary report.

Measuring partial body potassium in the arm versus total body potassium.

Skeletal muscle (SM), the body's main structural support, has been implicated in metabolic, physiological, and disease processes in humans. Despite being the largest tissue in the human body, its assessment remains difficult and indirect. However, being metabolically active it contains over 50% of the total body potassium (TBK) pool. We present our preliminary results from a new system for measuring partial body K (PBK) that presently are limited to the arm yet provide a direct and specific measure of the SM. This uniquely specific quantification of the SM mass in the arm, which is shielded from the body during measurement, allows us to simplify the assumptions used in deriving the total SM, thereby possibly improving the modeling of the human body compartments. Preliminary results show that PBK measurements are consistent with those from the TBK previously obtained from the same subjects, thus offering a simpler alternative to computed tomography and magnetic resonance imaging used for the same purposes. The PBK system, which can be set up in a physician's office or bedside in a hospital, is completely passive, safe, and inexpensive; it can be used on immobilized patients, children, pregnant women, or other at-risk populations.

A prospective study of prostate specific antigen levels in patients receiving radiotherapy for localized carcinoma of the prostate.

Prostate Specific Antigen (PSA) is becoming the preferred tumor marker in the management of prostate cancer. Prostate Specific Antigen levels fall exponentially after radical prostatectomy with a half-life of between 2 and 3 days. Persistently elevated Prostate Specific Antigen levels beyond 7 half-lives suggest occult residual disease and may serve as an indication for post operative adjunctive therapy. The change in Prostate Specific Antigen levels during a course of radical external beam radiotherapy for prostate cancer has not been described. In this study of 81 patients receiving radiotherapy for primary prostate cancer, 47 had elevated Prostate Specific Antigen levels prior to therapy and 35 had serial measurement of Prostate Specific Antigen during their course of treatment. Working on an assumption that in patients with radioresponsive localized prostate cancer Prostate Specific Antigen levels will fall exponentially during the radiotherapy, a half-life of 43 +/- 11 days was derived. Prostate Specific Antigen half-life appears independent of stage, grade, or pretreatment Prostate Specific Antigen level and may be an independent prognostic indicator. A prolonged Prostate Specific Antigen half-life may suggest untreated or resistant disease and serve as an indication for adjuvant hormonal treatment in patients receiving radiotherapy for primary prostate cancer.

Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the epithermal neutron beam at the Brookhaven National Laboratory.

OBJECTIVE: Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear reactions that occur when boron (10B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial were to study the feasibility and safety of single-fraction BNCT in patients with GBM. MATERIALS AND METHODS: The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximately 4 weeks of the biodistribution study. From September 1994 to July 1995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue samples collected during surgical debulking were analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood 10B concentrations measured before and during treatment were used to calculate the time of reactor irradiation that would deliver the prescribed dose. RESULTS: 10B concentrations in specimens of scalp and tumor were higher than in blood by factors of approximately 1.5 and approximately 3.5, respectively. The 10B concentration in the normal brain was < or = that in the blood; however, for purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy-Eq), which is the sum of the various physical dose components multiplied to appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in-field alopecia. No CNS toxicity attributed to BNCT was observed. The median time to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median survival time from diagnosis was 13.5 months. CONCLUSION: It is feasible to safely deliver a single fraction of BPA-based BNCT. At the dose prescribed, the patients did not experience any morbidity. To further evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a minimum target volume dose of 17 Gy-Eq is in progress.

Noninvasive in-vivo measurement of hepatic and cardiac iron.

This study describes a new noninvasive in-vivo method of appraising human iron stores by nuclear resonance scattering (NRS). Manganese-56 is used as a source of 847 keV gamma rays which scatter resonantly from the iron in the liver and heart of patients with Cooley's anemia (thalassemia major). These patients have heavy iron overload that may lead to cardiac and other organ failure. The NRS iron quantitation of the liver compared favorably, in a linear fashion, with the iron in the liver biopsies. Above initial value, the hepatic iron correlates with the cardiac NRS signal. There is no correlation, however, between liver enzymes and degree of iron load. NRS appears to be a reliable method for measuring cardiac and hepatic iron. It may be repeated as needed to determine the effectiveness, selectivity and compliance to therapy and prognosis.

Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance.

UNLABELLED: This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to investigate radiation-induced lung changes in eight patients undergoing radiotherapy for lung or breast carcinoma. The sensitivity of the method was compared with chest radiography for detecting radiation-induced changes in the lung, regional alterations within (irradiated region) and outside (shielded region) the treatment ports, effect of irradiated lung volume, and dependence on time after radiotherapy. METHODS: Serial DTPA lung clearance studies were performed before the first radiation treatment (baseline), then weekly during a 5- to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The total activity deposited in the lungs for each study was approximately 150 microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the biological half-time, t 1/2, was computed from the slopes of the least-squares fit regression lines of the time-activity curves for the first 10 min for irradiated and shielded lung regions. RESULTS: Major findings include: (a) significant and early DTPA t 1/2 changes were observed in all patients during and after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both irradiated and shielded lung regions in all patients suggesting a radiation-induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p < 0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2 values were observed in three patients who subsequently presented with clinical symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2 felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining patients [p < 0.01]); (e) the onset of decreased DTPA t 1/2 values in these three patients occurred 35-84 days before clinical symptoms and/or radiographic changes; and (f) DTPA t 1/2 tended to approach baseline values with time after radiotherapy, suggesting a long-term recovery in lung injury. CONCLUSION: These observations show significant and early alterations in DTPA lung clearance during and after radiotherapy that may provide a sensitive assay to monitor changes in radiation-induced lung injury and may facilitate early therapeutic intervention.

Boron neutron capture therapy: re-irradiation response of the rat spinal cord.

PURPOSE: To evaluate the retreatment response of the CNS to BNC irradiation using a rat spinal cord model. MATERIALS AND METHODS: Fischer 344 rats were irradiated with single doses of 6 MeV X-rays which were 22, 40 or 80% of a total effect (TE). An additional group of rats was irradiated with a single exposure of thermal neutrons in the presence of the neutron capture agent boronophenylalanine (BPA) to a dose that represented 82% of the TE. After an interval of 26 weeks, animals were re-irradiated using various single doses of thermal neutrons in combination with BPA. RESULTS: The re-irradiation ED50 doses represented 77, 80 or 50% of the TE after an initial X-ray dose of 22, 40 or 80% of the TE, respectively. The re-irradiation ED50 dose was 55% of the TE after an initial BNC irradiation dose representing 82% of the TE. CONCLUSION: The level of the initial radiation damage had a direct bearing on the re-irradiation response. Recovery following initial treatment with BNC irradiation was similar to that after initial irradiation with X-rays.

Analysis of 5-iodo-2'-deoxyuridine incorporation in murine melanoma for photon activation therapy.

Quantitative evaluation of the dose enhancement obtained with analog nucleoside agents such as iododeoxyuridine (IdUrd) requires knowledge of the degree to which the thymidine (Thd) in DNA is replaced by IdUrd. In the present investigation, mice were infused with IdUrd using an intravenous infusion apparatus capable of delivering continuous multi-day infusions without restraining the mice. The absolute incorporation of IdUrd in DNA was measured by 125IdUrd label, both in whole tissue and extracted DNA, showing a good correlation between levels observed in DNA and whole tissue. Replacement in a Harding-Passey murine melanoma tumor carried in BALB/c mice approached 10%. In addition, a Neutron Activation Analysis (NAA) technique was developed which showed in vitro, a sensitivity sufficient to evaluate the % replacement of Thd by IdUrd in small biological samples with a sensitivity greater than 0.1 ppm, at 1% replacement in mg samples. This method can provide information on iodine substitution in DNA in humans where the use of a radioactive DNA-seeking substance would be undesirable. Analyses of IdUrd incorporation in cultured cells by NAA and 125I counting showed good agreement.

Sequential measurements of bone lead content by L X-ray fluorescence in CaNa2EDTA-treated lead-toxic children.

With the development of L X-ray fluorescence (LXRF) to measure cortical bone lead directly, safely, rapidly, and noninvasively, the present study was undertaken to a) evaluate LXRF as a possible replacement for the CaNa2EDTA test; b) quantify lead in tibial cortical bones of mildly to moderately lead-toxic children before treatment; and c) quantify lead in tibial cortical bones of lead-toxic children sequentially following one to two courses of chelation therapy. The clinical research design was based upon a longitudinal assessment of 59 untreated lead-toxic children. At enrollment, if the blood lead (PbB) was 25 to 55 micrograms/dL and the erythrocyte protoporphyrin (EP) concentration was greater than or equal to 35 micrograms/dL, LXRF measurement of tibial bone lead was carried out. One day later, each child underwent a CaNa2EDTA provocative test. If this test was positive, lead-toxic children were admitted to the hospital for 5 days of CaNa2EDTA therapy. These tests were repeated 6 weeks and 6 months after enrollment. Abatement of lead paint hazards was achieved in most apartments by the time of initial hospital discharge. The LXRF instrument consists of a low energy X-ray generator with a silver anode, a lithium-doped silicon detector, a polarizer of incident photons, and a multichannel X-ray analyzer. Partially polarized photons are directed at the subcutaneous, medial mid-tibial cortical bone. The LXRF spectrum, measured 90 degrees from the incident beam, reveals a peak in the 10.5 KeV region, which represents the lead L alpha line.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential measurements of bone lead content by L X-ray fluorescence in CaNa2EDTA-treated lead-toxic children.

With the development of L X-ray fluorescence (LXRF) to measure cortical bone lead directly, safely, rapidly, and noninvasively, the present study was undertaken to a) evaluate LXRF as a possible replacement for the CaNa2EDTA test; b) quantify lead in tibial cortical bones of mildly to moderately lead-toxic children before treatment; and c) quantify lead in tibial cortical bones of lead-toxic children sequentially following one to two courses of chelation therapy. The clinical research design was based upon a longitudinal assessment of 59 untreated lead-toxic children. At enrollment, if the blood lead (PbB) was 25 to 55 micrograms/dL and the erythrocyte protoporphyrin (EP) concentration was greater than or equal to 35 micrograms/dL, LXRF measurement of tibial bone lead was carried out. One day later, each child underwent a CaNa2EDTA provocative test. If this test was positive, lead-toxic children were admitted to the hospital for 5 days of CaNa2EDTA therapy. These tests were repeated 6 weeks and 6 months after enrollment. Abatement of lead paint hazards was achieved in most apartments by the time of initial hospital discharge. The LXRF instrument consists of a low energy X-ray generator with a silver anode, a lithium-doped silicon detector, a polarizer of incident photons, and a multichannel X-ray analyzer. Partially polarized photons are directed at the subcutaneous, medial mid-tibial cortical bone. The LXRF spectrum, measured 90 degrees from the incident beam, reveals a peak in the 10.5 KeV region, which represents the lead L alpha line.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of dose and radiation quality on the shape and power saturation of the EPR signal in alanine.

Variations in the shape and the power saturation of EPR spectra of L-alanine irradiated with photons, electrons, neutrons and protons are reported. It is shown that the ratio of the intensities of the satellite lines attributable to "spin flips" and the central line depend on the EPR microwave power, and it is proposed as a quantitative measure of the signal saturation effect. Dependence of this ratio on the microwave power is affected by the radiation quality and for doses in excess of 10 kGy by the absorbed dose. At high doses of low-LET radiation these changes are attributed to a high local density of free radicals, while for low doses of high-LET radiation these are due to changes induced in the crystal lattice. Consequently, the conventional peak-to-peak amplitude measurement of the EPR signal intensity is inaccurate when used for high doses and for comparison between radiations with different beam quality. The possibility to determine radiation quality from an EPR measurement is discussed.

The effects of boron on the electron paramagnetic resonance spectra of alanine irradiated with thermal neutrons.

The effects of boric acid admixture on the intensity and line structure of EPR spectra of free radicals produced in alanine by thermal neutrons are presented. The EPR signal enhancement, up to a factor of 40 depending on the boron concentration, is related to additional energy deposition in alanine crystals by the disintegration products resulting from the capture of a thermal neutron by boron, 10B(n,alpha)7Li. The changes in the shape of the EPR spectra observed by changing the microwave power are due to the differences in the microwave power saturation of the free radicals produced by a low-LET radiation and those produced by the high-LET components of the radiation after the neutron capture reaction.

The effect of high-linear energy transfer ions on the electron paramagnetic resonance signal induced in alanine.

Microcrystalline samples of L-alanine irradiated with energetic high-LET cobalt and iron ions had different EPR spectra compared to alanine samples irradiated with low-LET photons. The differences in the shapes of the EPR spectra and their dependence on the microwave power are related to the differences in the microwave power saturation of the radicals induced by the various types of ionizing radiation. The changes in the shape of the EPR spectra, which were caused by increasing microwave power, were more pronounced in samples irradiated with low-LET radiation than with high-LET particles. This effect showed a long-term stability and can be used to monitor radiation quality.

The equal effectiveness ratio: a quantitative approach to the evaluation of compounds for boron neutron capture therapy.

The resurgence of interest in boron neutron capture therapy (BNCT) as a potential treatment for glioblastomas and melanomas has resulted in a quest to identify and synthesize candidate compounds which can physiologically target the 10B atoms to tumor cells. Numerous boron-carrying compounds are now available and awaiting evaluation. Because the products of the boron neutron capture (BNC) reaction generally contribute greater than 50% of the dose in BNCT, the evaluation of the efficacy of boron compounds would be more precise if it were possible to remove, quantitatively, the dose contributed by the external reactor radiations. The purpose of this study is to report a method which does just that, i.e., leaves for precise evaluation the biological effect that is ascribable to the BNC products only. The evaluation involves a series of separately quantifiable factors, the product of which provides an overall "figure of merit" for the compound.

Gamma resonance absorption. New approach in human body composition studies.

The main stream of body elemental analysis is based on the delayed, prompt, and inelastic neutron interactions with the main elements found in the human body, and subsequent analysis of the measured delayed or prompt gamma ray spectra. This methodology traditionally was, and still is, applied for whole body analysis and requires relatively high radiation doses. A new method, based on gamma nuclear resonance absorption (GNRA), is being established at Brookhaven National Laboratory as part of its body composition program. The method is element specific with a high tomographic spatial-resolution capability, at a small fraction of the radiation dose used in the current system. The new system, with its components and capabilities, is described below.

High-energy x-ray beam characterization using photonuclear reaction.

Spectral changes in the primary photon beam of a high-energy medical electron accelerator have been monitored using photonuclear reactions. The beam across the radiation field was measured using induced activity in Teflon cylinder and copper foil samples at several off-axis angles, at different SSDs in air and in a solid water phantom. The induced activities of the positron emitters were measured using a coincidence detection system. The experimental results are in agreement with Monte Carlo calculations and Schiff's theory.

Application of the library least-squares analysis to whole-body counter spectra derived from an array of detectors.

The library least-squares method was applied to the analysis of gamma-ray spectra obtained from an array of 54 NaI(T1) detectors in a whole-body counter. The analysis of spectra which were obtained over a period of 8 yr demonstrates the applicability of the method despite inherent variations encountered in large counting systems. The elements of interest analyzed were total-body K, Ca, Na, Cl, and P. Least-squares fits obtained with library standards derived from distributed sources were better than those obtained from library standards derived from localized sources.

Semianalytical expressions for (L/rho)(air)med and P(repl) for electron beams.

The tables of the mean restricted collision mass stopping power ratios for water, polystyrene and acrylic relative to air given in the AAPM TG-21 protocol have been fitted to an expression with 20 coefficients using the depth in the phantom and the mean incident electron energy as two independent variables. Using these expressions, the calculated values agree with the tabulated values within +0.5% in 85% of the cases and within +/- 1.0% in 95% of the cases. For each of the four cylindrical chamber inner diameters, given in the protocol, the electron fluence correction Prepl has been fitted to an expression with four coefficients using the mean electron energy at depth z as an independent variable.

The energy response of agar-alanine phantom dosimeter to gamma radiation.

Calculations of the energy response of an electron paramagnetic resonance (EPR) signal induced by gamma radiation in an agar-alanine phantom dosimeter are presented. Theoretically calculated slopes of the EPR signal calibration lines are comparable with those obtained experimentally for low-(50 kVp), medium-(662 keV), and high-(15 MVp) energy photons. The sensitivity of the phantom dosimeter (EPR signal amplitude/Gray) varies less than 2% within the 150- to 20-MeV energy range. For energies above 150 keV, the influence of variations in the size of alanine crystals is negligible.

Dose enhancement in buildup region by lead, aluminum, and lucite absorbers for 15 MVp photon beam.

Changes in dose distributions in buildup region resulting from the presence of lead, aluminum, and lucite absorbers above the surface of a polystyrene phantom were evaluated. The surface dose, as a function of the absorber thickness, is presented as well as the influence of the air gap between the lead absorber and the phantom surface. It has been found that the surface dose does not depend on absorber thickness for absorbers thicker than the range of secondary electrons in the absorber material (after corrections for the attenuation of the primary beam in the absorber). Similarly, the depth dose curves in the phantom were elevated only at depths lower than the range of secondary electrons in the phantom. The applicability of the presented data in clinical radiotherapy is discussed.