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Biomedical subjects

P L Micca

Publications and source records attributed to P L Micca.

47 records · Page 3Linked to original sources
PubMed1988

Boron neutron capture therapy of a murine melanoma.

Boron neutron capture therapy has been carried out on BALB/c mice carrying the Harding-Passey melanoma s.c. on the thigh. p-Boronophenylalanine (BPA), a boronated analogue of natural melanin precursors, was used to target boron selectively to melanoma. BPA was administered to the mice either via i.p. injection or p.o. by intubation. 10B concentrations in tumor ranged from 15 to 40 ppm depending on the route and timing of administration. Irradiations with a predominantly thermal neutron beam were performed at the Brookhaven Medical Research Reactor. In the absence of BPA, only transient tumor growth delays were observed at low neutron fluences. At 5 x 10(16) n/m2, 4 of 22 tumors irradiated in the absence of BPA underwent long-term tumor growth control; after p.o. administration of BPA (40 ppm 10B in the tumor), the fraction of tumors controlled increased to 11 of 19. The average dose to the tumor in the latter group was 17.8 Gy, of which 14.8 Gy were due to the 10B neutron capture reaction. The biological effectiveness of the absorbed dose from the neutron capture reaction, at the 50% tumor control level, was found to be twice that of 100 kVp X-rays.

Animals↗
PubMed1985

The stability of DNA in human cerebellar neurons.

Human tissues have carbon-isotope ratios (13C/12C) that reflect dietary ratios. This observation has been used to determine the extent of metabolic turnover of DNA in cells of the adult human cerebellum (90 percent of which are neuronal). If adult human neuronal DNA were metabolically stable, its 13C/12C would reflect that in the maternal diet during fetal development as nearly all neurons are formed during maturation of the fetal brain and do not undergo cell division thereafter. The 13C/12C ratios in the food chains and body tissues of Europeans differ from corresponding American ratios by about 50 parts per million on the average. Therefore, turnover was studied by comparing 13C/12C ratios in cerebellar DNA of American-born Americans, European-born Americans, and European-born Europeans. The 13C/12C ratios in cerebellar DNA from European-born Americans were closer to 13C/12C ratios in cerebellar DNA from European-born Europeans than from American-born Americans, indicating that there was little or no turnover of neuronal DNA.

Adult↗
PubMedDate not supplied

Optimization of boron and neutron delivery for neutron capture therapy.

A number of groups in the United States have received funding that will permit evaluation of the clinical efficacy of the neutron capture therapy (NCT) procedure. Various reactors are being modified to allow the construction of an epithermal neutron beam. At the Brookhaven Medical Research Reactor (BMRR), the patient irradiation facility is being modified to produce an optimized epithermal neutron beam. An 80-cm-thick A1-D2O mixture (184 g/cm2, 25% D2O by volume) is being installed in the shutter assembly. One-dimensional calculations indicate that this configuration should provide an epithermal neutron flux density of approximately 1 x 10(9) n/cm2/sec at 3 MW and a concomitant fast neutron dose rate of approximately 2 x 10(-11) rad per epithermal neutron (assuming a homogeneous A1-D2O mixture). The actual geometry will be an inhomogeneous array of D2O and A1 layers producing parameters somewhat less favorable than those listed above; experimental verification is in progress. Significant gains have recently been made in selectively targeting B to melanoma with various melanaffinic compounds, including p-boronophenylalanine, and with boronated porphyrins that may be applicable to a variety of tumors. Neutron capture radiographs have been obtained with the above compounds, and efforts have been made to quantitate boron uptake in growing and quiescent or necrotic regions of tumor via double-labeling techniques obtained with tritiated thymidine. A correlation between therapeutic efficacy and the ability to deliver boron to viable areas of tumor has been observed.

Animals↗
PubMedDate not supplied

Microanalytical techniques for boron analysis using the 10B(n,alpha)7Li reaction.

In order to predict the efficacy of boronated compounds for neutron capture therapy (NCT), it is mandatory that the boron concentration in tissues be known. Various techniques for measurement of trace amounts of boron (1-100 ppm) are available, including chemical and physical procedures. Experience has shown that, with the polyhedral boranes and carboranes in particular, the usual colorimetric and spark emission spectroscopic methods are not reliable. Although these compounds may be traced with additional radiolabels, direct physical detection of boron by nondestructive methods is clearly preferable. Boron analysis via detection of the prompt-gamma ray from the 10B(n, alpha)7Li reaction has been shown to be a reliable technique. Two prompt-gamma facilities developed at Brookhaven National Laboratory are described. One, at the 60-MW high flux beam reactor, uses sophisticated beam extraction techniques to enhance thermal neutron intensity and reduce fast neutron and gamma contamination. The other was constructed at Brookhaven's 5-MW medical research reactor and uses conventional shielding and electronics to provide an "on-line" boron analysis facility adjacent to beams designed for NCT, thus satisfying one of the requisites for clinical application of this procedure. Technical restrictions attendant upon the synthesis and testing of boronated biomolecules often require the measurement of trace amounts of boron in extremely small (mg) samples. A track-etching technique capable of detecting ng amounts of boron in mg liquid or cell samples is described. Thus it is possible to measure the boron content in small amounts (mg samples) of antibodies, or boron uptake in cells grown in tissue culture.

Biopsy, Needle↗