Bio-distribution

Quantitative boron distribution study

Case Report 1

A biodistribution study of carboran sugar

I. Snajdr1, R. Satapathy1, NS. Hosmane1, M. Takagaki2, S. Masunaga3

1Dept Chem & Biochem, Northern Illinois Univ

2Louis Pasteur Center for Medical Research

3Research Reactor Institute, Kyoto University

Carboran sugar (carboranyl-thio-d-glucoses :TDG) has been chemically modified via novel approach and reduction of its IC50has been achieved to be verylow 5.3x10E-2M, that is almost half of that of BSH (2.75x10E-2M).

Inthis study, biodistribution of TDG has been preliminary investigated via a-autoradiography. C6 tumor cells were inplanted via stereotactic maneubers in to Wister’s rat brain. 100mg TDG/kg body weight was injected into peritoneal space. 3hs after injection, whole brain was removed and rapidly frozen in liquid nitrogen. Frozen sections were mounted onto the solid state track detectors: Kodak LR 115 and were exposed by thermal neutrons. The detector were then etched in 10% NaOH solution at 60℃to emerge a- and/or recoil 7Li particles tracks of B-10(n,alpha)Li-7 that could be numerically evaluated via an ordinary light microscop.

Figure 1 showed the alpha particle track autoradiography of TDG in a rat C6 brain tumor.

Alpha-track autoradiography of B-com biodistribution.

The biodistribution of TDG was very similar with that of BSH. Perhaps TDG distribute in the brain via non-permeable fashion of blood brain barrier, but blood tumor barrier.

Although our preliminary in vitro-BNCT of TDG showed the surviving fraction of TDG was smaller than that of BPA (ibid), but its tumor cell killing effect is still low for clinical purpose as BPA. Perhaps TDG has a both charactors of BSH and BP. Further modification of TDG will be required.

Snajdr, I.et al. 2013 European J. Chemistry (ibid)

Case Report 2

Precise determination of boron location in tissue via e-tracks

M. Takagaki, NS. Hosmane*and S. Masunaga**

Louis Pasteur Center for Medical Research

*Dept Chem & Biochem, Northern Illinois Univ

**Research Reactor Institute, Kyoto University

In this report our basic research for e-track are presented instead of paucity of annual progressive results for BNCT agents. For bio-distribution study of boron atom in tissue section, alpha particle track using solid state track detector (SSTD) have been investigated. We present one of how to determine micro-distribution of boron in ultra thin section using electron microscopic alpha particle track (e-track).

Experiment 1: Ultra thin SSTD was prepared using formval membrane method using cellulose nitrate solution. After aray bombardment by Rad+E isotope, the SSTD was etched in 1N NaOH solution at RT. Various shapes of etched tracks were observed via electron microscope (Fig.1).

Fig. 1 Electron microscopic views of shell shaped e-tracks.

E-tracks strongly geometrically related to the incident angle and direction of e-tracks (Fig.2).

Fig. 2 Relation ship between particle incidence of e-tracks.

Experiment 2: Ultra thin resin containing 1000ppm B-10 was mounted on the SSTD and was bombarded with thermal neutron to produce aand/or recoil Li-7 particles in the resin. The free surface of the SSTD has been etched and e-tracks are shown in Figure 3.

Fig. 3 Electron microscopic views of semi-shell form e-tracks (arrow head).

Geometric relationship between the shape of e-track and the boron location in tissue is shown in Figure 4.

Fig. 4 Relation ship between boron location and e-track.

In conclusion, in our experimental condition using ultra thin SSTD in the thickness of ca. 100nm, the possible location of boron atom in tissue can be determined with an accuracy of ca. 100nm.