World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website http://www.wjon.org

Original Article

Volume 3, Number 3, June 2012, pages 103-112

Evaluating the Usefulness of a Novel 10B-Carrier Conjugated With Cyclic RGD Peptide in Boron Neutron Capture Therapy

Figures

Figure 1.
Figure 1. Chemical structure of disodium mercaptododecaborate-10B (BSH), 1, 2-dicarba-closo-dodecaborane (o-carborane), cyclo(-Arg-Gly-Asp-D-Phe-Lys-) {c(RGDfK)} and GPU-201.
Figure 2.
Figure 2. Time course of changes in 10B concentrations in the solid tumors, brain, blood collected from heart, liver, muscle, and skin of SCC VII tumor-bearing mice after intraperitoneal administration of each 10B-carrier at a dose of 0.75 µmole/g. △: BSH, □: BSH-CD,*: GPU-201.
Figure 3.
Figure 3. Clonogenic cell survival curves after irradiation in vivo using reactor neutron beams (•, ▲, ■, *) or γ-rays (○, △, □, x) following administration of a 10B-carrier (GPU-201, BSH-CD or BSH). •, ○: without a 10B-carrier, ▲, △: with BSH, ■, □: with BSH-CD, *, x: with GPU-201. Bars represent standard errors (n = 9).
Figure 4.
Figure 4. Net micronucleus (MN) frequencies after irradiation in vivo using reactor neutron beams (•, ▲, ■, *) or γ-rays (○, △, □, x) following administration of 10B-carrier (GPU-201, BSH-CD or BSH) as a function of the physically absorbed radiation dose in total (left panel) and quiescent (Q, right panel) tumor cell populations. •, ○: without a 10B-carrier, ▲, △: with BSH, ■, □: with BSH-CD, *, x: with GPU-201. Bars represent standard errors (n = 9).
Figure 5.
Figure 5. Tumor growth curves for SCC VII tumors with (•, ▲, ■, *) or without (○, △, □, x) neutron beam irradiation following the administration of each 10B-carrier. •, ○: without a 10B-carrier, ▲, △: with BSH, ■, □: with BSH-CD, *, x: with GPU-201. Bars represent standard errors (n = 9).

Tables

Table 1. Plating Efficiencies and Micronucleus Frequencies at 0 Gy
 
No10B-carrierBSH*BSH-CD#GPU-201#
*: Sodium borocaptate-10B dissolved in physiological (0.9%) saline; #: BSH and GPU-201 dissolved in physiological (0.9%) saline containing 10% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD); **: Mean ± standard deviation (n = 9).
Plating efficiency (%)
Total cell population		70.7 ± 8.8**64.0 ± 5.014.9 ± 1.714.3 ± 1.6
Micronucleus frequency
Total cell population		0.027 ± 0.0050.034 ± 0.0040.067 ± 0.0060.070 ± 0.007
Quiescent cells0.053 ± 0.0040.057 ± 0.0050.090 ± 0.0100.100 ± 0.012

 

Table 2. The Effects* of Drugs on Each Endpoint
 
BSH#BSH-CD**GPU-201**
*:The dose of radiation required to obtain each endpoint without a drug in relation to that required to obtain each endpoint with a drug; #: Sodium borocaptate-10B dissolved in physiological (0.9%) saline; **: BSH and GPU-201 dissolved in physiological (0.9%) saline containing 10% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD); ##: Numbers in parentheses are 95% confidence limits, determined using mean values, standard deviations, and the numbers of observations on which the means and standard deviations were based.
Surviving fraction = 0.3
Total cell population
  Neutron Beams1.4 (1.3-1.5)##1.7 (1.5-1.9)2.3 (2.1-2.5)
  γ-Rays1.05 (1.0-1.1)1.15 (1.0-1.3)1.25 (1.1-1.4)
Net micronucleus frequency = 0.2
Total cell population
  Neutron Beams1.8 (1.65-1.95)2.2 (1.9-2.5)3.2 (2.9-3.5)
  γ-Rays1.05 (1.0-1.1)1.1 (1.0-1.2)1.15 (1.05-1.25)
Quiescent cells
  Neutron Beams1.5 (1.35-1.65)1.5 (1.35-1.65)3.2 (2.9-3.5)
  γ-Rays1.0 (1.0-1.1)1.05 (1.0-1.1)1.1 (1.0-1.2)

 

Table 3. Dose Ratios* for Quiescent Tumor Cells Relative to the Total Tumor Cell Population
 
No 10B-carrierBSH#BSH-CD**GPU-201**
*:The dose of radiation required to obtain each net micronucleus frequency in quiescent tumor cells in relation to that required to obtain each net micronucleus frequency in the total tumor cell population; #: Sodium borocaptate-10B dissolved in physiological (0.9%) saline; **: BSH and GPU-201 dissolved in physiological (0.9%) saline containing 10% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD); ##; Numbers in parentheses are 95% confidence limits, determined using mean values, standard deviations, and the numbers of observations on which the means and standard deviations were based.
Net micronucleus frequency = 0.2
  Neutron Beams1.25 (1.15-1.35)##1.7 (1.55-1.85)1.5 (1.4-1.6)1.25 (1.15-1.35)
  γ-Rays1.7 (1.55-1.85)1.75 (1.6-1.9)1.75 (1.6-1.9)1.7 (1.55-1.85)

 

Table 4. The Period (Days) Required for Each Tumor to Become Three Times as Large as on Day 14 After Tumor Cell Inoculation
 
No 10B-carrierBSH#BSH-CD**GPU-201**
#: Sodium borocaptate-10B dissolved in physiological (0.9%) saline; **: BSH and GPU-201 dissolved in physiological (0.9%) saline containing 10% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD); ##: Numbers in parentheses are 95% confidence limits, determined using mean values, standard deviations, and the numbers of observations on which the means and standard deviations were based.
Without irradiation11.2 (9.7-12.7)##10.3 (9.0-11.6)8.6 (7.7-9.5)11.1 (9.5-12.7)
With irradiation at 1.825 Gy13.4 (11.9-14.9)15.0 (13.5-16.5)17.0 (15.2-19.8)20.0 (18.0-22.0)