Homogeneous boron targeting of heterogeneous tumors for boron neutron capture therapy (BNCT): chemical analyses in the hamster cheek pouch oral cancer model.
OBJECTIVE
BNCT is a tumour cell targeted radiation therapy. Uniform targeting of heterogeneous tumours with therapeutically effective boron carriers would contribute to a therapeutic effect on all tumour cell populations and avoid radioresistant fractions. This remains an unresolved challenge. The aim of the present study was to evaluate the degree of variation in boron content delivered by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and the combined administration of (BPA+GB-10) in different portions of tumour, precancerous tissue around tumour and normal pouch tissue in the hamster cheek pouch oral cancer model.


METHODS
Samples of different areas of tumour, precancerous tissue and normal pouch tissue were taken from tumour-bearing hamsters, 3h post-administration of i.p. BPA (15.5mg B/kg b.w.), or i.v. GB-10 (50mg B/kg b.w.), or 3h and 1.5h post-administration respectively of i.v. GB-10 (34.5mg B/b.w.) and sequential i.p. injections of BPA (total dose 31mg B/kg b.w.) given jointly. Boron content was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The degree of homogeneity in boron targeting was assessed in terms of the coefficient of variation (V: [S.D./mean]x100) of boron values. Statistical analysis of the results was performed by one-way ANOVA and the least significant difference test.


RESULTS
GB-10 and GB-10 plus BPA achieved respectively a statistically significant 1.8- and 3.3-fold increase in targeting homogeneity over BPA.


CONCLUSIONS
The combined boron compound administration protocol contributes to homogeneous targeting of heterogeneous tumours and would be expected to increase therapeutic efficacy of BNCT.
Heber
Elisa M
EM
Department of Radiobiology, National Atomic Energy Commission, Av. General Paz 1499, B1650KNA San Martin, Prov. Buenos Aires, Argentina.
Trivillin
Verónica A
VA
Nigg
David W
DW
Itoiz
Maria E
ME
Gonzalez
Beatriz N
BN
Rebagliati
Raúl J
RJ
Batistoni
Daniel
D
Kreimann
Erica L
EL
Schwint
Amanda E
AE
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001894:Borohydrides / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002610:Cheek; D006224:Cricetinae; D004195:Disease Models, Animal; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000532:radiotherapy; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000532:radiotherapy
C436045:4-dihydroxyborylphenylalanine; D001894:Borohydrides; D001896:Boron Compounds; D010649:Phenylalanine; D015127:9,10-Dimethyl-1,2-benzanthracene