A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model.
Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain. The animals were infused intravenously with either BSH (25 micrograms or 175 micrograms of boron per gram of body weight) or BOPP (12 micrograms of boron per gram body weight). For the low dose of BSH, the maximum tumor-boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor-boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci.
Ceberg
C P
CP
Department of Radiation Physics, Lund University Hospital, Sweden.
Brun
A
A
Kahl
S B
SB
Koo
M S
MS
Persson
B R
BR
Salford
L G
LG
D000818:Animals; D001825:Body Fluid Compartments; D001894:Borohydrides / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002421:Caudate Nucleus; D003905:Deuteroporphyrins / Q000493:pharmacokinetics*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006207:Half-Life; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009336:Necrosis; D051381:Rats; D011916:Rats, Inbred F344; D012044:Regression Analysis; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D000098851:Carboranes
D001894:Borohydrides; D001896:Boron Compounds; D003905:Deuteroporphyrins; D013438:Sulfhydryl Compounds; C080251:2,4-(alpha,beta-dihydroxyethyl)deuteroporphyrin IX tetrakiscarborane carboxylate ester; D000098851:Carboranes; C014651:mercaptoundecahydrododecaborate