Toxicity, biodistribution, and convection-enhanced delivery of the boronated porphyrin BOPP in the 9L intracerebral rat glioma model.
OBJECTIVE
To investigate the toxicity, biodistribution, and convection-enhanced delivery (CED) of a boronated porphyrin (BOPP) that was designed for boron neutron capture therapy and photodynamic therapy.


METHODS
For the toxicity study, Fischer 344 rats were injected with graded concentrations of BOPP (35-100 mg/kg) into the tail vein. For boron biodistribution studies, 9L tumor-bearing rats received BOPP either systematically (intravenously) or locally.


RESULTS
All rats that received 70 mg/kg BOPP and 70% of rats that received < or = 60 mg/kg BOPP i.v. either had to be euthanized or died within 4 days of injection. In the biodistribution study, boron levels were relatively high in liver, kidney, spleen, and adrenal gland tissue, and moderate levels were found in all other organs. The maximum tumor boron concentration was 21.4 mug/g at 48 h after i.v. injection; this concentration of boron in brain tumors is at the low end of the range considered optimal for therapy. In addition, the tumor/blood ratio (approximately 1.2) was not optimal. When BOPP was delivered directly into intracerebral 9L tumors with CED, we obtained tumor boron concentrations much greater than those obtained by i.v. injection. Convection-enhanced delivery of 1.5 mg BOPP produced an average tumor boron level of 519 mug/g and a tumor/blood ratio of approximately 1850:1.


CONCLUSIONS
Our study demonstrates that changing the method of BOPP delivery from i.v. to CED significantly enhances the boron concentration in tumors and produces very favorable tumor/brain and tumor/blood ratios.
Ozawa
Tomoko
T
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143-0446, USA.
Afzal
Javed
J
Lamborn
Kathleen R
KR
Bollen
Andrew W
AW
Bauer
William F
WF
Koo
Myoung-Seo
MS
Kahl
Stephen B
SB
Deen
Dennis F
DF
D000818:Animals; D001895:Boron / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy; D045744:Cell Line, Tumor; D003905:Deuteroporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D015918:Infusion Pumps, Implantable; D007273:Injections, Intramuscular; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D000098851:Carboranes
D001895:Boron; D001896:Boron Compounds; D003905:Deuteroporphyrins; C080251:2,4-(alpha,beta-dihydroxyethyl)deuteroporphyrin IX tetrakiscarborane carboxylate ester; D000098851:Carboranes