Selective tumor uptake of a boronated porphyrin in an animal model of cerebral glioma.
The prognosis for patients with high-grade cerebral glioma is poor. Most treatment failures are due to local recurrence of tumor, indicating that a more aggressive local therapy could be beneficial. Adjuvant treatments such as porphyrin-sensitized photodynamic therapy (PDT) or boron neutron capture therapy (BNCT) have the potential to control local recurrence. The selective tumor uptake of a boronated porphyrin was studied in CBA mice bearing an implanted intracerebral glioma. Biopsy samples of tumor, normal brain, and blood were analyzed by a fluorometric assay following intraperitoneal and intravenous administration of boronated protoporphyrin (BOPP). This compound was selectively localized to tumor at ratios as high as 400:1 relative to normal brain. Confocal laser scanning microscopy of glioma cells in vitro and in vivo showed that BOPP was localized within mitochondria and excluded from the nucleus of these cells. This discrete subcellular localization was confirmed by density gradient ultracentrifugation after homogenization of mouse tumor biopsies. The selective discrete localization of these compounds within the tumor suggests that this compound may be used as a dual PDT/BNCT sensitizer.
Hill
J S
JS
Department of Surgery, University of Melbourne, Victoria, Australia.
Kahl
S B
SB
Kaye
A H
AH
Stylli
S S
SS
Koo
M S
MS
Gonzales
M F
MF
Vardaxis
N J
NJ
Johnson
C I
CI
D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D007554:Isotopes; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D010778:Photochemotherapy / Q000379:methods; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics*; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats
D001896:Boron Compounds; D007554:Isotopes; D011166:Porphyrins; D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; C073289:boron protoporphyrin