In vivo evaluation of the boronated porphyrin TABP-1 in U-87 MG intracerebral human glioblastoma xenografts.

Boron neutron capture therapy (BNCT) is an adjuvant therapy that has the potential to control local tumor growth. A selective delivery of sufficient amounts of boron to individual tumor cells, compared to surrounding normal tissues, is the key for successful BNCT. We have designed and synthesized a new highly water-soluble boronated porphyrin, TABP-1, as a possible BNCT agent. When we injected the maximum tolerated dose (MTD: 15 mg/kg) of TABP-1 systemically into the tail vein of athymic rats bearing intracerebral (i.c.) human glioblastoma U-87 MG xenografts, the compound accumulated preferentially in brain tumors compared to normal brain; however, the level of boron in the tumors was less than the 30 microg/g of tissue that is generally considered necessary for BNCT. We next investigated whether convection-enhanced delivery (CED) could improve the boron distribution. The compound was administered directly into i.c. tumors using an osmotic minipump attached to a brain-infusion cannula. TABP-1 doses from 0.25 to 1.0 mg infused locally over 24 h produced tumor boron concentrations greater than those obtained by systemic administration at the MTD. For example, CED administration of 0.5 mg of TABP-1 produced a tumor boron level of 65.4 microg/g of tumor, whereas the serum level was only 0.41 microg/g (tumor to serum ratio of approximately 160:1). CED also produced relatively high tumor to normal brain ratios of approximately 5:1 for ipsilateral brain and approximately 26:1 for contralateral brain tissues at the 0.5 mg dose. Thus, we may be able to achieve therapeutic BNCT efficacy with minimal systemic toxicity or radiation-induced damage to normal tissue by administering TABP-1 using CED.