Boron neutron capture therapy of a murine mammary carcinoma using a lipophilic carboranyltetraphenylporphyrin.
The first control of a malignant tumor in vivo by porphyrin- mediated boron neutron capture therapy (BNCT) is described. In mice bearing implanted EMT-6 mammary carcinomas, boron uptake using a single injection of either p-boronophenylalanine (BPA) or mercaptoundecahydrododecaborane (BSH) was compared with either a single injection or multiple injections of the carboranylporphyrin CuTCPH. The BSH and BPA doses used were comparable to the highest doses of these compounds previously administered in a single injection to rodents. For BNCT, boron concentrations averaged 85 microg (10)B/g in the tumor and 4 microg (10)B/g in blood 2 days after the last of six injections (over 32 h) that delivered a total of 190 microg CuTCPH/g body weight. During a single 15, 20, 25 or 30 MW-min exposure to the thermalized neutron beam of the Brookhaven Medical Research Reactor, a tumor received average absorbed doses of approximately 39, 52, 66 or 79 Gy, respectively. A long-term (>200 days) tumor control rate of 71% was achieved at a dose of 66 Gy with minimal damage to the leg. Equivalent long-term tumor control by a single exposure to 42 Gy X rays was achieved, but with greater damage to the irradiated leg.
Miura
M
M
Medical Department, Building 490, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Morris
G M
GM
Micca
P L
PL
Lombardo
D T
DT
Youngs
K M
KM
Kalef-Ezra
J A
JA
Hoch
D A
DA
Slatkin
D N
DN
Ma
R
R
Coderre
J A
JA
D000818:Animals; D001894:Borohydrides / Q000493:pharmacokinetics; D001895:Boron / Q000032:analysis / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy; D004337:Drug Carriers; D005260:Female; D006614:Hindlimb; D057927:Hydrophobic and Hydrophilic Interactions; D007274:Injections, Intraperitoneal; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics; D013909:Thorax; D014018:Tissue Distribution
D001894:Borohydrides; D001896:Boron Compounds; D004337:Drug Carriers; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine; D001895:Boron; C033685:4-boronophenylalanine