ISSN:
1432-1335
Schlagwort(e):
Boron neutron-capture therapy (BNCT)
;
Anti-AFP monoclonal antibody
;
Boron-10
;
Prompt-γ-ray spectrometry
;
Thermal neutron
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract We described previously that10B atoms delivered by monoclonal antibody (mAb) exerted a cytotoxic effect on AH66 cells in a dose-dependent manner upon thermal neutron irradiationin vitro. In the present study, the delivering capacity of boronated anti-(α-fetoprotein) (AFP) mAb to carry10B atoms to AFP-producing tumor xenografts in nude mice was determined. Boronated mAb was prepared by conjugating 50 mM 10B compound to an anti-AFP mAb (2 mg/ml) usingN-succinimidyl-3-) (2-pyridyldithio) propionate. The number of10B atoms conjugated directly to the mAb was estimated to be 459/antibody by prompt γ-ray spectrometry. Boron concentrations in tumor tissue obtained 12, 24, 72, and 120 h after injection of 3.0 mg10B-conjugated anti-AFP mAb were 11.10±3.12 (SD,n=6), 29.30±5.11, 33.02±11.8, and 12.91±5.62 ppm respectively. For control10B-conjugated anti-dinitrophenol (DNP) mAb, the values were 9.59±0.99, 10.37±2.86, 10.00±2.95, and 8.83±4.71 ppm respectively. The concentrations in blood were less than 0.40±0.10 ppm with anti-AFP mAb and less than 0.51±0.15 ppm with anti-DNP mAb at each sampling time (12, 24, 72, and 120 h). The number of10B atoms delivered to the tumor cells was calculated to be 0.62×109, 1.63×109, 1.84×109 and 0.72×109 at each sampling time after injection of10B-anti-AFP mAb. The amount of10B atoms necessary for effective boron neutron-capture therapy was estimated to be 109/tumor cell. We were able to carry 1.84×109 10B atoms to AH66 tumor cells by using10B-anti-AFP mAb. The accumulation reached its peak 72 h after injection. These data indicated that the10B-conjugated antitumor mAb could deliver a sufficient amount of10B atoms to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal neutron irradiation.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF01245373
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