Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: an experimental study that supports a potential new application of BNCT.
We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.
Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires, Argentina.
A
A
Monti Hughes
E M
EM
Heber
E
E
Pozzi
D W
DW
Nigg
O
O
Calzetta
H
H
Blaumann
J
J
Longhino
S I
SI
Nievas
R F
RF
Aromando
M E
ME
Itoiz
V A
VA
Trivillin
A E
AE
Schwint
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D001894:Borohydrides / Q000493:pharmacokinetics / Q000627:therapeutic use; D001896:Boron Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D006224:Cricetinae; D009062:Mouth Neoplasms / Q000532:radiotherapy; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D016609:Neoplasms, Second Primary / Q000532:radiotherapy; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
D001894:Borohydrides; D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine; D015127:9,10-Dimethyl-1,2-benzanthracene; C033685:4-boronophenylalanine