Effects of employing a ¹⁰B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy.

Abstract

OBJECTIVES:

To evaluate the effects of employing a (10)B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells.

METHODS:

B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a (10)B-carrier [L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation.

RESULTS:

BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a (10)B-carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT.

CONCLUSION:

BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases.

• Authors: S Masunaga, Y Sakurai, H Tanaka, M Suzuki, Y Liu, N Kondo, A Maruhashi, Y Kinashi, K Ono
• Journal: The British journal of radiology (Br J Radiol) Vol. 85 Issue 1011 Pg. 249-58 (Mar 2012) ISSN: 1748-880X [Electronic] England
• PMID: 22391496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Borohydrides
• Radiation-Sensitizing Agents
• Sulfhydryl Compounds
• Vitamin B Complex
• mercaptoundecahydrododecaborate
• Niacinamide
• Bromodeoxyuridine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Borohydrides (pharmacology)
• Boron Neutron Capture Therapy (methods)
• Bromodeoxyuridine
• Cell Hypoxia (drug effects)
• Female
• Hyperthermia, Induced (methods)
• Lung Neoplasms (prevention & control, secondary)
• Melanoma, Experimental (pathology, radiotherapy)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Niacinamide (pharmacology)
• Radiation-Sensitizing Agents (pharmacology)
• Skin Neoplasms (radiotherapy)
• Sulfhydryl Compounds (pharmacology)
• Vitamin B Complex (pharmacology)