Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells

Abstract

were determined from tumors that were not pretreated with BrdU. Without TPZ or MTH, BPA-ol increased both frequencies most markedly, especially for total cells. However, as with BPA, the sensitivity difference between total and Q cells was much larger than with BSH. On combined treatment with both MTH and TPZ, this sensitivity difference was markedly reduced, similarly to when BPA was used. MTH increased the 10 B uptake of all 10 B-compounds into both tumor cells. BPA-ol has good potential as a 10 B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ.

Boron Neutron Capture Therapy

“…Examples include various derivatives of BPA and other boron-containing amino acids (e.g., glycine, alanine, aspartic acid, tyrosine, cysteine, methionine), as well as non-naturally occurring amino acids (45)(46)(47)(48)(49)(50). The most recently reported delivery agents contain one or more boron clusters and concomitantly larger amounts of boron by weight compared with BPA.…”

An attempt to improve the therapeutic effect of boron neutron capture therapy using commonly employed 10B-carriers based on analytical studies on the correlation among quiescent tumor cell characteristics, tumor heterogeneity and cancer stemness

“…Concerning newly-developed 10 B-carriers, therapeutic effects of α-amino alcohol para-boronophenylalaninol [ 40 ] and its enantiomers [ 41 ], 2-nitroimidazole- 10 B-carriers [ 42 ], hypoxia-oriented bioreductive agent-BSH hybrid compounds [ 43 , 44 ], transferrin-pendant-type polyethyleneglycol liposomes encapsulating 10 B-decahydrodecaborate (GB-10) or BSH [ 45 ], and a novel 10 B-carrier conjugated with a cyclic RGD (arginine-glycine-aspartic acid) peptide [ 46 ] were analyzed and examined on both total and Q tumor cell populations. Incidentally, the cyclic RGD peptide specifically binds to αvβ3 integrin, which is known to be overexpressed on activated endothelial cells of growing vessels and also on melanoma, glioma, lung, ovarian and breast cancer cells [ 47 ].…”

“…Since p53 status is reported to be often mutated in malignant tumors, a relatively even distribution of 10 B in tumors with mutant-type rather than wild-type normal tissue can be expected, leading to the usefulness of BNCT in the treatment of malignant tumors [ 63 ]. Actually, it was shown that in BNCT the combination of both continuous TPZ administration and MTH at the time of administration of these 10 B-carriers can more effectively enhance the control of the local tumor as a whole, including the control of Q tumor cells, than any other combination treatment design [ 40 , 41 ].…”

Synthesis of boronated phenylalanine analogues with a quaternary center for boron neutron capture therapy

“…Consequently, the synthesis of BPA analogues, including boronated natural and unnatural amino acids and amino alcohols, is the subject of active research. [15][16][17][18][19][20][21] Recently, it was shown that amino acids, such as 1-aminocycloalkanoic acids, cross the blood brain barrier and localize in Glioblastoma Multiforme and metastatic malignant melanoma more avidly than BPA. 22 This observation prompted a search for BPA analogues and other boronic acids containing 1-aminocycloalkanecarboxylic acid moiety.…”