Kenneth Shelly

Frontiers in neutron capture therapy

Frontiers in Neutron Capture Therapy Contents of Volume I: Medicine and Physics. Preface. In Memoriam. Acknowledgments. Introductory Overviews. Clinical Experiences. Treatment Planning and Clinical Considerations. Reactor Neutron Sources and Facilities. Accelerators and Other Neutron Sources. Dosimetry. Fast Neutron Studies. Author Index, Vol. I. Keyword Index, Vol. I. Frontiers in Neutron Capture Therapy Contents of Volume II: Chemistry and Radiobiology. Chemistry and Synthesis. Imaging and Analysis of Nuclides. Pharmacology and Compound Evaluation. Tissue Targeting. Preclinical Dosimetry. Preclinical Radiobiology. Future Directions and Emerging Applications. Author Index, Vol. II. Keyword Index, Vol. II. List of Symposium Participants.

Liposomes as drug delivery vehicles for boron agents.

The successful treatment of cancer by boron neutroncapture therapy (BNCT) requires the selective concentration ofboron-10 within malignant tumors. The potential of liposomesto deliver boron-rich compounds to tumors has beenassessed by examination of the biodistribution of borondelivered by liposomes in tumor-bearing mice. Small unilamellarvesicles have been found to stably encapsulate highconcentrations of water-soluble ionic boron compounds. Alternatively, lipophilicboron-containing species have been embedded within the phospholipidbilayer of liposomes, and both hydrophilic and lipophilicboron compounds have been incorporated within the sameliposome formulation.The biodistribution of boron was determined at severaltime points over 48 hr after i.v. injection ofliposomal suspensions in BALB/c mice bearing EMT6 tumors.The tumor-selective delivery of boron by the liposomeswas demonstrated as tumor-boron concentrations increased for severalhours post-injection. Even at the low injected dosesemployed (6–18 mg boron/kg body weight) therapeutic tumor boronconcentrations were observed (>30 μg boron/g tissue) andhigh tumor/blood ratios were achieved (>5). The mostfavorable results were obtained with the polyhedral boraneNa3[a2-B20H17NH2CH2CH2NH2]. Liposomes encapsulating this species produced a tumorboron concentration of 45 μg/g tissue at 30hr post-injection,at which time the tumor/blood boron ratio was9.3.

Susceptibility and Mössbauer study of an antiferromagnetically coupled admixed‐intermediate spin state in Fe(TPP) (FSbF5)⋅C6H5F

Magnetic properties of the synthetic hexafluoroantimonate complex of iron (III) tetraphenylporphyrin, Fe(TPP) (FSbF5)⋅C6H5F, were studied by susceptibility and Mossbauer techniques. The measured effective magnetic moment varies from 1.7 β at 1.5 K to 4.14 β at 300 K. The data were analyzed with the ‘‘Maltempo model’’ combined with a mean field antiferromagnetic treatment. This analysis shows that the system is predominantly in the S=3/2 spin state (98%) with an unusually small spin–orbit coupling constant ζ=79 cm−1. The net interaction of a given spin with the thermal average of all the spins is (1.39 cm−1)S⋅〈S〉T. Mossbauer spectra were recorded from 4.2 to 64 K in fields 0 to 6 T. The chemical shift δ=0.39 (Fe) mm/s and quadrupole splitting ΔE=4.29 mm/s are temperature independent and typical of ferric ions in the admixed–intermediate spin state. Mossbauer analysis confirms that the exchange interaction must couple many spins rather than forming spin pairs as seen in earlier work. The analysis also provi...

A New Isomer of the [B20H18]2− Ion: Synthesis, Structure, and Reactivity ofcis-[B20H18]2− andcis-[B20H17NH3]−

New connections for old borane cages: Oxidation of suitable precursors in which two decaborate cages are linked in an apical–equatorial fashion provides the borane ions 1 and 2. The two nonequivalent cage fragments are cis-linked, in contrast to the trans-[B20H18]2− ion that has been known for over 30 years. Reductive substitution of 1 and 2 leads to new apical–apical linked anions and disubstituted [B20H18] anions. •=B, ○=BH.

Formation of a Novel Amidinium‐Bridged Polyhedral Borane Ion by Incorporation of an Acetonitrile Solvent Molecule

Acetonitrile acts as more than a solvent in the oxidation of the ammonioborate [B20H17NH3]3− with benzoquinone. The unusual product 1 contains an amidinium group that bridges both decaborate cages. Further oxidation yields 2, in which the unusually short C−N bond lengths indicate considerable double-bond character. •=B, ○=BH.

Recent Results with Liposomes as Boron Delivery Vehicles for Boron Neutron Capture Therapy

The slow evolution of effective drug-targeting methodologies for the selective delivery of boron to cancer cells persists as an important obstacle to the development of boron neutron capture therapy.1 Simple boron compounds offer the convenience of availability and ease of synthesis but often exhibit low selectivity and require large injected doses in order to produce the required boron concentrations in tumor. The development of new boron compounds with natural tumor selectivity is problematic. The conjugation of boron-rich moieties to existing tumor-selective substrates often leads to problems with loss of tumor specificity, water solubility, and toxicity.

Liposomal Delivery of Boron for BNCT

The development of effective targeting strategies for the selective transport of boron to cancer cells has been the single most urgent problem in the area of BNCT. Successful therapy requires the site-specific delivery of relatively large amounts of boron to tumors. Strategies employed have included the use of boron compounds with some natural affinity for tumors such as 4-(dihydroxyboryl)phenylalanine (BPA)1 or B12H11SH2- ,2 the attachment of boron species to other molecules such as porphyrins,3and the conjugation of boron compounds with tumor-specific monoclonal antibodies.4 In any targeting strategy, the primary difficulties are delivering therapeutic quantities of boron, lack of specifiCity, and loss of specifiCity after incorporating useful amounts of boron in the targeting agent.

The versatile chemistry of the [B20H18]2- ions: novel reactions and structural motifs.

Among the polyhedral [closo-BnHn]2- ion series (n = 5-12 inclusive) the aromatic [closo-B10H10]2- ion is both readily available and quite reactive. Among its many reactions which retain its cage structure one finds the oxidative dimerization reaction in which two [closo-B10H12]2- ions each formally lose a hydride ion and undergo dimerization of the resulting [closo-B10H9]- ions to produce the [trans-B20H18]2- ion. The two-component [closo-B10H9]- ions of the latter are linked together by a pair of unique B-B-B bonds which provide unprecedented reactivity to the structure. Among these reactions are the two-electron reduction to a set of three interconvertible [B20H18]4- ions having intercage B-B bonds and the related reductive substitution reaction in which [trans-B20H18]2- undergoes attack by nucleophile, L, to produce [B20H18L]2-. The latter species is formally a substituted [B20H19]3- (L = H) ion formed by B-B bond protonation of one of the isomeric [B20H18]4- ions. These and a variety of novel reactions are described here along with interrelated reaction mechanisms considered for the first time.

In Vivo and in Vitro Uptake of Boronated Compounds by B16-BL6 Murine Melanoma

A crucial requirement for effective boron neutron capture therapy (BNCT) of cancer is the selective localization of high concentrations of boron in tumor tissue relative to adjacent normal tissue, thus minimizing damage to normal tissues caused by the neutron beam. Several promising boron compounds are presently available as boron-delivery agents for neutron capture therapy of malignant melanoma. More are expected to be developed in the near future. Therefore, there is a need to experimentally describe these boron-delivery compounds in vitro and in vivo, to screen these agents by critically comparing their efficacies with known boronated agents, and to effectively optimize their BNCT potential.

EIN NEUARTIGES AMIDINIUM-VERBRUCKTES POLYEDRISCHES BORAN-ION DURCH EINBAU EINES ACETONITRILMOLEKULS DES SOLVENS

Nicht nur als Losungsmittel fungiert Acetonitril bei der Oxidation des Ammonioborats [B20H17NH3]3− mit Benzochinon. Im unerwarteten Reaktionsprodukt 1 verbruckt eine Amidiniumgruppe die beiden Decaboratkafige. Die ungewohnlich kurzen C-N-Abstande (1.319 und 1.335 A) in dem durch weitere Oxidation erhaltlichen 2 lassen betrachtliche Doppelbindungsanteile vermuten. •= B, ○ = BH.