Boron Contents of German Mineral and Medicinal Waters and Their Bioavailability in Drosophila melanogaster and Humans.

SCOPE: Boron is a trace element that naturally occurs in soil, making mineral and medicinal water important contributors to overall intake. Thus, in a systematic screening, the mean boron concentrations of 381 German mineral and medicinal waters are determined. METHODS AND RESULTS: Boron concentrations in mineral and medicinal waters are analyzed by inductively coupled mass spectrometry (ICP-MS). Highest boron values find in waters from the southwest of Germany. The boron content of the waters is positively correlated with the concentration of most other analyzed bulk elements, including calcium, potassium, magnesium, and sodium. Mineral waters with either low (7.9 µg L-1 ), medium (113.9 µg L-1 ), or high (2193.3 µg L-1 ) boron content are chosen for boron exposure experiments in fruit flies (Drosophila melanogaster) and humans. In flies, boron-rich mineral water significantly increases boron accumulation, with the accumulation predominantly occurring in the exoskeleton. In humans, serum boron and 24-h urinary boron excretion significantly increase only in response to the intake of boron-rich mineral water. CONCLUSION: Overall, the current data demonstrate that mineral and medicinal waters vary substantially in the content of boron and that boron-rich mineral water can be used to elevate the boron status, both in flies and humans.

Synthesis, Molecular Docking, and In Vitro Boron Neutron Capture Therapy Assay of Carboranyl Sinomenine.

In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by 1H, 13C, and 11B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.

Transcriptomic analysis of selenium accumulation in Puccinellia distans (Jacq.) Parl., a boron hyperaccumulator.

Selenium (Se) is present in a wide variety of natural and man-made materials on Earth. Plants are able to tolerate and (hyper)accumulate Se to different extents. In fact, some species can tolerate and accumulate multiple elements. Puccinellia distans (P. distans), weeping alkali grass, is known to hyperaccumulate extreme concentrations of boron and tolerate high levels of salinity, therefore, we investigated the Se accumulation and tolerance capacities of this species. In addition, P. distans' Se tolerance mechanism was studied using a transcriptomic approach. The results of this study indicated that, when grown in a hydroponic system containing 80 or 120 µM Se, P. distans shoots accumulated from 1500 to 2500-fold more Se than plants grown without the element. Thus, P. distans was discovered to be a novel Se accumulator plant. RNA sequencing results and biochemical analyses helped to shed light on the Se tolerance and accumulation mechanism of P. distans. Here, we suggest that upregulation of Se assimilation and stress response genes may be due to induction of jasmonic acid signaling. In addition, we propose that the cell wall may play an important role in restriction of Se movement to the cytoplasm. Also, we hypothesize that Se accumulates in cells by sequestration of selenate in the vacuole.

Boronic-targeted albumin-shell oily-core nanocapsules for synergistic aromatase inhibitor/herbal breast cancer therapy.

Multi-modality strategies of albumin-mediated drug accumulation in tumor, boronate-based active tumor targeting and synergistic cancer therapy were combined together for effective treatment of breast cancer. Herein we report the development of albumin-shell oily-core nanocapsules (NCs), loaded with novel combination of hydrophobic drugs, exemestane (EXE) and hesperetin (HES), for targeted breast cancer therapy. This protein-lipid nanohybrid carrier was successfully fabricated using a simple protein-coating method based on the electrostatic adsorption of negatively charged albumin shell onto the oily core containing cationic surfactant. While EXE was directly encapsulated into the oily core, HES was pre-formulated in the form of phospholipid complex before solubilization in oily phase. In addition to albumin-mediated binding to albondin and SPARC, phenylboronic acid was chemically coupled to the albumin shell to confer additional tumor targeting. The targeted nanocarrier (TNC) demonstrated enhanced internalization into MCF-7 breast cancer cells resulting in synergistic cytotoxic activity with a combination index (CI) of 0.662 and dose reduction index (DRI) of 8.22 and 1.84 for EXE and HES, respectively. In vivo, TNC displayed superior anti-cancer activity in tumor-bearing mice compared to their non-targeted counterparts and the free drug combination. A significant reduction of both tumor volume (7-folds) and Ki67 expression (3-folds) was obtained by the targeted nanocarriers compared to positive control. Overall, the boronic-targeted albumin NCs offer a promising platform for hydrophobic drug combination against cancer therapy.

Manganese tolerance in Verbascum olympicum Boiss. affecting elemental uptake and distribution: changes in nicotinic acid levels under stress conditions.

A multielemental determination methodology in conjunction with an organic acid analysis that were supplemented with other stress parameters and an ultrastructural analysis used herein to study Verbascum olympicum Boiss. (Scrophulariaceae) under Mn stress. Uptake and accumulation characteristics of B, Cu, Fe, Mn, Mo, and Zn were evaluated in 8-week-old seedlings grown in Hoagland's nutrient solution and exposed to 5 (CK), 50, and 200 µM MnSO4 for 7 days. Hydrogen peroxide levels were determined to evaluate oxidative stress, and changes in compatible substance levels (total phenolic contents, glutathione and glutathione disulfide levels) were determined to assess antioxidant defense mechanisms. The distribution of manganese on the root surface was characterized by scanning electron microscopy images and energy-dispersive X-ray spectroscopy analysis. The levels of nicotinic acid, which is involved in nicotinamide adenine dinucleotide biosynthesis, were determined in roots and leaves to assess tolerance mechanisms. V. olympicum exhibited the ability to cope with oxidative stress originating from excessive Mn, while increased Mn concentrations were observed in both roots and leaves. The translocation factor of B was the most affected among other studied elements under the experimental conditions. Total nicotinic acid levels exhibited a trend of reduction in the roots and leaves, which could be attributed to the appropriate metabolic progress associated with oxidative stress based on the nicotinamide adenine dinucleotide cycle that may reach glutathione in response to manganese stress during plant growth.

Effects of Boron Supplementation on Peripartum Dairy Cows' Health.

Although many different dietary studies on the prevention of negative energy balance related diseases are often encountered, this is the first study investigating the effects of boron supplementation on peripartum dairy cows' health in the light of an omics approach. Twenty-eight healthy cows (1 control and 3 experimental groups) were enrolled from 2 months before predicted calving until 2 months after calving. Experimental groups were assigned to receive boron at increasing doses as an oral bolus. Production parameters, biochemical profile, Nuclear Magnetic Resonance based metabolomics profile, and mRNA abundance of gluconeogenic enzymes and lipid oxidation genes were determined. Pivotal knowledge was obtained on boron distribution in the body. Production parameters and mRNA abundance of the genes were not affected by the treatments. Postpartum nonesterified fatty acids, ß-hydroxybutyrate, and triglyceride concentrations were significantly decreased in experimentals. The primary differences among groups were in lipid-soluble metabolites. There were significant differences in metabolites including postpartum valine, ß-hydroxybutyrate, polyunsaturated fatty acid and citrate, propionate, isobutyrate, choline metabolites (betaine, phosphatidylcholine, and sphingomyelin), and some types of fatty acids and cholesterol in experimentals. Boron appears to be effective in minimizing negative energy balance and improving health of postpartum dairy cows.

Boron biodistribution study in colorectal liver metastases patients in Argentina.

Ex-situ BNCT for multifocal unresectable liver metastases employing whole or partial autograft techniques requires knowledge of boron concentrations in healthy liver and metastases following perfusion and immersion in Wisconsin solution (W), the procedure employed for organ preservation during ex-situ irradiation. Measurements of boron concentration in blood, liver and metastases following an intravenous infusion of BPA-F in five colorectal liver metastases patients scheduled for surgery were performed. Tissue samples were evaluated for boron content pre and post perfusion and immersion in W. Complementary histological studies were performed. The data showed a dose-dependent BPA uptake in liver, a boron concentration ratio liver/blood close to 1 and a wide spread in the metastases/liver concentration ratios in the range 0.8-3.6, partially attributable to histological variations between samples. Based on the boron concentrations and dose considerations (liver < or =15 Gy-Eq and tumor> or =40 Gy-Eq) at the RA-3 thermal neutron facility (mean flux of about (6+/-1) x 10(9) n cm(-2)s(-1)), ex-situ treatment of liver metastases at RA-3 would be feasible.

Boron neutron capture therapy (BNCT) for the treatment of spontaneous nasal planum squamous cell carcinoma in felines.

Recently, Boron neutron capture therapy (BNCT) was successfully applied to treat experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa, with no damage to normal tissue. It was also shown that treating spontaneous nasal planum SCC in terminal feline patients with low dose BNCT is safe and feasible. In an extension of this work, the present study aimed at evaluation of the response of tumor and dose-limiting normal tissues to potentially therapeutic BNCT doses. Biodistribution studies with (10)B-boronophenylalanine (BPA enriched in (10)B) as a (10)B carrier were performed on three felines that showed advanced nasal planum SCC without any standard therapeutic option. Following the biodistribution studies, BNCT mediated by (10)BPA was done using the thermalized epithermal neutron beam at the RA-6 Nuclear Reactor. Follow-up included clinical evaluation, assessment of macroscopic tumor and normal tissue response and biopsies for histopathological analysis. The treated animals did not show any apparent radiation-induced toxicity. All three animals exhibited partial tumor control and an improvement in clinical condition. Enhanced therapeutic efficacy was associated with a high (10)B content of the tumor and a small tumor size. BNCT is therefore believed to be potentially effective in the treatment of spontaneous SCC. However, improvement in targeting (10)B into all tumor cells and delivering a sufficient dose at a greater depth are still required for the treatment of deep-seated, large tumors. Future studies are needed to evaluate the potential efficacy of the dual mode cellular (e.g. BPA-BNCT) and vascular (e.g. GB-10-BNCT) targeting protocol in a preclinical scenario, employing combinations of (10)B compounds with different properties and complementary uptake mechanisms.

Biodistribution of 10B in a rat liver tumor model following intra-arterial administration of sodium borocaptate (BSH)/degradable starch microspheres (DSM) emulsion.

We reported that intra-arterial administration of borocaptate sodium (BSH)/lipiodol emulsion provided selectively high (10)B concentrations (approximately 200 ppm 6 h after administration) in experimental liver tumors. In the present study, we investigated the pharmacokinetics of BSH following intra-arterial administration of BSH with other embolizing agent, degradable starch microspheres (DSM). The (10)B concentration in the tumor at 1 h after administration of BSH with DSM was 231 ppm. At 6 h, the (10)B concentration in the tumor in BSH with DSM group was 81.5 ppm. The (10)B concentration in the liver at 1 h after administration of BSH with DSM was 184 ppm. At 6 h, the(10)B concentration in the liver in BSH with DSM group was 78 ppm. The tumor/liver (10)B concentration ratios (T/L ratio) in the "BSH+DSM" group were significantly smaller than those in the "BSH+lipiodol" group at 1 h (1.4 vs. 3.6) and 6h (1.1 vs. 14.9). BSH/DSM-boron neutron capture therapy (BNCT) was not suitable for treatment of multiple liver tumors due to the low T/L (10)B concentration ratio. However, the high (10)B accumulation in the liver tumors following intra-arterial administration of BSH/DSM emulsion suggests that BSH/DSM-BNCT has the potential for application to malignant tumors in other sites.

Growth conditions, elemental accumulation and induced physiological changes in Chinese cabbage.

Soils contaminated with low levels of heavy metals and other trace elements are now frequently used for vegetable growing. In this situation, heavy metals and trace elements from these polluted soils may accumulate in the agricultural plants being grown in them and thereby enter the human food chain. The objectives of this study are to elucidate the effects of growth conditions, manipulated by the crop covers, on the phytoaccumulation of elements, and to investigate the conceivable influences of these conditions on the plant biochemistry. In three consecutive years of field experiments, open air (T(0)), and floating rowcover treatments (T(1): perforated polyethylene 50 micrometers; T(2): polypropylene 17 gm(-2)) were used to produce different environmental conditions for the growth of Chinese cabbage [Brassica rapa L. (Pekinensis group) cv. 'Nagaoka 50']. Five samplings (whole tops) were carried out from transplanting to harvest and measurements of B, Al, Ag, Si and Ca concentration as well as phenolics (orto-diphenols, total phenols and anthocyanins), pectic fractions, amino acids (histidine, phenylalanine and tyrosine) and polyphenol oxidase activity, were carried out in samples. The T(1) (perforated polyethylene sheet) gave greater B, Al, Ag and Si concentration and phytoextraction (in weight units) than the open-air control. These findings can help to develop new cost-effective techniques for phytoremediation as the application of plastic covers in the field. The build-up of heavy metals in those crops would make the product less suitable for human consumption.

Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial.

PURPOSE: The uptake of the boron compound Na2B12H10-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial 'Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility' (protocol 11961). METHODS AND MATERIALS: The boron concentration in blood, tumor, normal brain, dura, muscle, skin and bone was detected using inductively coupled plasma-atomic emission spectroscopy in 13 evaluable patients. In a first group of 10 patients 100 mg BSH/kg bodyweight (BW) were administered; a second group of 3 patients received 22.9 mg BSH/kg BW. The toxicity due to BSH was evaluated. RESULTS: The average boron concentration in the tumor was 19.9 +/- 9.1 ppm (1 standard deviation (SD)) in the high dose group and 9.8 +/- 3.3 ppm in the low dose group, the tumor/blood ratios were 0.6 +/- 0.2 and 0.9 +/- 0.2, respectively. The highest boron uptake has been detected in the dura, very low uptake was found in the bone, the cerebro-spinal fluid and especially in the brain (brain/blood ratio 0.2 +/- 0.02 and 0.4 +/- 0.2). No toxicity was detected except flush-like symptoms in 2 cases during a BSH infusion at a much higher speed than prescribed. CONCLUSION: BSH proved to be safe for clinical application at a dose of 100 mg BSH/kg infused and at a dose rate of 1 mg/kg/min. The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis. The boron concentration in blood seems to be a quite reliable parameter to predict the boron concentration in other tissues.

Irrigation of broccoli and canola with boron- and selenium-laden effluent.

Selenium (Se), boron (B), and salinity contamination of agricultural drainage water is potentially hazardous for water reuse strategies in central California. To demonstrate the feasibility of using plants to extract Se from drainage water, Se accumulation was determined in canola (Brassica napus L.) and broccoli (Brassica oleracea L.) irrigated with drainage effluent in the San Joaquin Valley, California. In the 2-yr field study, both crops were irrigated with a typical drainage water containing Se (150 microg L(-1)), B (5 mg L(-1)), and a sulfate dominated salinity (EC of 7 dS m(-1)). Total dry matter yields were at least 11 Mg ha(-1) for both canola and broccoli, and plant tissue Se concentrations did not exceed 7 mg kg(-1) DM for either crop. Based on the amount of soluble Se applied to crops with drainage water and the estimated amount of soluble Se remaining in soil to a depth of 90 cm at harvest, both canola and broccoli accumulated at least 40% of the estimated soluble Se lost from the soil for both years. Applied Se not accounted for in plant tissue or as soluble Se in the soil was presumably lost by biological volatilization. This study suggests that irrigating two high value crops such as canola and broccoli with Se-laden effluent helps manage Se-laden effluent requiring treatment, and also produces economically viable Se-enriched crops. Future research should focus on managing residual salt and B in the soil for sustaining long time water reuse strategies.

[Study on metabolism of preventive anti-fluorine agent on rats].

In order to study the metabolism of preventive anti-fluorine agent, 30 rats are randomly divided into high-dose, low-dose and a control groups. The high dose (400 mg/kg.d) and low dose (16 mg/kg.d) are orally administrated respectively, and the content of boron and/or zinc in urine, dung, serum, bone, liver, muscles, brain tissues is determined. The results showed that during the administration of this agent, the content of boron in urine and the content of zinc in dung increases obviously in both high-dose and low-dose groups and their discharge rate is consistent with the dose given. The content of boron and zinc in bone, liver, and zinc in serum, muscles, brain tissues increases evidently compared to that in control group but decreases rapidly after administration of the agent. The findings revealed that there is a rapid metabolism of boron and zinc in the body of rats. The highest content of the agent is observed in bones. The content ranks second in liver and muscles but no accumulative effects are observed.

Boron-lipiodol: a potential new drug for the treatment of liver tumors.

BACKGROUND: Boron neutron capture therapy (BNCT) is a form of radiation therapy and has been proposed for the treatment of some malignancies with encouraging results. However, none of them has ever been applied to liver malignancy. The purpose of this study was to evaluate the potential of boron-lipiodol (B-lipiodol) for the treatment of VX2 liver tumor via BNCT. MATERIALS AND METHODS: Twelve New Zealand rabbits were randomly separated into two groups: lipiodol and boron-lipiodol groups. The rabbits were anesthetized, a midline incision was made and the left lobe of the liver was injected with 0.1 ml of VX2 tumor cells. After the tumor reached 2-3 cm in diameter, the rabbits were anesthetized and 0.5 ml of boron-lipiodol was injected into the hepatic artery via an angiocatheter. Liver function tests and renal function tests were performed before, at 12 hours, 24 hours, 48 hours and 7 days after injection of drugs in both groups. The concentration of boron in various tissues was determined on the 7th day after injection. RESULTS: Liver function was abnormal at 12 hours after injection, and then gradually returned to normal at 7 days, indicative of acute temporary hepatic damage. As for the renal function, no significant change was noted in either group. The boron level was 49.7 ppm in tumor and 6.31 ppm in the healthy liver 7 days after injection of B-lipiodol. The ratio of boron concentrations between the tumor and the normal liver tissue was 7.87. As for blood and other organs including spleen, heart and kidney, the concentration of boron was low. In the lipiodol group, the boron concentrations in tumor and various organs were low. CONCLUSION: The high concentration of boron after intra-arterial injection of B-lipiodol can be used for neutron capture therapy. B-lipiodol has potential for the treatment of liver malignancy.

Metals, boron, and selenium in Neosho Madtom habitats in the Neosho River in Kansas, U.S.A.

In 1991 and 1992 we determined the levels of metals, arsenic, boron, and selenium in the Neosho River drainage in southeastern Kansas, the primary habitat for the threatened Neosho madtom (Noturus placidus). We evaluated concentrations in sediments, mussels (Quadrula pustulosa and Q. metanevra), and fish (Percina phoxocephala, Cyprinus carpio, and Ictiobus bubalus) from three sites on the Neosho River and one site on the Cottonwood River. We also evaluated contaminant concentrations in C. carpio composite samples collected by the Kansas Department of Health and Environment (KDHE) at two additional locations on the Neosho River in 1990-92. Sediments were contaminated by lead. Concentrations of selenium, boron, and most metals in mussels were low to normal for biota. Arsenic levels in mussels and fish suggest low-level contamination of biota. Aluminum, barium, manganese and strontium concentrations were much higher in mussels than in fish. Five fish composite samples had cadmium concentrations that indicate chronic deleterious effects on biota. Lead concentrations in six fish samples were elevated. Mercury concentrations in most large fish composites exceeded concentration for protection of animals that might consume them. We believe that reductions in cadmium, lead, and mercury contamination, in particular, would benefit aquatic life in the river.

[Effect of NPK and B supply levels on boron uptake and biological properties of different genotypic oilseed rape].

Pot experiment was conducted to study the boron absorption by oilseed rape(Brassica napus), the mechanism of its resistance to boron deficiency, and the effect of boron deficiency on its biological properties under different NPK supply levels. The results indicated that under boron deficiency, increasing NPK supply aggravated boron deficiency symptoms, which led to the decrease of leaf area and its growth rate and nitrate reductase activity(NRA) and the increase of chlorophyll(a + b) content at seedling stage, and the decrease of the number of productive branches and pods of each plant and seed yield at maturity. It was suggested that the ratio of boron concentration in youngest open leaves(YOL) to youngest mature leaves(YML) at seedling stage could be an index to judge the boron mobility in plants of different genotypic oilseed rape. Boron mobility and its utilization efficiency were one of the important nutritional mechanisms responsible for the difference in response of different genotypic oilseed rapes to boron deficiency.

Pharmacokinetics and effects after intravenous administration of high-dose boron to rat.

Boron (B) compounds have been widely used in the chemical industry, agriculture, and environmental science. The kinetics and toxicity of B were studied by analyzing several serum and urine parameters after a single intravenous injection of sodium tetraborate solution (B: 85.7 mg/kg) in Wistar male rats. Blood samples were removed at 0, 1, 2, 4, and 6 h after injection. The serum parameters studied included: B, Na, Ca, K, P, Mg, gamma-GTP, AST, ALT, BUN, Cr, CK, LDH and ALD. Plasma concentration-time profiles of B were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Urine samples were collected from the bladder following infusion. The urinary parameters that were studied included urine volume and excretion of B, Cr and NAG. Results indicated that a two-compartment model could describe the elimination of B from plasma after intravenous administration. Urine volume significantly increased. A diuretic effect of B was noted.

Boron neutron capture therapy for glioblastoma: improvement of boron biodistribution by hyaluronidase.

Boron neutron capture therapy (BNCT) represents a highly promising therapeutic alternative for the treatment of the most common malignant brain tumor, glioblastoma multiforme. Both the efficacy and safety of BNCT are greatly dependent on the pattern of 10B biodistribution. The present study investigates the influence of systemic hyaluronidase applied in combination with Na2B12H11SH (BSH), a boron carrier used in current clinical trials. The application of hyaluronidase was associated with a statistically significant improvement in the tumor/blood boron concentration ratio which suggests that hyaluronidase is capable of enhancing the therapeutic potential of BSH.

Long term effects of boron on layer bone strength and production parameters.

1. The effects of dietary boron (0, 50, 100, 200, and 400 mg/kg) on bone strength characteristics and egg production of white leghorn layers were investigated. 2. The shear fracture energy increased in the tibia and radius at 72 weeks for birds started on the 200 mg/kg supplement at 32 weeks of age. 3. The shear force, stress, and fracture energy of the tibia and radius increased for the non-egg producing birds at 72 weeks. 4. Bird body weight, food consumption, egg weight, and egg production all decreased at 400 mg/kg boron. 5. Boron concentrations in the breast, liver, thigh and bone tissue increased with increasing concentrations of supplemental boron.

Model studies directed toward the application of boron neutron capture therapy to rheumatoid arthritis: boron delivery by liposomes in rat collagen-induced arthritis.

The application of boron neutron capture therapy to rheumatoid arthritis requires the selective delivery of the boron-10 isotope to the synovitic tissue. The use of liposomes as a boron delivery method has been explored through the measurement of the time course biodistribution of boron in rats with collagen-induced arthritis (CIA). Small unilamellar vesicles were composed of a 1:1 mixture of distearoylphosphatidylcholine and cholesterol, incorporated K[nido-7-CH3(CH2)15-7,8-C2B9H11] as an addend in the lipid bilayer and encapsulated Na3[a2-B20H17NH2CH2CH2NH2] in the aqueous core. The tissue concentration of boron delivered by liposomes was determined by inductively coupled plasma-atomic emission spectroscopy after intravenous injection of liposome suspensions into Louvain rats with CIA. With the low injected doses of boron used [13-18 mg of boron per kg (body weight)], the peak boron concentration observed in arthritic synovium was 29 microg of boron per g of tissue. The highest synovium/blood boron ratio observed was 3.0, when the synovial boron concentration was 22 microg of boron per g of tissue. In an attempt to increase the synovium/blood boron ratio by lowering the blood boron concentration, a liposomal formulation characterized by a shorter blood clearance time was examined. Thus, the biodistribution of liposomes with additional K[nido-7-CH3(CH2)15-7, 8-C2B9H11] incorporated in the vesicle membrane not only demonstrated more rapid blood clearance and slightly higher synovium/blood boron ratios but also exhibited reduced boron uptake in synovial tissue. These studies with boron neutron capture therapy for CIA suggest that this form of therapy may be feasible in the treatment of rheumatoid arthritis.