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Background: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous study identified glutamine metabolism to be critical for CRPC growth. The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) blocks both carbon and nitrogen pathways but has dose-limiting toxicity. The prodrug DRP-104 is expected to be preferentially converted to DON in tumor cells to inhibit glutamine utilization with minimal toxicity. However, CRPC cells' susceptibility to DRP-104 remains unclear., Methods: Human PCa cell lines (LNCaP, LAPC4, C4-2/MDVR, PC-3, 22RV1, NCI-H660) were treated with DRP-104, and effects on proliferation and cell death were assessed. Unbiased metabolic profiling and isotope tracing evaluated the effects of DRP-104 on glutamine pathways. Efficacy of DRP-104 in vivo was evaluated in a mouse xenograft model of neuroendocrine PCa, NCI-H660., Results: DRP-104 inhibited proliferation and induced apoptosis in CRPC cell lines. Metabolite profiling showed decreases in the tricarboxylic acid cycle and nucleotide synthesis metabolites. Glutamine isotope tracing confirmed the blockade of both carbon pathway and nitrogen pathways. DRP-104 treated CRPC cells were rescued by the addition of nucleosides. DRP-104 inhibited neuroendocrine PCa xenograft growth without detectable toxicity., Conclusions: The prodrug DRP-104 blocks glutamine carbon and nitrogen utilization, thereby inhibiting CRPC growth and inducing apoptosis. Targeting glutamine metabolism pathways with DRP-104 represents a promising therapeutic strategy for CRPC., (© 2023 Wiley Periodicals LLC.)

Objective: To evaluate the prevalence and clinical significance of nonuniform technetium ( 99m Tc) uptake among patients with Graves' disease (GD)., Design, Patients and Measurements: Patients with GD, referred between July 2005 and March 2018, had Tc 99 - uptake scans and TSH-receptor antibody (TRAb) measured before antithyroid drug (ATD) therapy. Risk of relapse after ATD cessation was monitored until June 2021 and compared between GD patients based on uptake patterns., Results: Of the 276 GD patients (mean age, 49.8 years; 84% female), 25 (9.0%) had nonuniform Tc 99 uptake. At diagnosis, individuals with nonuniform uptake were older (mean age of 61.8 vs. 48.5 years, p < .001), had lower mean thyroid hormone levels (free thyroxine: 36.3 vs. 45.4  pmol/L, p = .04 and free triiodothyronine: 10.0 vs. 17.8 pmol/L, p < .001) and median TRAb levels (4.2 vs. 6.6 U/L, p = .04) compared with those with a uniform uptake. Older age was a significant predictor for the presence of nonuniform uptake in GD patients; odds ratio (95% confidence intervals) of 1.07 (1.03 - 1.10). The risk of relapse was similar in both groups after a median (IQR) follow-up of 41 (13-74) months after ATD cessation (56.0% vs. 46.3%, respectively); hazard ratio (95% confidence intervals) of 1.74 (0.96-3.15)., Conclusions: Nonuniform radio-isotope uptake is seen in 1 in 11 patients with GD which could be misdiagnosed as toxic multinodular goitre if TRAb levels are not measured. Treatment of GD patients with nonuniform radio-isotope uptake with ATD therapy as first-line appears to be equally effective as compared with those with uniform uptake. TRAb testing should be the main diagnostic test for patients with suspected GD with radio-labelled uptake scans being reserved for those who are TRAb negative., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Boron neutron capture therapy (BNCT) is a type of radiation therapy and a new modality for cancer treatment. The radiation used in BNCT is a very low energy neutron called a "thermal neutron", and unlike other radiation, it has no effect on treating cancer on its own. However, when this neutron collides with boron-10 ( 10 B), which is a stable isotope of boron, fission occurs into a high-energy helium nucleus (α-particle) and a lithium nucleus. Moreover, the effect of this fission reaction is limited to a range of about 10 μm, which corresponds to the approximate size of one cell. Therefore, the basic principle of BNCT is "cell-selective" radiation therapy that only damages cells that have taken up 10 B present in the area irradiated with thermal neutrons. For the practical application of BNCT, it is indispensable to generate a boron drug capable of selectively accumulating 10 B in cancer cells. We have successfully developed a boron drug for BNCT targeting amino acid transporters. We have obtained manufacturing and marketing approval for the world's first boron drug for BNCT, Steboronine ® intravenous drip bag 9000 mg/300 mL (March 25, 2020), for indications of locally unresectable recurrent or advanced unresectable head and neck cancer. This uses Borofalan ( 10 B), which is 10 B introduced into l-phenylalanine, as a drug substance. This review describes the progress of drug development and future prospects of boron drugs for BNCT.

Gadolinium neutron capture therapy (GdNCT) is a form of binary radiotherapy. It utilizes nuclear reactions that occur when gadolinium-157 is irradiated with thermal neutrons, producing high-energy γ-rays and Auger electrons. Herein, we evaluate the potential of GdNCT for cancer treatment using PEGylated liposome incorporated with an FDA-approved MRI contrast agent. The clinical gadolinium complex (Gadovist®) was successfully encapsulated inside the aqueous core of PEGylated liposomes by repeated freeze and thaw cycling. At a concentration of 152 μM Gd, the Gd-liposome showed high cytotoxicity upon thermal-neutron irradiation. In animal experiments, when a CT26 tumor model was administered with Gd-liposomes (19 mg 157 Gd per kg) followed by 20-min irradiation of thermal neutron at a flux of 1.94 × 10 4  cm -2  s -1 , tumor growth was suppressed by 43%, compared to that in the control group, on the 23rd day of post-irradiation. After two-cycle GdNCT treatment at a 10-day interval, tumor growth was more efficiently retarded. On the 31st day after irradiation, the weight of the excised tumor in the GdNCT group (38 mg 157 Gd per kg per injection) was only 30% of that of the control group. These results demonstrate the potential of GdNCT using PEGylated liposomes containing MRI contrast agents in cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The shortcomings in Boron neutron capture therapy (BNCT) and Hyperthermia for killing the tumor cell desired for the synthesis of a new kind of material suitable to be first used in BNCT and later on enable the conditions for Hyperthermia to destroy the tumor cell. The desire led to the synthesis of large band gap semiconductor nano-size Boron-10 enriched crystals of hexagonal boron nitride ( 10 BNNCs). The contents of 10 BNNCs are analyzed with the help of x-ray photoelectron spectroscopy (XPS) and counter checked with Raman and XRD. The 10 B-contents in 10 BNNCs produce 7 Li and 4 He nuclei. A Part of the 7 Li and 4 He particles released in the cell is allowed to kill the tumor (via BNCT) whereas the rest produce electron-hole pairs in the semiconductor layer of 10 BNNCs suggested to work in Hyperthermia with an externally applied field., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Boron neutron capture therapy (BNCT) is a binary radiotherapy based on nuclear reactions that occur when boron-10 is irradiated with neutrons, which result in the ejection of high-energy alpha particles. Successful BNCT requires the efficient delivery of a boron-containing compound to effect high concentrations in tumor cells while minimizing uptake in normal tissues. In this study, PEGylated liposomes were employed as boron carriers to maximize delivery to tumors and minimize uptake in the reticuloendothelial system (RES). The water-soluble potassium salt of nido-7,8-carborane, nido-carborane, was chosen as the boron source due to its high boron content per molecule. Nido-carborane was encapsulated in the aqueous cores of PEGylated liposomes by hydrating thin lipid films. Repeated freezing and thawing increased nido-carborane loading by up to 47.5 ± 3.1%. The average hydrodynamic diameter of the prepared boronated liposomes was determined to be 114.5 ± 28 nm through dynamic light scattering (DLS) measurement. Globular liposomes approximately 100 nm in diameter were clearly visible in transmission electron microscope (TEM) images. The viability of tumor cells following BNCT with 70 μM nido-carborane was reduced to 17.1% compared to irradiated control cells, which did not contain boronated liposomes. Confocal microscopy revealed that fluorescently labeled liposomes injected into the tail veins of mice were deeply and evenly distributed in tumor tissues and localized in the cytoplasm of tumor cells. When mice were properly shielded with a 12 mm-thick polyethylene board during in-vivo irradiation at a thermal neutron flux of 1.94 × 10 4 /cm 2 ·sec, almost complete tumor suppression was achieved in tumor models injected with boronated liposomes (21.0 mg 10 B/kg). Two BNCT cycles spaced 10 days apart further enhanced the therapeutic anti-tumor effect, even when the dose was lowered to 10.5 mg 10 B/kg. No notable weight loss was observed in the tumor models during the BNCT study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This article presents the original descriptions of some recent physics mechanisms (based on the thermodynamic, kinetic, and quantum tunnel effects) providing stable 2 H/ 1 H isotope fractionation, leading to the accumulation of particular isotopic forms in intra- or intercellular space, including the molecular effects of deuterium interaction with 18 O/ 17 O/ 16 O, 15 N/ 14 N, 13 C/ 12 C, and other stable biogenic isotopes. These effects were observed mainly at the organelle (mitochondria) and cell levels. A new hypothesis for heavy nonradioactive isotope fractionation in living systems via neutron effect realization is discussed. The comparative analysis of some experimental studies results revealed the following observation: "Isotopic shock" is highly probable and is observed mostly when chemical bonds form between atoms with a summary odd number of neutrons (i.e., bonds with a non-compensated neutron, which correspond to the following equation: Nn - Np = 2k + 1, where k ϵ Z, k is the integer, Z is the set of non-negative integers, Nn is number of neutrons, and Np is number of protons of each individual atom, or in pair of isotopes with a chemical bond). Data on the efficacy and metabolic pathways of the therapy also considered 2 H-modified drinking and diet for some diseases, such as Alzheimer's disease, Friedreich's ataxia, mitochondrial disorders, diabetes, cerebral hypoxia, Parkinson's disease, and brain cancer.

Purpose To compare the performance of three-dimensional radial ultrashort echo time (UTE) oxygen-enhanced (OE) MRI with that of hyperpolarized helium 3 ( 3 He) MRI with respect to quantitative ventilation measurements in patients with cystic fibrosis (CF). Materials and Methods In this prospective study conducted from June 2013 to May 2015, 25 participants with CF aged 10-55 years (14 male; age range, 13-55 years; 11 female; age range, 10-37 years) successfully underwent pulmonary function tests, hyperpolarized 3 He MRI, and OE MRI. OE MRI used two sequential 3.5-minute normoxic and hyperoxic steady-state free-breathing UTE acquisitions. Seven participants underwent imaging at two separate examinations 1-2 weeks apart to assess repeatability. Regional ventilation was quantified as ventilation defect percentage (VDP) individually from OE MRI and hyperpolarized 3 He MRI by using the same automated quantification tool. Bland-Altman analysis, intraclass correlation coefficient (ICC), Spearman correlation coefficient, and Wilcoxon signed-rank test were used to evaluate repeatability. Results In all 24 participants, the global VDP measurements from either OE MRI (ρ = -0.66, P < .001) or hyperpolarized 3 He MRI (ρ = -0.75, P < .001) were significantly correlated with the percentage predicted forced expiratory volume in 1 second. VDP reported at OE MRI was 5.0% smaller than (P = .014) but highly correlated with (ρ = 0.78, P < .001) VDP reported at hyperpolarized 3 He MRI. Both OE MRI-based VDP and hyperpolarized 3 He MRI-based VDP demonstrated good repeatability (ICC = 0.91 and 0.95, respectively; P ≤ .001). Conclusion In lungs with cystic fibrosis, ultrashort echo time oxygen-enhanced MRI showed similar performance compared with hyperpolarized 3 He MRI for quantitative measures of ventilation defects and their repeatability. © RSNA, 2018 Online supplemental material is available for this article.

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope, boron-10, is irradiated with neutrons to produce high energy alpha particles. This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system. Two low molecular weight boron-containing drugs currently are being used clinically, boronophenylalanine (BPA) and sodium borocaptate (BSH). Although they are far from being ideal, their therapeutic efficacy has been demonstrated in patients with high grade gliomas, recurrent tumors of the head and neck region, and a much smaller number with cutaneous and extra-cutaneous melanomas. Because of their limitations, great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use. These include boron-containing porphyrins, amino acids, polyamines, nucleosides, peptides, monoclonal antibodies, liposomes, nanoparticles of various types, boron cluster compounds and co-polymers. Currently, however, none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies. Therefore, at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH, either alone or in combination, with the hope that future research will identify new and better boron delivery agents for clinical use.

The analysis of the distribution and density of nuclear tracks forming an autoradiography in a nuclear track detector (NTD) allows the determination of 10 B atoms concentration and location in tissue samples from Boron Neutron Capture Therapy (BNCT) protocols. This knowledge is of great importance for BNCT dosimetry and treatment planning. Tissue sections studied with this technique are obtained by cryosectioning frozen tissue specimens. After the slicing procedure, the tissue section is put on the NTD and the sample starts drying. The thickness varies from its original value allowing more particles to reach the detector and, as the mass of the sample decreases, the boron concentration in the sample increases. So in order to determine the concentration present in the hydrated tissue, the application of corrective coefficients is required. Evaporation mechanisms as well as various factors that could affect the process of mass variation are outlined in this work. Mass evolution for tissue samples coming from BDIX rats was registered with a semimicro analytical scale and measurements were analyzed with software developed to that end. Ambient conditions were simultaneously recorded, obtaining reproducible evaporation curves. Mathematical models found in the literature were applied for the first time to this type of samples and the best fit of the experimental data was determined. The correlation coefficients and the variability of the parameters were evaluated, pointing to Page's model as the one that best represented the evaporation curves. These studies will contribute to a more precise assessment of boron concentration in tissue samples by the Neutron Autoradiography technique.

Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high Linear Energy Transfer (LET). It is considered a potential therapeutic approach for non-small cell lung cancer (NSCLC). It could avoid the inaccurate treatment caused by the lung motion during radiotherapy, because the dose deposition mainly depends on the boron localization and neutron source. Thus, B concentration and neutron sources are both principal factors of BNCT, and they play significant roles in the curative effect of BNCT for different cases. The purpose was to explore the feasibility of BNCT treatment for NSCLC with either of two neutron sources (the epithermal reactor at the Massachusetts Institute of Technology named "MIT source" and the accelerator neutron source designed in Argentina named "MEC source") and various boron concentrations. Shallow and deeper lung tumors were defined in the Chinese hybrid radiation phantom, and the Monte Carlo method was used to calculate the dose to tumors and healthy organs. The MEC source was more appropriate to treat the shallow tumor (depth of 6 cm) with a shorter treatment time. However, the MIT source was more suitable for deep lung tumor (depth of 9 cm) treatment, as the MEC source is more likely to exceed the skin dose limit. Thus, a neutron source consisting of more fast neutrons is not necessarily suitable for deep treatment of lung tumors. Theoretical distribution of B in tumors and organs at risk (especially skin) was obtained to meet the treatable requirement of BNCT, which may provide the references to identify the feasibility of BNCT for the treatment of lung cancer using these two neutron sources in future clinical applications.

Purpose To evaluate the effect of oxygen pressure during incubation with a (10)B-carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumor cells. Materials and methods Cultured human head and neck squamous cell carcinoma cell line transfected with mutant TP53 (SAS/mp53), or with a neo vector as a control (SAS/neo) was incubated with L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH) as a (10)B-carrier at the (10)B concentration of 60 ppm for 24 h under aerobic (20.7% of oxygen) or hypoxic (0.28% of oxygen) conditions. Immediately after incubation, cultured tumor cells received reactor thermal neutron beams, and a cell survival assay was performed. (10)B concentration of cultured SAS/neo or SAS/mp53 cells incubated under aerobic or hypoxic conditions was determined with a thermal neutron guide tube. Results Hypoxic incubation significantly decreased (10)B concentration of cultured cells with a clearer tendency observed following BPA than BSH treatment in both SAS/neo and SAS/mp53 cells. Following neutron beam irradiation, SAS/mp53 cells showed significantly higher relative biological effectiveness values than SAS/neo cells because of the significantly lower radiosensitivity of SAS/mp53 to γ-rays than SAS/neo cells. Conclusion Oxygen pressure during incubation with a (10)B-carrier had a critical impact on (10)B uptake of cultured tumor cells.

Purpose: MRI of lung airspaces using gases with MR-active nuclei ((3) He, (129) Xe, and (19) F) is an important area of research in pulmonary imaging. The volume-controlled administration of gas mixtures is important for obtaining quantitative information from MR images. State-of-the-art gas administration using plastic bags (PBs) does not allow for a precise determination of both the volume and timing of a (3) He bolus., Methods: A novel application unit (AU) was built according to the requirements of the German medical devices law. Integrated spirometers enable the monitoring of the inhaled gas flow. The device is particularly suited for hyperpolarized (HP) gases (e.g., storage and administration with minimal HP losses). The setup was tested in a clinical trial (n = 10 healthy volunteers) according to the German medicinal products law using static and dynamic ventilation HP-(3) He MRI., Results: The required specifications for the AU were successfully realized. Compared to PB-administration, better reproducibility of gas intrapulmonary distribution was observed when using the AU for both static and dynamic ventilation imaging., Conclusion: The new AU meets the special requirements for HP gases, which are storage and administration with minimal losses. Our data suggest that gas AU-administration is superior to manual modes for determining the key parameters of dynamic ventilation measurements., (© 2014 Wiley Periodicals, Inc.)

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam., Methods and Materials: Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulations were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator., Results: A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin., Conclusions: Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Radiation doses during boron neutron capture therapy for body-trunk tumors were estimated for various internal organs, using data from patients treated at Kyoto University Research Reactor Institute. Dose-volume histograms were constructed for tissues of the lung, liver, kidney, pancreas, and bowel. For pleural mesothelioma, the target total dose to the normal lung tissues on the diseased side is 5Gy-Eq in average for the whole lung. It was confirmed that the dose to the liver should be carefully considered in cases of right lung disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In the frame of accelerator-based BNCT, the (9)Be(d,n)(10)B reaction was investigated as a possible source of epithermal neutrons. In order to determine the configuration in terms of bombarding energy, target thickness and Beam Shaping Assembly (BSA) design that results in the best possible beam quality, a systematic optimization study was carried out. From this study, the optimal configuration resulted in tumor doses ≥40Gy-Eq, with a maximum value of 51Gy-Eq at a depth of about 2.7cm, in a 60min treatment. The optimal configuration was considered for the treatment planning assessment of a real Glioblastoma Multiforme case. From this, the resulted dose performances were comparable to those obtained with an optimized (7)Li(p,n)-based neutron source, under identical conditions and subjected to the same clinical protocol., (© 2013 Published by Elsevier Ltd.)

Mercaptoundecahydrododecaborate (BSH)-encapsulating 10% distearoyl boron lipid (DSBL) liposomes were developed as a boron delivery vehicle for neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in addition to its encapsulated agents. BSH-encapsulating 10% DSBL liposomes have high boron content (B/P ratio: 2.6) that enables us to prepare liposome solution with 5000 ppm boron concentration. BSH-encapsulating 10% DSBL liposomes displayed excellent boron delivery efficacy to tumor: boron concentrations reached 174, 93, and 32 ppm at doses of 50, 30, and 15 mg B/kg, respectively. Magnescope was also encapsulated in the 10% DSBL liposomes and the real-time biodistribution of the Magnescope-encapsulating DSBL liposomes was measured in a living body using MRI. Significant antitumor effect was observed in mice injected with BSH-encapsulating 10% DSBL liposomes even at the dose of 15 mg B/kg; the tumor completely disappeared three weeks after thermal neutron irradiation ((1.5-1.8) × 10(12) neutrons/cm(2)). The current results enabled us to reduce the total dose of liposomes to less than one-fifth compared with that of the BSH-encapsulating liposomes without reducing the efficacy of boron neutron capture therapy (BNCT).

Boron neutron capture therapy (BNCT) is a binary radiotherapy based on thermal-neutron irradiation of cells enriched with (10)B, which produces α particles and (7)Li ions of short range and high biological effectiveness. The selective uptake of boron by tumor cells is a crucial issue for BNCT, and studies of boron uptake and washout associated with cell survival studies can be of great help in developing clinical applications. In this work, boron uptake and washout were characterized both in vitro for the DHDK12TRb (DHD) rat colon carcinoma cell line and in vivo using rats bearing liver metastases from DHD cells. Despite a remarkable uptake, a large boron release was observed after removal of the boron-enriched medium from in vitro cell cultures. However, analysis of boron washout after rat liver perfusion in vivo did not show a significant boron release, suggesting that organ perfusion does not limit the therapeutic effectiveness of the treatment. The survival of boron-loaded cells exposed to thermal neutrons was also assessed; the results indicated that the removal of extracellular boron does not limit treatment effectiveness if adequate amounts of boron are delivered and if the cells are kept at low temperature. Cell survival was also investigated theoretically using a mechanistic model/Monte Carlo code originally developed for radiation-induced chromosome aberrations and extended here to cell death; good agreement between simulation outcomes and experimental data was obtained., (© 2011 by Radiation Research Society)

HeLa cells were incubated with neutron capture nuclei (boron-10 and gadolinium)-containing carbon nanoparticles, followed by irradiation of slow thermal neutron beam. Under a neutron flux of 6 x 10(11) n/cm(2) (or 10 min irradiation at a neutron flux of 1 x 10(9) n/cm(2) s), the percentages of acute cell death at 8 h after irradiation are 52, 55, and 28% for HeLa cells fed with BCo@CNPs, GdCo@CNPs, and Co@CNPs, respectively. The proliferation capability of the survived HeLa cells was also found to be significantly suppressed. At 48 h after neutron irradiation, the cell viability further decreases to 35 +/- 5% as compared to the control set receiving the same amount of neutron irradiation dose but in the absence of carbon nanoparticles. This work demonstrates "proof-of-concept" examples of neutron capture therapy using (10)B-, (157)Gd-, and (59)Co-containing carbon nanoparticles for effective destruction of cancer cells. It will also be reported the preparation and surface functionalization of boron or gadolinium doped core-shell cobalt/carbon nanoparticles (BCo@CNPs, GdCo@CNPs and Co@CNPs) using a modified DC pulsed arc discharge method, and their characterization by various spectroscopic measurements, including TEM, XRD, SQUID, FT-IR, etc. Tumor cell targeting ability was introduced by surface modification of these carbon nanoparticles with folate moieties., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the efficacy of beta-irradiation therapy with rhenium 188 ((188)Re) mercaptoacetyltriglycine (MAG3)-filled balloon dilation to prevent neointimal hyperplasia after stent placement in a canine iliac artery model., Materials and Methods: A total of 15 stents were implanted into the iliac arteries of eight dogs (one or two stents in each dog). Rhenium 188 MAG3-filled balloon dilation was performed immediately after placement of 10 bare stents-20 Gy in group II (n = 5) and 40 Gy in group III (n = 5)-and conventional balloon dilation was performed immediately after placement of the remaining five bare stents (group I). A follow-up angiogram was obtained 8 weeks after the procedure, and percentage of luminal stenosis was calculated for the proximal and distal ends of each stent. Neointimal thickening (expressed as the neointimal area divided by the sum of neointimal area and media area) was assessed for microscopic examination., Results: All eight dogs survived until they were euthanized 8 weeks after the procedures. The mean luminal stenosis measurements at 8-week follow-up angiography in groups I, II, and III were 26.63%, -0.44%, and 10.53%, respectively. The mean neointimal thickening measurements in groups I, II, and III were 0.77, 0.21, and 0.34, respectively. The mean percentage of luminal stenosis and neointimal thickening differed significantly among the three groups (P < .05)., Conclusions: beta-Irradiation with (188)Re-MAG3-filled balloon dilation has the potential to reduce neointimal hyperplasia secondary to stent placement in a canine iliac artery model. A dose of 20 Gy may be preferable versus a dose of 40 Gy to reduce neointimal hyperplasia., (Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: For the treatment of some cancerous tumors using brachytherapy methods and low-energy photon sources, such as 125I and 103Pd, the American Association of Physicists in Medicine Task Group No. 43U1 report recommends that the dosimetric parameters of a new brachytherapy source must be determined in two experimental and Monte Carlo theoretical methods before using each new source clinically. This study presents the results of Monte Carlo calculations of the dosimetric parameters for IR08-103Pd brachytherapy source design. IR08-103Pd seed has been manufactured at the Agricultural, Medical and Industrial Research School., Methods: Version 5 of the (MCNP) Monte Carlo radiation transport code was used to calculate the dosimetry parameters around the source. Three geometric models of the seed, based on different locations of beads inside the titanium capsule, were simulated. The seed contains five resin beads of 0.6 mm diameter having 103Pd uniformly absorbed in the bead volume, which were contained within a cylindrical titanium capsule having 0.8 mm outside diameter and 4.8 mm length., Results: The Monte Carlo calculated dose rate constant of the IR08-103Pd seed was found to be 0.695 +/- 0.021 cGyU(-1) h(-1). Also in this study, the geometry function G(r, theta), line and point-source radial dose functions gL(r) and gP(r), and the anisotropy function F(r, theta), have been calculated at distances from 0.25 to 7 cm. The results of these calculations have been compared with measured values for an actual IR08-103Pd seed., Conclusions: There are no statistical significant dosimetric differences among the three seed orientations in this study (i.e., ideal, vertical, and diagonal). However, the observed differences between the calculated and measured values could be explained by the measurement uncertainty and the configuration of the resin beads within the capsule and capsule orientation.

Purpose: The present report addresses the question of what could be the appropriate dose and dose rate for 125I and 103PD permanent seed implants for breast cancer as monotherapy for early stage breast cancer. This is addressed by employing a radiobiological methodology, which is based on the linear quadratic model, to identify a biologically effective dose (BED) to the prescription point of the brachytherapy implant, which would produce equivalent cell killing (or same cell survival) when compared to a specified external radiotherapy scheme., Methods: In the present analysis, the tumor and normal tissue BED ratios of brachytherapy and external radiotherapy are examined for different combinations of tumor proliferation constant (K), alpha/beta ratios, initial dose rate (R0), and reference external radiotherapy scheme (50 or 60 Gy in 2 Gy per fraction). The results of the radiobiological analysis are compared against other reports and clinical protocols in order to examine possible opportunities of improvement., Results: The analysis indicates that physical doses of approximately 100-110 Gy delivered with an initial dose rate of around 0.05 Gyh(-1) and 78-80 Gy delivered at 0.135 Gyh(-1) for 125I and 103Pd permanent implants, respectively, are equivalent to 50 Gy external beam radiotherapy (EBRT) in 2 Gy per fraction. Similarly, for physical doses of approximately 115-127 Gy delivered with an initia dose rate of around 0.059 Gyh(-1) and 92 Gy delivered at 0.157 Gyh(-1) for 125I and 103Pd, respectively, are equivalent to 60 Gy EBRT in 2 Gy per fraction. It is shown that the initial dose rate required to produce isoeffective tumor response with 50 or 60 Gy EBRT in 2 Gy per fraction increases as the repopulation factor K increases, even though repopulation is also considered in EBRT. Also, the initial dose rate increases as the value of the alpha/beta ratio decreases. The impact of the different alpha/beta ratios on the ratio of the tumor BEDs is significantly large for both the 125I and 103Pd implants with the deviation between the alpha/beta = 10.0 Gy ratios and those using the 4.0 and 3.5 Gy values ranging between 18% and 22% in most of the cases., Conclusions: For the cases of 125I and 103Pd, the equivalent physical doses to 50 Gy EBRT in 2 Gy per fraction are associated with an overdosage of the involved normal tissue in the range of 4%-16% and an underdosage by 10%-15% for a BED for normal tissue, using an alpha/beta value of 3.0 Gy (BEDNT,3 Gy) of 100 Gy. These values are lower by 10%-20% than the published value of 124 Gy for 125I and by about 13% when compared to the published isoeffective dose of 90 Gy for 103Pd. Similarly, the equivalent physical doses to 60 Gy EBRT in 2 Gy per fraction are associated with an overdosage of the involved normal tissue by 10%-20% and an underdosage by 4%-10% for BEDNT,3 Gy of 110 Gy.

Purpose: The aim of this study was to evaluate tumour regression in a large series of choroidal melanomas, which were treated with three different eye-sparing treatment modalities., Patients and Methods: Retrospective review of the treatment results in all eyes with malignant choroidal melanoma, which were treated in the University Eye Clinic of Mainz consecutively in the time span 1.1992 to 12.2000 with transpupillary thermotherapy (TTT, standard protocol Oosterhuis JA 1995), ruthenium brachytherapy (RB, tumor apex dose 150 Gy) or sandwich therapy (ST). One-step ST was defined as TTT followed by RB with 100 Gy tumor apex dose within 48 hours. The treatment of residual prominences with TTT secondary to RB after different time spans was called two-step ST. Follow-up was 2 years., Results: 131 eyes with malignant choroidal melanoma (mean tumour thickness: 4.5 mm) were treated with RB (66 eyes), TTT (26 eyes) or ST (39 eyes). Preservation of the globe was achieved in 109 eyes (81 %). Local tumour control was found in small melanomas (prominence up to 3 mm) in 89 %, in large tumors (prominence 8 mm and higher) in 50 %. In a subgroup of small posterior melanomas (n = 70 eyes, prominence up to 4.5 mm, located posterior to the equator) local tumour control was noted in 91 %. The time span to reach local tumour control (Kaplan-Meier estimates) was the shortest after TTT (median: 20 weeks), compared with RB (48 weeks) and one-step ST (29 weeks)., Conclusions: In choroidal melanomas the chance of local tumour control and preservation of the globe decreases with increase of the tumour prominence. In small choroidal melanomas with posterior location local tumour control was achieved significantly faster after TTT than after RB., (Copyright Georg Thieme Verlag KG Stuttgart . New York.)

An undersampled diffusion-weighted stack-of-stars acquisition is combined with iterative highly constrained back-projection to perform hyperpolarized helium-3 MR q-space imaging with combined regional correction of radiofrequency- and T1-related signal loss in a single breath-held scan. The technique is tested in computer simulations and phantom experiments and demonstrated in a healthy human volunteer with whole-lung coverage in a 13-sec breath-hold. Measures of lung microstructure at three different lung volumes are evaluated using inhaled gas volumes of 500 mL, 1000 mL, and 1500 mL to demonstrate feasibility. Phantom results demonstrate that the proposed technique is in agreement with theoretical values, as well as with a fully sampled two-dimensional Cartesian acquisition. Results from the volunteer study demonstrate that the root mean squared diffusion distance increased significantly from the 500-mL volume to the 1000-mL volume. This technique represents the first demonstration of a spatially resolved hyperpolarized helium-3 q-space imaging technique and shows promise for microstructural evaluation of lung disease in three dimensions., (Copyright (c) 2009 Wiley-Liss, Inc.)

For the application of the BNCT for the excorporal treatment of organs at the TRIGA Mainz, the basic characteristics of the radiation field in the thermal column as beam geometry, neutron and gamma ray energies, angular distributions, neutron flux, as well as absorbed gamma and neutron doses must be determined in a reproducible way. To determine the mixed irradiation field thermoluminescence detectors (TLD) made of CaF(2):Tm with a newly developed energy-compensation filter system and LiF:Mg,Ti materials with different (6)Li concentrations and different thicknesses as well as thin gold foils were used.

High accumulation and selective delivery of boron into tumor tissues are the most important requirements to achieve efficient neutron capture therapy of cancers. We focused on liposomal boron delivery system in order to achieve a large amount of boron delivery to tumor. We synthesized the double-tailed boron cluster lipid 4c according to our reported procedure with modification. Size distribution of liposomes prepared from the boron cluster lipid 4c, DMPC, PEG-DSPE, and cholesterol was determined as 100 nm in diameter by an electrophoretic light scattering spectrophotometer. A high level of (10)B concentration (22 ppm) was observed in tumor tissue at 24 h after the administration of boron liposomes.

A thorax phantom has been designed, consisting of PMMA and PE plates containing a cavity filled with a laboratory-made lung-substitute. Fricke-gel dosimeters have been placed in the lung-substitute volume, and the phantom has been irradiated at the epithermal column of LVR-15 reactor. Absorbed dose images have been obtained for both gamma radiation and charged particles emitted in the (10)B reactions with thermal neutrons. Measurements with thermoluminescence dosimeters (TLDs) and Monte Carlo (MC) calculations have been performed too, in order to attain inter-comparison of results.

Osteosarcoma is the most common non-hematologic primary cancer type that develops in bone. Current osteosarcoma treatments combine multiagent chemotherapy with extensive surgical resection, which in some cases makes necessary the amputation of the entire limb. Nevertheless its infiltrative growth leads to a high incidence of local and distant recurrences that reduce the percentage of cured patients to less than 60%. These poor data required to set up a new therapeutic approach aimed to restrict the surgical removal meanwhile performing a radical treatment. Boron neutron capture therapy (BNCT), a particular radiotherapy based on the nuclear capture and fission reactions by atoms of (10)B, when irradiated with thermal neutrons, could be a valid alternative or integrative option in case of osteosarcoma management, thanks to its peculiarity in selectively destroying neoplastic cells without damaging normal tissues. Aim of the present work is to investigate the feasibility of employing BNCT to treat the limb osteosarcoma. Boronophenylalanine (BPA) is used to carry (10)B inside the neoplastic cells. As a first step the endocellular BPA uptake is tested in vitro on the UMR-106 osteosarcoma cell line. The results show an adequate accumulation capability. For the in vivo experiments, an animal tumor model is developed in Sprague-Dawley rats by means of an intrafemoral injection of UMR-106 cells at the condyle site. The absolute amounts of boron loading and the tumor to normal tissue (10)B ratio are evaluated 2 h after the i.v. administration of BPA. The boron uptake by the neoplastic tissue is almost twice the normal one. However, higher values of boron concentration in tumor are requested before upholding BNCT as a valid therapeutic option in the treatment of osteosarcoma.

We report on a new solid state dosimeter based on chemical vapor deposition (CVD) single crystal diamond fabricated at Roma "Tor Vergata" University laboratories. The dosimeter has been specifically designed for direct neutron dose measurements in boron neutron capture therapy (BNCT). The response to thermal neutrons of the proposed diamond dosimeter is directly due to (10)B and, therefore, the dosimeter response is directly proportional to the boron absorbed doses in BNCT. Two single crystal diamond detectors are fabricated in a p-type/intrinsic/metal configuration and are sandwiched together with a boron containing layer in between the metallic contacts (see Fig.1). Neutron irradiations were performed at the Frascati Neutron Generator (FNG) using the 2.5 MeV neutrons produced through the D(d,n)(3)He fusion reaction. Thermal neutrons were then produced by slowing down the 2.5 MeV neutrons using a cylindrical polymethylmethacrylate (PMMA) moderator. The diamond dosimeter was placed in the center of the moderator. The products of (10)B(n,alpha)Li nuclear reaction were collected simultaneously giving rise to a single peak. Stable performance, high reproducibility, high efficiency and good linearity were observed.

Three treatment planning systems developed for clinical boron neutron capture therapy (BNCT) use are SERA developed by INL/Montana State University, NCTPlan developed by the Harvard-MIT and the CNEA group and JAEA computational dosimetry system (JCDS) developed by Japan Atomic Energy Agency (JAEA) in Japan. Previously, performance of the SERA and NCTPlan has been compared in various studies. In this preliminary study, the dose calculations performed with SERA and JCDS systems were compared in single brain cancer patient case with the FiR 1 epithermal neutron beam. A two-field brain cancer treatment plan was performed with the both codes. The dose components to normal brain, tumor and planning target volume (PTV) were calculated and compared in case of one radiation field and combined two fields. The depth dose distributions and the maximum doses in regions of interest were compared. Calculations with the treatment planning systems for the thermal neutron induced ((10)B and nitrogen) dose components and photon dose were in good agreement. Higher discrepancy in the fast neutron dose calculations was found. In case of combined two-field treatment plan, overall discrepancy of the maximum weighted dose was approximately 3% for normal brain and PTV and approximately 4% for tumor dose.

In the present study, we aimed to evaluate a T2 corrected quantification method of l-p-boronophenylalanine (BPA) concentration using proton magnetic resonance spectroscopy (MRS). We used five phantoms containing BPA (1.5, 3.0, 5.0, 7.5, and 10 mmol/kg=15, 30, 50, 75, and 100 microg(10)B/g), N-acetyl-aspartic acid (NAA: 3.0 mmol/kg), creatine (Cr: 5.0 mmol/kg), and choline (Cho: 3.0 mmol/kg). The signal intensities of BPA and internal water were corrected by T2 relaxation time. The absolute concentrations of BPA were calculated by proton MRS using an internal water signal as a standard. The major BPA peaks were detected between 7.1 and 7.6 ppm. Mean T2 relaxation time was 314.3+/-10.8 ms in BPA, 885.1+/-39.7 ms in internal water. The calculated BPA concentrations were almost same as the actual concentration of BPA and the correlation coefficient was 0.99. Our BPA quantification method was very simple and non-invasive, also it had high accuracy. Therefore, our results indicate that proton MRS can be potentially useful technique for in vivo BPA quantification in boron neutron capture therapy (BNCT).

Tsing Hua open-pool reactor (THOR) at Tsing Hua University in Taiwan has been used to investigate the feasibility and to enhance the technology of boron neutron capture therapy (BNCT) for years. A rebuilt epithermal beam port for BNCT at THOR was finished in the summer of 2004, and then researches and experiments were performed to hasten the first clinical treatment case of BNCT in Taiwan in the near future. NCTPlan, a Monte Carlo-based clinical treatment planning code, was used to calculate the dose-rate distributions of BNCT in this work. A self-made Snyder head phantom with a servo-motor control system was irradiated in front of the THOR BNCT beam exit. The phantom was made from a 3mm shell of quartz wool impregnated with acrylic casting resin mounted on an acrylic base, and was filled with water. Gold foils (bare and cadmium-covered) and paired ion chambers (one with graphite wall and filled with CO(2) gas, another with A-150 plastic tissue equivalent wall and filled with tissue equivalent gas) were placed inside the Snyder phantom to measure and estimate the depth-dose distributions in the central axis of the beam. Dose components include the contribution of thermal neutrons, fast neutrons, photons and emitted alpha particles from (10)B(n,alpha)(7)Li reaction. Comparison and analysis between computed and measured results of depth-dose distributions were made in this work. Dose rate scaling factors (DRSFs) were defined as normalization factors derived individually for each dose component in the BNCT in-phantom radiation field that provide the best agreement between measured and computed data. This paper reports the in-phantom calculated and experimental dosimetry and the determined DRSFs used in NCTPlan code for the BNCT beam of THOR.

The evaluation of possible improvement in the use of Gd in cancer therapy, in reference to gadolinium in cancer therapy (GdNCT), has been analysed. At first the problem of the gadolinium compounds toxicity was reviewed identifying the Motexafin Gadolinium as the best. Afterwards, the spectrum of IC and Auger electrons was calculated using a special method. Afterwards, this electron source has been used as input of the PENELOPE code and the energy deposit in DNA was well defined. Taking into account that the electron yield and energy distribution are related to the neutron beam spectrum and intensity, the shaping assembly architecture was optimised through computational investigations. Finally the study of GdNCT was performed from two different points of view: macrodosimetry using MCNPX, with calculation of absorbed doses both in tumour and healthy tissues, and microdosimetry using PENELOPE, with the determination of electron RBE through the energy deposit. The equivalent doses were determined combining these two kinds of data, introducing specific figures of merit to be used in treatment planning system (TPS). According to these results, the GdNCT appears to be a fairly possible tumour therapy.

This article reports on the development of a prototype of a SPECT tomograph system for online dosimetry in BNCT based on LaBr(3)(Ce) scintillation detectors. The setup shielding was optimized to be used in the accelerator based BNCT facility of the University of Birmingham. The system was designed and built. An image of a (241)Am point source was reconstructed. A projection of a phantom with two tumors with 400 microg/g of (10)B was measured at the BNCT facility.

The purpose of the work was to build a prompt gamma neutron activation analysis (PGNAA) facility at the MEPhI reactor for analyzing the content of various elements for NCT. The facility was implemented on a monochromatic neutron beam. Methods of quantitative (10)B and Gd measurement have been developed for pharmacokinetic studies. The facility is capable of measuring 1 microg of (10)B and 10 microg of Gd in biological samples with an error less than 10%. The detection limit of the facility is 0.3 microg of (10)B and 2 microg of Gd. Neutron flux attenuation within biological tissue samples was estimated and a new system for determining the elemental concentration was suggested.

Positron emission tomography (PET) has become a key imaging tool in clinical practice and biomedical research to quantify and study biochemical processes in vivo. Physiologically active compounds are tagged with positron emitters (e.g. (18)F, (11)C, (124)I) while maintaining their biological properties, and are administered intravenously in tracer amounts (10(-9)-10(-12)M quantities). The recent physical integration of PET and computed tomography (CT) in hybrid PET/CT scanners allows a combined anatomical and functional imaging: nowadays PET molecular imaging is emerging as powerful pharmacological tool in oncology, neurology and for treatment planning as guidance for radiation therapy. The in vivo pharmacokinetics of boron carrier for BNCT and the quantification of (10)B in living tissue were performed by PET in the late nineties using compartmental models based on PET data. Nowadays PET and PET/CT have been used to address the issue of pharmacokinetic, metabolism and accumulation of BPA in target tissue. The added value of the use of L-[(18)F]FBPA and PET/CT in BNCT is to provide key data on the tumour extraction of (10)B-BPA versus normal tissue and to predict the efficacy of the treatment based on a single-study patient analysis. Due to the complexity of a binary treatment like BNCT, the role of PET/CT is currently to design new criteria for patient enrolment in treatment protocols: the L-[(18)F]BPA/PET methodology could be considered as an important tool in newly designed clinical trials to better estimate the concentration ratio of BPA in the tumour as compared to neighbouring normal tissues. Based on these values for individual patients the decision could be made whether BNCT treatment could be advantageous due to a selective accumulation of BPA in an individual tumour. This approach, applicable in different tumour entities like melanoma, glioblastoma and head and neck malignancies, make this methodology as reliable prognostic and therapeutic indicator for patient undergoing BNCT.

At the boron neutron capture therapy (BNCT) facility in Petten, the Netherlands, (10)B concentrations in biological materials are measured with the prompt gamma ray analyses facility that is calibrated using certified (10)B solutions ranging from 0 to 210 ppm. For this study, newly certified (10)B solutions ranging up to 1972 ppm are added. MCNP simulations of the setup range to 5000 ppm. A second order polynomial (as already used) will fit (10)B-concentrations less than 300 ppm. Above 300 ppm a fitted third order polynomial is needed to describe the calibration curve accurately.

The collision type central to BNCT is (10)B(n, alpha)(7)Li, however, other types of nuclear reactions also take place in the patient. In addition to the major elements (H, C, N, O), minor elements such as Na, Mg, P, S, Cl, K, Ca and Fe present in body tissues also interact in neutron collisions. Detailed accounting of the above not only provides a better understanding of radiation transport in the human body during BNCT, but such knowledge affects the design of the facility, as well as treatment planning, imaging and verification for a given BNCT agent. Of the methods of investigation currently available, only Monte Carlo simulation could provide the detailed accounting and breakdown of the quantities required. We report Monte Carlo simulation of an anthropomorphic voxel phantom, the VIP-Man and show how these quantities change with different (10)B concentrations in the tumour, the blood and the remaining tissues. The (10)B biodistribution has been chosen to be the variable of interest, since it is not accurately known, is frequently approximated and is a crucial quantity upon which dose calculations are based.

To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney.

This work provides the basis of a methodology to build a deterministic model for the spatial distribution of the (10)B(n,alpha)(7)Li reaction rate in boron neutron capture therapy (BNCT), as a function of space variables, boron concentration and beam incidence angle in homogeneous isotropic environments but also in different heterogeneous environments. Building the analytic function in a simple homogeneous environment with numerical methods leads to a mathematical formulation of the (10)B(n,alpha)(7)Li reactions rate.

We aimed at securing sufficient concentrations of (10)B in boron neutron capture therapy (BNCT) by developing a new drug delivery system. We have designed and developed a novel lipid analog and succeeded in using it to develop the new boron component liposome. It consisted of three different kinds of amino acid derivatives and two fatty acids, and could react directly with the peptide synthesized first on resin by Fmoc solid-phase synthesis. In this study, lipid analog conjugated with HIV-TAT peptide (domain of human immunodeficiency virus TAT protein) and boronophenylalanine (BPA) was synthesized and successfully incorporated into liposomes.

The spectroscopic output of low dose rate (LDR) brachytherapy sources is dependent on the physical design and construction of the source. Characterization of the emitted photons from 12 125I and 3 103Pd LDR brachytherapy source models is presented. Photon spectra, both along the transverse bisector and at several polar angles, were measured in air with a high-purity reverse electrode germanium (REGe) detector. Measured spectra were corrected to in vacuo conditions via Monte Carlo and analytical methods. The tabulated and plotted spectroscopic data provide a more complete understanding of each source model's output characteristics than can be obtained with other measurement techniques. The variation in fluorescence yield of the 125I sources containing silver caused greater differences in the emitted spectra and average energies among these seed models than was observed for the 103Pd sources or the 125I sources that do not contain silver. Angular spectroscopic data further highlighted the effects of source construction unique to each model, as well as the asymmetric output of many seeds. These data demonstrate the need for the incorporation of such physically measured output characteristics in the Monte Carlo modeling process.

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.

Objective: To report the biochemical progression-free survival (BPFS) in hormone-naive men aged < or = 54 years who underwent brachytherapy with or without supplemental external beam radiation therapy (EBRT), as despite favourable biochemical control rates with brachytherapy, there remains a reluctance to recommend non-extirpative approaches for young men with clinically localized prostate cancer., Patients and Methods: From April 1995 to October 2002, 108 hormone-naive patients aged < or = 54 years (median 52 years, range 45-54) had permanent interstitial brachytherapy for clinical stage T1c-T2c NXM0 (2002 American Joint Committee on Cancer staging) prostate cancer. No patient had a seminal vesicle biopsy or pathological lymph node staging. The mean (sd, median) follow-up was 5.3 (1.8, 4.8) years. BPFS was defined by a prostate-specific antigen (PSA) level of < or = 0.40 ng/mL after the nadir. Risk groups were assigned using the Memorial Sloan-Kettering Cancer Center criteria. Several clinical, treatment and dosimetric variables were evaluated for their effect on BPFS., Results: For the entire group, the actuarial 8-year BPFS was 96%; for low- (57 men), intermediate- (47) and high- (four) risk patients, the BPFS rates were 96%, 100% and three of four, respectively. For biochemically disease-free patients, the median PSA level after treatment was 0.05 ng/mL. In a multivariate analysis, only pretreatment PSA level predicted biochemical control, while dosimetry variables after treatment were almost statistically significant., Conclusions: Hormone-naive patients aged < or = 54 years have a high probability of a good 8-year BPFS after permanent interstitial brachytherapy with or without supplemental EBRT.

Significant improvement of in vivo stability of 211At-labeled radioimmunoconjugates achieved upon employment of a recently reported new linker, succinimidyl N-2-(4-[211At]astatophenethyl)succinamate (SAPS), prompted additional studies of its chemistry. The 211At radiolabeling of succinimidyl N-2-(4-tributylstannylphenethyl)succinamate (1) was noted to decline after storage at -15 degrees C for greater than 6 months. Compound 1 was found to degrade via a ring closure reaction with the formation of N-2-(4-tributylstannylphenethyl)succinimide (3), and a modified procedure for the preparation of 1 was developed. The N-methyl structural analog of 1, succinimidyl N-2-(4-tributylstannylphenethyl)-N-methyl succinamate (SPEMS), was synthesized to investigate the possibility of improving the stability of reagent-protein linkage chemistry. Radiolabeling of SPEMS with 211At generates succinimidyl N-2-(4-[211At]astatophenethyl)-N-methyl succinamate (Methyl-SAPS), with yields being consistent for greater than 1 year. Radiolabelings of 1 and SPEMS with 125I generated succinimidyl N-2-(4-[125I]iodophenethyl)succinamate (SIPS) and succinimidyl N-2-(4-[125I]iodophenethyl)-N-methyl succinamate (Methyl-SIPS), respectively, and showed no decline in yields. Methyl-SAPS, SAPS, Methyl-SIPS and SIPS were conjugated to Herceptin for a comparative assessment in LS-174T xenograft-bearing mice. The conjugates of Herceptin with Methyl-SAPS or Methyl-SIPS demonstrated immunoreactivity equivalent to if not superior to the SAPS and SIPS paired analogs. The in vivo studies also revealed that the N-methyl modification resulted in a superior statinated product.

For radiation therapy with carbon ion beams, either for the stable isotope (12)C or for the radioactive one (11)C, it has been demonstrated that the beta(+)-activity distribution created or deposited, respectively, within the irradiated volume can be visualized by means of positron emission tomography (PET). The PET images provide valuable information for quality assurance and precision improvement of ion therapy. Dedicated PET scanners have been integrated into treatment sites at the Heavy Ion Medical Accelerator at Chiba (HIMAC), Japan, and the Gesellschaft für Schwerionenforschung (GSI), Germany, to make PET imaging feasible during therapeutic irradiation (in-beam PET). A similar technique may be worthwhile for radiotherapy with high-energy bremsstrahlung. In addition to monitoring the dose delivery process which in-beam PET has been primarily developed for, it may be expected that radiation response of tissue can be detected by means of in-beam PET. We investigate the applicability of PET for treatment control in the case of using bremsstrahlung spectra produced by 15-50 MeV electrons. Target volume activation due to (gamma, n) reactions at energies above 20 MeV yields moderate beta(+)-activity levels, which can be employed for imaging. The radiation from positrons produced by pair production is not presently usable because the detectors are overloaded due to the low duty factor of medical electron linear accelerators. However, the degradation of images caused by positron motion between creation and annihilation seems to be tolerable.