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1.
Ecotoxicol Environ Saf ; 214: 112113, 2021 May.
Article in English | MEDLINE | ID: mdl-33690006

ABSTRACT

The main purpose of this work is to thoroughly describe the implementation protocol of laser-induced breakdown spectroscopy (LIBS) method in the plant analysis. Numerous feasibility studies and recent progress in instrumentation and trends in chemical analysis make LIBS an established method in plant bioimaging. In this work, we present an easy and straightforward phytotoxicity case study with a focus on LIBS method. We intend to demonstrate in detail how to manipulate with plants after exposures and how to prepare them for analyses. Moreover, we aim to achieve 2D maps of spatial element distribution with a good resolution without any loss of sensitivity. The benefits of rapid, low-cost bioimaging are highlighted. In this study, cabbage (Brassica oleracea L.) was treated with an aqueous dispersion of photon-upconversion nanoparticles (NaYF4 doped with Yb3+ and Tm3+ coated with carboxylated silica shell) in a hydroponic short-term toxicity test. After a 72-hour plant exposure, several macroscopic toxicity end-points were monitored. The translocation of Y, Yb, and Tm across the whole plant was set by employing LIBS with a lateral resolution 100 µm. The LIBS maps of rare-earth elements in B.oleracea plant grown with 50 µg/mL nanoparticle-treated and ion-treated exposures showed the root as the main storage, while the transfer via stem into leaves was minimal. On the contrary, the LIBS maps of plants exposed to the 500 µg/mL nanoparticle-treated and ion-treated uncover slightly different trends, nanoparticles as well as ions were transferred through the stem into leaves. However, the main storage organ was a root as well.


Subject(s)
Brassica/metabolism , Fluorides/administration & dosage , Nanoparticles/administration & dosage , Silicon Dioxide/administration & dosage , Thulium/toxicity , Ytterbium/administration & dosage , Yttrium/administration & dosage , Lasers , Plant Leaves/metabolism , Plant Roots/metabolism , Plant Stems/metabolism , Spectrum Analysis
2.
Int J Radiat Oncol Biol Phys ; 105(4): 875-883, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31330175

ABSTRACT

PURPOSE: To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo-based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. METHODS AND MATERIALS: Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. RESULTS: In comparison to segmentation scheme 4, TG-43-based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. CONCLUSIONS: Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging-based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.


Subject(s)
Brachytherapy/methods , Iridium Radioisotopes/administration & dosage , Organs at Risk/radiation effects , Radioisotopes/administration & dosage , Rectal Neoplasms/radiotherapy , Selenium Radioisotopes/administration & dosage , Ytterbium/administration & dosage , Brachytherapy/instrumentation , Femur/radiation effects , Humans , Monte Carlo Method , Organs at Risk/diagnostic imaging , Pelvic Bones/radiation effects , Radiotherapy Dosage , Rectum/radiation effects , Tomography, X-Ray Computed , Urinary Bladder/radiation effects
3.
Dalton Trans ; 45(36): 14101-14108, 2016 Sep 13.
Article in English | MEDLINE | ID: mdl-27711690

ABSTRACT

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.


Subject(s)
Coordination Complexes , Light , Metal Nanoparticles , Rhenium , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Chitosan/administration & dosage , Chitosan/chemistry , Chitosan/radiation effects , Coordination Complexes/administration & dosage , Coordination Complexes/chemistry , Coordination Complexes/radiation effects , Fluorides/administration & dosage , Fluorides/chemistry , Fluorides/radiation effects , Humans , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Rhenium/administration & dosage , Rhenium/chemistry , Rhenium/radiation effects , Thulium/administration & dosage , Thulium/chemistry , Thulium/radiation effects , Ytterbium/administration & dosage , Ytterbium/chemistry , Ytterbium/radiation effects , Yttrium/administration & dosage , Yttrium/chemistry , Yttrium/radiation effects
4.
Nano Lett ; 16(3): 1695-703, 2016 Mar 09.
Article in English | MEDLINE | ID: mdl-26845418

ABSTRACT

The recent development of core/shell engineering of rare earth doped luminescent nanoparticles has ushered a new era in fluorescence thermal biosensing, allowing for the performance of minimally invasive experiments, not only in living cells but also in more challenging small animal models. Here, the potential use of active-core/active-shell Nd(3+)- and Yb(3+)-doped nanoparticles as subcutaneous thermal probes has been evaluated. These temperature nanoprobes operate in the infrared transparency window of biological tissues, enabling deep temperature sensing into animal bodies thanks to the temperature dependence of their emission spectra that leads to a ratiometric temperature readout. The ability of active-core/active-shell Nd(3+)- and Yb(3+)-doped nanoparticles for unveiling fundamental tissue properties in in vivo conditions was demonstrated by subcutaneous thermal relaxation monitoring through the injected core/shell nanoparticles. The reported results evidence the potential of infrared luminescence nanothermometry as a diagnosis tool at the small animal level.


Subject(s)
Luminescent Measurements/instrumentation , Nanoparticles/chemistry , Neodymium/chemistry , Thermometers , Ytterbium/chemistry , Administration, Cutaneous , Animals , Body Temperature , Infrared Rays , Luminescence , Mice , Nanoparticles/administration & dosage , Neodymium/administration & dosage , Skin Physiological Phenomena , Ytterbium/administration & dosage
5.
Appl Radiat Isot ; 101: 75-82, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25846454

ABSTRACT

This paper describes development of (169)Yb-seeds by encapsulating 0.6-0.65 mm (ϕ) sized (169)Yb2O3 microspheres in titanium capsules. Microspheres synthesized by a sol-gel route were characterized by XRD, SEM/EDS and ICP-AES. Optimization of neutron irradiation was accomplished and (169)Yb-seeds up to 74 MBq of (169)Yb could be produced from natural Yb2O3 microspheres, which have the potential for use in prostate brachytherapy. A protocol to prepare (169)Yb-brachytherapy sources (2.96-3.7 TBq of (169)Yb) with the use of enriched targets was also formulated.


Subject(s)
Brachytherapy/methods , Radioisotopes/administration & dosage , Radiopharmaceuticals/administration & dosage , Ytterbium/administration & dosage , Humans , Male , Microspheres , Neutrons , Prostatic Neoplasms/radiotherapy , Radioisotopes/therapeutic use , Radiopharmaceuticals/therapeutic use , Spectrometry, X-Ray Emission , Surface Properties , Titanium , Ytterbium/therapeutic use
6.
Dalton Trans ; 43(10): 3861-70, 2014 Mar 14.
Article in English | MEDLINE | ID: mdl-24442070

ABSTRACT

Herein, alkali ion doped CaF2 upconversion nanoparticles (UCNPs) were first reported as a multifunctional theranostic platform for dual-modal imaging and chemotherapy. Interestingly, we found that the alkali ions doping approach could efficiently enhance the upconversion luminescence (UCL) intensity, whereas slightly affect the phase and morphology of the resulting products. In order to further improve the UCL efficacy for bioimaging, a pristine CaF2 shell was grown on the CaF2:Yb, Er core surface to enhance the UCL intensity. After being transferred into hydrophilic UCNPs, these water-soluble UCNPs could be served as contrast agents for in vitro/in vivo UCL imaging and X-ray computed tomography (CT) imaging. Furthermore, the as-prepared UCNPs could also be employed as nano-carriers for drug delivery. Doxorubicin (DOX) can be easily loaded onto the UCNPs and the DOX-loaded UCNPs exhibit a good cell killing ability. Therefore, the multifunctional core-shell CaF2 UCNPs with UCL/CT imaging and drug carrier properties may find extensive applications in simultaneous imaging diagnosis and therapy.


Subject(s)
Calcium Fluoride/chemistry , Contrast Media/chemistry , Erbium/chemistry , Nanoparticles/chemistry , Ytterbium/chemistry , Alkalies , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/chemistry , Calcium Fluoride/administration & dosage , Cell Line, Tumor , Cell Survival/drug effects , Contrast Media/administration & dosage , Diagnostic Imaging , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Drug Delivery Systems , Erbium/administration & dosage , HeLa Cells , Humans , Mice , Microscopy, Electron, Transmission , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Ytterbium/administration & dosage
7.
Biomaterials ; 34(30): 7444-52, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23849344

ABSTRACT

Nanoparticulate contrast agents have attracted a great deal of attention along with the rapid development of modern medicine. Here, a binary contrast agent based on PAA modified BaYbF5:Tm nanoparticles for direct visualization of gastrointestinal (GI) tract has been designed and developed via a one-pot solvothermal route. By taking advantages of excellent colloidal stability, low cytotoxicity, and neglectable hemolysis of these well-designed nanoparticles, their feasibility as a multi-modal contrast agent for GI tract was intensively investigated. Significant enhancement of contrast efficacy relative to clinical barium meal and iodine-based contrast agent was evaluated via X-ray imaging and CT imaging in vivo. By doping Tm(3+) ions into these nanoprobes, in vivo NIR-NIR imaging was then demonstrated. Unlike some invasive imaging modalities, non-invasive imaging strategy including X-ray imaging, CT imaging, and UCL imaging for GI tract could extremely reduce the painlessness to patients, effectively facilitate imaging procedure, as well as rationality economize diagnostic time. Critical to clinical applications, long-term toxicity of our contrast agent was additionally investigated in detail, indicating their overall safety. Based on our results, PAA-BaYbF5:Tm nanoparticles were the excellent multi-modal contrast agent to integrate X-ray imaging, CT imaging, and UCL imaging for direct visualization of GI tract with low systemic toxicity.


Subject(s)
Barium Compounds/chemistry , Fluorides/chemistry , Gastrointestinal Tract/diagnostic imaging , Lanthanoid Series Elements/chemistry , Molecular Probes/chemistry , Nanoparticles/chemistry , Ytterbium/chemistry , Acrylic Resins/administration & dosage , Acrylic Resins/chemical synthesis , Acrylic Resins/chemistry , Acrylic Resins/toxicity , Administration, Oral , Animals , Barium Compounds/administration & dosage , Barium Compounds/chemical synthesis , Barium Compounds/toxicity , Fluorides/administration & dosage , Fluorides/chemical synthesis , Fluorides/toxicity , Hep G2 Cells , Humans , Lanthanoid Series Elements/administration & dosage , Lanthanoid Series Elements/toxicity , Mice , Molecular Probes/administration & dosage , Molecular Probes/chemical synthesis , Molecular Probes/toxicity , Multimodal Imaging , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Radiography , Spectroscopy, Fourier Transform Infrared , Temperature , X-Ray Diffraction , Ytterbium/administration & dosage , Ytterbium/toxicity
8.
Theranostics ; 3(3): 210-22, 2013.
Article in English | MEDLINE | ID: mdl-23471455

ABSTRACT

Upconversion nanocrystals with small size and strong fluorescent signals own great potential in applications such as biomolecule-labeling, in vivo tracking and molecular imaging. Herein we reported that NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with small size and strong fluorescent signals were controllably synthesized by oleic acid (OA)/ ionic liquid (IL) two-phase system for targeted fluorescent imaging of gastric cancer in vivo. The optimal synthesis condition of NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals by OA/IL two-phase system was established, adding more metal ion such as Na(+) ion could facilitate the size control and crystal-phase transition, more importantly, markedly enhancing fluorescent intensity of beta-phase nanocrystals compared with traditional methods. Alpha-phase NaYbF4, 2%Tm upconversion nanocrystals with less than 10nm in diameter and beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with 30 nm or so in diameter and strong fluorescent signals were obtained, these synthesized nanocrystals exhibited very low cytotoxicity. Folic acid-conjugated silica-modified beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals were prepared, could actively target gastric cancer tissues implanted into nude mice in vivo, and realized targeted fluorescent imaging. Folic acid-conjugated silica-modified NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals show great potential in applications such as targeted near infared radiation fluorescent imaging, magnetic resonance imaging and targeted therapy of gastric cancer in the near future.


Subject(s)
Fluorides/administration & dosage , Fluorides/pharmacokinetics , Nanoparticles/administration & dosage , Optical Imaging/methods , Sodium Compounds/administration & dosage , Sodium Compounds/pharmacokinetics , Stomach Neoplasms/diagnosis , Ytterbium/administration & dosage , Ytterbium/pharmacokinetics , Animals , Disease Models, Animal , Fluorides/chemical synthesis , Fluorides/chemistry , Ionic Liquids/chemistry , Mice , Mice, Nude , Nanoparticles/chemistry , Oleic Acid/chemistry , Sodium Compounds/chemical synthesis , Sodium Compounds/chemistry , Stomach Neoplasms/pathology , Ytterbium/chemistry
9.
Int J Nanomedicine ; 5: 601-9, 2010 Sep 07.
Article in English | MEDLINE | ID: mdl-20856835

ABSTRACT

Four rare earth oxides have been shown to induce autophagy. Interestingly, we often noticed plentiful vacuolization, which was not always involved in this autophagic process. In this study, we investigated three other rare-earth elements, including Yttrium (Y), Ytterbium (Yb), and Lanthanum (La). Autophagic effect could be induced by all of them but only Y(2)O(3) and Yb(2)O(3) could cause massive vacuolization. Y(2)O(3) and Yb(2)O(3) treated by sonication or centrifugation to reduce particle size were used to test vacuolization level in HeLa cell lines. The results showed that rare earth oxides-induced vacuolization is size-dependent and differs from autophagic pathway. To further clarify the characteristics of this autophagic process, we used MEF Atg-5 (autophagy associated gene 5) knockout cell line, and the result showed that the autophagic process induced by rare earth oxides is Atg-5-dependent and the observed vacuolization was independent from autophagy. Similar results could also be observed in our tests on 3-methyladenine(3-MA), a well-known autophagy inhibitor. In conclusion, for the first time, we clarified the relationship between massive vacuolization and autophagic process induced by rare earth oxides and pointed out the size effect of rare earth oxides on the formation of vacuoles, which give clues to further investigation on the mechanisms underlying their biological effects.


Subject(s)
Autophagy/drug effects , Metal Nanoparticles/administration & dosage , Metals, Rare Earth/administration & dosage , Vacuoles/drug effects , Animals , Autophagy/physiology , Autophagy-Related Protein 5 , Cell Line , Gene Knockout Techniques , Green Fluorescent Proteins/metabolism , HeLa Cells , Humans , Lanthanum/administration & dosage , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Mice , Microscopy, Electron, Transmission , Microscopy, Fluorescence , Microtubule-Associated Proteins/deficiency , Microtubule-Associated Proteins/genetics , Nanomedicine , Oxides/administration & dosage , Particle Size , Vacuoles/physiology , Vacuoles/ultrastructure , Ytterbium/administration & dosage , Yttrium/administration & dosage
10.
J Nutr ; 138(4): 710-7, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18356325

ABSTRACT

Ruminal administration of a triple indigestible marker system comprised of cobalt EDTA (CoEDTA), ytterbium acetate (YbAc), and chromium-mordanted straw (CrS) decreases product:substrate ratios for Delta9-desaturase in bovine milk fat. This experiment was designed to identify the marker(s) responsible and develop an alternative system for simultaneous determination of nutrient flow in the gastro-intestinal tract and milk fatty acid composition. Five lactating dairy cows were used in a 5 x 5 Latin square with 21-d periods to evaluate the effects of YbAc, CoEDTA, and CrS independently or as part of a triple marker system (TMS), and CrEDTA as an alternative to CoEDTA on milk fat composition. Markers were administered in the rumen over a 7-d interval and samples of milk were collected on d -1, 3, 7, and 11. Both TMS and CoEDTA alone reduced the concentrations of milk fatty acids containing a cis-9 double bond, whereas YbAc, CrS, and CrEDTA had no effect. Reductions in product:substrate ratios for Delta9-desaturase were time dependent and evident within 3 d of administration. Ruminal infusion of CoEDTA for 7 d induced mean decreases in milk cis-9 14:1/14:0, cis-9 16:1/16:0, cis-9 18:1/18:0, and cis-9, trans-11 conjugated linoleic acid/trans-11 18:1 concentration ratios of 47.7, 26.7, 40.3, and 42.6%, respectively. In conclusion, ruminal infusion of CoEDTA alters milk fatty acid composition and appears to inhibit Delta9-desaturase activity in the bovine mammary gland. Results indicate that a TMS based on CrEDTA, YbAc, and indigestible neutral detergent fiber can be used for estimating nutrient flow without altering milk fat composition in lactating cows.


Subject(s)
Cattle/metabolism , Edetic Acid/pharmacology , Fatty Acids/analysis , Mammary Glands, Animal/enzymology , Milk/chemistry , Rumen/metabolism , Stearoyl-CoA Desaturase/metabolism , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Biomarkers , Chromium/administration & dosage , Chromium/pharmacology , Chromium/urine , Edetic Acid/administration & dosage , Edetic Acid/urine , Female , Lactation , Time Factors , Ytterbium/administration & dosage , Ytterbium/pharmacology , Ytterbium/urine
11.
J Dairy Sci ; 89(8): 3006-10, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16840616

ABSTRACT

Accurate determination of the flow of nutrients at the omasum requires the use of a triple marker system. Typically, a system based on ruminal administration of the lithium salt of CoEDTA, ytterbium acetate (Yb-Ac), and chromium-mordanted straw (Cr-S) has been used. However, there is evidence to suggest that product:substrate ratios for stearoyl-coenzyme A desaturase (Delta(9)-desaturase) are lower in milk fat from cows administered a combination of CoEDTA, Yb-Ac, and Cr-S, indicating reduced Delta(9)-desaturase activity. To evaluate this hypothesis, samples of milk were collected 1 d before, and on d 2, 6, and 9 of administering the CoEDTA, Yb-Ac, and Cr-S triple marker system into the rumen of 4 cows. A 4 x 4 Latin square with 28-d experimental periods was used to assess the effects of 0, 75, 150, and 300 g/d of fish oil in the diet on ruminal and mammary lipid metabolism. Irrespective of the amount of fish oil in the diet, concentrations of all milk fatty acids containing a cis-9 double bond were reduced after markers were given. Milk fatty acid pairs dependent on Delta(9)-desaturase were decreased over time, with responses reaching a nadir within 6 d of marker administration. Overall, administering markers into the rumen was associated with a mean decrease in milk cis-9 10:1/ 10:0, cis-9 12:1/12:0, cis-9 14:1/14:0, cis-9 16:1/16:0, cis-9 17:1/17:0, cis-9 18:1/18:0, and cis-9,trans-11 conjugated linoleic acid/trans-11 18:1 concentration ratios of 44.6, 52.7, 58.7, 36.8, 37.2, 44.3, and 43.0%, respectively. In conclusion, one or more of the markers administered altered milk fatty acid composition and may act as an inhibitor of Delta(9)-desaturase in the bovine mammary gland.


Subject(s)
Cattle/metabolism , Digestion , Fatty Acids/analysis , Mammary Glands, Animal/enzymology , Milk/chemistry , Stearoyl-CoA Desaturase/analysis , Acetates/administration & dosage , Animals , Chromium/administration & dosage , Edetic Acid/administration & dosage , Enzyme Inhibitors/administration & dosage , Female , Rumen/drug effects , Rumen/metabolism , Stearoyl-CoA Desaturase/antagonists & inhibitors , Ytterbium/administration & dosage
12.
Clin Cancer Res ; 5(5): 953-61, 1999 May.
Article in English | MEDLINE | ID: mdl-10353726

ABSTRACT

The tumor-associated glycoprotein 72 (TAG-72) antigen is present on a high percentage of tumor types including ovarian carcinomas. Antibody B72.3 is a murine monoclonal recognizing the surface domain of the TAG-72 antigen and has been widely used in human clinical trials. After our initial encouraging studies (M. G. Rosenblum et al., J. Natl. Cancer Inst., 83: 1629-1636, 1991) of tissue disposition, metabolism, and pharmacokinetics in 9 patients with ovarian cancer, we designed an escalating dose, multi-arm Phase I study of 90Y-labeled B72.3 i.p. administration. In the first arm of the study, patients (3 pts/dose level) received an i.p. infusion of either 2 or 10 mg of B72.3 labeled with either 1, 10, 15, or 25 mCi of 90Y. Pharmacokinetic studies demonstrated that concentrations of 90Y-labeled B72.3 persist in peritoneal fluid with half-lives >24 h after i.p. administration. In addition, 90Y-labeled B72.3 was absorbed rapidly into the plasma with peak levels achieved within 48 h, and levels declined slowly thereafter. Cumulative urinary excretion of the 90Y label was 10-20% of the administered dose which suggests significant whole-body retention of the radiolabel. Biopsy specimens of bone and marrow obtained at 72 h after administration demonstrated significant content of the label in bone (0.015% of the dose/g) with relatively little in marrow (0.005% of the dose/g). The maximal tolerated dose was determined to be 10 mCi because of hematological toxicity and platelet suppression. This typically occurred on the 29th day after administration and was thought to be a consequence of the irradiation of the marrow from the bony deposition of the radiolabel. In an effort to suppress the bone uptake of 90Y, patients were treated with a continuous i.v. infusion of EDTA (25 mg/kg/12 h x 6) infused immediately before i.p. administration of the radiolabeled antibody. Patients (3 pts/dose level) were treated with doses of 10, 15, 20, 25, 30, 35, 40, or 45 mCi of 90Y-labeled B72.3 for a total of 38 patients. EDTA administration resulted in significant myeloprotection, which allowed escalation to the maximal tolerated dose of 40 mCi. Dose-limiting toxicity was thrombocytopenia and neutropenia. Studies of plasma and peritoneal fluid pharmacokinetics demonstrate no changes compared with patients without EDTA pretreatment. Cumulative urinary excretion of the radiolabel was not increased in patients pretreated with EDTA compared with the untreated group. However, analysis of biopsy specimens of bone and marrow demonstrated that bone and marrow content of the 90Y label was 15-fold lower (<0.001% injected dose/g) than a companion group without EDTA. Four responses were noted in patients who received 15-30 mCi of 90Y-labeled B72.3 with response durations of 1-12 months. These results demonstrate the myeloprotective ability of EDTA, which allows safe i.p. administration of higher doses of 90Y-labeled B72.3 and, therefore, clearly warrant an expanded Phase II trial in patients with minimal residual disease after standard chemotherapy or for the palliation of refractory ascites.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Neoplasm/therapeutic use , Antigens, Neoplasm/immunology , Bone Marrow Diseases/prevention & control , Carcinoma/radiotherapy , Chelating Agents/therapeutic use , Edetic Acid/therapeutic use , Glycoproteins/immunology , Ovarian Neoplasms/radiotherapy , Radiation Injuries/prevention & control , Radioimmunotherapy , Radioisotopes/therapeutic use , Ytterbium/therapeutic use , Adult , Aged , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Neoplasm/administration & dosage , Antibodies, Neoplasm/immunology , Ascites/radiotherapy , Ascitic Fluid/chemistry , Bone Marrow/chemistry , Bone Marrow/radiation effects , Bone Marrow Diseases/chemically induced , Bone and Bones/chemistry , Carcinoma/pathology , Carcinoma/secondary , Carcinoma/therapy , Chelation Therapy , Dose-Response Relationship, Immunologic , Dose-Response Relationship, Radiation , Edetic Acid/administration & dosage , Edetic Acid/pharmacology , Fallopian Tube Neoplasms/pathology , Fallopian Tube Neoplasms/radiotherapy , Fallopian Tube Neoplasms/therapy , Female , Half-Life , Humans , Injections, Intraperitoneal , Mice , Middle Aged , Neoplasm, Residual , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/radiotherapy , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Radiation Injuries/chemically induced , Radioimmunotherapy/adverse effects , Radioisotopes/administration & dosage , Radioisotopes/adverse effects , Radioisotopes/pharmacokinetics , Radiotherapy Dosage , Tissue Distribution , Treatment Outcome , Ytterbium/administration & dosage , Ytterbium/adverse effects , Ytterbium/pharmacokinetics
13.
Clin Cancer Res ; 5(5): 1025-33, 1999 May.
Article in English | MEDLINE | ID: mdl-10353735

ABSTRACT

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.


Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Neoplasm Proteins/antagonists & inhibitors , Octreotide/analogs & derivatives , Radioisotopes/therapeutic use , Radiopharmaceuticals/therapeutic use , Receptors, Somatostatin/antagonists & inhibitors , Ytterbium/therapeutic use , Adult , Astrocytoma/metabolism , Astrocytoma/pathology , Astrocytoma/radiotherapy , Binding, Competitive , Brain Edema/chemically induced , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Diffusion , Disease Progression , Female , Glioblastoma/metabolism , Glioblastoma/pathology , Glioblastoma/radiotherapy , Glioma/metabolism , Glioma/pathology , Humans , Injections, Intralesional , Male , Middle Aged , Octreotide/administration & dosage , Octreotide/adverse effects , Octreotide/pharmacokinetics , Octreotide/therapeutic use , Oligodendroglioma/metabolism , Oligodendroglioma/pathology , Oligodendroglioma/radiotherapy , Pilot Projects , Radioisotopes/administration & dosage , Radioisotopes/adverse effects , Radioisotopes/pharmacokinetics , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/pharmacokinetics , Radiotherapy Dosage , Stereotaxic Techniques , Tissue Distribution , Ytterbium/administration & dosage , Ytterbium/adverse effects , Ytterbium/pharmacokinetics
14.
Phys Med Biol ; 42(9): 1727-36, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9308079

ABSTRACT

Recently, Yb-169 has been considered as a potential replacement for I-125 and Pd-103 in permanent implants. In spite of the uncertainties in the parameters necessary for an accurate radiobiological modelling, the linear quadratic model can be useful in the comparative evaluation of the radiotherapeutic merit of similar implants. In order to find out if a Yb-169 permanent implant can be made biologically 'equivalent' to an I-125 implant, we studied the dependence of local control on the tumour cell radiosensitivity and on the balance between the rate of tumour cell killing and tumour cell proliferation, for rapidly and slowly proliferating tumours. The extrapolated response dose (ERD) has been calculated for tumour and late reacting normal tissue for both types of implants and the possible biological restrictions due to the normal tissue tolerance have been discussed. Our theoretical analysis is consistent with the clinical results published for I-125 permanent implants in prostate tumours and meningiomas. It predicts that Yb-169, which has only recently been used in human tumours, can provide comparable tumour control for permanent implants in slowly proliferating tumours with an initial dose rate of 13 cGy h-1. Control might be extended to rapidly proliferating tumours by increasing the initial dose rate within a range consistent with an acceptable level of normal tissue late reaction.


Subject(s)
Brachytherapy/methods , Iodine Radioisotopes/administration & dosage , Radioisotopes/administration & dosage , Ytterbium/administration & dosage , Biophysical Phenomena , Biophysics , Cell Death/radiation effects , Cell Division/radiation effects , Half-Life , Humans , Iodine Radioisotopes/therapeutic use , Neoplasms/pathology , Neoplasms/radiotherapy , Radiobiology , Radioisotopes/therapeutic use , Relative Biological Effectiveness , Ytterbium/therapeutic use
15.
Phys Med Biol ; 40(8): 1317-30, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7480115

ABSTRACT

Unlike previous brachytherapy sources a number of published studies have been addressed to the dosimetry of 169 Yb seeds, manufactured in several prototypes, before widespread clinical use has been made. Discrepancies seen in the dosimetry obtained for ytterbium seed prototypes appear to be related to inconsistency and non-reproducibility in the vendor's calibration procedure to determine contained activity. Av. The comparison of 169 Yb seed dosimetries demonstrates a need for more accurate implementation of calibration procedures to determine the air kerma rate for the definitive 169 Yb seed design. This paper reports an experimental procedure to determine the reference air kerma rate, Kr (mu Gy h-1), defined as the kerma rate at 1 m along the source transverse axis in free space for the new 169 Yb seed, model X1267. A mean value of the ratio Kr/Av = 1.53 mu Gy h-1 mCi-1 was obtained from determining the Kr value of eleven seeds. Since this ratio is only 3% less than the air kerma rate constant for the 169 Yb point source, (gamma delta)k = 1.58 mu Gy h-1 m2 mCi-1, this means that the Av is closer to an apparent activity than a contained activity, Ac. A Monte Carlo simulation to determine the ratio between reference air kerma rate and the contained activity gave Kr/Ac = 1.33 mu Gy h-1 mCi-1. For the dose rate constant in water we obtained DKr (1, pi/2) = 1.20 +/- 0.05 cGy h-1 (mu Gy h-1)-1, using calibrated thermoluminescent dosimeters (TLDs) and DKr (1, pi/2) = 1.21 +/- 0.03 cGy h-1 (mu Gy h-1)-1 by Monte Carlo simulation. TLDs were used both to determine the radial dose distribution along the seed transverse axis and to calibrate GAFChromic films to obtain the two-dimensional dose distribution around the seed.


Subject(s)
Brachytherapy/methods , Radioisotopes/administration & dosage , Thermoluminescent Dosimetry/methods , Ytterbium/administration & dosage , Biophysical Phenomena , Biophysics , Computer Simulation , Humans , Monte Carlo Method , Radiation Dosage , Radioisotopes/therapeutic use , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Thermoluminescent Dosimetry/statistics & numerical data , Ytterbium/therapeutic use
16.
Phys Med Biol ; 40(8): 1331-8, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7480116

ABSTRACT

The adequacy of an interstitial implant carried out with a new radioactive source, the 169 Yb seed model X1267, has been examined by computing volumetric indices based on dose-volume histograms. The comparison of these indices with the ones computed for 125I seed implantations shows that the use of ytterbium seeds presents an improvement of the dose homogeneity in interstitial implants. This is due to the significant build-up associated with 169 Yb photons that reduces the rapid dose fall-off with the distance from the source. Moreover, relative to 192Ir, the lower photon energy gives 169 Yb the advantage in clinical use of reduced radiation exposure (i) to health care workers, (ii) to relatives of treated patients and (iii) to healthy neighbouring tissues of the patients if appropriate thin shielding is used.


Subject(s)
Brachytherapy/methods , Radioisotopes/administration & dosage , Ytterbium/administration & dosage , Biophysical Phenomena , Biophysics , Computer Simulation , Humans , Iridium Radioisotopes/administration & dosage , Iridium Radioisotopes/therapeutic use , Photons , Radioisotopes/therapeutic use , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Ytterbium/therapeutic use
17.
Phys Med Biol ; 40(5): 741-56, 1995 May.
Article in English | MEDLINE | ID: mdl-7652005

ABSTRACT

Ytterbium-169 (169Yb) is a promising new intermediate low-energy isotope for interstitial implantation. To date, no air kerma strength (SK) standard for this source exists that can serve as a sound foundation for comparing various dose measurements and theoretical calculations. We have solved this problem by adapting the free air measurement technique of Goetsch et al, originally developed for 192Ir. Using a 100 cm3 spherical ion chamber with NIST traceable external beam calibrations in a free air geometry, we have measured the air kerma strength of six different source batches (two type 6 batches, three type 8 batches, and one experimental high-intensity source). Room scatter corrections, derived from an empirical fit to the data (following Goetsch et al) and/or directly by Monte Carlo simulation, yielded identical results with a reproducibility of 1%. The ratio [SK/Avendor] of measured SK to the vendor's contained activity assay averaged 1.554 cGy cm2 mCi-1 h-1 (0.0420 microGy m2 MBq-1 h-1), in conflict with the expected value of 1.34 (0.0362), derived from Monte Carlo calculations. The measured [SK/Avendor] for the type 8 seeds varies by as much as 10% whereas the SK/dose calibrator reading ratio varies by no more than 0.3%, suggesting that the reproducibility of Avendor is relatively poor. These discrepancies may help explain the variation (as large as 28%) in published dose rate constants for 169Yb.


Subject(s)
Brachytherapy/standards , Radioisotopes/standards , Ytterbium/administration & dosage , Ytterbium/standards , Air , Biophysical Phenomena , Biophysics , Humans , Monte Carlo Method , Radioisotopes/administration & dosage , Radiometry/instrumentation , Reference Standards , Scattering, Radiation
18.
Nuklearmedizin ; 32(2): 99-105, 1993 Apr.
Article in German | MEDLINE | ID: mdl-8479937

ABSTRACT

169Yb complexes with known biokinetics in tumour-bearing mice up to 48 h p.i. were injected into healthy mice to study the radionuclide biodistribution in various organs and tissues for 672 h after injection, in order to obtain reliable biokinetic data in an animal model, not affected by tumour-growth, as a basis for the calculation of biological half-life and dose distribution. The results demonstrated the existence of at least two components with different biological half-lives in the organs and tissues investigated. The effective half-lives of these components decreased with increasing stability of the complexes administered. The effective half-life of the fast component was a few hours and that of the slow one between about 200 and 800 h.


Subject(s)
Citrates/pharmacokinetics , Edetic Acid/analogs & derivatives , Nitrilotriacetic Acid/pharmacokinetics , Radioisotopes/pharmacokinetics , Ytterbium/pharmacokinetics , Animals , Citrates/administration & dosage , Citric Acid , Edetic Acid/administration & dosage , Edetic Acid/pharmacokinetics , Injections, Intravenous , Male , Mice , Mice, Inbred Strains , Nitrilotriacetic Acid/administration & dosage , Radioisotopes/administration & dosage , Time Factors , Tissue Distribution , Ytterbium/administration & dosage
19.
J Anim Sci ; 69(11): 4611-6, 1991 Nov.
Article in English | MEDLINE | ID: mdl-1752833

ABSTRACT

Six ruminally fistulated crossbred steers (BW = 369 kg) were used in a randomized complete block experiment to test the efficacy of continuous-infusion pumps and controlled-release boluses for administering external markers to predict fecal output. Steers, limit-fed chopped alfalfa hay at 2% of BW daily, were fitted with continuous-infusion pumps that administered Co-EDTA and YbCl3 solutions intraruminally. In addition, a controlled-release bolus containing Cr2O3 was inserted into the rumen of each steer. Fecal grab samples were taken every 6 h for 7 d during initial marker equilibration; after this period, fecal grab samples were taken every 3 h for 48 h to evaluate diurnal variation patterns. Steers were subsequently fitted with fecal bags for 7 d to allow total fecal collection. Grab samples also were taken during the total fecal collection period at 0600 (AM) and 1400 (PM). The marker X time effect was nonsignificant. Similarly, time of grab sampling (AM or PM) did not affect estimates of fecal output (P greater than .10), but the Cr2O3 bolus overestimated fecal output (P less than .05). Fecal marker concentrations during the 48-h profile showed little diurnal variation regardless of marker used. All markers equilibrated in the feces at approximately 100 to 120 h after initiating infusions. The continuous-infusion pumps evaluated were efficacious for administering markers for estimating total fecal output in limit-fed steers; however, the Cr2O3 boluses evaluated overestimated fecal output when the manufacturer's suggested release rate was used for fecal output calculations.


Subject(s)
Cattle/physiology , Cobalt , Defecation , Feces/chemistry , Ytterbium , Animals , Chromium/administration & dosage , Cobalt/administration & dosage , Delayed-Action Preparations , Infusion Pumps/veterinary , Male , Ytterbium/administration & dosage
20.
Int J Appl Radiat Isot ; 35(12): 1134-5, 1984 Dec.
Article in English | MEDLINE | ID: mdl-6530303

ABSTRACT

The incorporation of Se and Yb into the eyes of mice has been studied. Selenodiglutathione, (GS)2Se, or ytterbium chloride, YbCl3, were injected intraperitoneally into mice: either alone, combined, or after various time intervals. Instrumental neutron activation analysis was applied as the analytical method for the determination of the levels of Se and Yb. The concentrations of both investigated elements were highest in the retinal tissue of the eye. YbCl3 influenced the distribution of Se in the eye.


Subject(s)
Eye/metabolism , Selenium/metabolism , Ytterbium/metabolism , Animals , Chlorides/administration & dosage , Injections, Intraperitoneal , Male , Mice , Tissue Distribution , Ytterbium/administration & dosage
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