RESUMEN
An automated, portable 178W/178Ta generator system has been developed for use in first-pass radionuclide angiography studies with the multiwire gamma camera. Eluant (0.03N HCI, 0.1% H2O2) and buffer (0.13 N Na2HPO4) are delivered with a dual channel peristaltic pump. The generator column is a borosilicate glass tube with 30 microns fused glass frit containing 0.75 ml AG1X8 anion exchange resin. This column and associated plumbing are assembled, integrally autoclaved, and then connected to sterile eluant and buffer containers. Automatic push-button elution directly into an injection syringe is provided. Three such generators have been employed in the study of 78 patients in the catheterization laboratory utilizing a mobile, multiwire gamma camera. Over a 3-mo period, 301 sterile pyrogen-free doses ranging from 15 to 99.5 mCi were supplied with a mean breakthrough level of 2.1 +/- 3.6 microCi. This automated, portable, high-yield 178W/178Ta generator represents a major advancement that will significantly facilitate first-pass radionuclide angiography with 178Ta and the multiwire gamma camera.
Asunto(s)
Radioisótopos , Generadores de Radionúclidos/instrumentación , Tantalio , Tungsteno , Ventriculografía de Primer Paso , Angioplastia Coronaria con Balón , Diseño de Equipo , Cámaras gamma , HumanosRESUMEN
An objective approach to determine whether there was an advantage of using 99mTc-MDP or 99mTc-HMDP for bone imaging, particularly in elderly subjects, was evaluated by measuring the bone to soft-tissue ratio in relation to age. This was done by quantifying analog images of the femoral region by using an optical densitometer. A ratio (mean for right and left thighs) was determined for mid-femur to adjacent soft-tissue. These values were analyzed in relation to the age of patients studied with either MDP or HMDP. Little correlation with age was observed. An analysis at 10-year intervals of age indicated a decline in the ratio after 70 years, without any significant difference between MDP and HMDP.
Asunto(s)
Envejecimiento , Huesos/diagnóstico por imagen , Medronato de Tecnecio Tc 99m , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , CintigrafíaRESUMEN
Through the use of iododemercuration, 5-[123/125I]iodo-2'-deoxyuridine was synthesized rapidly and with high radiochemical purity from 5-chloromercuri-2'-deoxyuridine. The synthesis of radioiodinated 2'-deoxyuridine was achieved in one step in the presence of Iodogen in 50% yield after isolation by reverse phase high performance column chromatography. The radiochemical purity was greater than 99%. The ease and the absence of any starting material, suggests that radiohalodemercuration may be the method of choice for this and structurally similar compounds.
Asunto(s)
Idoxuridina/síntesis química , Radioisótopos de Yodo , MétodosRESUMEN
We have developed a simple, rapid, and reproducible method for conjugating the bifunctional metal chelator diethylenetriaminepentaacetic acid (DTPA) to an IgM monoclonal antibody (MoAb) without first isolating the MoAb from the ascites fluid. Treatment of the protein mixture in the ascites fluid with cyclic DTPA anhydride (cDTPAA) followed by HPLC purification on a size exclusion column allowed isolation of the DTPA-IgM conjugate which could then be labeled with 111In in greater than or equal to 80% yield. Over the range of total protein concentrations used (11-44 mg/mL), the number of DTPA molecules per molecule of IgM was approximately one-half the molar ratio of cDTPAA to total protein. We have used this method to prepare an 111In labeled anti-Thy 1.2 IgM, a MoAb with specificity for a murine cell-surface antigen found on normal and malignant T cells and neuroectodermal tissues. Analysis of the DTPA-IgM conjugate prior to and after 111In labeling using indirect immunofluorescence flow cytometry and a target-cell binding assay showed that the antigen specificity of this anti-Thy 1.2 MoAb is not substantially altered by the presence of up to 8 DTPA molecules per IgM molecule.
Asunto(s)
Anticuerpos Monoclonales , Líquido Ascítico , Inmunoglobulina M , Ácido Pentético , Animales , Antígenos de Superficie , Cromatografía Líquida de Alta Presión , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Técnicas In Vitro , Radioisótopos de Indio , Ratones , Ácido Pentético/análogos & derivados , Antígenos Thy-1RESUMEN
Rhodamine 123, a mitochondrial stain that preferentially accumulates in certain cancer cells, has been reduced and iodinated by using NaI in the presence of N-chlorosuccinimide. The various mono-, di-, and triiodo derivatives have been isolated and characterized. These nonfluorescent compounds are taken up by mammalian cells, become fluorescent within the cytoplasm (presumably following oxidation), and show the same pattern of localization as the parent compound. Iodination with no-carrier-added Na125I yields the same mixture of compounds. All 125I derivatives accumulate preferentially in PC3 adenocarcinoma cells compared with V79 lung fibroblasts, with the differential being greatest for the monoiodo compound, followed by the di- and triiodo derivatives.
Asunto(s)
Radioisótopos de Yodo , Rodaminas/síntesis química , Xantenos/síntesis química , Adenocarcinoma/metabolismo , Animales , Línea Celular , Cricetinae , Cricetulus , Fibroblastos/metabolismo , Humanos , Pulmón/metabolismo , Masculino , Microscopía Fluorescente , Neoplasias de la Próstata/metabolismo , Rodamina 123 , Rodaminas/farmacología , Yoduro de Sodio , SuccinimidasRESUMEN
Rabbit immunoglobulin G (RIgG) was reduced with dithioerythritol and analyzed by high performance liquid chromatography. A quantitative method for determining the percentage of reduced half-molecules in the mixture was developed. An acetic acid concentration-dependent rate of dissociation of reduced half-molecules was observed. The specific optical absorptivity was determined for whole molecules and half-molecules and found to be significantly greater for the half-molecules. Purified half-molecules were reconstituted into RIgG with a yield greater than 90% following a 16 h incubation at pH 8.0 and room temperature.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Inmunoglobulina G/análisis , Acetatos , Ácido Acético , Animales , Especificidad de Anticuerpos , Ditioeritritol , Oxidación-Reducción , Conformación Proteica , ConejosRESUMEN
A simple and efficient method of covalently coupling the strong chelator diethylenetriaminepentaacetic acid to proteins was developed for radiolabeling immunoglobulin G antibodies. After being coupled and labeled with indium-111, a monoclonal antibody to carcinoembryonic antigen retained its ability to bind to its antigen in vitro and in vivo. In nude mice with a human colorectal xenograft, 41 percent of the injected radioactivity became localized in each gram of xenograft at 24 hours compared with 9 percent for control antibody and 19 percent for radioiodinated antibody to carcinoembryonic antigen.
Asunto(s)
Anticuerpos , Marcaje Isotópico/métodos , Animales , Anticuerpos Monoclonales/inmunología , Antígeno Carcinoembrionario/inmunología , Cromatografía Líquida de Alta Presión , Humanos , Inmunoglobulina G/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Ácido PentéticoRESUMEN
In earlier work, DTPA has been covalently coupled to albumin via the cyclic anhydride of DTPA. Using fibrinogen, we have studied the effect of such coupling on protein viability by both an in vitro and an in vivo assay. Clotting time remained identical to that of the native protein whether the anhydride-to-protein molar ratio was 1:1 or 5:1. In vivo studies were done in dogs, with human fibrinogen labeled with 1-125 and In-111. Throughout 130 hr, blood clearances for the two tracers agreed whether with 1:1 or 5:1 coupling. In a dog model with a thrombogenic catheter, the clot-to-blood ratios for the two radiotracers agreed within experimental error. Finally, 1:1-coupled canine fibrinogen, labeled with In-111, was administered to dogs with a catheter in a jugular vein, and scintigrams at 24 hr clearly showed clotting along the length of the catheter. We conclude that fibrinogen, coupled to DTPA, retains its viability, behaving like radioiodinated fibrinogen in vivo, and In-111 labeled fibrinogen looks promising as a clinical diagnostic agent.
Asunto(s)
Fibrinógeno/metabolismo , Indio , Ácido Pentético/metabolismo , Animales , Perros , Estudios de Evaluación como Asunto , Humanos , Radioisótopos de Yodo , Tasa de Depuración Metabólica , Tiempo de TrombinaRESUMEN
A new method has been developed for the coupling of diethylenetriaminepentaacetic acid (DTPA) to proteins using the cyclic anhydride of DTPA. The anhydride, prepared by a simple one-step synthesis, is added as the solid to the solid protein. Coupling is completed in minutes at room temperature following the addition of aqueous pH 7 buffer. The coupling has been characterized by the use of exhaustive dialysis, gel chromatography, and u.v. spectrophotometry. Under optimal conditions of anhydride: protein molar ratio and protein concentration, up to 70% of the DTPA groups may be coupled to protein. Essentially all free DTPA may be removed from DTPA-coupled albumin preparations by a single passage through a 20-cm gel filtration column. Biodistributions in normal mice at 45 min obtained for 111In-albumin showed 33 +/- 1% injected dose per gram in blood compared to 35 +/- 3% for 125I-albumin. Results for all tissue samples are in agreement within two standard deviations. The simplicity with which albumin has been coupled with DTPA by this method contrasts sharply with existing methods and is an attractive area of research for the labeling of a variety of proteins with a variety of metallic radionuclides.