RESUMEN
Galactose-targeted delivery of macromolecules and drug conjugates to asialoglycoprotein receptor (ASGPR) positive cells has been widely documented in animals, although targeting in humans has never been demonstrated. In this study we report the pharmacokinetics and imaging determined in the first patient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)methacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK2. Gradient high performance liquid chromatography (HPLC) evaluation of plasma and urine has been combined with 123I-based imaging to show biphasic clearance of the drug from the plasma (half-lives of 78+/-1 and 990+/-15), and approximately 30% delivery of the drug to the hepatic region, as determined by planar whole body imaging at 24 h. This patient has a multifocal hepatoma, and single photon emission computed tomography (SPECT) analysis showed a ratio of tumour tissue to normal liver uptake of approximately 1:3, at 24 h. On the basis of this patient, effective hepatic targeting can be achieved following an intravenous dose of 20 mg/m2 doxorubicin as PK2, however the therapeutic usefulness of this targeted drug has yet to be established.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacocinética , Daunorrubicina/farmacocinética , Galactosamina/administración & dosificación , Galactosamina/farmacocinética , Ácidos Polimetacrílicos/farmacocinética , Biotransformación , Carcinoma Hepatocelular/tratamiento farmacológico , Portadores de Fármacos , Humanos , Radioisótopos de Yodo , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Tomografía Computarizada de Emisión de Fotón Único , Recuento Corporal TotalRESUMEN
A prospective survey was performed in 17 nuclear medicine departments during 1996 in an attempt to provide reliable data on the prevalence of adverse reactions to radiopharmaceuticals. All adverse events following radiopharmaceutical administration were recorded, irrespective of the severity or likelihood of causality, and subsequently analysed using an algorithm developed by Silberstein et al., designed to establish a cause-effect relationship. A prevalence of 11 events per 10(5) administrations was obtained (95% confidence limits 3.3-19.2). No serious of life-threatening events were reported. This rate is slightly higher than that obtained in a larger scale study in the United States (2.3 events per 10(5) administrations, 95% confidence limits 1.2-3.4). The difference may be due to the decision to include or exclude vasovagal events from the analysis, the way in which the algorithm was used and the comparative size and time scale of the two studies. The prevalence of adverse reactions is approximately 1000-fold than less that occurring with iodinated contrast media and drugs.
Asunto(s)
Radiofármacos/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Algoritmos , Recolección de Datos , Europa (Continente)/epidemiología , Humanos , Prevalencia , Estudios ProspectivosRESUMEN
An audit document is presented which can be used to assess the radiopharmacy service in a particular institute. It can be used for self-assessment or can form the basis for peer review. The document covers a wide range of aspects of radiopharmacy. It is acknowledged that the document will need constant review and where appropriate, modification, in order to reflect changes in practice or legislation.
Asunto(s)
Servicio de Farmacia en Hospital/organización & administración , Radioisótopos/normas , Recolección de Muestras de Sangre , Humanos , Revisión por Pares , Servicio de Farmacia en Hospital/normas , Garantía de la Calidad de Atención de Salud , Control de Calidad , Seguridad , Autoevaluación (Psicología) , Encuestas y CuestionariosRESUMEN
Considerable information on documented drug and radiopharmaceutical interactions has been assembled in a tabular form, classified by the type of nuclear medicine study. The aim is to provide a rapid reference for nuclear medicine staff to look for such interactions. The initiation of drug chart monitoring or drug history taking of nuclear medicine patients and the reporting of such events are encouraged.
Asunto(s)
Interacciones Farmacológicas , Preparaciones Farmacéuticas , Radioisótopos , Cintigrafía , HumanosRESUMEN
Platelet concentrates (PCs) were stored for 4 days at 22 degrees C in 400 ml second-generation (PL1240) platelet packs with either constant agitation, manual mixing once every 24 h or without agitation at any time. After 4 days storage, in vivo recovery, survival and biodistribution were determined following indium-111 labelling of platelets and infusion into autologous volunteers. In vitro assays of platelet function and biochemistry were likewise carried out after 4 days storage. The PCs stored without agitation had significantly lower in vivo recoveries, pH and aggregation responses to ionophore A23187 and a combination of collagen and epinephrine and significantly higher beta-thromboglobulin and indium-111 release than the agitated PCs. The manually mixed PCs were not significantly different from the constantly agitated PCs. PCs mixed simply once every 24 h remained viable with active oxidative phosphorylation and a pH above 6.74 in all but 1 case indicating that PCs stored at 22 degrees C for up to 4 days with only intermittent mixing are satisfactory for transfusion. A change from constant agitation would reduce capital costs in mixing equipment and simplify the transport of PCs from the transfusion centre to small hospital blood banks.
Asunto(s)
Bancos de Sangre/normas , Plaquetas , Conservación de la Sangre/métodos , Supervivencia Celular , Femenino , Cámaras gamma , Humanos , Masculino , Control de Calidad , Reino Unido , VibraciónRESUMEN
We report the results of imaging with labelled white cells in 52 patients before the revision of 54 cemented joint prostheses at which the diagnosis of infection was made from biopsies. Twenty-five hips were imaged with 111In-oxine-labelled cells; 20 hips and 11 knees were imaged with 99mTc-hexamethylpropylene-amineoxime-labelled cells. Of these, 13 hips and five knees proved to be infected. The scans taken together had an accuracy of 82%, a sensitivity of 44% and a specificity of 100%. Indium scans gave 37% sensitivity, 99mTc labelling 50% sensitivity. Infected arthroplasties with positive scans had presented significantly earlier than those with negative scans, the time after the original insertion being 1.1 years for the true-positive scans and 6.1 years for the false-negative scans. The value of labelled white-cell scans in the detection of infection in failed joint replacements is dependent on the activity of the infection. There is reduced sensitivity to the more insidious infections which affect arthroplasties and aspiration under controlled conditions remains an important investigation.
Asunto(s)
Prótesis de Cadera/efectos adversos , Prótesis de la Rodilla/efectos adversos , Leucocitos , Compuestos Organometálicos , Compuestos de Organotecnecio , Oximas , Oxiquinolina/análogos & derivados , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Biopsia con Aguja/normas , Diagnóstico Diferencial , Estudios de Evaluación como Asunto , Humanos , Radioisótopos de Indio , Infecciones Relacionadas con Prótesis/epidemiología , Cintigrafía , Sensibilidad y Especificidad , Exametazima de Tecnecio Tc 99m , Factores de TiempoRESUMEN
BACKGROUND: The aim of this study was to elucidate the inflammatory infiltrate in pouchitis and define the changes following metronidazole therapy. METHODS: Twenty-seven patients underwent functional grading, sigmoidoscopic and histological scoring, 111In-labeled granulocyte scanning, and 4-day fecal collections for 111In-labeled granulocyte excretion. Six of the patients with pouchitis underwent repeat studies after 1-month treatment with metronidazole, 400 mg three times daily. RESULTS: The grade of macroscopic inflammation in the pouch mucosa (sigmoidoscopic score) correlated well with the acute histological score (P < 0.0001), chronic histological score (P < 0.001), 4-hour 111In scan (P < 0.001), 24-hour 111In scan (P < 0.001), and with 4-day fecal 111In excretion (P < 0.001). After metronidazole therapy there was decreased inflammatory grade sigmoidoscopically and histologically on the 4- and 24-hour scans and decreased 4-day fecal 111In granulocyte excretion. CONCLUSIONS: This study confirms that the inflammatory infiltrate in pouchitis is acute or chronic, is characterized by neutrophils, is usually localized to pouch mucosa, and is always decreased after metronidazole therapy.
Asunto(s)
Granulocitos/fisiología , Radioisótopos de Indio , Inflamación/fisiopatología , Mucosa Intestinal/patología , Metronidazol/uso terapéutico , Proctocolectomía Restauradora/efectos adversos , Enfermedad Aguda , Biopsia , Enfermedad Crónica , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/patología , Granulocitos/patología , Humanos , Inflamación/tratamiento farmacológico , SigmoidoscopíaRESUMEN
A polymer-coated capsule has been used in eight volunteer subjects to deliver 111In-resin into the ileocaecal region. The images were acquired for up to 3 days to follow transit through the colon. Expressing the results of individual studies is difficult and time-activity curves for each region are confusing. Calculation of the geometric centre indicates only where the middle of the activity has reached. We describe a new method of presenting colonic transit data as parametric images. The parametric images show the amount of activity in each area of interest as the study progresses. This is readily understood and allows segmental movement of the isotope, either forward or retrograde, to be examined. The geometric mean of activity in four areas of the colon were also calculated. Four hours after reaching the ileocaecal region, 65% (S.D. 24%) of the activity was in the caecum and 26% (S.D. 20%) in the transverse colon. By 24 h three controls had excreted most of the activity, in two the activity was mainly in the rectum and in two there was still some activity in the transverse colon. A protocol for colonic transit studies, problems with analysis and a new method of presentation of data are discussed.
Asunto(s)
Colon/fisiología , Tránsito Gastrointestinal , Radioisótopos de Indio , Resinas Acrílicas , Adulto , Cápsulas , Colon/diagnóstico por imagen , Femenino , Humanos , Radioisótopos de Indio/administración & dosificación , Masculino , Persona de Mediana Edad , Ácidos Polimetacrílicos , CintigrafíaRESUMEN
A 48-year-old woman presented with disseminated cholangiocarcinoma and diffuse joint pain. A technetium 99m methylene diphosphonate bone scan revealed no bony abnormality, but intense bilateral renal uptake was seen. There was temporary renal impairment following imaging, but the cause of this is uncertain. An association between cholangiocarcinoma and 'hot kidneys' on bone imaging scanning has not been previously reported.
Asunto(s)
Adenoma de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Riñón/diagnóstico por imagen , Medronato de Tecnecio Tc 99m , Femenino , Humanos , Persona de Mediana Edad , CintigrafíaRESUMEN
Analysis of the workload of a nuclear medicine department over the period 1982 to 1986 has shown the prevalence of repeated investigations in individual patients. Records from 23,152 investigations on 17,063 patients indicated that 88.5% received a single administration and only 0.5% received more than four doses of the same radiopharmaceutical. Patterns of usage of a wide range of radiopharmaceuticals are presented and show that the technetium bone imaging agent is the radiopharmaceutical most commonly used for repeated administrations. Analysis of the radiation dose to individual patients arising from radiopharmaceutical administration has shown that only two patients in the survey exceeded 50 mSv per annum and approximately 25% of patients exceeded 5 mSv per annum.
Asunto(s)
Departamentos de Hospitales , Servicio de Medicina Nuclear en Hospital , Radioisótopos , Cintigrafía/estadística & datos numéricos , Inglaterra , Humanos , Dosis de Radiación , TecnecioRESUMEN
The application of the 1985 Ionizing Radiations Regulations and Approved Code of Practice to a typical Nuclear Medicine Department has been considered. References to the Regulations are given so that their implications in a given department may be examined. The radiopharmacy, radioisotope dispensary and injection room will need to be Controlled Areas. It will also be necessary to designate Controlled Areas if radiopharmaceuticals are injected in imaging rooms or on wards. Waiting rooms will need to be Controlled Areas. The area around individual patients will, however, not need to be Controlled except for some patients receiving therapeutic doses of 131I for thyrotoxicosis. It should not generally be necessary to designate employees as Classified persons. Major problems in implementing the Regulations are not envisaged in situations where the previous Code of Practice has been followed.
Asunto(s)
Regulación y Control de Instalaciones/legislación & jurisprudencia , Departamentos de Hospitales/legislación & jurisprudencia , Servicio de Medicina Nuclear en Hospital/legislación & jurisprudencia , Enfermedades Profesionales/prevención & control , Protección Radiológica , Inglaterra , Humanos , Radioisótopos de Yodo , Radioisótopos de Fósforo , SeguridadRESUMEN
The radiation dose to the pulp of both index fingers has been measured in a radiopharmacy supplying 11 000 patient doses a year, in a hospital dispensary (4500 doses a year) and in its injection area. Tungsten syringe shields were used for one week and not used during the other week. In the radiopharmacy and the dispensary the highest finger dose recorded was 6.8 mSv, which corresponds to an annual figure of 330 mSv. Syringe shields gave a protection factor of less than two, and the dose to the left hand was approximately half that to the right. When giving injections the corresponding weekly and annual doses were 4.6 and 220 mSv respectively. If all injections had been given by a single person the corresponding annual dose would have been 430 mSv. Using syringe shields this could be reduced by factors of at least eight for the right hand but only 1.3 for the left hand. Dose rates for unshielded syringes expressed per 10 GBq handled are similar to other data in the literature. However, syringe shields reduce the dose rates less than anticipated. Tungsten 1.94 to 3.05 mm thick would be expected to give an attenuation factor of 27 to 178.