[The radiolabeled blood cell: Finding a legal qualification]. / La cellule sanguine marquée par un radionucléide : recherche d'une qualification juridique.

Radiolabelling of blood cells is a technique commonly used as a diagnostic tool in nuclear medicine; it has never been legally defined. This lack of legal status is a factor of uncertainty for both patients and health care professionals. The aim of this work was to identify what could be the legal nature of the radiolabelled blood cells by comparing their constitutive elements to the various existing legal categories applicable, according to the law applicable to living organisms as well as the regulations for other health products. The study concludes that, as it stands, the radiolabelled blood cells undoubtedly belong to the category of a drug by function for diagnostic purpose. More precisely, it is compared to a radiopharmaceutical medicinal product resulting from a well characterised manufacturing process. In order to increase visibility and thus the actors' awareness of the constraints arising from this specific status, it is proposed to create a specific legal regime for the radiolabelled blood cells by including in Article L. 5121-1 of the French Public Health Code a new category of health product which could be called: radiopharmaceutical preparation of cellular blood component for diagnostic purposes. The consequence of this proposal will mechanically place the radiolabelled blood cell preparation under the exclusive competences of radiopharmacists practising in an hospital pharmacy. Another important consequence will be that the radiolabelling process of blood cells will have to fulfil the rules of the French good hospital pharmacy practices and good preparation practices, for the benefit of patient protection and safety.

18F-FDG labelling of hematopoietic stem cells: Dynamic study of bone marrow homing by PET-CT imaging and impact on cell functionality.

PURPOSE OF THE STUDY: After transplantation, cord blood (CB) hematopoietic stem and progenitor cells (HSPCs) are able to home to the bone marrow niche and to reconstitute the hematopoietic system. PET-CT imaging may be a useful method to monitor this parameter in different conditions. The aim of our study was to set up an efficient method for HSPC radiolabelling with [18F] fluorodeoxyglucose (18F-FDG) and to follow early HSPC homing through PET-CT in mice. MATERIALS AND METHODS: Purified CB HSPCs were radiolabelled with 18F-FDG at 37° C with various conditions of cell concentration, incubation time and radioactivity concentration in order to define the in vitro condition that allows both sufficient 18F-FDG uptake to get high quality PET imaging, and preservation of HSPC viability and functional properties during 3h after radiolabelling. Then, 24h after 2.25Gy irradiation, eight NOD-scid/γc-/- mice were injected with 18F-FDG-labelled HSPCs, the biodistribution of which was followed using micro-PET-CT. RESULTS: The optimal incubation time was 45min with a stability of 48.3%±12.8% after 180min. The radio-uptake rate we obtained was 7.2%±1.7% with an activity of 5.6±2.1 MBq. Three hours after radiolabelling, viability was 96.7%±3.4%. Fifteen hours after radiolabelling, cell viability was 64.0%±2.3%, migration ability diminished from 51.0%±23.6% to 12.0%±9.1%, clonogenic capacity was null, and long-term engraftment in NSG mice also decreased compared to unlabelled cells. Micro-PET-CT experiments showed an accumulation of radiolabelled HSPCs for 2.5h after injection in the bone marrow and a slight elution of 18F-FDG. CONCLUSION: The activity of the obtained 18F-FDG-labelled HSPCs was sufficient to perform the micro-PET-CT imaging. Although the radiolabelling had a significant toxicity on HSPCs 15h after labelling, this technique allowed monitoring the beginning of HSPC homing into the bone marrow.

[Extravasation of radiopharmaceuticals: preventive measures and management recommended by SoFRa (Société Française de Radiopharmacie)]. / Extravasation des médicaments radiopharmaceutiques : mesures préventives et prise en charge recommandées par la SoFRa (Société française de radiopharmacie).

Radiopharmaceuticals extravasation is rare but may have serious clinical issues. Because no specific recommendations are being proposed to date, the goals of our working group created within the French Society of Radiopharmacy are to determine preventive measures and to establish a pragmatic management of extravasation of these drugs. Our preventive measures are to recognize the symptoms (erythema, venous discoloration, swelling), to know the risk factors (which are related to radiopharmaceutical, patient, site of injection, injection technique) and severity (from erythema to skin necrosis, depending on the radionuclide) and how to avoid them (training and awareness of staff, choice of injection site, route of drug administration test, use of a catheter for administration of therapeutic radiopharmaceuticals). Management should be immediate. It can be facilitated by a specific emergency kit. General measures recommended are the immediate cessation of injection, aspiration of fluid extravasation, delimitation of the extravasated area with an indelible pen, informing the doctor. Specific measures taking into account the radiotoxicity of the radionuclide and the type of radiopharmaceutical were also established. The patient should be informed by the doctor about the risks and how to take care of. Traceability of the incident must be ensured. A multidisciplinary reflexion is essential to manage the extravasation as early and effectively as possible.

[Stable iodine as a prophylaxis therapy following exposure to radioactive iodines: pharmacological and pharmaceutical characteristics]. / Iode stable et prévention de la contamination par les iodes radioactifs : données pharmacologiques et pharmaceutiques.

More or less rapid radio-induction of thyroidian cancers is the main pathological consequence of an accidental exposure to ingested or inhaled radioactive iodines following a nuclear power plant accident. The prophylactic administration of potassium iodine in a single oral dose has to be practiced as soon as possible after the nuclear accident. The efficacy of this therapy depends on pharmacokinetics of radioidines. Iodines are rapidly and completely absorbed as iodides. The radioactive iodines, mainly iodine 131, concentrate in the thyroid gland because of a carrier-mediated transport by the Na-I symporter. Administration of stable iodine results in the symporter blockade, which limits the uptake of radioactive iodines by the thyroid and the duration of the internal irradiation. This irradiation will never exceed 3days if the therapy is started between 6h before the accidental exposure and 1h after. The pharmacist asked to dispense the tablets of stable iodine has a important place because, besides his advices on the optimal modalities of taking stable iodine and the risks of unwanted effects, he extend these advices to information on the radioactive risk and on measures of civil and sanitary protection.

[Evaluation of the performance of transfer devices in a closed system using a radioactive solution of [(99m)Tc]]. / Évaluation de la performance de dispositifs de transfert en système clos au moyen d'une solution radioactive de [(99m)Tc].

INTRODUCTION: The exposure of workers to antineoplastic agents is potentially dangerous in the long term because of the teratogenic, carcinogenic and mutagenic hazardous of these products. These risks could be reduced by individual and collective shield measures. It's recommended to use transfer devices in a closed system for preparation of chemotherapy. METHOD: The aim of the survey is to analyse for five devices (four devices in a closed system transfer and a needle equipped with an air intake), the following criteria: transfer performance of a solution of a vial to another one, no leakage of the device and practicality in the use. A method implementing a radioactive solution of sodium pertechnetate [(99m)Tc] is used. RESULTS: Teva(®) and Cardinal(®) devices seem to be more efficient according to the ability to transfer one solution from a vial to another one with a low dead volume and low-level contamination in the around of the manipulation area. The Hospira(®) device appears an intermediate solution, while the Phaseal(®) device may be irrelevant for the transfer of a solution. DISCUSSION-CONCLUSION: Our study could attest that the methodology is simple to implement and cheap to compare devices on multiple selection criteria. This evaluation method is interesting because it allows a classification according to several criteria weighted according to the type of intended use. In addition to economic issues and protection of the worker, the use of such devices should be extended to other areas as the preparation of chemotherapy such as preparation of radiopharmaceuticals drugs.

[Contribution of radioimmunotherapy to the treatment of lymphoma]. / Apport de la radio-immunothérapie au traitement des lymphomes.

Radioimmunotherapy (RIT) is an emerging treatment option for non-Hodgkin's lymphoma. Only Zevalin (Bayer Schering Pharma) radiolabeled with yttrium 90 ((90)Y) is approved in France for the treatment of adult patients with rituximab relapsed or refractory CD20+ follicular B-cell non-Hodgkin's lymphoma. This radioimmunotherapeutic agent consists of ibritumomab, a murine anti-CD20 monoclonal antibody, conjugated to the metal chelator tiuxetan for retention of the beta emitter (90)Y. This review presents the concept of RIT. The pharmacological characteristics of [(90)Y]-ibritumomab tiuxetan, the specificity of its preparation and its special precautions for use will be described. The other radionuclides and antibodies in development will also be mentioned.

[Hospital and environment: waste disposal]. / Hôpital et environnement: l'élimination des déchets.

Like all production units, hospitals produce waste and are responsible for waste disposal. Hospital waste is particular due to the environmental risks involved, particularly concerning infection, effluents, and radionucleide contamination. Management plans are required to meet environmental, hygiene and regulatory obligations and to define reference waste products. The first step is to optimize waste sorting, with proper definition of the different categories, adequate containers (collection stations, color-coded sacks), waste circuits, intermediate then central storage areas, and finally transfer to an incineration unit. Volume and delay to elimination must be carefully controlled. Elimination of drugs and related products is a second aspect: packaging, perfusion pouches, tubing, radiopharmaceutic agents. These later products are managed with non-sealed sources whose elimination depends on the radioactive period, requiring selective sorting and specific holding areas while radioactivity declines. Elimination of urine and excreta containing anti-cancer drugs or intravesical drugs, particularly coming from protected rooms using radioactive iodine is another aspect. There is also a marginal flow of unused or expired drugs. For a health establishment, elimination of drugs is not included as part of waste disposal. This requires establishing a specific circuit with selective sorting and carefully applied safety regulations. Market orders for collecting and handling hospital wastes must be implemented in compliance with the rules of Public Health Tenders.

A comparison of radiopharmaceutical agents used for the diagnosis of pulmonary embolism.

Radioactive gas or technetium-99m aerosols are used to perform pulmonary ventilation scintigraphy. The aim of this study was to compare three radiopharmaceuticals, Kryptoscan, Technegas and Venticis II, in terms of their costs and user preferences rather than on the basis of diagnostic efficacy. For each radiopharmaceutical agent, an analysis questionnaire was sent to nuclear medicine departments setting out the criteria (and subcriteria) to be assessed: diagnosis quality: imaging quality, distribution homogeneity, examination procedures and capacity to examine particular patients (e.g. smokers); safety: for patient, paramedical and medical staff and the environment; use: availability in cases of emergency, ergonomics of the apparatus, simplicity and time of preparation. A score, ranging from 0 to 5, and a weighting (importance of one criterion with regard to the others) were assigned to each criterion. The direct cost of a ventilation (drugs, generator systems, disposable materials) was calculated for each radiopharmaceutical agent according to the number of patients examined per day (1-6) and the number of examination days per week (2-5). Fourteen questionnaires concerning at least two of the products were returned out of the 30 mailed. A 'preference score' was calculated using Pharma Decision software. The mean score of Kryptoscan was significantly higher than that of Venticis II (444 vs. 286, P < 0.001) and higher than the mean score of Technegas (444 vs. 344, P < 0.01). For Venticis II and Technegas, the changes in patient direct costs were minor and depended on the number of patients per day and the number of examination days per week. Respectively, they were: $US 117.66 (5 patients.day-1; 5 days.week-1) to $US 147.74 (2 patients.day-1; 2 days.week-1) and $US 56.60 (6 patients.day-1; 5 days.week-1) to $US 132.08 (2 patients.day-1; 2 days.week-1). The direct cost of ventilation using Kryptoscan varied only according to the number of patients examined per day: $US 104.66 (6 patients.day-1) to $US 266.47 (2 patients.day-1). This study shows that Kryptoscan appears to be preferable for ventilation scintigraphy whenever at least four patients are examined daily.