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.