Standard Operating Procedure for In-house Preparation of (131)I-rituximab for Radioimmunotherapy of Non-Hodgkin's Lymphoma.

A Standard Operating Procedure (SOP) has been formulated for in-house preparation, quality control, dispensing and administration of (131)I-rituximab appropriate for the safe, effective, radioimmunotherapy of non-Hodgkin lymphoma. A decade of experience of semi-automated radioiodination of rituximab in our hospital radiopharmaceutical laboratory was analysed. The methodology was then refined for safe, practical, affordable application to radioimmunotherapy of lymphoma in departments of nuclear medicine in developing countries. This SOP has the potential to be incorporated into good laboratory practice conditions appropriate for local regulatory agency requirements.

Carry-over effects reveal reproductive costs in a long-distance migrant.

1. It has been known for some time that the consequences of 'decisions' made at one point in an animal's life may not always be borne immediately. For example, numerous studies have demonstrated the trade-off between current and future breeding success across multiple taxa. 2. It is becoming increasingly clear that such processes may also operate among seasons, such that the conditions experienced at one point in the annual cycle may have significant downstream impacts, or 'carry-over effects', and this is particularly evident among migratory species. We might therefore predict that certain combinations of reproductive and migratory strategy could lead to profound carry-over effects. However, the extent to which these phenomena might generate variation in fitness within a population is unclear. 3. Here, we investigate how winter habitat selection in a long-distance migrant, with extended parental care (the Light-bellied Brent goose) is influenced by parental status and how this has a counterintuitive effect on subsequent breeding success. 4. Dominant individuals and groups generally monopolize the best quality resources. In the case of geese, families are dominant; however, our findings highlight a hidden cost to raising a family. Stable isotope analysis demonstrates that later in the non-breeding season, adults with families utilize lower quality resources than non-breeders. This is probably caused by parents being constrained in habitat choice by the lower foraging efficiency of their juveniles. Consequently, parental adults end the winter in poorer condition than non-breeders. 5. We further demonstrate that parents in one year are less likely than expected to breed again in the next year and suggest that this is caused by conditions during the non-breeding period being carried over into the breeding season. In conclusion, we demonstrate previously hidden costs to raising a family, which are likely to be important in terms of life-history evolution.

Delivery of an erythropoietin-Fc fusion protein by inhalation in humans through an immunoglobulin transport pathway.

A novel drug delivery platform has been developed that utilizes a naturally occurring receptor known as the neonatal Fc receptor (FcRn). The receptor is specific for the Fc fragment of IgG and is expressed in epithelial cells where it functions to transport immunoglobulins across these cell barriers. It has been shown that FcRn is expressed in both the upper and central airways in non-human primates as well as in humans. Pulmonary delivery of an erythropoietin- Fc fusion molecule (EpoFc) was previously demonstrated in non-human primates using this FcRn pathway. We have now conducted a phase I clinical study to test whether the FcRn pathway functioned similarly in man using human erythropoietin (Epo) fused to the Fc portion of human IgG1. The design was a three leg, non-randomized study conducted in healthy male volunteers with rising doses (3, 10, and 30 microg/kg) of the fusion protein targeted to the central lung regions. Using a target range of 10-30% vital capacity and 15 breaths per minute, approximately 70% of the lung-deposited dose of aerosolized EpoFc was delivered safely and effectively to the central lung regions. We showed dose-dependent concentrations of the fusion protein in the serum and an increase in circulating reticulocytes was evident in the highest dose group, thus demonstrating that large therapeutic molecules can be delivered to humans via the lung, with retention of biological activity, using the FcRn-mediated transport pathway.

Improved lung delivery from a passive dry powder inhaler using an Engineered PulmoSphere powder.

PURPOSE: To assess the pulmonary deposition and pharmacokinetics of an engineered PulmoSphere powder relative to standard micronized drug when delivered from passive dry powder inhalers (DPIs). METHODS: Budesonide PulmoSphere (PSbud) powder was manufactured using an emulsion-based spray-drying process. Eight healthy subjects completed 3 treatments in crossover fashion: 370 microg budesonide PulmoSphere inhaled from Eclipse DPI at target PIF of 25 L x min(-1) (PSbud25), and 50 L x min(-1) (PSbud50), and 800 microg of pelletized budesonide from Pulmicort Turbuhaler at 60 L x min(-1)(THbud60). PSbud powder was radiolabeled with 99mTc and lung deposition determined scintigraphically. Plasma budesonide concentrations were measured for 12 h after inhalation. RESULTS: Pulmonary deposition (mean +/- sd) of PSbud was 57+/-7% and 58+/-8% of the nominal dose at 25 and 50 L x min(-1), respectively. Mean peak plasma budesonide levels were 4.7 (PSbud25), 4.0 (PSbud50), and 2.2 ng x ml(-1) (THbud60). Median t(max) was 5 min after both PSbud inhalations compared to 20 min for Turbuhaler (P < 0.05). Mean AUCs were comparable after all inhalations, 5.1 (PSbud25), 5.9 (PSbud50), and 6.0 (THbud60) ng x h x ml(-1). The engineered PSbud powder delivered at both flow rates from the Eclipse DPI was twice as efficiently deposited as pelletized budesonide delivered at 60 L x min(-1) from the Turbuhaler. Intersubject variability was also dramatically decreased for PSbud relative to THbud. CONCLUSION: Delivery of an engineered PulmoSphere formulation is more efficient and reproducible than delivery of micronized drug from passive DPIs.