Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP.

INTRODUCTION: (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration. METHODS: We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice. RESULTS: The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP. CONCLUSIONS: For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 µmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs. ADVANCES IN KNOWLEDGE: Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo. IMPLICATIONS FOR PATIENT CARE: The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided.

A woman with Cushing's syndrome after use of an Indonesian herb: a case report.

A 69-year-old woman developed Cushing's syndrome after long-term use of Sinatren, an Indonesian over the-counter drug, which was pharmacologically analysed three times before the correct content was discovered. After discontinuation she developed adrenal insufficiency, for which she needed substitution of steroids. Physicians should be aware of the presence of corticosteroids in over-the-counter products, that are not mentioned on the instruction leaflet.

[No advantage to referring patients with acute myocardial infarction from a general hospital to an intervention clinic for percutaneous coronary intervention; comparison of mortality rates in 2000 and 2003 in the Meander Medical Centre, Amersfoort]. / Geen voordeel voor patiënten met een acuut myocardinfarct die vanuit een algemeen ziekenhuis verwezen werden naar een interventiecentrum voor dotterbehandeling; vergelijking van mortaliteitscijfers van 2000 en 2003 in het meander medisch centrum, amersfoort.

OBJECTIVE: To evaluate whether implementation of the 2000 Netherlands Society of Cardiology guideline 'ST-elevation acute coronary syndromes', which recommends the use ofpercutaneous coronary intervention (PCI), has reduced mortality and complication rates in a general hospital, and whether patient characteristics and outcomes are comparable to those reported in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT) 2 and 3 trials. DESIGN: Retrospective outcomes study. METHOD: Data from 2003 were compared with data from 2000 regarding patients with acute myocardial infarction who received thrombolysis at the Meander Medical Centre in Amersfoort, the Netherlands, or percutaneous transluminal coronary angioplasty (PTCA) after referral to an intervention clinic. Data included baseline characteristics, type of treatment, outcomes and complications. Age, sex and mortality ofall patients were compared to data from the ASSENT 2 and 3 trials. RESULTS: Data were included from 130/132 patients treated in 2003 and 145/145 patients treated in 2000. Baseline characteristics were comparable, except age: there were significant more elderly patients in 2003 (p = 0.006). After implementation of the guideline, significantly more patients underwent PTCA (odds ratio (OR) 4.41 (95% CI: 2.51-7.75)). After adjusting for confounding factors there was no significant difference in in-hospital mortality (adjusted OR 1.11 (95% CI: 0.48-2.60)), 30-day mortality and 1-year mortality. Significantly more minor complications were reported (OR 2.58 (95% CI: 1.07-6.19)). Significantly more women and patients older than 75 years were treated compared with the ASSENT 2 and 3 trials. The 30-day mortality rate was significantly higher compared with ASSENT 2 (OR 1.60 (95% CI: 1.07-2.41)) and ASSENT 3 (OR1.74 (95% CI: 1.14-2.66)). CONCLUSION: The implementation of new guidelines 'ST-elevation acute coronary syndromes' did not result in lower mortality or fewer complications.