Relationship between serum hsCRP concentration and biochemical bone turnover markers in healthy pre- and postmenopausal women.

OBJECTIVE: Although osteoporosis and atherosclerosis seem to be related, the mechanisms are not yet understood. We previously observed that women with higher serum concentrations of high sensitivity C-reactive protein (hsCRP), a strong risk factor for atherosclerosis, had lower bone mineral density (BMD). However, the relationship of hsCRP level with bone turnover rate, an independent risk factor for osteoporotic fracture, is not known. DESIGN: Cross-sectional hospital-based survey. PATIENTS: Apparently healthy pre- and postmenopausal women (n = 39 and 150, respectively). MEASUREMENTS: Urinary N-terminal telopeptide of type I collagen (NTx) and serum bone specific alkaline phosphatase (BALP) were measured using commercially available immunoassay kits. Serum hsCRP concentrations were measured by a particle-enhanced immunoturbidometric method. RESULTS: Both urinary NTx (gamma = 0.288, P < 0.001) and serum BALP (gamma = 0.260, P < 0.001) were positively correlated with serum hsCRP levels. Significance remained even after adjustment for age, body mass index and years since menopause (gamma = 0.257, P < 0.001, and gamma = 0.163, P = 0.027, respectively). Compared with subjects in the lowest hsCRP quartile (< or = 0.6 mg/l), those in the highest hsCRP quartile (> or = 1.6 mg/l) had significantly higher urinary NTx concentrations (P = 0.001) after adjustment for confounding variables. There was an increasing trend of serum BALP concentrations in the higher hsCRP quartile groups (P = 0.073). CONCLUSION: These findings suggest that low grade systemic inflammation may be a common linking factor between development of atherosclerosis and increased bone turnover rate.

Simple and highly efficient synthesis of 3'-deoxy-3'-[18F]fluorothymidine using nucleophilic fluorination catalyzed by protic solvent.

PURPOSE: The aim of this study was to develop a method of radiochemical synthesis of 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) with an improved radiochemical yield using nucleophilic substitution catalyzed by protic solvent. METHODS: We introduced t-butanol (t-BuOH) as a new reaction solvent for nucleophilic [18F]fluorination with [18F]fluoride using (5'-O-DMTr-2'-deoxy-3'-O-nosyl-beta-D-threo-pentofuranosyl)-3-N-BOC-thymine to synthesize [18F]FLT. [18F]F- was eluted with (1) tetrabutylammonium bicarbonate (TBAHCO3), (2) Cs2CO3 and kryptofix 2.2.2 (K222) after trapping of [18F]F- on an ion exchange cartridge, or (3) addition of tetrabutylammonium hydroxide (TBAOH) and [18F]F- to the reactor without trapping [18F]F- on an ion exchange cartridge. We optimized [18F]fluorination conditions with t-butanol and then applied them to automatic synthesis using commercially available radiochemistry modules (TracerLab MX, GE Healthcare). RESULTS: We achieved a high radiochemical yield of 85.3+/-3.5% by radio-TLC with TBAHCO3 as an elution solvent and 20 mg of precursor at 100 degrees C (n=4). With the same labeling conditions, use of Cs2CO3 and K222 with t-BuOH and TBAOH with t-BuOH generated radiochemical yields of 57.1+/-22.5% and 55.0+/-18.8% by radio-TLC, respectively (n=3 for each condition). Automated synthesis with TBAHCO3 and 20 mg of precursor at 120 degrees C for 10 min of [18F]fluorination led to radiochemical yields of 60.2+/-5.2% after HPLC purification with an MX module (n=10). Synthesized [18F]FLT was stable for 6 h. CONCLUSION: [18F]FLT was synthesized with a significantly improved radiochemical yield by nucleophilic substitution catalyzed by protic solvent with mild reaction conditions and a short preparation time.