The Astounding Thriving Muscle In FRAX597

[11C]ABP688 was synthesized using a procedure previously described (Ametamey et al., 2007) with slight modification. Briefly, 1 mg of desmethyl-ABP688 in Bcl-2 inhibitor 200 ?L of dimethylformamide was added to 0.5 mg of sodium hydride and reacted with [11C]methyl iodide at 80��C for 5 min. The product was purified by semipreparative high-performance liquid chromatography using a Phenomenex C18(2) Luna column (250 �� 10 mm, 5 ?m) and eluting with 60:40 acetonitrile:water (0.1 M ammonium formate) at a flow rate of 10 mL/min. The collected fraction (tR?=?5.3 min) was diluted with 50 mL of water and loaded onto a Waters C18 Sep-Pak plus. The Sep-Pak was washed with 10 mL of normal saline and eluted with 1 mL of ethanol. The ethanol solution was diluted with 10 mL of saline and filtered through a 0.22 ?m Millex-FG sterile filter. The average specific activity at end-of�Csynthesis was 500?��?259 GBq/?mol (13.5?��?7.0 Ci/?mol). The experimental protocol was approved by the Animal Care and Use Committee of the Johns Hopkins Medical Institutions. PET experiments were performed on four male Isoxsuprine baboons (Papio anubis) on a High Resolution Research Tomograph with an axial resolution?��?2 mm (HRRT, CPS Innovations, Knoxville, TN). Each animal underwent one baseline scan and one or two blocking scans following pretreatment with fenobam at various dose levels on separate dates (Table 1). The animals were fasted for 12 h prior to each PET study. Anesthesia was induced with intramuscular Ketamine (5�C10 Cytoskeletal Signaling inhibitor mg/kg) and maintained with a continuous intravenous infusion of Propofol at 0.4�C0.6 mg/kg/min throughout the PET experiment. One venous catheter was inserted for the radioligand injection, and one arterial catheter was inserted to obtain arterial blood samples for radioactivity determination in plasma. The head of the animal was immobilized with a thermoplastic mask to reduce head motion inside the PET scanner. A transmission scan was acquired using a rotating Cs-137 source for attenuation correction. Then a dynamic PET acquisition was performed in a three-dimensional list mode for 90 min following an intravenous bolus injection over 30 s of [11C]ABP688 (Radioactivity range: 492�C777 MBq (13.3�C21.0 mCi); Cold mass range: 0.21�C1.45 ?g). For the blocking scans, fenobam was dissolved in 0.5 mL of ethanol made acidic with 20 ?L of acetic acid and diluted with 4.5 mL of polyethylene glycol and 5.0 mL of normal saline. After sterile filtration (0.22 ?m), the 10 mL of fenobam solution was given intravenously 5 min before the start of the second emission PET scan. In all scans, arterial blood samples were collected at very short intervals (