Synthesis and evaluation of (S)-[F-18]-fluoroethylcarazolol for in vivo beta-adrenoceptor imaging in the brain

The beta-adrenergic receptor ligand (S)-4-(3-(2'-[F-18]-fluoroethylamino)-2-hydroxypropoxy)-carbazol ((S)-[F-18]-fluoroethylcarazolol) was prepared by reaction of [F-18]-fluoroethylamine with the corresponding (S)-epoxide and was evaluated in rats by studying its pharmacokinetics and its binding profile both in vitro and in vivo. In vitro, (S)-fluoroethylearazolol binds preferentially to beta-adrenoceptors (pK(i) = 9.3 for beta(1) and 9.4 for beta(2)) and has less affinity to 5HT(1A) and 5HT(1D) receptors (pK(i) = 6.7 and 5.2). In vivo, standard uptake values (SUVs) up to 0.63 +/- 0.07 in cortical regions were found after 60 min. Metabolites (90%) appeared within 10 min in plasma, whereas, in brain 70-75% parent compound was found after 60 min. Clearance from plasma occurred within 5 min. Cerebral uptake could be blocked by 'cold' fluoroethylearazolol in every region, except medulla. Uptake was also blocked by propranolol and pindolol, but not by WAY 100635. ICI 89406 hardly lowered [F-18] levels in brain. ICI 118551 reduced uptake of [F-18] in cerebellum (mainly 132) by 30%. Specific binding (tissue minus medulla values) in various brain regions corresponded with those observed for [F-18]-fluorocarazolol (r(2) = 0.95) and with in vitro beta-adrenoceptor densities (r(2) = 0.76). Autoradiography using phosphor images of (S)-[F-18]-fluoroethylcarazolol in rat brain showed the characteristic binding pattern of beta-antagonists, while propranolol treatment resulted in low and homogenous uptake. Regional tissue minus medulla values corresponded with in vitro P-adrenoceptor densities (r(2) = 0.77). We conclude that (S)-[F-18]-fluoroethylearazolol is a high affinity ligand that binds specifically to cerebral beta-adrenoceptors in vivo and may be of use for P-adrenoceptor imaging in the brain with PET. (C) 2002 Elsevier Science Ltd. All rights reserved

Coercion and Resistance in the Colonial Market: Cotton in Britain’s African Empire

Throughout the nineteenth century, the American South was the world’s leading producer of raw cotton. European — especially British — textile firms used American cotton to supply the world with cheap manufactured cloth. The African continent was on the periphery of this transatlantic circuit: forced into slavery and transported to the Americas, African peoples supplied much of the agricultural labour on which the cotton industry rested, but the African continent itself remained isolated from the expanding reach of the ‘empire of cotton’

The Role of Imaging in Nuclear Medicine: The Medical Perspective

The era of clinical nuclear medicine started already 70 years ago with the first human examination of the thyroid (Fig. 2.1). Iodine's natural affinity for the gland was used for these first examinations in patients. In 1938 the first paper on the diagnostic uses of 131I in thyroid diseases in humans was published [1]. The development of this discipline has thereafter been tremendous, and still we have not seen the end of progress. Nuclear medicine has a large input in the clinical handling of patients with different diseases and is a modality to examine different physiological function in humans. It is a molecular imaging method based on emission gain by injecting the patients with a very small amount of a radioactive radiopharmaceutical or tracer. The distribution is measured with a gamma camera, a single-photon emission computed tomography (SPECT) camera or a positron emission tomography (PET) camera. In gamma and SPECT camera, radionuclides with gamma decay are used and in PET camera with positron emission.</p