title: 99mTcO(BAT-NI), a novel nitroimidazole tracer: in vivo uptake studies in ischaemic myocardium.
abstract: Myocardial perfusion single-photon emission tomography (SPET) performed with cationic technetium-99m complexes indicates ischaemic areas as cold lesions. By contrast, nitroimidazole derivatives labelled with fluorine-18 or (99m)Tc have recently shown promising results for hot spot imaging of ischaemic myocardium. This study evaluates (99m)TcO(BAT-NI), a new (99m)Tc complex comprising the nitroimidazole ligand, 2,10-dimercapto-2,10-dimethyl-4,8-diaza-6-[4-(2-nitroimidazolyl)butyl]undecane, in a low-flow in vivo model of myocardial ischaemia in thoracotomised rats. To elucidate the influence of the 2-nitroimidazole group on ischaemia-induced uptake, comparisons with ligand derivatives were performed where (a) the 2-nitro group was deleted [(99m)TcO(BAT-I)], (b) the 2-nitroimidazole functionality was replaced by a Br atom [(99m)TcO(BAT-Br)] and (c) the (99m)TcO(BAT) moiety was replaced by an iodine-125 iodophenoxybutyl ligand ((125)IP-NI). The radiolabelled compounds were i.v. injected 15 min after reducing resting myocardial blood flow by 50-60% and the uptake of radioactivity was assessed 90 min post injection. Autoradiography of left ventricular short-axis slices showed median uptake ratios of ischaemic/non-ischaemic myocardium (I/N) of 3.4, 4.5 and 3.4 for (99m)TcO(BAT-NI), (99m)TcO(BAT-I) and (99m)TcO(BAT-Br), respectively. In contrast, (125)IP-NI was not preferentially taken up by ischaemic myocardium. Accumulation of (99m)TcO(BAT-NI) in ischaemic heart regions was comparable to that in the liver. Biodistribution studies showed a median uptake of 0.65% ID/g of (99m)TcO(BAT-NI) in ischaemic tissue and an I/N of 3.3. On planar images of the thorax and upper abdomen the ischaemic hearts were visualised faintly; the median heart to lung count ratio for (99m)TcO(BAT-NI) was 1.7, and the median heart to liver count ratio was 1.0. We conclude that uptake of (99m)TcO(BAT-NI) in ischaemic myocardium does not depend on the nitroimidazole moiety but is intrinsic to the BAT complex. Clinical use of the (99m)TcO(BAT)-labelled tracers seems unlikely owing to their low uptake and their low ischaemic tissue contrast on planar images in vivo.
authors.affiliation: Department of Radiology, Division of Nuclear Medicine, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. johannes_hoffend@med.uni-heidelberg.de
authors.forename: J
authors.initials: J
authors.lastname: Hoffend
authors.forename: G
authors.initials: G
authors.lastname: Linke
authors.forename: A
authors.initials: A
authors.lastname: Mohammed
authors.forename: C P
authors.initials: CP
authors.lastname: Tiefenbacher
authors.forename: M
authors.initials: M
authors.lastname: Eisenhut
authors.forename: U
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D000818:Animals; D001345:Autoradiography; D005240:Feasibility Studies; D005260:Female; D007093:Imidazoles / Q000493:pharmacokinetics*; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011920:Rats, Inbred WF; D014018:Tissue Distribution
chemical_list: D007093:Imidazoles; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C482144:technetium Tc 99m, 2,10-dimercapto-2,10-dimethyl-4,8-diaza-6-(4-(2-nitroimidazolyl)butyl)undecane