Portal de Periódicos da CAPES

Rapid hepatic clearance of 99m Tc‐TMEOP: a new candidate for myocardial perfusion imaging

2010; Hindawi Publishing Corporation; Volume: 6; Issue: 4 Linguagem: Inglês

10.1002/cmmi.413

1555-4317

Lode Goethals, Isabel Santos, Vicky Caveliers, António Paulo, Frank De Geeter, Patrício G. Lurdes, Célia Fernandes, Tony Lahoutte,

Cardiac Imaging and Diagnostics

Abstract Background 99m Tc labeled radiotracers used in clinical practice lack the perfect characteristics for myocardial perfusion imaging. In particular, the high liver uptake can interfere in the interpretation of the inferior myocardial wall. Within the tricarbonyl approach, we used tris(pyrazolyl)methane 99m Tc organometallic complexes as a lead structure. Herein we present the production, in vivo and in vitro metabolic studies in rats and the first in vivo biodistribution in rats for tri‐methoxy‐tris‐pyrazolyl‐ 99m Tc‐(CO) 3 ( 99m Tc‐TMEOP), compared with 99m Tc‐sestamibi and 99m Tc‐tetrofosmin. Methods The chemical identity of 99m Tc‐TMEOP was characterized by RP‐HPLC. The octanol–water partition coefficient was determined under physiological conditions. In vitro stability and protein binding were determined using RP‐HPLC. In vivo stability was determined in blood, heart, liver and kidney homogenates, intestine and urine using RP‐HPLC. In vivo biodistribution was determined using dynamic planar acquisitions. Pinhole gated SPECT images were performed in other animals. Cardiac, liver and lung uptake were expressed as differential uptake ratios by drawing regions of interest in the organs of interest and around the total body. Heart–liver and heart–lung ratios were derived. Cardiac uptake was also expressed as percentage of injected activity. SPECT images were processed to determine the heart–liver ratio on SPECT images, to compare functional parameters between different tracers and to visualize homogeneous intracardiac tracer distribution. Results 99m Tc‐TMEOP is a moderately lipophilic cation, is stable and does not undergo any transformation in vitro . 99m Tc‐TMEOP also shows a high in vivo stability. In vivo imaging shows liver kinetics faster than those of 99m Tc‐sestamibi and 99m Tc‐tetrofosmin. Cardiac uptake and functional analysis of pinhole gated SPECT data are comparable to those of 99m Tc‐sestamibi and 99m Tc‐tetrofosmin. Conclusion Although 99m Tc‐TMEOP shows a cardiac uptake between those of 99m Tc‐sestamibi and 99m Tc‐tetrofosmin, a better heart–liver ratio is obtained due to the faster liver washout. These results suggest possible faster cardiac perfusion imaging using 99m Tc‐TMEOP without liver activity interference. Copyright © 2010 John Wiley & Sons, Ltd.