ORIGINAL ARTICLE In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport Arnaud Briat & Lotfi Slimani & Pascale Perret & Danièle Villemain & Serge Halimi & Jacques Demongeot & Daniel Fagret & Catherine Ghezzi Received: 1 December 2006 / Accepted: 28 March 2007 / Published online: 26 May 2007 # Springer-Verlag 2007 Abstract Purpose Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [ 123 I]6-deoxy-6-iodo-D-glucose (6DIG). Methods We investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45 min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain frac- tional transfer coefficients of 6DIG from the blood to the heart. Results These coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16±0.06 vs 2.28± 0.18 (p <0.001) for the fructose-fed group, 0.92±0.05 vs 1.62±0.25 (p <0.01) for the Zucker group and 1.34± 0.06 vs 2.01±0.26 (p <0.05) for the ZDF group. Conclusion These results show that 6DIG could be a useful tracer to image cardiac insulin resistance. Keywords Radiopharmaceutical . Insulin resistance . Mathematical modelling . Nuclear medicine . Diabetes Introduction Insulin resistance, characterised by a depressed cellular sensitivity to insulin in insulin-sensitive organs, is a central feature of the metabolic syndrome and a risk factor for cardiovascular disease and type 2 diabetes [1–6]. It is unanimously admitted that no simple method is available in clinical practice for assessment of insulin resistance. At present, the gold standard for investigating and quantifying insulin resistance is still the hyperinsulinaemic euglycaemic clamp. Nevertheless, this technique is complicated and cumbersome, and its use is therefore restricted to the experimental setting. For this reason, numerous indices based on simpler clinical measurements have been pro- posed [7]. Some of these have been validated, including the homeostasis model assessment of insulin resistance (HOMA-IR) [8, 9], but none has become the standard for assessing insulin resistance. All these clinical measurements Eur J Nucl Med Mol Imaging (2007) 34:1756–1764 DOI 10.1007/s00259-007-0453-y A. Briat : L. Slimani : P. Perret (*) : D. Villemain : D. Fagret : C. Ghezzi INSERM, E0340, Radiopharmaceutiques Biocliniques, Grenoble 38000, France e-mail: pascale.perret@ujf-grenoble.fr A. Briat : L. Slimani : P. Perret : D. Villemain : S. Halimi : J. Demongeot : D. Fagret : C. Ghezzi Univ Grenoble, Grenoble 38000, France S. Halimi CHRU Grenoble, Hôpital Michallon, Service de Diabétologie, Grenoble 38000, France J. Demongeot CNRS, UMR 5525, Grenoble 38000, France