Serial reference tissue-based quantitative and volumetric analysis of integrin-targeted angiogenesis imaging: Chronic canine model of myocardial infarction

1710 Objectives Integrin-targeted imaging has been used for imaging of angiogenesis following myocardial infarction (MI), however, a reliable method for estimation of these images has not been established. Methods MI was induced in 10 dogs by percutaneous balloon occlusion, and serial SPECT was performed with an αvβ3 integrin-targeted agent (99mTc-NC100692) in combination with 201Tl SPECT, echocardiography, and measurement of serum brain natriuretic peptide (BNP) at 1, 2, 3, 6, 9, and 12 weeks after MI until sacrifice. Maximal uptake ratio (URmax), volume of increase uptake (VU), and uptake-volume product (UVP) of myocardium were measured from 99mTc-NC100692 SPECT, by a simple reference tissue-based method using the spine as the reference tissue. Dogs were sacrificed at 2 (n = 2), 3 (n = 4), 6 (n = 1), and 12 (n = 3) weeks after MI, and the method was validated using tissue well-counting. Results Increased 99mTc-NC100692 uptake was observed in infarction lesions. URmax correlated with maximum myocardial activity on well-counting (r = 0.780, P = 0.068). URmax, VU, and UVP were all significantly increased at 1 to 3 weeks post-MI compared to baseline (P = 0.002, 0.008, 0.011, respectively), although there was no significant difference by 6 weeks post-MI. The change in BNP between 1 and 2 weeks post-MI exhibited a fair correlation with URmax at 2 weeks post-MI (r = 0.771, P = 0.085). When dogs were classified by BNP-change, URmax, VU, and UVP were significantly higher in high BNP-change group (P Conclusions Temporal change of regional angiogenesis in myocardium post-MI can be tracked non-invasively with a reference-tissue based quantitative and volumetric analysis of integrin-targeted images. Integrin activation post-MI correlated with BNP.