64Cu-DOTA as a surrogate positron analog of Gd-DOTA for cardiac fibrosis detection in a rat model of chronic MI.

1472 Objectives To investigate the pharmacokinetics of 64Cu-DOTA, a positron surrogate analog of late Gd-enhancement cardiac magnetic resonance agent, Gd-DOTA in a rat model of chronic myocardial infarction (MI) and its micro-distribution in the cardiac fibrosis by autoradiography and histology. Methods DOTA was labeled with 64Cu-acetate. CD rats (n=3-5) with MI by LAD ligation and 2 normal rats were injected iv with the 64Cu-DOTA (0.5 mCi with 0.02 mmol DOTA/Kg). The PET imaging was performed for 60 min after injection at 7 and 14 week post MI. 18F-FDG PET imaging was performed to identify the viable myocardium. In addition, 64Cu-acetate PET was performed for both MI and normal rat. For the VOI analysis, the 64Cu-DOTA PET image was co-registered to the 18F-FDG PET image. To validate the PET images, slices of heart samples from base to apex were analyzed using autoradiography and histological staining with Masson’s Trichrome. Results The dynamic PET imaging showed that the presence of the radioactivity reflected the blood pool signal with high levels of radioactivity in perfusion-rich tissues including lungs, cardiac fibrosis, myocardium and liver. However, 64Cu-DOTA was retained longer in fibrotic tissue than the normal tissues, and excreted rapidly via the renal system. And SUVs (30-60 min) in fibrosis were 1.53 ± 0.25 and 1.54 ± 0.12 at 7 and 14 week post-MI, respectively. The fibrosis/remote myocardium ratios were 2.53 ± 0.18 and 2.17 ± 0.25 at 7 and 14 week post-MI, respectively and the corresponding fibrosis/blood ratios were 1.53 ± 0.21 and 1.37 ± 0.13, respectively. For 64Cu-acetate, there was no accumulation in myocardium. The autoradiography and histology analysis indicate that 64Cu-DOTA accumulated on collagen rich area of cardiac fibrosis. Conclusions 64Cu-DOTA is retained longer in collagen rich area in the extracellular space and may be useful as a surrogate positron analog of Gd-DOTA to quantify its absolute uptake in cardiac fibrosis. Research Support Clinical Center, NIH and NCI Contract No. HHSN261200800001E