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

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