68Ga-DOTA chelate, a novel imaging agent for assessment of myocardial perfusion and infarction detection in a rodent model

J Nucl Cardiol. 2020 Jun;27(3):891-898. doi: 10.1007/s12350-019-01752-6. Epub 2019 May 29.

Abstract

Background: Magnetic resonance imaging (MRI) with Gadolinium 1,4,7,10-tetraazacyclododecane-N',N″,N''',N″″-tetraacetic acid (Gd-DOTA) enables assessment of myocardial perfusion during first-pass of the contrast agent, while increased retention can signify areas of myocardial infarction (MI). We studied whether Gallium-68-labeled analog, 68Ga-DOTA, can be used to assess myocardial perfusion on positron emission tomography/computed tomography (PET/CT) in rats, comparing it with 11C-acetate.

Methods: Rats were studied with 11C-acetate and 68Ga-DOTA at 24 hours after permanent ligation of the left coronary artery or sham operation. One-tissue compartmental models were used to estimate myocardial perfusion in normal and infarcted myocardium. After the PET scan, hearts were sectioned for autoradiographic detection of 68Ga-DOTA distribution.

Results: 11C-acetate PET showed perfusion defects and histology showed myocardial necrosis in all animals after coronary ligation. Kinetic modeling of 68Ga-DOTA showed significantly higher k1 values in normal myocardium than in infarcted areas. There was a significant correlation (r = 0.82, P = 0.001) between k1 values obtained with 68Ga-DOTA and 11C-acetate. After 10 minutes of tracer distribution, the 68Ga-DOTA concentration was significantly higher in the infarcted than normal myocardium on PET imaging and autoradiography.

Conclusions: Our results indicate that acute MI can be detected as reduced perfusion, as well as increased late retention of 68Ga-DOTA.

Keywords: PET; myocardial infarction; myocardial perfusion; rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography / methods*
  • Contrast Media
  • Cyclotrons
  • Disease Models, Animal
  • Gallium Radioisotopes*
  • Heart / diagnostic imaging*
  • Heterocyclic Compounds, 1-Ring*
  • Kinetics
  • Male
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Perfusion Imaging / methods*
  • Myocardium / pathology*
  • Positron Emission Tomography Computed Tomography / methods
  • Radiopharmaceuticals
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Contrast Media
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Radiopharmaceuticals
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Gallium-68