Evaluation of Gd-DOTA as a marker for myocardial blood flow in comparison with simultaneous 68Ga-DOTA and the gold standard 15O-water PET in PET-MRI
Authors: Kero T , Kvernby S , Eggers K M , Rischpler C , Sorensen J , Velikyan I , Lubberink M 
Published: June 2024

Abstract

Background
Gadolinium-DOTA (Gd-DOTA) and similar MRI contrast agents are increasingly being used as markers for myocardial blood flow (MBF). Accurate quantification of MBF with MR contrast agents is challenging as it requires (1) correct conversion of the MR signal to Gd concentration, (2) an appropriate kinetic model to estimate the uptake rate constant from plasma to tissue, and (3) correction for the limited extraction of the contrast agent. An earlier comparison showed moderate agreement between MBF using single-sequence Gd-DOTA MRI and simultaneous 15O-water PET (1) but new dual-sequence methods are suggested to overcome some of the challenges of quantitative Gd-DOTA MRI. Contrary to MRI, the PET signal is directly proportional to radioactivity concentration and hence a PET analogue of Gd-DOTA, 68Ga-DOTA, could be used to assess the kinetics of DOTA without the challenges of measuring Gd concentrations with MRI.

Purpose
The aim of the present work was to assess the suitability of DOTA as a marker of MBF by comparing 68Ga-DOTA and Gd-DOTA to the gold standard for non-invasive measurement of MBF, 15O-water PET.

Methods
25 patients underwent dynamic 15O-water-PET during rest and pharmacological stress followed by simultaneous dynamic rest and stress 68Ga-DOTA-PET and single-sequence (N=14) or dual-sequence (N=11) Gd-DOTA dynamic contrast enhanced MRI on an integrated PET-MR scanner. 15O-water PET was analysed automatically, and volumes of interest were transferred to the co-registered 68Ga-DOTA-PET images. 68Ga-DOTA-PET and Gd-DOTA MRI were analysed using the single tissue compartment model and the uptake rate constant K1 of 68Ga-DOTA and Gd-DOTA was compared to that of 15O-water. Permeability-surface area product of DOTA was estimated using the Renkin-Crone equation.

Results
Kinetics of 68Ga-DOTA were well-described by a single-tissue compartment model. Extraction was low for DOTA, with average whole myocardium 68Ga-DOTA K1 values ranging between 0.28 and 1.13 mL/cm3/min compared to 0.62 and 4.20 mL/cm3/min for 15O-water. The permeability surface area product of 68Ga-DOTA was 0.48 mL/cm3/min, corresponding to an extraction of around 20% at typical hyperemic MBF values. Correlations between 68Ga-DOTA and 15O-water K1 stress values were poor (r2 0.29 at the global and 0.26 at the regional level). Single-sequence Gd-DOTA significantly overestimated K1 compared to 68Ga-DOTA (regression slope 1.4; Wilcoxon p 0.002) whereas there was no significant difference and a moderate correlation (slope 1.1; r2 0.54) between dual-sequence Gd-DOTA K1 and 68Ga-DOTA K1.

Conclusion
Extraction of DOTA is low resulting in a high uncertainty in hyperemic MBF values. Although new dual-sequence techniques seem to overcome some of the challenges of quantitative Gd-DOTA MRI, the low DOTA extraction along with the complexity of quantifying Gd-DOTA concentrations with MRI suggest that DOTA cannot be considered a suitable agent for accurate measurement of MBF.