Evaluation of DOTA as a marker for myocardial blood flow using 68Ga-DOTA and 15O-water PET

Introduction: Gd-DOTA (DOTAREM) and similar MRI contrast agents are often suggested as markers for myocardial blood flow (MBF). Accurate quantification of MBF with MR contrast agents requires correct conversion of the MR signal to Gd concentration which is challenging; analysis with an appropriate kinetic model; and correction for the limited extraction of Gd-DOTA using the relationship between the uptake rate of the contrast agent and true MBF. Contrary to MRI, the PET signal is directly proportional to radioactivity concentrations and hence a PET analogue, ⁶⁸Ga-DOTA, could be used to assess the kinetics of DOTA without the challenges of measuring Gd concentration with MRI. The aim of the present work was to assess the kinetics of DOTA by comparing ⁶⁸Ga-DOTA to the gold standard for non-invasive measurement of MBF, ¹⁵O-water PET.

Methods: Nine patients underwent 4 min dynamic ¹⁵O-water-PET followed by 10 min dynamic ⁶⁸Ga-DOTA-PET during rest and pharmacological stress on a Signa PET/MR scanner. ¹⁵O-water PET was analysed automatically using aQuant software, and volumes of interest were transferred to the co-registered ⁶⁸Ga-DOTA-PET images. ⁶⁸Ga-DOTA-PET was analysed using single- and two-tissue irreversible compartment models and the uptake rate constant K₁ of ⁶⁸Ga-DOTA was compared to that of ¹⁵O-water. Permeability-surface area product for ⁶⁸Ga-DOTA was estimated using the Renkin-Crone equation.

Results: Kinetics of ⁶⁸Ga-DOTA was well described by a single-tissue compartment model. Correlation between ⁶⁸Ga-DOTA and ¹⁵O-water K₁ values was moderate (Spearman rho 0.82 at the global and 0.72 at the regional level, P < 0.005). Extraction of ⁶⁸Ga-DOTA was low with average whole myocardium ⁶⁸Ga-DOTA K₁ values ranging between 0.28 and 0.88 mL/cm³/min compared to 0.72 and 4.2 mL/cm³/min for ¹⁵O-water. The permeability surface area product of ⁶⁸Ga-DOTA was 0.38 mL/cm³/min. Regional ⁶⁸Ga-DOTA K₁ versus ¹⁵O-water MBF values, as well as ⁶⁸Ga-DOTA MBF values after applying the Renkin-Crone equation, are shown in the Figure below.

Conclusions: Extraction of DOTA is low, and much lower than for e.g., ⁸²Rb or even ^99mTc-sestamibi, resulting in a high uncertainty in hyperemic MBF and coronary flow reserve values. Based on these results, and even when Gd-DOTA concentration can be accurately quantified using MRI, DOTA cannot be considered a suitable agent for accurate measurement of MBF.

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