New Approach to Quantification of Molecularly Targeted Radiotracer Uptake from Hybrid Cardiac SPECT/CT: Methodology and Validation

Quantification of molecularly targeted radiotracer uptake in the myocardium from SPECT remains challenging in part due to potentially low levels of focal tracer uptake of presently available molecularly targeted agents and further degradation of cardiac SPECT by extracardiac radioactivity and partial-volume effect. The purpose of this study was to derive and validate a new SPECT quantification method for assessments of absolute radiotracer uptake in the myocardium. Methods: The method was integrated with a hybrid micro-SPEC/CT imaging protocol to calculate radiotracer uptake of a molecularly targeted agent in the ischemic myocardium. CT coregistered with SPECT was used to identify the position and orientation of the left ventricle. Corrections for extracardiac activity and partial-volume errors were performed via a heuristic method derived with a total count sampling scheme. Myocardial radiotracer uptake was quantified from SPECT using an external point source as a known reference. Methods were validated using an ischemic rat model injected with a Tc-99m-labeled SPECT radiotracer targeted at alpha(v)beta(3) integrin. SPECT-quantified myocardial radiotracer uptake was compared with postmortem myocardial tissue well-counted radioactivity. Results: Initial correlation between SPECT-quantified and well-counted radioactivity was fair (R-2 = 0.19, y = 0.50x + 0.05, P = 0.06) when no correction was applied to SPECT quantification. Correlation was significantly improved with tissue weight correction (R-2 = 0.84, y = 1.82x - 0.01, P < 0.001), and a trend toward the improvement of correlation was observed with extracardiac activity correction (R-2 = 0.85, y = 1.54x - 0.01, P < 0.001) and partial-volume correction (R-2 = 0.86, y = 1.68x - 0.01, P < 0.001). Reproducibility of the SPECT quantification was excellent, either with no correction (R-2 = 0.99, y = 1.00x + 0.00, P < 0.001) or with all corrections (R-2 = 1.00, y = 1.00x - 0.00, P < 0.001). Conclusion: Corrections for the myocardial tissue weight, extracardiac activity, and partial-volume errors are crucial for precise assessments of myocardial radiotracer uptake using micro-SPECT/CT. The quantitative SPECT/CT approach developed provides a reasonable and reproducible in vivo estimation of absolute radiotracer uptake in a model of myocardial injury and should permit quantitative serial monitoring of subtle changes in the myocardial uptake of targeted radiotracers.