A Clinically Suitable Approach to Whole-Body Imaging for Quantification of Regional Perfusion: Validation of Positron Emission Tomography (PET) with 62Cu-ETS and Image-based Tracer Kinetic Modeling

Abstract

Background & Hypothesis: We hypothesize that whole-body PET imaging with 62Cu-ETS and readily implemented tracer kinetic models, can enable absolute quantification of regional perfusion (mL•min-1•g-1) in a fashion that is reproducible; readily standardized across institutions; and logistically suitable for clinical implementation. 
 Experimental Design: Thirty-five paired 62Cu-ETS and H215O studies were performed in six Göttingen minipigs to validate the use of image-derived input functions. H215O estimates of tissue perfusion served as a reference standard for comparison with 62Cu-ETS. To demonstrate quantitative whole-body perfusion imaging in humans, paired 62Cu-ETS and H215O studies were performed in 14 renal cell carcinoma patients both prior to and following sunitinib therapy. 
 Results: The pig studies showed a strong correlation between regional blood flow estimates made with 62Cu-ETS and H215O, using image-derived input functions with tracer kinetic model-based corrections for 62Cu-ETS decomposition in blood (slope=0.932, R2=0.746). High quality voxel-wise 62Cu-ETS perfusion and blood volume parametric images demonstrated a strong correlation with H215O across all tissues within the imaging field-of-view. Using a same-day test-retest design, which was then repeated across two weeks, the animal study demonstrated good test-retest variability (TRV) for 62Cu-ETS and H215O with TRV of 6.3% ± 5.40% and 5.0% ± 4.77%, respectively. These findings strongly support application of the modeling methods to the human data, which is currently in progress. 
 Conclusion & Potential Impact: Whole-body imaging to non-invasively quantify regional perfusion holds promising potential for clinical implementation, using 62Cu-ETS PET coupled with tracer kinetic models that rely solely on the acquired imaging data.