Whole-body PET/CT evaluation of tumor perfusion using generator-based 62Cu-ethylglyoxal bis(Thiosemicarbazonato) copper(II): Validation by direct comparison to 15O-water in metastatic renal cell carcinoma

Abstract

This study was undertaken to demonstrate the feasibility of whole-body 62Cu-ethylglyoxal bis(thiosemicarbazonato)copper(II) (62Cu-ETS) PET/CT tumor perfusion imaging in patients with metastatic renal carcinoma and to validate 62Cu-ETS as a quantitative marker of tumor perfusion by direct comparison with 15O-water perfusion imaging. Methods: PET/CT imaging of 10 subjects with stage IV renal cell cancer was performed after intravenous administration of 15O-water (10-min dynamic list-mode study) with the heart and at least 1 tumor in the PET field of view, followed 10 min later by intravenous 62Cu-ETS (6-min list-mode study). Whole-body 62Cu imaging was then performed from 6 to 20 min at 2-3 min/bed position. Blood flow (K1) was quantified with both agents for normal and malignant tissues in the 21.7-cm dynamic field of view. The required arterial input functions were derived from the left atrium and, in the case of 62Cu-ETS, corrected for partial decomposition of the agent by blood with data from an in vitro analysis using a sample of each patient's blood. This imaging protocol was repeated at an interval of 3-4 wk after initiation of a standard clinical treatment course of the antiangiogenic agent sunitinib. Results: All subjects received the scheduled 62Cu-ETS doses for the dynamic and subsequent whole-body PET/CT scans, but technical issues resulted in no baseline 15O-water data for 2 subjects. Direct comparisons of the perfusion estimates for normal tissues and tumor metastases were made in 18 paired baseline and treatment studies (10 subjects; 8 baseline studies, 10 repeated studies during treatment). There was an excellent correlation between the blood flow estimates made with 62Cu-ETS and 15O-water for normal tissues (muscle, thyroid, myocardium) and malignant lesions (pulmonary nodules, bone lesions); the regression line was y 5 0.85x 1 0.15, R2 5 0.83, for the 88 regions analyzed. Conclusion: 62Cu-ETS provided high-quality whole-body PET/CT images, and 62Cu-ETS measures of blood flow were highly and linearly correlated with 15O-water- derived K1 values (mL-1-min-1-g). This tracer is suitable for use as a PET tracer of tumor perfusion in patients with metastatic renal cell carcinoma.