Whole-body PET/CT evaluation of tumor perfusion using generator-based ⁶²Cu-ETS: Validation by direct comparison to ¹⁵O-water

Objectives The purpose of the present study was: (i) to demonstrate the feasibility of whole-body ⁶²Cu-ETS PET/CT tumor perfusion imaging in patients with metastatic renal carcinoma; and (ii) to validate ⁶²Cu-ETS as a quantitative marker of tumor perfusion by direct comparison to ¹⁵O-water perfusion imaging.

Methods PET/CT imaging (64-slice Siemens Biograph) of 14 subjects with stage IV renal cell cancer was performed after i.v. administration of ¹⁵O-water (10-minute dynamic list mode study), followed 10-minutes later by i.v. ⁶²Cu-ETS with the heart and at least one tumor in the PET field-of-view (6-min list mode study). Whole body imaging of the ⁶²Cu was then carried out from 6-20 min using 2-3 minutes/bed. Proportional Technologies, Inc. produced and shipped the required ⁶²Zn/⁶²Cu-generators, and the lyophilized cold kits for on-demand preparation of the ⁶²Cu-ETS radiopharmaceutical (IND #75,018). Blood flow (k₁) was quantified with both agents for both 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 using data from an in vitro analysis with a sample of each patient’s blood.

Results A good correlation was found between the k₁ values of the two agents. For the normal tissues (muscle, myocardium, and thyroid), y = 0.909x + 0.106, r² = 0.86, while the normal tissues plus malignant lesions in the bone and lung gave y = 0.824x + 0.160, r² = 0.78. Paired 2-tailed t-test for normal and malignant tissues indicated no significant difference in k₁ values between the two tracers.

Conclusions ⁶²Cu-ETS provided high quality whole-body PET/CT images, and appears suitable for use as a PET tracer of tumor perfusion in patients with metastatic renal carcinoma.

Research Support RO1 CA 140299