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

J Nucl Med. 2015 Jan;56(1):56-62. doi: 10.2967/jnumed.114.148106. Epub 2014 Dec 18.


This study was undertaken to demonstrate the feasibility of whole-body (62)Cu-ethylglyoxal bis(thiosemicarbazonato)copper(II) ((62)Cu-ETS) PET/CT tumor perfusion imaging in patients with metastatic renal carcinoma and to validate (62)Cu-ETS as a quantitative marker of tumor perfusion by direct comparison with (15)O-water perfusion imaging.

Methods: PET/CT imaging of 10 subjects with stage IV renal cell cancer was performed after intravenous administration of (15)O-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 (62)Cu-ETS (6-min list-mode study). Whole-body (62)Cu 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 (62)Cu-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 (62)Cu-ETS doses for the dynamic and subsequent whole-body PET/CT scans, but technical issues resulted in no baseline (15)O-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 (62)Cu-ETS and (15)O-water for normal tissues (muscle, thyroid, myocardium) and malignant lesions (pulmonary nodules, bone lesions); the regression line was y = 0.85x + 0.15, R(2) = 0.83, for the 88 regions analyzed.

Conclusion: (62)Cu-ETS provided high-quality whole-body PET/CT images, and (62)Cu-ETS measures of blood flow were highly and linearly correlated with (15)O-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.

Keywords: 15O-water; 62Cu PET; 62Cu-ETS [ethylglyoxal bis(thiosemicarbazonato)copper(II)]; renal cell carcinoma; tumor perfusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Carcinoma, Renal Cell / blood supply
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / pathology
  • Feasibility Studies
  • Female
  • Humans
  • Kidney Neoplasms / blood supply
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Multimodal Imaging / methods*
  • Neoplasm Metastasis
  • Organometallic Compounds*
  • Oxygen Radioisotopes
  • Perfusion Imaging / methods*
  • Positron-Emission Tomography
  • Thiosemicarbazones*
  • Tomography, X-Ray Computed
  • Water*
  • Whole Body Imaging / methods*


  • Organometallic Compounds
  • Oxygen Radioisotopes
  • Thiosemicarbazones
  • ethylglyoxal bis(thiosemicarbazonato)copper(II)
  • Water