title: 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 (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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana jwfletch@iupui.edu.
authors.forename: James W
authors.initials: JW
authors.lastname: Fletcher
authors.affiliation: The Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Logan
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Eitel
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Mathias
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Yen
authors.initials: Y
authors.lastname: Ng
authors.affiliation: Proportional Technologies, Inc., Houston, Texas.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Lacy
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Green
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds; D010104:Oxygen Radioisotopes; D055420:Perfusion Imaging / Q000379:methods*; D049268:Positron-Emission Tomography; D013882:Thiosemicarbazones; D014057:Tomography, X-Ray Computed; D014867:Water; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D009942:Organometallic Compounds; D010104:Oxygen Radioisotopes; D013882:Thiosemicarbazones; C530436:ethylglyoxal bis(thiosemicarbazonato)copper(II); D014867:Water
keywords: 15O-water; 62Cu PET; 62Cu-ETS [ethylglyoxal bis(thiosemicarbazonato)copper(II)]; renal cell carcinoma; tumor perfusion