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

James Fletcher, Theodore Logan, Jacob A. Eitel, Carla J. Mathias, Yen Ng, Jeffrey L. Lacy, Gary Hutchins, Mark Green

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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.

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number1
DOIs
StatePublished - Jan 1 2015

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Renal Cell Carcinoma
Perfusion
Water
Perfusion Imaging
Neoplasms
Whole Body Imaging
Angiogenesis Inhibitors
Tumor Biomarkers
Heart Atria
Intravenous Administration
Myocardium
Thyroid Gland
Therapeutics
ethylglyoxal bis(thiosemicarbazonato)copper(II)
Neoplasm Metastasis
Carcinoma
Kidney
Bone and Bones
Muscles
Lung

Keywords

  • O-water
  • Cu PET
  • Cu-ETS [ethylglyoxal bis (thiosemicarbazonato)copper(II)]
  • Renal cell carcinoma
  • Tumor perfusion

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

@article{a7d161dbf1264f1a9bf44320729acd40,
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 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.",
keywords = "O-water, Cu PET, Cu-ETS [ethylglyoxal bis (thiosemicarbazonato)copper(II)], Renal cell carcinoma, Tumor perfusion",
author = "James Fletcher and Theodore Logan and Eitel, {Jacob A.} and Mathias, {Carla J.} and Yen Ng and Lacy, {Jeffrey L.} and Gary Hutchins and Mark Green",
year = "2015",
month = "1",
day = "1",
doi = "10.2967/jnumed.114.148106",
language = "English",
volume = "56",
pages = "56--62",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "1",

}

TY - JOUR

T1 - Whole-body PET/CT evaluation of tumor perfusion using generator-based 62Cu-ethylglyoxal bis(Thiosemicarbazonato) copper(II)

T2 - Validation by direct comparison to 15O-water in metastatic renal cell carcinoma

AU - Fletcher, James

AU - Logan, Theodore

AU - Eitel, Jacob A.

AU - Mathias, Carla J.

AU - Ng, Yen

AU - Lacy, Jeffrey L.

AU - Hutchins, Gary

AU - Green, Mark

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - O-water

KW - Cu PET

KW - Cu-ETS [ethylglyoxal bis (thiosemicarbazonato)copper(II)]

KW - Renal cell carcinoma

KW - Tumor perfusion

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DO - 10.2967/jnumed.114.148106

M3 - Article

C2 - 25525184

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JO - Journal of Nuclear Medicine

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