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Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine 2 Washington University School of Medicine DIFFERENTIAL UPTAKE BETWEEN DIFFERENTIAL UPTAKE BETWEEN 64 64 Cu-ATSM AND Cu-ATSM AND 18 18 F-FDG IN F-FDG IN CERVICAL CANCER CERVICAL CANCER
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Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

Jan 18, 2018

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Tumoral Hypoxia Plays a significant role in tumor heterogeneity Correlated with increased angiogenic, growth, and survival factors such as VEGFR, EGFR, and COX-2 Associated with poor patient survival, therapeutic resistance, and aggressive tumor phenotype
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Page 1: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

Albert J. Chang, MD, PhD1

Farrokh Dehdashti, MD2

Perry W. Grigsby, MD, MS1

Department of Radiation Oncology1

Department of Radiology and Nuclear Medicine2

Washington University School of Medicine

DIFFERENTIAL UPTAKE DIFFERENTIAL UPTAKE BETWEEN BETWEEN 6464Cu-ATSM AND Cu-ATSM AND 1818F-F-

FDG IN CERVICAL CANCERFDG IN CERVICAL CANCER

Page 2: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

• Standard of care for initial staging.• Prognostic factors for lymph node

involvement, response to therapy, and recurrence– SUVmax

– Metabolic tumor volume– Intratumoral heterogeneity

1818FDG-PET in Cervical CancerFDG-PET in Cervical Cancer

Page 3: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

Tumoral HypoxiaTumoral Hypoxia• Plays a significant role in tumor heterogeneity• Correlated with increased angiogenic, growth,

and survival factors such as VEGFR, EGFR, and COX-2

• Associated with poor patient survival, therapeutic resistance, and aggressive tumor phenotype

Page 4: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

6464Cu-ATSMCu-ATSM• Non-invasive agent for PET

imaging of intratumoral hypoxia

• Improved sensitivity and kinetics compared with prior hypoxia PET imaging agents (18F-MISO and 64Cu-PTSM)

• Elevated uptake assocaited with poor response to therapy in head and neck, lung, rectal, and cervical cancer

Page 5: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

PURPOSE: To evaluate the relationship between 64Cu-ATSM and 18F-FDG intratumoral uptake in

cervical cancer.

Page 6: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

METHODS• Ten patients with squamous cell carcinoma (SCC) of the cervix underwent

64Cu-ATSM and 18F-FDG PET/CT before beginning treatment.

• 64Cu-ATSM and 18F-FDG images were coregistered. At the level of the tumor epicenter, metabolic tumor volumes were auto-contoured at 9 different thresholds on the 64Cu-ATSM and also on the 18F-FDG set of images: SUV 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%.

• Concordance indexes (C.I.) were generated to evaluate the relationship between intratumoral distribution of 64Cu-ATSM and 18F-FDG, concordance indexes were generated.

Tumor Volume as determined by 40% threshold contour from 18F-FDG Volume of overlap from 64Cu-ATSM and 18F-FDG C.I. =

Page 7: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

PATIENT CHARACTERISTICS

SUVmaxPatient

no. Age (y)FIGO Stage Lesion Size (cm) 64Cu-ATSM 18F-FDG

1 60 IIIB 3.8 3.3 202 65 IIIA 5.7 4.1 8.23 79 IVA 3 6.6 8.44 77 IB 9.5 6.4 9.65 47 IIIB 7 3.2 13.46 60 IIB 5.3 4.3 9.97 70 IIA 6.4 5.3 19.28 57 IVA 16.8 6.2 33.19 58 IIIB 11.94 4 17.5

10 48 IIB 6 4.6 14.4

Page 8: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

CORRELATION OF AUTOCONTOURED CORRELATION OF AUTOCONTOURED VOLUMES FROM VOLUMES FROM

6464Cu-ATSM AND Cu-ATSM AND 1818F-FDG IMAGESF-FDG IMAGES

Page 9: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

A

B

C

SPATIAL MISMATCH OF SPATIAL MISMATCH OF 6464Cu-ATSM in Cu-ATSM in 1818F-FDG UPTAKE F-FDG UPTAKE

Page 10: Albert J. Chang, MD, PhD 1 Farrokh Dehdashti, MD 2 Perry W. Grigsby, MD, MS 1 Department of Radiation Oncology 1 Department of Radiology and Nuclear Medicine.

SUMMARYSUMMARY• 64Cu-ATSM MTV generated by 30% SUVmax correlates well with

18F-FDG MTV generated by 40% SUVmax and may be utilized to estimate tumor volume.

• Intratumoral uptake patterns of 64Cu-ATSM and 18F-FDG were discordant indicating that regions of increased hypoxia have low levels of glucose metabolism.

• The differential uptake between 64Cu-ATSM and 18F-FDG within tumors may be utilized to tailor future therapies.