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.

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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 64 Cu-ATSM AND 18 F- FDG IN CERVICAL CANCER

Standard of care for initial staging. Prognostic factors for lymph node involvement, response to therapy, and recurrence –SUV max –Metabolic tumor volume –Intratumoral heterogeneity 18 FDG-PET in Cervical Cancer

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

64 Cu-ATSM Non-invasive agent for PET imaging of intratumoral hypoxia Improved sensitivity and kinetics compared with prior hypoxia PET imaging agents ( 18 F-MISO and 64 Cu-PTSM) Elevated uptake assocaited with poor response to therapy in head and neck, lung, rectal, and cervical cancer

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

METHODS Ten patients with squamous cell carcinoma (SCC) of the cervix underwent 64 Cu-ATSM and 18 F-FDG PET/CT before beginning treatment. 64 Cu-ATSM and 18 F-FDG images were coregistered. At the level of the tumor epicenter, metabolic tumor volumes were auto-contoured at 9 different thresholds on the 64 Cu-ATSM and also on the 18 F-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 64 Cu-ATSM and 18 F-FDG, concordance indexes were generated. Tumor Volume as determined by 40% threshold contour from 18 F-FDG Volume of overlap from 64 Cu-ATSM and 18 F-FDG C.I. =

PATIENT CHARACTERISTICS SUVmax Patient no.Age (y) FIGO StageLesion Size (cm) 64 Cu-ATSM 18 F-FDG 160IIIB IIIA IVA IB IIIB IIB IIA IVA IIIB IIB

CORRELATION OF AUTOCONTOURED VOLUMES FROM 64 Cu-ATSM AND 18 F-FDG IMAGES

A B C SPATIAL MISMATCH OF 64 Cu-ATSM in 18 F-FDG UPTAKE

SUMMARY 64 Cu-ATSM MTV generated by 30% SUV max correlates well with 18 F-FDG MTV generated by 40% SUV max and may be utilized to estimate tumor volume. Intratumoral uptake patterns of 64 Cu-ATSM and 18 F-FDG were discordant indicating that regions of increased hypoxia have low levels of glucose metabolism. The differential uptake between 64 Cu-ATSM and 18 F-FDG within tumors may be utilized to tailor future therapies.