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 2 Washington University School of Medicine DIFFERENTIAL UPTAKE BETWEEN 64 Cu-ATSM AND 18 F- FDG IN CERVICAL CANCER

2. 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

3. 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

4. 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

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

6. 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. =

7. PATIENT CHARACTERISTICS SUVmax Patient no.Age (y) FIGO StageLesion Size (cm) 64 Cu-ATSM 18 F-FDG 160IIIB3.83.320 265IIIA5.74.18.2 379IVA36.68.4 477IB9.56.49.6 547IIIB73.213.4 660IIB5.34.39.9 770IIA6.45.319.2 857IVA16.86.233.1 958IIIB11.94417.5 1048IIB64.614.4

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

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

10. 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.