Abstract
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Introduction: Epithelial ovarian cancer is associated with high mortality. The optimal treatment of ovarian cancer is surgical debulking with systemic chemotherapy. Standard of care imaging for patients with a pelvic mass suspicious for ovarian malignancy is CT. In up to 50% of cases, CT will fail to localize the true extent of metastatic disease or identify the sub-population likely to benefit from neoadjuvant chemotherapy. Thus, with the currently offered standard of care procedures, patients with ovarian cancer are likely being treated without an accurate estimate of metastatic disease. 18F-Fluciclovine is a synthetic amino acid PET radiotracer that is transported via amino acid transporters such as LAT1, which is upregulated in ovarian cancer cells. 18F-Fluciclovine PET/CT scan is approved for restaging of prostate cancer. The use of 18F-fluciclovine PET/CT scan in ovarian cancer has not been evaluated. Our goal is to characterize 18F-fluciclovine uptake in patients with known ovarian cancer.
Methods: Seven female subjects with confirmed primary or recurrent ovarian cancer underwent an 18F-fluciclovine PET/CT scan with dual time-point imaging using two minutes per bed position. Early and delayed images were obtained at 4-22 and 24-42 minutes, respectively. Target and background structures (aorta, L3 vertebral marrow, liver, and bladder) tracer uptake was recorded using max and mean standardized uptake values (SUVs). Target lesions uptake was qualitatively graded by comparing SUVmax to the SUVmean of background structures; the reading criteria was adopted from prostate cancer interpretation guidelines. Lesions were defined as suspicious if uptake was above marrow background on early and delayed images for lesions ≥1 cm or significantly above blood pool (i.e. approaching marrow uptake) for lesions <1 cm. True positive tumors and lymph nodes (T, N) were determined by histology. Metastatic implants (M) were defined by histology and/or by imaging criteria. The averages of tumor SUVmax and background structures SUVmean were plotted on time-activity curves for tumor lesions ≥1 cm and <1 cm.
Results: Of the 7 subjects included in this study, 1/7 had primary ovarian cancer and 6/7 had recurrence. 18F-Fluciclovine PET/CT yielded 100% sensitivity with indexed 41 true positive locoregional and distant metastatic lesions. Average SUVmax (± SD) uptake in the malignant lesions was 5.92 ± 2.56 and 5.10 ± 2.00 on early and delayed images, respectively. For lesions ≥1 cm, uptake was 6.57 ± 2.29 for early and 5.65 ± 1.72 for delayed images, while uptake in lesions <1 cm was 2.76 ± 1.04 and 2.41 ± 0.57, respectively. The average SUVmean (± SD) of background structures on early and delayed images was 1.67 ± 0.40 and 1.53 ± 0.37 respectively for aorta and 3.21 ± 0.70 and 2.51 ± 0.53 respectively for marrow. Tracer washout into the bladder increased over time with SUVmean (± SD) of 0.71 ± 0.30 and 5.19 ± 3.64 for early and delayed images, respectively. Despite accrual bias of only enrolling subjects with known positive ovarian lesions, 51.9% more lesions were detected by 18F-fluciclovine PET/CT compared to standard of care CT, resulting in 34.1% discordance.
Conclusions: 18F-Fluciclovine uptake within malignant ovarian lesions is markedly above background, supporting its potential use in the clinical evaluation of patients with ovarian cancer.