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The presence of metastasis in local lymph nodes (LNs) is a key factor influencing choice of therapy and prognosis in cervical and endometrial cancers; therefore, the exploration of sentinel LNs (SLNs) is highly important. Currently, however, SLN mapping requires LN biopsy for pathologic evaluation, since there are no clinical imaging approaches that can identify tumor-positive LNs in early stages. Staging lymphadenectomy poses risks, such as leg lymphedema or lymphocyst formation. Furthermore, in 80%-90% of patients, the explored LNs are ultimately tumor-free, meaning most patients are unnecessarily subjected to lymphadenectomy. Methods: Current lymphoscintigraphy methods identify only the anatomic location of the SLNs and do not provide information on their tumor status. There are no noninvasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, in which 18 F-FDG is injected interstitially into the uterine cervix on the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic PET/CT. We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18 F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole-body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all of these LNs (including 1 with a focus of only 80 tumor cells) were identified by PLG. There were 2 (10%) false-positive cases with PLG, in which the final pathology of the corresponding SLNs was negative for tumor. Conclusion: This first-in-humans study of PLG in women with uterine and cervical cancer demonstrates its feasibility and its ability to identify patients with nodal metastases and warrants further evaluation in additional studies.

Positron Lymphography via Intracervical 18F-FDG Injection for Presurgical Lymphatic Mapping in Cervical and Endometrial Malignancies

Positron Lymphography via Intracervical ¹⁸F-FDG Injection for Presurgical Lymphatic Mapping in Cervical and Endometrial Malignancies