Introduction: [68Ga]Ga-FAPI-46 PET/CT is an innovative imaging modality for imaging the tumor-associated fibroblasts. The detection of tumor spread in patients with squamous penile cancer, a rare tumor entity, is crucial for therapy planning. Hence, we assessed the clinical feasibility of [68Ga]Ga-FAPI-46 PET/CT in this rare tumor entity. Methods: Patients with suspected or recurrent penile cancer underwent [68Ga]Ga-FAPI-46 PET/CT imaging for evaluation of the primary tumor site and locoregional lymph node status prior to partial/total penectomy or inguinal/pelvic lymphadenectomy (LAE). Uptake intensities were assessed at the primary sites and at lymph nodes and then compared to histopathological results in a second step. Results: 11 patients with penile cancer (mean 70.1 years) were included and underwent [68Ga]Ga-FAPI-46 PET/CT prior surgical treatment. 7/11 (63.6%) patients received local surgical therapy (partial/total penectomy), 3/11 (27.3%) patients were planned for inguinal/pelvic LAE and 1/11 patients received combined surgery. In 4/8 patients undergoing penectomy, the primary tumor showed increased FAPI uptake (SUVmax 16.2 (9.1 – 25.8)) while in the other 4 patients, the evaluation of primary tumoral site was hampered due to increased urinary activity. 4/11 patients underwent inguinal/pelvic LAE: 3/4 had at least one histopathologically proven pelvic and/or inguinal LN metastasis; all lymph node metastases showed an increased FAPI uptake (SUVmax 17.9 (16.4 – 23.5)) and an enlarged short-axis diameter (1.8 (1.2 – 2.5) cm). Furthermore, in 2/7 patients receiving penectomy only, [68Ga]Ga-FAPI-46 PET/CT revealed enlarged inguinal/pelvic lymph nodes with an distinctly increased FAPI uptake (SUVmax 16.5 (11.4 – 21.6) that could not be addressed during surgery and were subsequently treated by chemotherapy. Conclusions: In these first experiences in penile cancer, [68Ga]Ga-FAPI-46 PET shows promising clinical performance. [68Ga]Ga-FAPI-46 PET identified all histologically proven lymph node metastases, which might avoid unnecessary LAE and might lead to a reduced morbidity.Improved imaging protocols (e.g. omission of furosemide and urination prior to the scan) might improve evaluation of local tumor burden. SOURCE OF Funding: No funding
