CD70-Targeted [¹⁸F]RCCB6 Immuno-PET/CT for Diagnosing Clear Cell Renal Cell Carcinoma Metastases: A Prospective Study

Clear cell renal cell carcinoma (ccRCC) frequently metastasizes after surgical resection, and accurate diagnosis of ccRCC metastases remains a significant clinical challenge. This study aims to evaluate the expression of CD70 and carbonic anhydrase IX (CAIX) in pulmonary metastases of ccRCC and assess the value of CD70-targeted [¹⁸F]RCCB6 immuno-PET/CT in diagnosing ccRCC metastases. Methods: We retrospectively reviewed the cases of patients who underwent lung surgery at our hospital between January 2016 and December 2024. Available specimens of pathology-confirmed ccRCC lung metastases were collected and stained for CD70 and CAIX expression. Four of these patients were enrolled to receive CD70-targeted [¹⁸F]RCCB6 immuno-PET/CT to detect potential metastases. The diagnostic performance of [¹⁸F]RCCB6 immuno-PET/CT was validated in an independent cohort of 51 patients with suspected ccRCC lung metastases. Results: Of the 13,037 patients who underwent lung surgery, 305 had lung metastases, including 40 patients with ccRCC lung metastases. Immunohistochemical analysis of 28 lung metastasis specimens revealed higher expression of CD70 than CAIX (P < 0.05). Four of the 28 patients received CD70-targeted [¹⁸F]RCCB6 immuno-PET/CT imaging, of whom 1 exhibited recurrent multiple pulmonary metastases and 3 showed no evidence of disease. In an independent validation cohort of 51 patients with suspected ccRCC lung metastases, 26 underwent dual-tracer [¹⁸F]RCCB6 and [¹⁸F]FDG PET/CT. In addition to detecting a greater number of metastases, [¹⁸F]RCCB6 demonstrated significantly higher tumor uptake (SUV_max) than did [¹⁸F]FDG PET/CT in the lung (7.61 vs. 4.28; P < 0.001), lymph nodes (10.49 vs. 6.30; P < 0.001), and other distant metastases (13.84 vs. 4.92; P < 0.001). Conclusion: CD70 is a viable biomarker for ccRCC lung metastases. CD70-targeted [¹⁸F]RCCB6 immuno-PET/CT accurately detects ccRCC lung metastases and other distant metastases.