This is a prospective, single-center, single-arm, comparative phase 2 study in patients with metastatic clear cell renal cell carcinoma. The goal is to determine the sensitivity of 68Ga-NY104 PET/CT in patients with metastatic clear cell renal cell carcinoma and compare it with 18F-FDG PET/CT.

This is a prospective, single-center, single-arm, comparative phase 2 study in patients with metastatic clear cell renal cell carcinoma. Each patient will receive one dose of 68Ga-NY104 and one dose of 18F-FDG by intravenous route. Dedicated whole-body PET/CT imaging will be performed. PET/CT studies will be interpreted by two readers, both of whom will provide independent, blinded interpretations. Imaging interpretations and a composite reference standard will be used to estimate the sensitivity of each modality. The tumor uptake will also be compared for matched lesions.

39 patients will be recruited in Peking Union Medical College Hospital.

Inclusion Criteria:

1. Age ≥ 18 y
2. Histopathological diagnosis of clear cell renal cell carcinoma
3. Metastatic disease confirmed by histopathology or typical appearance of multifocal metastatic disease
4. Expected survival of at least 6 months
5. ECOG ≤ 2
6. Written informed consent provided for participation in the trial
7. In the opinion of investigator, willing and able to comply with required study procedures.

Exclusion Criteria:

1. On VEGF TKI treatment less than 1 week before 68Ga-NY104 PET/CT. TKI is known to affect girentuximab binding in patients with ccRCC and is expected to have the same effect on 68Ga-NY104. If patients were on VEGF TKI treatment, such as sunitinib, sorafenib, cabozantinib, pazopanib, or lenvatinib, a washout of one week before 68Ga-NY104 PET/CT is required.
2. Patients on HIF antagonist treatment < 3 months before 68Ga-NY104 PET/CT. CA9, which encodes carbonic anhydrase IX (CAIX), is one of the genes most strongly upregulated by HIF-1. HIF antagonist, such as Belzutifan, might affect the expression of CAIX and thus the binding of 68Ga-NY104 to tumor. Withdraw of at least 3 months is required for HIF antagonist.
3. Pregnancy or breastfeeding.
4. Severe claustrophobia.

Available upon request

Within 2 years after the publication of the main results

No limit.