Multicenter Study of 18F-Labeled NY104 for PET/CT Imaging in Renal Cell Carcinoma

Currently, the global population with kidney diseases exceeds 500 million, and the number of kidney disease patients in China is approximately 120 million, accounting for about 10.8% of the adult population. Among various kidney diseases, renal cell carcinoma (RCC) is the most severe kidney-destructive lesion. In recent years, the incidence of RCC in China has been increasing at an annual rate of approximately 3%, making it one of the most common malignant tumors in the urinary system. The disease is more prevalent in urban areas than rural regions, more frequent in males than females (gender ratio), with the high-risk age group being 45-65 years old. RCC is a highly aggressive tumor; about one-third of patients already present with metastasis at diagnosis, and over 40% of patients ultimately succumb to the disease. Currently, the etiology of RCC remains unclear. Early-stage RCC is asymptomatic but can be detected through health screenings. Compared to other cancers, RCC has a relatively better prognosis, yet 20%-40% of patients still develop metastasis after surgery.

Carbonic anhydrase IX (CAIX) is a newly discovered isoform of the carbonic anhydrase family, composed of acidic amino acids as a transmembrane glycoprotein. Located downstream of the VHL (von Hippel-Lindau) tumor suppressor gene, it is activated by the hypoxia-inducible factor-1 (HIF-1) pathway and plays a significant role in regulating cell proliferation and transformation. CAIX catalyzes the hydrolysis of carbon dioxide into bicarbonate and water, participating in acid-base balance regulation and modulating intracellular/extracellular pH. It is minimally expressed in normal tissues but highly expressed in hypoxic tumors such as RCC, promoting tumor growth and metastasis, and is closely associated with prognosis. Therefore, CAIX is a specific target for RCC, and its high tissue-specific expression holds critical importance for RCC diagnosis, staging, and treatment selection.

¹⁸F-NY104 is a novel PET imaging agent with a simple preparation process, whose yield and radiochemical purity meet clinical requirements. Preclinical studies demonstrate its specific binding to CAIX on tumor cell surfaces, superior pharmacokinetics and imaging performance compared to similar tracers, and promising potential for non-invasive, real-time, and comprehensive imaging diagnosis of CAIX-positive tumors. This project utilizes ¹⁸F-NY104 PET/CT to detect primary, recurrent, and metastatic RCC lesions, aiming to achieve comprehensive tumor localization and quantitative monitoring, thereby supporting early clinical diagnosis, staging, and restaging.

Inclusion criteria

• (1)Capable of understanding and voluntarily signing the informed consent form; able to complete the trial in accordance with the protocol requirements; (2)Age 18-75 years; no gender restrictions; (3)Clinically diagnosed/suspected as renal cell carcinoma or clinically diagnosed/suspected recurrence/metastasis after RCC treatment; (4)At least 1 measurable solid lesion in the subject, which can be accurately and continuously measured using modified RECIST criteria (version 1.1); (5)ECOG performance status score of 0-2; (6)Laboratory parameters must meet:

• Hematology: WBC ≥4.0×10⁹/L or neutrophils ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90g/L; PT or APTT ≤1.5×ULN (upper limit of normal);
• Liver and kidney function: T-Bil ≤1.5×ULN, ALT/AST ≤2.5×ULN or ≤5×ULN (for subjects with liver metastasis), ALP ≤2.5×ULN (if bone or liver metastasis present, ALP ≤4.5×ULN); BUN ≤1.5×ULN, SCr ≤1.5×ULN;
• Other routine tests within normal ranges or deemed acceptable by the investigator; (7)Expected survival ≥12 weeks; (8) Female subjects: Effective contraception (defined as sterilization, intrauterine hormone device, condoms, contraceptives/agents, abstinence, or partner vasectomy) must be used during the study and for 6 months post-study; Male subjects: Agreement to use contraception during the study and for 6 months post-study.

Exclusion criteria

• Recovery from major trauma (including surgery) within 4 weeks prior to study examination;
• Patients with systemic or local severe infections or other serious comorbidities;
• Severe hepatic or renal dysfunction;
• Refusal to participate in this clinical study;
• Patients with a history of allergy to any component of the imaging agent (including antibodies) or allergic constitution;
• Childbearing-aged male or female subjects who cannot adopt effective contraception;
• Women planning pregnancy, currently pregnant, or lactating;
• Patients unable or unwilling to undergo PET/CT scanning;
• Other subjects deemed ineligible by the investigator.