The positron-emission tomography (PET) tracer zirconium (Zr)-89–DFO-girentuximab may accurately identify patients with clear cell renal cell carcinoma and differentiate the disease from other types of renal tumors, according to findings presented by Calais et al at the Society of Nuclear Medicine & Molecular Imaging 2023 Annual Meeting (Abstract 257). The study demonstrated that with its excellent specificity and sensitivity, as well as its high positive predictive value, Zr-89–DFO-girentuximab may have the potential to become a clinical standard in the identification and characterization of clear cell renal cell carcinoma.
Background
The current standard of identification of renal tumors consists of conventional structural imaging—such as computed tomography (CT) or ultrasound scans—or renal biopsy, but these methods have proven insufficient. Structural imaging cannot differentiate between benign and malignant tumors, and renal biopsy is invasive, subject to sampling errors, and cannot detect extrarenal disease.
“There is an unmet need for accurate, noninvasive imaging tools to aid in the diagnosis and the reliable characterization of renal [tumors] to help risk stratify patients and guide treatment decisions,” emphasized lead study author Jeremie Calais, MD, MSc, Associate Clinical Professor of Molecular and Medical Pharmacology and Director of the Clinical Research Program at the Ahmanson Translational Theranostics Division at the University of California, Los Angeles.
Study Methods and Results
In the new ZIRCON trial, researchers enrolled 34 patients who had undefined renal tumors and planned surgery in order to assess the effectiveness of the Zr-89–DFO-girentuximab PET/CT scans in detecting renal cell carcinomas. The researchers assigned the patients to receive a single dose of Zr-89–DFO-girentuximab and subsequent PET/CT scan 5 days later to determine the tracer uptake in the tumors. The patients then underwent a nephrectomy, and tissue samples were collected from the renal tumors to determine a final histology.
Among the 34 patients, 68% (n = 23) of them were diagnosed with clear cell renal cell carcinoma. Zr-89–DFO-girentuximab was read as positive in 87% (n = 20/23) of the clear cell renal cell carcinoma cases, and all benign and non–clear cell renal cell carcinomas were read as negative on the scans. The positive predictive value of the Zr-89–DFO-girentuximab PET scan was 100%.
Conclusions
“Zr-89–DFO-girentuximab imaging has the potential to be practice-changing by guiding patient management—for example, in the selection of surgical vs conservative management and in helping avoid unnecessary biopsies or surgeries and the associated risks and costs,” commented Dr. Calais. “Given its excellent diagnostic performance in very small lesions, imaging with Zr-89–DFO-girentuximab also has the potential to support earlier diagnosis, which could substantially reduce patients’ emotional burden—especially for those in active surveillance. Other potential clinical uses of Zr-89–DFO-girentuximab include whole-body distant staging, posttreatment surveillance, … treatment monitoring, [and] theranostic applications,” he suggested.
An expanded access program—in which the U.S. Food and Drug Administration helps provide access to investigational therapies outside of clinical trials to patients with serious or life-threatening diseases for whom there are no comparable or satisfactory alternate therapies—is in the final stages of launch for Zr-89–DFO-girentuximab. If approved, the program will allow the radiopharmaceutical to be made available for use in the characterization of clear cell renal cell carcinomas previously identified with CT or magnetic resonance imaging scans.
