A new PET tracer targeting carbonic anhydrase IX (CAIX) has demonstrated exceptional sensitivity and high tumor-to-background contrast in detecting clear cell renal cell carcinoma (ccRCC), according to early clinical research. The newly developed tracer, 68Ga-RCC78, successfully identified additional metastatic lesions missed by standard imaging while significantly reducing abdominal background noise, offering a powerful new tool for kidney cancer staging. This research was presented at the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting.
ccRCC is characterized by a unique, constitutive overexpression of CAIX, making it an attractive target for molecular imaging. Despite this, developing effective CAIX-targeted radiopharmaceuticals has been historically challenging. The physiological expression of CAIX in the gastrointestinal tract often creates high background interference, obscuring abdominal metastases.
While traditional antibody-based tracers for CAIX require days to clear the body, our novel cyclic peptide probe achieves high-contrast visualization rapidly."
Sixuan Cheng, MD, researcher, Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China
In the study, 16 novel CAIX-specific cyclic peptides were synthesized and radiolabeled with 68Ga to develop radiotracers. Cellular uptake studies were performed in CAIX-high and CAIX-low cell lines, as well as CAIX-blocked controls. PET/CT imaging, biodistribution, and immunohistochemistry were conducted in ccRCC xenografts and patient-derived xenograft models. The tracer with the best performance, 68Ga-RCC78, was subsequently evaluated in a first-in-human study including 13 ccRCC patients.
In mice bearing CAIX-high xenografts, 68Ga-RCC78 demonstrated high and sustained tumor uptake with rapid background clearance. In patients, 68Ga-RCC78 accurately distinguished CAIX-positive tumors from CAIX-negative cases, consistent with biopsy immunostaining. For CAIX-positive cases, primary and metastatic tumor uptake markedly exceeded that of 18F-FDG, and low intestinal activity enabled clear visualization of intra-abdominal and metastatic lesions. Benefiting from higher tumor uptake and reduced background retention, 68Ga-RCC78 also enabled the detection of additional tumor lesions.
"This research provides a more precise molecular map for kidney cancer," said Dawei Jiang, PhD, professor and deputy director of Nuclear Medicine Department at Wuhan Union Hospital. "Our new probe, 68Ga-RCC78, strikes a vital balance by minimizing background noise in the abdominal cavity while maintaining the highest possible uptake in tumors, and hopefully representing a significant step toward personalized radiotheranostics in ccRCC."
He continued, "We have not only developed a diagnostic tool but also hope to provide a blueprint for treatment. Currently, this same molecule is being labeled with therapeutic isotopes to deliver targeted radiation directly to cancer cells while sparing healthy organs."
The research is currently in an early phase of clinical evaluation, with efforts underway to advance toward larger clinical trials. Access through clinical trials at specialized institutions may be possible within the next one to two years, with broader clinical availability contingent upon further regulatory approvals.
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