Los Angeles -- 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," said Sixuan Cheng, MD, researcher in the Department of
Nuclear Medicine at 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.