Indeterminate renal masses (IRMs) are a common diagnostic challenge, often leading to invasive biopsies, unnecessary surgery, or prolonged surveillance due to imaging uncertainty. The ZIRCON-X analysis evaluated whether adding TLX250-CDx PET/CT, a carbonic anhydrase IX (CAIX)-targeted molecular imaging agent, could improve real-world clinical decision making. By providing non-invasive, biologically specific characterization of suspected clear cell renal cell carcinoma (ccRCC), TLX250-CDx has the potential to guide individualized treatment strategies and reduce reliance on conventional imaging alone.
Clinical Takeaway
In ZIRCON-X, CAIX-targeted TLX250-CDx PET/CT altered management in nearly half of patients with indeterminate renal masses, including major treatment shifts and biopsy avoidance, enhancing diagnostic confidence in settings where conventional imaging often leaves uncertainty.
Imaging Agent Profile
- Agent: TLX250-CDx (Zircaix®, ⁸⁹Zr-DFO-girentuximab)
- Class: Molecular PET imaging agent
- Molecular Target: Carbonic anhydrase IX (CAIX)
- Imaging Modality: PET/CT
- Clinical Purpose: Non-invasive characterization of IRMs and ccRCC localization
Target Population
- Patients with:
- IRMs
- Suspected localized ccRCC
- Candidates for biopsy, surgery, or active surveillance
ZIRCON-X Study Design
- Study Type: Non-interventional, prospective, post-hoc analysis
- Parent Study: Phase III ZIRCON (NCT03849118)
- Population: 294 evaluable patients with indeterminate renal masses
- Assessment Method: Multidisciplinary team (MDT) consensus
- Comparator: Standard contrast-enhancing imaging versus SOC plus TLX250-CDx PET/CT
- Primary Objective: Impact on clinical decision making
Key Endpoints
- Primary Endpoint:
- Proportion of any change in planned clinical management
- Key Secondary Endpoints:
- Major versus minor management changes
- Treatment escalation or de-escalation
- Potential biopsy avoidance
- Surgical planning modifications
Clinical Decision Impact Outcomes
In ZIRCON-X, TLX250-CDx PET/CT changed planned management in 48.6% of patients, with 37.4% experiencing major changes, including treatment escalation or de-escalation, potential biopsy avoidance (>20%), and shifts from active surveillance to immediate treatment (18 patients). These results demonstrate that TLX250-CDx PET/CT frequently altered physician confidence and clinical intent, rather than serving as a purely confirmatory diagnostic tool.
Surgical Planning Insights
TLX250-CDx PET/CT provided improved spatial localization of ccRCC, supporting decisions on partial versus radical nephrectomy, guiding the choice between surgery and biopsy, and helping avoid unnecessary additional diagnostics.
Key Clinical Implications
✔ Molecular imaging can substantially alter management in patients with indeterminate renal masses
✔ TLX250-CDx PET/CT supports individualized risk-adapted decision making
✔ Potential to reduce unnecessary biopsies and surgeries
✔ Enhances surgical planning and MDT confidence
✔ Represents a shift toward biologically informed renal cell cancer diagnostics
Bottom Line
The ZIRCON-X analysis demonstrates that TLX250-CDx PET/CT meaningfully influences clinical decision making in nearly half of patients with indeterminate renal masses. By enabling non-invasive, CAIX-targeted molecular characterization, this imaging approach has the potential to refine diagnostic pathways, optimize treatment selection, and reduce unnecessary interventions in suspected ccRCC.
Sources:
- National Institutes of Health. (n.d.). 89Zr-TLX250 for PET/CT imaging of clear cell renal cell carcinoma (ZIRCON). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03849118
- Shuch, B. M., Goffin, K., Wagner, T., Ceci, F., Raman, S. S., Calais, J., Donin, N., Joniau, S., Albersen, M., Bex, A., Walkden, M., Mumtaz, F., Orsi, F., Musi, G., Ferris, M., & Liu, D. (2025). Impact of 89Zr-girentuximab PET/CT versus conventional imaging on clinical decision-making in patients with indeterminate renal masses (ZIRCON-X) [Abstract]. Society of Urologic Oncology 26th Annual Meeting. https://suo-abstracts.secure-platform.com/a/gallery/rounds/24/details/4869
- Telix Pharmaceuticals Limited. (2025, November 20). ZIRCON-X analysis: TLX250-CDx impacts clinical decision making for almost half of patients with indeterminate renal masses. Telix Pharmaceuticals. https://telixpharma.com/news-views/zircon-x-analysis-tlx250-cdx-impacts-clinical-decision-making-for-almost-half-of-patients-with-indeterminate-renal-masses/
