# ZIRCON: [89Zr]Zr-girentuximab PET-CT for detecting clear-cell renal cell carcinoma

Source: https://nuclide.cc/key-papers/paper-zircon-lancet-oncol-2024/  
Nuclide record `paper-zircon-lancet-oncol-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

A PET scan using a radioactively-labelled antibody could tell, without surgery, whether a suspicious kidney lump was the most common type of kidney cancer - correctly in about 9 out of 10 people.

## Summary

ZIRCON was a prospective, open-label, multicentre phase 3 trial at 36 sites in nine countries. Adults with an indeterminate renal mass of 7 cm or less (cT1), suspicious for clear-cell renal cell carcinoma (ccRCC) and scheduled for nephrectomy, received a single dose of [89Zr]Zr-girentuximab (37 MBq, 10 mg antibody) intravenously, followed by PET-CT 5 (±2) days later. Blinded central histopathological review of the surgical specimen was the reference standard. Co-primary endpoints were sensitivity and specificity for ccRCC detection.

Of 332 enrolled patients, 300 received the tracer and 284 were evaluable in the primary analysis. Mean sensitivity was 85.5% (95% CI 81.5-89.6) and mean specificity was 87.0% (81.0-93.1) across three independent readers; positive predictive value was around 93%. The safety profile was favourable: most adverse events occurred peri-operatively and were unrelated to the tracer, with no treatment-related deaths.

[89Zr]Zr-girentuximab (TLX250-CDx, Telix Pharmaceuticals) targets carbonic anhydrase IX (CAIX), which is highly expressed in ccRCC but not in other renal-mass pathologies (oncocytoma, papillary or chromophobe RCC, angiomyolipoma). Non-invasive discrimination of ccRCC from these mimics could reduce unnecessary biopsies and nephrectomies and guide a choice between surveillance and surgery for small renal masses - though as of this record's date the agent had not yet received a marketing authorisation.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: renal cell carcinoma; PET imaging; CAIX
- Journal: Lancet Oncology
- Year: 2024
- DOI: 10.1016/S1470-2045(24)00402-9
- Authors: Shuch B, Pantuck AJ, Bernhard JC, Morris MA, Master V, et al.
- Findings: Mean sensitivity for ccRCC detection: 85.5% (95% CI 81.5-89.6); mean specificity: 87.0% (95% CI 81.0-93.1) across three blinded central readers.; Positive predictive value approximately 93%, including in small and difficult-to-detect lesions (per company summary of the same dataset).; No treatment-related deaths; most adverse events (74%) occurred during or after surgery and were unrelated to the tracer.; Most common grade 3+ adverse events were post-procedural haemorrhage (2%), urinary retention (1%) and hypertension (1%), attributable to the surgery rather than the tracer.
- What it means: A single injection and a PET scan five days later can identify clear-cell kidney cancer accurately enough to help decide whether someone with a suspicious kidney lump needs surgery, avoiding some biopsies and unnecessary operations.
- Caveats: All participants were already scheduled for nephrectomy, so the trial does not directly show the agent changes management in a broader population of patients under surveillance.; As of the paper's publication the agent (TLX250-CDx / Zircaix) was investigational, not approved by FDA or EMA.; Performance in masses larger than 7 cm, or in patients unfit for surgery, was not the focus of this trial.

## Sources

- PubMed: ZIRCON trial (Lancet Oncol 2024): https://pubmed.ncbi.nlm.nih.gov/39270701/
- Telix Pharmaceuticals: ZIRCON results announcement: https://telixpharma.com/news-views/highly-accurate-telixs-phase-iii-zircon-trial-for-kidney-cancer-imaging-published-in-the-lancet-oncology/

## Connected records

- drugs: [Zirconium-89 girentuximab](https://nuclide.cc/drugs/girentuximab-zr89/)
- technologies: [CAIX PET (89Zr-girentuximab)](https://nuclide.cc/technologies/caix-pet/), [Immuno-PET](https://nuclide.cc/technologies/immuno-pet/)
- indications: [Renal cell carcinoma](https://nuclide.cc/indications/rcc/)
- companies: [Telix Pharmaceuticals](https://nuclide.cc/companies/telix/)
- isotopes: [Zirconium-89](https://nuclide.cc/isotopes/zr-89/)

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