# CAIX (carbonic anhydrase IX)

Source: https://nuclide.cc/targets/caix/  
Nuclide record `caix` (Target). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

A protein that clear cell kidney cancer makes almost all the time because of a gene fault. It helps the tumour survive in low-oxygen conditions, and antibodies that stick to it can be used to find or treat the cancer.

## Summary

Carbonic anhydrase IX is a transmembrane enzyme with an extracellular catalytic domain that helps regulate intracellular and extracellular pH, allowing tumour cells to survive an acidic, hypoxic microenvironment. Its expression is switched on by the HIF-1 transcription factor: in clear cell renal cell carcinoma (ccRCC), loss-of-function mutation or deletion of the VHL tumour-suppressor gene (found in roughly 75-95% of ccRCC cases) leaves HIF-1α constitutively active even without hypoxia, so CAIX is expressed diffusely and strongly on almost all ccRCC cells, in contrast to normal kidney, which does not express it.

This expression pattern (near-ubiquitous in ccRCC, essentially absent in normal renal parenchyma and in non-clear-cell kidney tumours) is what makes CAIX attractive: it is a differential diagnostic marker for ccRCC as well as a therapeutic target. The chimeric monoclonal antibody girentuximab (cG250) binds a conformational epitope on the catalytic domain, internalises via clathrin-coated vesicles and recycles rather than being degraded, giving long intracellular retention. Because girentuximab is a full antibody, tumour-to-background contrast builds slowly and imaging is typically read several days after injection.

As a target, CAIX's strength is its consistency and specificity in ccRCC; its weakness for antibody-based approaches is slow pharmacokinetics (days, not hours) and the fact that HIF-2α-driven, VHL-independent disease later in progression can show falling CAIX expression, which has been linked to worse prognosis. Small-molecule and peptide CAIX ligands (for example 68Ga-DPI-4452) have since been developed to give same-day imaging with high tumour-to-background contrast.

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: CA9; G250 antigen; MN antigen
- Tags: renal cell carcinoma; hypoxia; antibody target
- Symbol: CA9
- Class: enzyme
- Biology: A transmembrane carbonic anhydrase whose extracellular catalytic domain hydrates CO2 to bicarbonate and protons, helping tumour cells regulate pH and survive hypoxia. Its expression is switched on by the HIF-1 pathway, so it is expressed at very high, uniform density in VHL-mutant clear cell renal cell carcinoma while normal kidney does not express it.
- Where found: Clear cell renal cell carcinoma: overexpressed in >90-95% of cases, driven by VHL/HIF-1 pathway loss; Normal kidney parenchyma: essentially absent; Some hypoxic non-renal tumours (expression follows tumour hypoxia rather than a fixed tissue pattern); Normal gastrointestinal tract: low-level physiological expression

## Sources

- PMC review: CAIX in renal cell carcinoma, implications for imaging and therapy: https://pmc.ncbi.nlm.nih.gov/articles/PMC7582814/
- PMC: application of CAIX-targeted radiotracers in ccRCC: https://pmc.ncbi.nlm.nih.gov/articles/PMC12976585/
- Spandidos: monoclonal antibody G250 targeting CAIX, internalisation and epitope: https://www.spandidos-publications.com/10.3892/ijo.2014.2658/download
- JNM editorial: kick-starting molecular theranostics in renal cell carcinoma (VHL/HIF, girentuximab, 68Ga-DPI-4452): https://jnm.snmjournals.org/content/65/5/744

## Connected records

- drugs: [Zirconium-89 girentuximab](https://nuclide.cc/drugs/girentuximab-zr89/)
- technologies: [CAIX PET (89Zr-girentuximab)](https://nuclide.cc/technologies/caix-pet/)
- indications: [Renal cell carcinoma](https://nuclide.cc/indications/rcc/)
- pathways: [VHL / HIF oxygen sensing](https://nuclide.cc/pathways/hif-vhl/)
- ideas: [CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy](https://nuclide.cc/ideas/idea-caix-theranostics/)
- trials: [89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP Study](https://nuclide.cc/trials/nct06750419/), [Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC](https://nuclide.cc/trials/nct07197580/)
- companies: [Telix Pharmaceuticals](https://nuclide.cc/companies/telix/)
- isotopes: [Gallium-68](https://nuclide.cc/isotopes/ga-68/)
- opportunities: [CAIX imaging of the indeterminate renal mass](https://nuclide.cc/opportunities/opp-caix-indeterminate-renal-mass/)

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