P3, N=40, Recruiting, Telix Pharmaceuticals (Innovations) Pty Limited | Not yet recruiting --> Recruiting | Initiation date: Nov 2025 --> Mar 2026 | Trial primary completion date: Dec 2026 --> Aug 2027

Functional imaging in RCC is shifting from anatomical assessment to molecular characterisation. These advances can better select candidates for local versus systemic treatment, individualise therapy and enable novel theranostics. Further prospective trials should validate their performance and define their place in clinical pathways.

According to referring physicians, 89Zr-girentuximab PET/CT changed clinical management in six of seven patients and improved patient care in all cases. 89Zr-girentuximab PET/CT provides a noninvasive tool for characterizing indeterminate renal masses and metastatic ccRCC and may improve clinical problem-solving in complex scenarios.

P1/2, N=38, Not yet recruiting, Ospedale San Raffaele S.r.l.

Finally, single-dose [177Lu]Lu-girentuximab treatment induced cytotoxicity in PDOs in vitro and strongly reduced tumor burden in 2 independent xenografted mouse models, with no signs of toxicity. Our results demonstrate that CA-IX is a relevant target for a theragnostic strategy in mCRC, and provide the first demonstration in clinically-relevant models of metastasis that radiolabeled girentuximab can be used as a scouting agent to stratify and monitor mCRC patients and as a therapeutic alternative for patients with CA-IX-expressing tumors.

Comparison of the two most water-soluble chelators from the set of DFO, DFO* and D8W, showed that compared to [89Zr]Zr-DFO-mAb (mAb = Girentuximab), [89Zr]Zr-D8W-mAb had improved 89Zr radiolabeling kinetics and in vitro stability. Key to its utility, bone deposition of 89Zr was lower for [89Zr]Zr-D8W-mAb than [89Zr]Zr-DFO-mAb, as assessed by PET imaging in a CAIX-expressing HT-29 tumor-bearing Balb/C nude mouse model. The performance of D8W coupled with its water solubility supports its merit in its use in 89Zr-immunoPET agents.

The iridium(iii)-girentuximab conjugate described here could be of use for emissive detection of carbonic anhydrase IX positive tumour tissue to guide surgical resection as well as carbonic anhydrase IX targeted photodynamic therapy. The approach described here could be used with other tumour targeting antibodies.

In three-dimensional (3D) spheroids, compound 45 reduced the cumulative spheroid area approximately 10-fold more than the single-target inhibitors FK866 or SLC-0111 and induced apoptosis through NAD depletion, mitochondrial dysfunction, and suppression of ERK/mTOR signaling. These results support dual hCA IX/XII-NAMPT inhibition as an effective strategy to impair tumor growth and survival under hypoxic stress.

P1, N=24, Not yet recruiting, Institut Cancerologie de l'Ouest

[89Zr]Zr-girentuximab PET/CT is a sensitive imaging method and offers promise for novel theranostics for mTNBC patients.

A recent phase III trial (ZIRCON) is widely believed to have laid the groundwork for United States Food and Drug Administration approval of the CAIX monoclonal antibody 89Zr-girentuximab...Further, emerging new targeted radiotracers and techniques such as imaging biomarker discovery with artificial intelligence will bolster those concepts. In this manual, we synthesize key data into a recommended approach.

P1/2, N=100, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Oct 2025 --> Oct 2027