Abstract 69P
Background
Carbonic anhydrase IX (CAIX) is a transmembrane metalloenzyme that is frequently upregulated in solid hypoxic tumors to acidify their microenvironment, enhancing metastasis and invasiveness. Its overexpression on malignant cells and limited expression in normal tissues make CAIX an appealing target for theranostic applications.
Methods
A CAIX-targeting compound was conjugated to a DOTA chelator. The resulting DOTA conjugates were purified via reversed-phase HPLC and characterized using LC-MS. Radiolabeling protocols were optimized and the stability of the radioconjugate was assessed using radio-HPLC. Specific binding to CAIX-expressing HT29 colorectal cancer cells was evaluated under normoxic and hypoxia-mimicking conditions.
Results
The CAIX-targeting conjugate was labeled with terbium-161 achieving high radiochemical conversion and purity (RCP), with an apparent molar activity of 100 MBq/nmol at end of radiolabeling. With an ascorbate concentration of 40 mM, the radioconjugate was stable (RCP ≥ 96%) over four days in the radiolabeling buffer at 0.5 GBq/mL. In vitro pharmacokinetic experiments revealed its low nanomolar binding affinity with selective targeting of CAIX-positive HT29 cells under both normoxic and hypoxia-mimicking conditions.
Conclusions
The selective and potent CAIX-targeting radioconjugate shows promise for further preclinical evaluation. Ongoing studies include in vivo pharmacokinetics in tumor-bearing mice and subsequent assessments of in vitro and in vivo toxicity and therapeutic efficacy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.