@article{kristiansenRadiobiologicalInvestigations212PbPbcarbonic2026,
	title = {Radiobiological investigations of a [{212Pb}]{Pb}-carbonic anhydrase {IX}-targeting small-molecule ligand in renal cell carcinoma and colorectal cancer models},
	volume = {102},
	issn = {0955-3002},
	url = {https://doi.org/10.1080/09553002.2025.2595630},
	doi = {10.1080/09553002.2025.2595630},
	abstract = {Carbonic anhydrase IX (CAIX), overexpressed in multiple cancers but limited in normal tissue, is a promising target for radionuclide therapy. This study evaluates [212Pb]Pb-MKV-509, a novel DOTA-conjugated small-molecule ligand, for CAIX-targeted alpha therapy in preclinical renal carcinoma (SK-RC-52) and colorectal (HT-29) cancer models. [212Pb]Pb-MKV-509 was assessed for radiochemical purity and stability. Binding assays determined receptor density and dissociation constants. Clonogenic survival, flow cytometry (viability, DNA damage, cell cycle), and spheroid assays (cross-sectional area, doubling time) evaluated biological responses. An in vivo biodistribution study was performed in SK-RC-52 xenograft-bearing mice, with and without carbonic anhydrase pre-blocking using acetazolamide. [212Pb]Pb-MKV-509 exhibited high radiochemical purity ({\textgreater}96\%) and stability for up to 48 h. Specific binding was higher in SK-RC-52 than in HT-29 cells. Treatment induced activity-dependent clonogenic inhibition, G2/M arrest, and DNA damage, with greater sensitivity observed in SK-RC-52 cells. Clonogenic survival was reduced by 50\% at 3.4 kBq/mL (SK-RC-52) and 7.1 kBq/mL (HT-29). In spheroid models, 2.5–5.0 kBq/mL delayed growth and prolonged doubling time, indicating cross-fire effects. The biodistribution study revealed significant tumor uptake (4.7\%IA/g at 2 h), along with high gastrointestinal accumulation. Pretreatment with acetazolamide partially reduced uptake in the stomach and intestines as well as in the tumor. These findings highlight the potential of CAIX-targeted alpha therapy. CAIX expression and receptor density impact binding affinity and therapeutic response. The study demonstrates the importance of 3D tumor models in evaluating alpha-particle cross-fire effects. Further ligand optimization is warranted to enhance tumor specificity and minimize off-target uptake.},
	number = {2},
	urldate = {2026-01-30},
	journal = {International Journal of Radiation Biology},
	publisher = {Taylor \& Francis},
	author = {Kristiansen, Sandra K. and Shubin, Kirill and Zubrienė, Asta and Matulis, Daumantas and Dernjani, Nurtene and Juzenas, Petras and Bruland, Øyvind S. and Juzeniene, Asta},
	month = feb,
	year = {2026},
	note = {\_eprint: https://doi.org/10.1080/09553002.2025.2595630},
	keywords = {Carbonic anhydrase IX, hypoxia, lead-212, radiobiology, scientific-publication, targeted alpha-therapy},
	pages = {127--137},
}