99mTc-(HE)3-ZCAIX

**99mTc-(HE)3-ZCAIX** is a radiopharmaceutical imaging agent consisting of an Affibody molecule (ZCAIX:1) engineered to target **carbonic anhydrase IX (CAIX)**, a transmembrane enzyme frequently overexpressed in renal cell carcinoma and associated with tumor hypoxia. The molecule is labeled with technetium-99m (^99mTc), using an HEHEHE (HE)3-tag engineered at the N-terminus of the Affibody for site-specific labeling. Its primary potential use is **non-invasive SPECT imaging of CAIX-expressing tumors**, particularly metastatic renal cell carcinoma, to stratify patients for targeted therapies and to study tumor hypoxia. The agent demonstrates **high affinity binding to CAIX (KD ≈ 1.3 nM)**, rapid blood and tissue clearance (except kidneys), and high tumor-to-background ratios in mouse models. Renal uptake is high, characteristic for residualizing radiolabels and small scaffold proteins.