Synthesis and Construction of I-124 Labeled Small Molecular Probe for Noninvasive PET Imaging of CAIX Expression

Carbonic anhydrase IX (CAIX) which is high expression in the most of hypoxic tumor than normal tissue, promoting the growth, invasion, and metastasis of the tumor. Therefore, the study aimed to evaluate the retention and diagnostic ability of [¹²⁴I]I-XYIMSR- 01 in CAIX-overexpression tumor by using positron emission tomography (PET) imaging.

[^124/125I]I-XYIMSR- 01 was labeled by ^124/125I, and its CAIX-targeting properties in different cell lines were assayed by cell uptaken study. Its diagnose and retention ability in vivo were verified in different CAIX-expression models using PET imaging and biodistribution study. Pathological tissues were obtained for immunohistochemical (IHC) and Hematoxylin-Eosin (HE) staining to explore the relationship between CAIX and hypoxic, and further analyze PET/CT results.

[¹²⁴I]I-XYIMSR- 01 was obtained with high specific activity, good radiochemical purity, and good stability. The uptake of of [¹²⁴I]I-XYIMSR- 01 in HT- 29 cells, which have high CAIX expression, was significant higher than that in HCT116 cells with low CAIX expression (12.78 ± 0.47 vs 1.06 ± 0.10, p = 0.000, at 1 h). This indicated that the probe has good targeting capability and specificity for CAIX. In Micro-PET imaging, clear molecular images lasting for 48 h were achieved in HT29 model. Quantitative biodistribution results showed that the tumor and digestive tract background tissues had a good signal-to-noise ratio within 24 h after injection, indicating [¹²⁴I]I-XYIMSR- 01 could enable delayed imaging in digestive tract tumors (tumor-to-small intestine: 8.79 ± 0.98). Tumors uptakes were also confirmed by IHC pathology.

The study have shown that [¹²⁴I]I-XYIMSR- 01 is an ideal molecular probe for tumor hypoxia, enabling long-term dynamic monitoring and imaging of hypoxic tumors.