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Fluorine-18 click radiosynthesis and MicroPET/CT evaluation of a small peptide-a potential PET probe for carbonic anhydrase IX

DOI:10.1016/j.bmc.2019.01.014 期刊:Bioorganic & Medicinal Chemistry 出版年份:2019 更新时间:2025-09-19 17:15:36
摘要: Carbonic anhydrase IX (CA IX) is the first carbonic anhydrase found to be associated with cancer that is over-expressed in a variety of human solid tumors. As a surrogate marker for hypoxia, the expression of CA IX is strongly upregulated in hypoxic tumors by hypoxia and hypoxia-inducible factor 1a (HIF-1a). In our pursuit of a CA IX-specific PET probe, we designed and synthesized a peptide-based CA IX imaging probe by the efficient click reaction of 1,3-dipolar cycloaddition of terminal alkynes and organic azides. The probe 18F-CA IX-P1-4-10 was obtained with a radiochemical yield of 35-45% (n = 5) and radiochemical purity of >99% in 70-80 min (HPLC purification time included). 18F-CAIX-P1-4-10 had good stability in phosphate buffered saline (PBS), but about 51% peptide degradation was detected in new-born calf serum (NBCS) after incubation. Preliminary microPET/CT experiments demonstrated a specific uptake of 18F-CA IX-P1-4-10 in HT29 tumor and the uptake of 18F-CA IX-P1-4-10 was blocked by peptide CA IX-P1-4-10-Yne pretreatment. Immunohistochemical staining and western blotting studies confirmed the HT29 tumor was CA IX-positive which further proved tumor accumulation of 18F-CA IX-P1-4-10 was correlated with CA IX expression. The results suggest that 18F-CA IX-P1-4-10 is a promising PET tracer for the specific imaging of CA IX-expressing tumors at the molecular level.
作者: Lina Jia,Xiao Li,Dengfeng Cheng,Lan Zhang
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To design and synthesize a peptide-based PET probe for non-invasive imaging of carbonic anhydrase IX (CA IX) positive tumors, addressing the need for specific molecular imaging of hypoxic tumors.

18F-CA IX-P1-4-10 is a promising PET tracer for specific imaging of CA IX-expressing tumors, with good synthesis yield and specificity demonstrated in vivo. Future work should focus on improving stability and expanding to other cancer types.

The probe showed significant degradation in serum (51% after 3 hours in NBCS), indicating instability in biological environments. The study was preliminary, using a single tumor model (HT29), and further validation in other models and clinical settings is needed.

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