Truncated Evans blue modified fibroblast activating protein inhibitor as well as preparation method and application thereof

Abstract

The invention provides a truncated Evans blue modified fibroblast activating protein inhibitor compound, which is formed by connecting truncated Evans blue, a fibroblast activating protein inhibitor and a nuclide chelating group together by linking groups L1, L2, L3, L4 and X. The structure of the truncated Evans blue modified fibroblast activating protein inhibitor compound is as shown in formula (I), r1 is a fibroblast activating protein inhibitor; l1 is lysine, glutamic acid or a derivative structure thereof; l2 is-(CH2) n-, where n is an integer from 0 to 30, where each CH2 may be substituted individually with-O-,-NH (CO)-or-(CO)-NH-; l3 is-(CH2) m-, where m is an integer from 0 to 30, where each CH2 may be replaced individually with-O-, or-(CO)-; l4 is-(CH2) p-, where p is an integer from 0 to 30, where each CH2 may be substituted individually with-O-,-NH (CO)-or-(CO)-NH-; x is selected from N, C, O, S or R2 is a nuclide chelating group. The invention further provides a radioactive marker based on the structure of the compound, and the compound and the radioactive marker have remarkably prolonged blood circulation half-life period and enhanced tumor uptake enrichment and retention time, and are suitable for nuclide treatment and imaging of FAP protein high-expression tumors.

Description

technical field [0001] The invention relates to the fields of nuclear medicine and molecular imaging, in particular to a truncated Evans blue-modified fibroblast activation protein inhibitor and its preparation and application. Background technique [0002] Fibroblast activation protein (FAP) is a membrane serine peptidase expressed on the surface of activated fibroblasts in the tumor stroma and plays an important role in the development of tumors. Previous studies have shown that FAP is generally not expressed in normal human tissues, but it is selectively highly expressed on the surface of stromal fibroblasts in more than 90% of epithelial malignant tumors, including breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer and Pancreatic cancer, etc. In view of its widespread expression and important role in tumors, FAP has become an important target for tumor imaging and treatment. [0003] At present, radionuclide-labeled fibroblast activation prot...

AI Technical Summary

Problems solved by technology

Although recent research work has optimized the non-pharmacophore part of the FAPI structure, the improvement of the tumor uptake dose and retention time of FAPI is very limited and cannot meet the needs of therapeutic use

Those of ordinary skill in the art know that if the small molecule drug circulates in blood vessels for too short a time or is quickly cleared by the body, the combination of the drug and the target will be insufficient.

Therefore, when preparing FAPI probes, if the circulating half-life of the probes can be extended appropriately, it will be possible to increase the uptake dose and retention time of the probes at the target site.

Images