Language
English
Publication Date
9-14-2023
Journal
ACS Medicinal Chemistry Letters
DOI
10.1021/acsmedchemlett.3c00213
PMID
37736195
PMCID
PMC10510512
PubMedCentral® Posted Date
8-24-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Liver cancer is one of the leading causes of cancer-related deaths, with a significant increase in incidence worldwide. Novel therapies are needed to address this unmet clinical need. Indocyanine green (ICG) is a broadly used fluorescence-guided surgery (FGS) agent for liver tumor resection and has significant potential for conversion to a targeted therapy. Here, we report the design, synthesis, and investigation of a series of iodinated ICG analogs (I-ICG), which can be used to develop ICG-based targeted radiopharmaceutical therapy. We applied a CRISPR-based screen to identify the solute carrier transporter, OATP1B3, as a likely mechanism for ICG uptake. Our lead I-ICG compound specifically localizes to tumors in mice bearing liver cancer xenografts. This study introduces the chemistry needed to incorporate iodine onto the ICG scaffold and defines the impact of these modifications on key properties, including targeting liver cancer in vitro and in vivo.
Keywords
Fluorophore, Fluorescence-guided surgery, Hepatocellular carcinoma, Hepatoblastoma
Published Open-Access
yes
Recommended Citation
Marker, Sierra C; Espinoza, Andres F; King, A Paden; et al., "Development of Iodinated Indocyanine Green Analogs as a Strategy for Targeted Therapy of Liver Cancer" (2023). Faculty, Staff and Students Publications. 8317.
https://digitalcommons.library.tmc.edu/baylor_docs/8317