Carborane-FAPI conjugate: A potential FAP-targeted boron agent with improved boron content

Area of Science:

• Oncology
• Radiotherapy
• Medical Chemistry

Background:

• Boron neutron capture therapy (BNCT) is an advanced radiotherapy with potential for cancer treatment.
• Current BNCT faces challenges with poor selectivity and insufficient boron concentration in tumor tissues.
• Fibroblast activation protein (FAP) is a tumor-associated antigen, highly expressed in tumors and lowly in normal tissues, making it a potential therapeutic target.

Purpose of the Study:

• To design, synthesize, and evaluate a novel boron agent, Carborane-FAPI, for enhanced tumor targeting and boron delivery in BNCT.
• To improve upon existing boron delivery agents like Boronophenylalanine (BPA) by increasing molecular boron content and targeting specificity.

Main Methods:

• Coupling of o-carborane to the skeleton of a fibroblast activating protein inhibitor (FAPI).
• Preliminary evaluation of the synthesized Carborane-FAPI for toxicity and tumor-targeting capabilities.

Main Results:

• Carborane-FAPI demonstrated low toxicity towards normal cells.
• The agent showed selective enrichment in tumor tissues.
• The new agent offers increased boron content per molecule compared to Boronophenylalanine (BPA).

Conclusions:

• Carborane-FAPI is a promising novel boron drug candidate for BNCT.
• The agent exhibits improved tumor-targeting ability and boron content, addressing key limitations of current BNCT agents.
• Further investigation into Carborane-FAPI's potential in BNCT is warranted.