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[225Ac]Ac-DOTA-C595
- Development stage
- Preclinical
- Modality
- Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics, Alpha Emitters → Radiopharmaceuticals, Monoclonal Antibodies → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
[225Ac]Ac-DOTA-C595 is an alpha-emitting radioimmunotherapy agent currently in development for the treatment of pancreatic ductal adenocarcinoma (PDAC). The drug is a radioimmunoconjugate comprising the alpha-emitting radionuclide Actinium-225 conjugated to the C595 monoclonal antibody via a DOTA chelator. It specifically targets cancer-specific mucin 1 epitopes (MUC1-CE), which are highly overexpressed on the surface of PDAC cells. Upon binding and internalization, the Actinium-225 isotope undergoes a decay chain that releases high-energy alpha particles. These particles have a short range and high linear energy transfer, leading to dense cellular damage and double-strand DNA breaks (indicated by yH2AX expression). This mechanism allows the agent to effectively kill tumor cells while potentially overcoming therapeutic barriers such as hypoxia. [225Ac]Ac-DOTA-C595 represents a more potent alpha-emitting alternative to the previously studied beta-emitting conjugate [177Lu]Lu-DOTA-C595.
- Other names
- Actinium-225-DOTA-C595Actinium225-DOTA-C595Actinium 225-DOTA-C595225Ac-DOTA-C595Ac-225-DOTA-C595Ac225-DOTA-C595Ac 225-DOTA-C595
02
Targets
TA-MUC1 (Tumor-associated MUC1)DNA
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