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Updated: Jan 29, 2026
07:17
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
12.4K
Trop-2.2-Directed Radioimmunotherapy with 177Lu, 225Ac, and 212Pb in a Pancreatic Cancer Model
Edwin C Pratt1, David Bauer1, Lukas M Carter1
1Molecular Pharmacology Department, Memorial Sloan Kettering Cancer Center, New York, New York.
Summary
This study repurposes a Trop-2.2 antibody for targeted cancer radiotherapies, demonstrating therapeutic benefits in a pancreatic cancer model. Pretargeted strategies and fractionated dosing show promise for improved efficacy and reduced toxicity.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Molecular Imaging
Background:
- Trophoblast cell surface antigen-2 (Trop-2) is linked to cancer invasiveness and poor outcomes.
- Current antibody-drug conjugate therapy lacks patient selection based on Trop-2 expression, risking adverse effects.
- A theranostic approach using Trop-2 targeting can improve patient and therapy selection.
Purpose of the Study:
- To repurpose the Trop-2.2 antibody for targeted radiotherapies using Lutetium-177, Actinium-225, and Lead-212.
- To evaluate different radiopharmaceutical dosing strategies, including direct, tandem, pretargeted, and fractionated approaches.
- To assess the therapeutic efficacy and toxicity of these novel radiopharmaceutical variants in a Trop-2 expressing cancer model.
Main Methods:
- Repurposing the Trop-2.2 antibody for conjugation with various radioisotopes (Lu-177, Ac-225, Pb-212).
- Investigating direct, tandem, pretargeted, and fractionated dosing strategies for radiopharmaceutical delivery.
- Evaluating tumor regression, survival rates, and specific organ toxicities (renal, ovarian) in a preclinical cancer model.
Main Results:
- Actinium-225 therapy demonstrated significant tumor regression and improved survival in mice.
- Lead-212 was more effective with a pretargeting strategy than direct labeling.
- Fractionated Lead-212 dosing showed sustained tumor reduction with manageable toxicity, though renal and ovarian toxicity were observed with repeat administrations.
Conclusions:
- Direct and pretargeted radiopharmaceutical variants targeting Trop-2.2 offer therapeutic benefits.
- Pretargeting strategies and fractionated dosing show potential for optimized cancer radiotreatment.
- This work supports the theranostic potential of Trop-2.2 targeting for personalized cancer therapy.
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