177Lu-PSMA I&T Composition for Lower Healthy-Organ Radiation Dose
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Solution Overview
Problem
Existing 177Lu-PSMA I&T formulations for prostate cancer therapy result in undesirable absorbed doses of radiation to healthy organs, necessitating a need for a formulation that minimizes radiation exposure to non-targeted tissues and allows for longer treatment cycles.
Innovation Solution
A 177Lu-PSMA I&T composition with a molar ratio of PSMA I&T to 177Lu ranging from 3.0:1.0 to 8.0:1.0 and a PSMA I&T to [177Lu]Lu3+ ratio from about 0.20 to about 0.60, ensuring radiochemical purity ≥95% and stability for 72 hours or more, thereby reducing absorbed radiation doses to organs like kidneys, lacrimal glands, and liver.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If a molar ratio of PSMA I&T to 177Lu below 11.0:1.0 is used, then the treatment cycle can be extended and radiation dose to healthy organs can be reduced, but the radiochemical purity deteriorates below 95%
Solution Approach 1:
The patent applies parameter changes by optimizing the molar ratio of PSMA I&T to 177Lu from the conventional ≥11.0:1.0 down to 3.0:1.0 to 8.0:1.0, while simultaneously adjusting formulation parameters (buffer composition, pH, stabilizers) to maintain radiochemical purity ≥95% despite the lower ligand-to-radiometal ratio. This resolves the contradiction by finding a new operational parameter space that achieves both lower radiation dose to healthy organs and maintained purity.
2Reliability
If a molar ratio of PSMA I&T to 177Lu of at least 11.0:1.0 is used, then the radiochemical purity can be maintained at ≥95%, but the cumulative absorbed radiation dose to healthy organs increases
Solution Approach 1:
The patent fundamentally changes the molar ratio parameter from ≥11.0:1.0 to 3.0:1.0 to 8.0:1.0, which directly reduces the amount of 177Lu administered per treatment cycle. This parameter change, combined with optimized formulation conditions, maintains radiochemical purity while reducing cumulative radiation dose to healthy organs, thereby resolving the contradiction between reliability and harmful effects.
3Object-affected harmful factors
If the treatment cycle is extended to allow lower cumulative radiation dose, then the safety improves, but the radiochemical purity deteriorates over time
Solution Approach 1:
The patent applies preliminary action by pre-optimizing the formulation composition (buffers, stabilizers, pH adjustment) before administration to ensure the radiopharmaceutical remains stable at ≥95% radiochemical purity throughout the extended treatment cycle. This preliminary formulation optimization prevents purity deterioration over time, enabling extended treatment cycles with lower cumulative radiation dose.
Solution Approach 2:
The patent changes formulation parameters including buffer composition, pH, and stabilizer concentrations to enhance the temporal stability of the radiopharmaceutical composition. These parameter changes ensure that even with extended treatment cycles, the radiochemical purity remains ≥95%, resolving the contradiction between extended treatment duration and composition stability.
Data Source
AI summary
The present disclosure relates to a pharmaceutical composition comprising 177Lu-PSMA I&T and methods of administering the same. The administration of the composition results in a low absorbed radiation dose per gram of tissue in a human patient's body, including the kidneys, gastrointestinal tract, left colon, liver, rectum, red marrow, spleen, lacrimal glands, and salivary glands.