P3378 - A potential imaging reagent that specifically binds to tumor-associated clusterin
Targeting sCLU in solid tumors represents a very promising therapeutic avenue for the benefit of cancer patients. With the advent of personalized medicine, Alethia has undertaken the development of a companion diagnostic test with the goals of accurately identifying the cancer patients who would benefit the most from an anti-sCLU-based therapy and a monitoring of response to treatment. Our objective is to develop a new molecular imaging tool that would accurately target tumor-associated sCLU. In that regard, there is much evidence that peptide-based molecules display characteristics that are ideal for systemically administered diagnostic imaging agents including:
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๏rapid localization after administration with maximum target/background ratio
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๏high target uptake
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๏fast excretion of unbound agent
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๏rapid washed-out after imaging
P3378 is a clusterin-binding dodecapeptide which selectively homes to solid tumors expressing sCLU as shown in the figure below. P3378 labeled with Alexa680 was used to detect sCLU in mice harbouring 4T1 mammary carcinoma-derived tumors. The animals injected with P3378 (A, red circle) displayed a strong signal in the tumor that was visible over a period of greater than 120 minutes. By contrast, tumors were not labelled in animals injected with a control peptide.
The results obtained so far show the tremendous potential of the P3378 peptide as a tumor homing diagnostic molecule that could serve as a specific imaging tool for pre-emptive diagnostics, treatment response monitoring, and detection of recurrence.
