SUMMARY OF INVENTION
The combination of radiotherapy and chemotherapy is used widely to treat various types of cancer, with observed clinical benefits compared to radiotherapy or chemotherapy alone. However, toxicity of this combination strategy, largely due to the non-specific distribution of chemotherapy drugs, remains a problem.
Cerenkov luminescence is the faint glow emitted from many therapeutic and imaging isotopes. One of the challenges of the clinical application of Cerenkov luminescence is its low signal intensity, which requires highly sensitive cameras for detection.
MSK investigators have developed a specialized Cerenkov-activatable drug delivery and imaging system. This technology is a Cerenkov-activated agent which converts the faint Cerenkov signal into a stable and long-lasting, highly intense fluorescence signal. For the imaging application, a surgeon could inject a radiotracer, followed by the Cerenkov-activated agent, and image-guided surgery could be performed relying on the presence of fluorescence to mark tumor margins. For the therapeutic application, the Cerenkov-activated agent can be coupled to chemotherapies or small molecules for more specific and selective drug delivery to tumor sites.
Novel radiation-activated fluorescent agent allows for in vivo conversion of radioactive signals to fluorescent signals, allowing for intraoperative imaging
In vivo proof-of-concept for imaging application demonstrated in a mouse model of fibrosarcoma, showing that the agent effectively converts radiotracer signals to fluorescence
Could be used to deliver any small molecule drug or chemotherapy for therapeutic purposes specifically to tumor sites
In vitro proof-of-concept for therapeutic application demonstrates that the Cerenkov agent coupled to doxorubicin, when activated by Cerenkov luminescence, is significantly more toxic to breast cancer cells compared to doxorubicin alone.
This nanotechnology platform is a safe and efficient tool to deliver small molecule drugs and chemotherapies to tumors, with an additional application in intraoperative imaging.
STAGE OF DEVELOPMENT
PCT application PCT/US2016/043601 filed in July 2016
Jan Grimm, PhD, Laboratory Head, Molecular Pharmacology Program, Sloan Kettering Institute, MSK
MSK Internal Code: SK2015-018