Improved Molecular Imaging by Multi-Tracer PET

Dr. Eduardo Lage and Dr. Joaquín L. Herraiz, E. Addalsteinson (Consortium PI)

Grant code: —

Awardee Organization: MIT, Brigham & Women’s Hospital, CNIO, Gregorio Maranon Hospital

Project Start Date: January 2012

Project End Date: June 2014

Total Funding: 250,000 €

MEDIC Personnel included in the grant / Role: Dr.Eduardo Lage / PI

Abstract Text: The final objective of this project is to provide better tools for treatment selection of oncologic patients and to evaluate/ predict response to therapy in early stages of the treatment. 

A defining strength of Positron Emission Tomography (PET) is the ability to image any of a number of molecular or physiologic targets using different radiotracers, which has been shown to provide prognostic information and to improve disease diagnosis and classification. Thus, the extensive development of new probes for imaging hypoxia, cell proliferation, blood flow and numerous other molecular targets underscores the strong potential for image-guided personalized medicine. However, much of this potential remains unrealized because current technology permits only one PET tracer to be imaged at a time. Consequently, multiple scanning sessions need to be scheduled on different days to obtain complementary information resulting in high costs, image alignment issues, and an onerous experience for the patient. Thus, this project will develop technology compatible with existing PET scanners to enable, for the first time in vivo, multiplexed radiotracer imaging and separation, thereby clinically improving disease characterization and management.

Clinically, current imaging of tumors with PET is almost always performed with FDG to highlight metabolic activity. However, tumors are complex and variations in a tumor’s basic physiological and biomolecular characteristics have been shown to decrease the efficacy of basic chemo/radiotherapy treatments. On the other hand, to evaluate response to therapy in cancer patients it is necessary to wait until several cycles of chemo/radio therapy have been applied. However, several recent studies have demonstrated that it is possible to differentiate responders from no responders before starting the treatment and to evaluate response to therapy with PET in earlier stages of the treatment using a multi-tracer approach. Such timing would have a notable clinical impact because patients receiving ineffective treatment could be switched to alternative therapies and responding patients could receive more aggressive treatment. To address this limitation, and provide greater insight into a tumor’s characteristics which may impact treatment efficacy, we propose to combine and simultaneously image a tracer labeled with a pure positron emitting radionuclide with other tracers labeled with radionuclides that emit both positrons and additional prompt gamma rays. Detection of the auxiliary prompt gamma rays in coincidence with the annihilation events and in conjunction with differences in uptake, decay, and pharmacokinetics of each tracer will enable the de-coupling of the distinct radiotracers (radionuclides). The specific objectives of this project are:  to demonstrate the validity of the proposed approach using a preclinical scanner and to evaluate the performance of this technology in human systems.