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Dynamic Imaging of Transient Metabolic Processes by Small-Animal PET for the Evaluation of Photosensitizers in Photodynamic Therapy of Cancer

Sherbrooke Molecular Imaging Centre, Étienne-LeBel Clinical Research Centre, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada; and Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Correspondence: For correspondence or reprints contact: Roger Lecomte, PhD, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001 12th Ave. N., CRC/CHUS #1864, Sherbrooke, QC, Canada, J1H 5N4. E-mail: Roger.Lecomte{at}USherbrooke.ca

This study evaluated the potential use of dynamic PET to monitor transient metabolic processes and to investigate the mechanisms of action of new photosensitizing drugs in the photodynamic therapy (PDT) of cancer. Methods: Rats bearing 2 mammary tumors received different phthalocyanine-based photosensitizers. The following day, the animals were positioned in a Sherbrooke small-animal PET scanner and continuously infused with ¹⁸F-FDG while dynamic images were acquired for 2 h. During that period, one of the 2 tumors was exposed for 30 min to red light delivered by a small diode laser to activate PDT. Results: ¹⁸F-FDG time–activity curves during PDT showed distinct transient patterns characterized by a drop and subsequent recovery of tumor ¹⁸F-FDG uptake rates. Variations in these rates and response delay parameters revealed tumoral and systemic metabolic processes that correlated with differences in mechanism of action between drugs, that is, direct tumor cell kill or initial vascular shutdown. Conclusion: Real-time follow-up of tumor response to PDT as monitored by dynamic ¹⁸F-FDG PET has been shown to correlate with the mechanisms of action of photosensitizing drugs in vivo. This new imaging paradigm can be exploited to monitor a variety of transient cellular and molecular processes as they occur in vivo, enabling the mechanisms of action of therapeutic interventions to be scrutinized and their efficacy predicted in real time.

Key Words: small-animal PET • FDG • photodynamic therapy (PDT) • photosensitizer • transient metabolic process • tumor

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