Dynamic imaging of transient metabolic processes by small-animal PET for the evaluation of photosensitizers in photodynamic therapy of cancer.
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.


CONCLUSIONS
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.
Bérard
Véronique
V
Sherbrooke Molecular Imaging Centre, Etienne-LeBel Clinical Research Centre, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
Rousseau
Jacques A
JA
Cadorette
Jules
J
Hubert
Laurent
L
Bentourkia
M'hamed
M
van Lier
Johan E
JE
Lecomte
Roger
R
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008956:Models, Chemical; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D019788:Fluorodeoxyglucose F18; C013647:phthalocyanine