High-Resolution PET imaging for in vivo monitoring of tumor response afterphotodynamic therapy in mice

The aim of this study was to investigate the use of [F-18]fluoro-2- deoxy-D -glucose (FDG) and a small-animal PET scanner to assess early tumor respons e after photodynamic therapy (PDT) in mice. PDT consists of int ravenous ad ministration of a photosensitizer that accumulates preferentially in tumor tissue, followed by local illumination of the tumor with red light. Two dif ferent photosensitizers were used: Photofrin (PII), which has been approved for clinical use, and disulfonated aluminum phthalocyanine (AIPcS), which is a second-generation drug. These drugs have been shown to induce tumor ne crosis through different action mechanisms, i.e.,mainly initial vascular st asis.(Pll) or direct tumor cell kill (AIPcS). FDG PET was used to follow bo th perfusion and metabolic activity in the tumor tissue. Methods: The study was performed using a mouse model implanted with two contralateral murine mammary tumors (5 mm diameter x 2.5 mm thickness) on the back. Only one,tum or was subjected to PDT, whereas the other tumor served as a control. A tot al of 13 mice were studied, 1 without illumination, 3 at 30 min and 3 at 2 h after PDT with both PII-PDT and AIPcS-PDT. Dynamic PET imaging of the mic e, which were placed in pairs ina prostate position parallel to the transax ial planes of the Sherbrooke animal PET scanner, was performed after a bolu s injection of ii MBq (300 mu Ci) FDG. Blood samples were collected concurr ently from I mouse during each study using an automated microvolumetric blo od sampler. Results: Analysis of the tumor time-activity curves showed that (a) scans during the first 3 min provided an estimate of tumor perfusion, as confirmed by the blood samples; (b) the tumor FDG uptake after 15 min wa s a direct. measurement of tumor metabolism clearly demonstrating the relat ive efficacy of the two PDT drugs; and (c) the tumor tracer concentration i n the interval 3-15 min after FDG injection is an appropriate indicator of the different mechanisms of tumor necrosis through indirect vascular stasis (PII) or direct cell kill (AlPcS). Conclusion: This pilot study confirmed the feasibility of using dynamic in vivo PET imaging for assessing early tu mor response to PDT in mice.