High-resolution PET imaging for in vivo monitoring of tumor response after photodynamic therapy in mice.

Abstract

The aim of this study was to investigate the use of [18F]fluoro-2-deoxy-D-glucose (FDG) and a small-animal PET scanner to assess early tumor response after photodynamic therapy (PDT) in mice. PDT consists of intravenous administration of a photosensitizer that accumulates preferentially in tumor tissue, followed by local illumination of the tumor with red light. Two different 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 necrosis through different action mechanisms, i.e., mainly initial vascular stasis (PII) or direct tumor cell kill (AIPcS). FDG PET was used to follow both perfusion and metabolic activity in the tumor tissue. 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 tumor was subjected to PDT, whereas the other tumor served as a control. A total 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 mice, which were placed in pairs in a prostate position parallel to the transaxial planes of the Sherbrooke animal PET scanner, was performed after a bolus injection of 11 MBq (300 microCi) FDG. Blood samples were collected concurrently from 1 mouse during each study using an automated microvolumetric blood sampler. 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 was a direct measurement of tumor metabolism clearly demonstrating the relative efficacy of the two PDT drugs; and (c) the tumor tracer concentration in 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 (AIPcS). This pilot study confirmed the feasibility of using dynamic in vivo PET imaging for assessing early tumor response to PDT in mice.