Choline PET for monitoring early tumor response to photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a relatively new therapy that has shown promise for treating various cancers in both preclinical and clinical studies. The present study evaluated the potential use of PET with radiolabeled choline to monitor early tumor response to PDT in animal models.

Methods: Two human prostate cancer models (PC-3 and CWR22) were studied in athymic nude mice. A second-generation photosensitizer, phthalocyanine 4 (Pc 4), was delivered to each animal by a tail vein injection 48 h before laser illumination. Small-animal PET images with (11)C-choline were acquired before PDT and at 1, 24, and 48 h after PDT. Time-activity curves of (11)C-choline uptake were analyzed before and after PDT. The percentage of the injected dose per gram of tissue was quantified for both treated and control tumors at each time point. In addition, Pc 4-PDT was performed in cell cultures. Cell viability and (11)C-choline uptake in PDT-treated and control cells were measured.

Results: For treated tumors, normalized (11)C-choline uptake decreased significantly 24 and 48 h after PDT, compared with the same tumors before PDT (P < 0.001). For the control tumors, normalized (11)C-choline uptake increased significantly. For mice with CWR22 tumors, the prostate-specific antigen level decreased 24 and 48 h after PDT. Pc 4-PDT in cell culture showed that the treated tumor cells, compared with the control cells, had less than 50% (11)C-choline activity at 5, 30, and 45 min after PDT, whereas the cell viability test showed that the treated cells were viable longer than 7 h after PDT.

Conclusion: PET with (11)C-choline is sensitive for detecting early changes associated with Pc 4-PDT in mouse models of human prostate cancer. Choline PET has the potential to determine whether a PDT-treated tumor responds to treatment within 48 h after therapy.

FIGURE 1

Photographs of tumor-bearing mouse before PDT (A), 1 d after PDT (B), and 1 mo after PDT (C). CWR22 tumor (arrow) showed rapid response 1 d after treatment but had disappeared 1 mo after therapy.

FIGURE 2

Transverse small-animal PET images of 2 PC-3 tumors (arrows). Images of treated tumor before PDT (A) and 48 h after PDT (C) show that ¹¹C-choline uptake of treated tumor had decreased 48 h after PDT. Images of control tumor before PDT (B) and 48 h after PDT (D) show slightly increased ¹¹C-choline uptake 48 h after PDT. Quantitative analysis results of ¹¹C-choline uptake in treated and control tumors confirmed our visual inspection; these results are shown in Figure 3.

FIGURE 3

Time–activity curves of ¹¹C-choline in PDT-treated PC-3 tumors (n=4) (A) and in control tumors (n=4) (B) of same mice before PDT and 48 h after PDT. Uptake of ¹¹C-choline was measured as %ID/g. Error bars represent SEs.

FIGURE 4

Histologic images of treated and control PC-3 tumors at 48 h after PDT. Inflammatory response with edema was observed in treated tumor (A) but was not seen in control tumor (B). Rectangular areas on A and B are magnified and shown in C and D, respectively. In C, massive areas of treated tissue were damaged by PDT; however, control tumor cells remained intact (D).

FIGURE 5

Pc 4-PDT–induced changes in ¹¹C-choline uptake as function of post-PDT incubation time (5, 30, and 45 min). Activity of ¹¹C-choline in PC-3 cells was measured by g-counter, and unit was counted per minute (CPM). Each data point represents 3 wells of cells, and error bars are SD.