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Choline PET for Monitoring Early Tumor Response to Photodynamic Therapy

¹ Department of Radiology, Emory Center for Systems Imaging, Emory University, Atlanta, Georgia; ² Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; ³ Department of Radiology, Case Western Reserve University, Cleveland, Ohio; and ⁴ Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio

Correspondence: For correspondence or reprints contact: Baowei Fei, Department of Radiology, Emory Center for Systems Imaging, Emory University, 1841 Clifton Rd. NE, Atlanta, GA 30329. E-mail: bfei{at}emory.edu

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 ¹¹C-choline were acquired before PDT and at 1, 24, and 48 h after PDT. Time–activity curves of ¹¹C-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 ¹¹C-choline uptake in PDT-treated and control cells were measured. Results: For treated tumors, normalized ¹¹C-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 ¹¹C-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% ¹¹C-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 ¹¹C-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.

Key Words: small-animal PET • choline molecular imaging • photodynamic therapy (PDT) • prostate cancer • tumor response

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