Choline PET for monitoring early tumor response to photodynamic therapy.
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.


CONCLUSIONS
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.
Fei
Baowei
B
Department of Radiology, Emory Center for Systems Imaging, Emory University, Atlanta, Georgia 30329, USA. bfei@emory.edu
Wang
Hesheng
H
Wu
Chunying
C
Chiu
Song-mao
SM
D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002794:Choline / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000627:therapeutic use*; D054833:Isoindoles; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics
D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D019275:Radiopharmaceuticals; D002794:Choline; C013647:phthalocyanine