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 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.

[1]  Kashif Azizuddin,et al.  Fluorescence resonance energy transfer reveals a binding site of a photosensitizer for photodynamic therapy. , 2003, Cancer research.

[2]  Raymond F. Muzic,et al.  Registration of micro-PET and high-resolution MR images of mice for monitoring photodynamic therapy , 2004, SPIE Medical Imaging.

[3]  Kevin D Cooper,et al.  Photodynamic therapy with the phthalocyanine photosensitizer Pc 4: the case experience with preclinical mechanistic and early clinical-translational studies. , 2007, Toxicology and applied pharmacology.

[4]  N. Oleinick,et al.  Photodynamic therapy of human breast cancer xenografts lacking caspase-3. , 2002, Cancer letters.

[5]  J. Lechner,et al.  Establishment and characterization of a human prostatic carcinoma cell line (PC-3). , 1979, Investigative urology.

[6]  Tayyaba Hasan,et al.  Pretreatment photosensitizer dosimetry reduces variation in tumor response. , 2006, International journal of radiation oncology, biology, physics.

[7]  S B Malkowicz,et al.  Preliminary results of interstitial motexafin lutetium‐mediated PDT for prostate cancer , 2006, Lasers in surgery and medicine.

[8]  Youxin Mao,et al.  Feasibility of interstitial Doppler optical coherence tomography for in vivo detection of microvascular changes during photodynamic therapy , 2006, Lasers in surgery and medicine.

[9]  R. Coleman,et al.  Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  L. Lilge,et al.  Pc 4 photodynamic therapy of U87‐derived human glioma in the nude rat , 2005, Lasers in surgery and medicine.

[11]  N. Oleinick,et al.  Photodynamic Therapy-induced Apoptosis in Epidermoid Carcinoma Cells , 2001, The Journal of Biological Chemistry.

[12]  B. Nicolas Bloch,et al.  An illustration of the potential for mapping MRI/MRS parameters with genetic over-expression profiles in human prostate cancer , 2008, Magnetic Resonance Materials in Physics, Biology and Medicine.

[13]  Baowei Fei,et al.  High‐field magnetic resonance imaging of the response of human prostate cancer to Pc 4‐based photodynamic therapy in an animal model , 2007, Lasers in surgery and medicine.

[14]  E. Zuhowski,et al.  Plasma pharmacokinetics and tissue distribution in CD2F1 mice of Pc4 (NSC 676418), a silicone phthalocyanine photodynamic sensitizing agent , 1999, Cancer Chemotherapy and Pharmacology.

[15]  D. Hunting,et al.  PET imaging of apoptosis with 64Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[16]  Y. Yonekura,et al.  Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate. , 2004, Nuclear medicine and biology.

[17]  R. Coleman,et al.  Synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. , 2001, Cancer research.

[18]  R Lecomte,et al.  High-resolution PET imaging for in vivo monitoring of tumor response after photodynamic therapy in mice. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  E. P. Kennedy,et al.  The function of cytidine coenzymes in the biosynthesis of phospholipides. , 1956, The Journal of biological chemistry.

[20]  A. Bogni,et al.  [11C]Methylation on a C18 Sep-Pak cartridge: a convenient way to produce [N-methyl-11C]choline , 2000 .

[21]  R. Gillies,et al.  In vivo magnetic resonance spectroscopy in cancer. , 2005, Annual review of biomedical engineering.

[22]  Kai Zhang,et al.  Techniques for delivery and monitoring of TOOKAD(WST09)-mediated photodynamic therapy of the prostate: clinical experience and practicalities , 2005, SPIE BiOS.

[23]  M Emberton,et al.  Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer , 2006, Lasers in surgery and medicine.

[24]  M. Jacobs,et al.  Choline metabolism in cancer: implications for diagnosis and therapy , 2006, Expert review of molecular diagnostics.

[25]  David L. Wilson,et al.  Deformable and rigid registration of MRI and microPET images for photodynamic therapy of cancer in mice. , 2006, Medical physics.

[26]  Arjun G. Yodh,et al.  Noninvasive Monitoring of Murine Tumor Blood Flow During and After Photodynamic Therapy Provides Early Assessment of Therapeutic Efficacy , 2005, Clinical Cancer Research.

[27]  T. P. Pretlow,et al.  Transplantation of human prostatic carcinoma into nude mice in Matrigel. , 1991, Cancer research.

[28]  H Sterenborg,et al.  Phosphorescence-Fluorescence ratio imaging for monitoring the oxygen status during photodynamic therapy. , 2004, Optics express.

[29]  D. Feyes,et al.  A simplified method for preparation of 99mTc-annexin V and its biologic evaluation for in vivo imaging of apoptosis after photodynamic therapy. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  H. Degani,et al.  Differential routing of choline in implanted breast cancer and normal organs , 2001, Magnetic resonance in medicine.

[31]  M. Calin,et al.  Photodynamic therapy in oncology , 2006 .

[32]  D. Feyes,et al.  Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 of SW480 human colon cancer xenografts in athymic mice. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  Nancy L Oleinick,et al.  The role of apoptosis in response to photodynamic therapy: what, where, why, and how , 2002, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[34]  M. E. Kenney,et al.  NEW PHTHALOCYANINE PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY , 1993, Photochemistry and photobiology.

[35]  M. E. Kenney,et al.  Phthalocyanine 4 (Pc 4) Photodynamic Therapy of Human OVCAR‐3 Tumor Xenografts , 1999, Photochemistry and photobiology.

[36]  S. Karmakar,et al.  Inhibition of calpain and caspase-3 prevented apoptosis and preserved electrophysiological properties of voltage-gated and ligand-gated ion channels in rat primary cortical neurons exposed to glutamate , 2006, Neuroscience.

[37]  Jarod C Finlay,et al.  Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy. , 2005, Journal of photochemistry and photobiology. B, Biology.

[38]  M. Lein,et al.  Photodynamic Therapy of Prostate Cancer by Means of 5-Aminolevulinic Acid-Induced Protoporphyrin IX – In vivo Experiments on the Dunning Rat Tumor Model , 2004, Urologia Internationalis.

[39]  F. L. Hoch.  Cardiolipins and biomembrane function. , 1992, Biochimica et biophysica acta.

[40]  Roger Lecomte,et al.  Dynamic imaging of transient metabolic processes by small-animal PET for the evaluation of photosensitizers in photodynamic therapy of cancer. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.