title: Small-animal PET of tumor damage induced by photothermal ablation with 64Cu-bis-DOTA-hypericin.
abstract: The purpose of this study was to investigate the potential application of small-molecular-weight (64)Cu-labeled bis-DOTA-hypericin in the noninvasive assessment of response to photothermal ablation therapy.
  
  
  METHODS
  Bis-DOTA-hypericin was labeled with (64)Cu with high efficiency (>95% without purification). Nine mice bearing subcutaneous human mammary BT474 tumors were used. Five mice were injected intratumorally with semiconductor CuS nanoparticles, followed by near-infrared laser irradiation 24 h later (12 W/cm(2) for 3 min), and 4 mice were not treated (control group). All mice were intravenously injected with (64)Cu-bis-DOTA-hypericin (24 h after laser treatment in treated mice). Small-animal PET images were acquired at 2, 6, and 24 h after radiotracer injection. All mice were killed immediately after the imaging session for biodistribution and histology study. In vitro cell uptake and surface plasmon resonance studies were performed to validate the small-animal PET results.
  
  
  RESULTS
  (64)Cu-bis-DOTA-hypericin uptake was significantly higher in the treatment group than in the control group. The percentage injected dose per gram of tissue in the treated and control groups was 1.72 ± 0.43 and 0.76 ± 0.19, respectively (P = 0.017), at 24 h after injection. Autoradiography and histology results were consistent with selective uptake of the radiotracer in the necrotic zone of the tumor induced by photothermal ablation therapy. In vitro results showed that treated BT474 cells had a higher uptake of (64)Cu-bis-DOTA-hypericin than nontreated cells. Surface plasmon resonance study showed that bis-DOTA-hypericin had higher binding affinity to phosphatidylserine and phosphatidylethanolamine than to phosphatidylcholine.
  
  
  CONCLUSIONS
  (64)Cu-bis-DOTA-hypericin has a potential to image thermal therapy-induced tumor cell damage. The affinity of (64)Cu-bis-DOTA-hypericin for injured tissues may be attributed to the breakdown of the cell membrane and exposure of phosphatidylserine or phosphatidylethanolamine to the radiotracer, which binds selectively to these phospholipids.
authors.affiliation: Department of Experimental Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
authors.forename: Chiyi
authors.initials: C
authors.lastname: Xiong
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.forename: Geng
authors.initials: G
authors.lastname: Ku
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Leo G
authors.initials: LG
authors.lastname: Flores
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D055011:Ablation Techniques; D000818:Animals; D000873:Anthracenes; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D010455:Peptides / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D010718:Phosphatidylserines / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology; D020349:Surface Plasmon Resonance; D016896:Treatment Outcome
chemical_list: C559099:(64)Cu-bis-DOTA-hypericin; D000873:Anthracenes; D009942:Organometallic Compounds; D010455:Peptides; D010718:Phosphatidylserines; D013440:Sulfides; D010569:Perylene; C004965:hypericin