title: Systemic anti-tumour effects of local thermally sensitive liposome therapy.
abstract: OBJECTIVE
  There were two primary objectives of this study: (1) to determine whether treatment of a tumour site with systemically administered thermally sensitive liposomes and local hyperthermia (HT) for triggered release would have dual anti-tumour effect on the primary heated tumour as well as an unheated secondary tumour in a distant site, and (2) to determine the ability of non-invasive optical spectroscopy to predict treatment outcome. The optical end points studied included drug levels, metabolic markers flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide phosphate (NAD(P)H), and physiological markers (total haemoglobin (Hb) and Hb oxygen saturation) before and after treatment.
  
  
  METHODS
  Mice were inoculated with SKOV3 human ovarian carcinoma in both hind legs. One tumour was selected for local hyperthermia and subsequent systemic treatment. There were four treatment groups: control, DOXIL (non-thermally sensitive liposomes containing doxorubicin), and two different thermally sensitive liposome formulations containing doxorubicin. Optical spectroscopy was performed prior to therapy, immediately after treatment, and 6, 12, and 24 h post therapy.
  
  
  RESULTS
  Tumour growth delay was seen with DOXIL and the thermally sensitive liposomes in the tumours that were heated, similar to previous studies. Tumour growth delay was also seen in the opposing tumour in the thermally sensitive liposome-treated groups. Optical spectroscopy demonstrated correlation between growth delay, doxorubicin (DOX) levels, and changes of NAD(P)H from baseline levels. Hb and Hb saturation were not correlated with growth delay.
  
  
  CONCLUSIONS
  The study demonstrated that thermally sensitive liposomes affect the primary heated tumour as well as systemic efficacy. Non-invasive optical spectroscopy methods were shown to be useful in predicting efficacy at early time points post-treatment.
authors.affiliation: Department of Radiology, University of Michigan , Ann Arbor , Michigan and.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Viglianti
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: R J
authors.initials: RJ
authors.lastname: Boruta
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Chelsea
authors.initials: C
authors.lastname: Landon
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Fontanella
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Ashley
authors.initials: A
authors.lastname: Manzoor
authors.forename: Christina L
authors.initials: CL
authors.lastname: Hofmann
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Palmer
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D006979:Hyperthermia, Induced; D051379:Mice; D009249:NADP / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010100:Oxygen / Q000378:metabolism; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use; D013057:Spectrum Analysis; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D006454:Hemoglobins; C506643:liposomal doxorubicin; D005182:Flavin-Adenine Dinucleotide; D011092:Polyethylene Glycols; D009249:NADP; D004317:Doxorubicin; D010100:Oxygen
keywords: Hyperthermia; liposomes; spectroscopy; systemic therapy; thermal sensitive liposomes