title: Anti-angiogenic therapy and chemotherapy affect 99mTc sestamibi and 99mTc-HL91 accumulation differently in tumour xenografts.
abstract: BACKGROUND
  Favourable effects of cytotoxic chemotherapy for tumours are characterized by the reduced accumulation of radiotracers such as 99mTc sestamibi (MIBI). Anti-angiogenic therapy is primarily cytostatic; consequently, its influence on tracer accumulation may differ from that of cytotoxic treatments.
  
  
  METHODS
  Anti-angiogenic therapy employing 2-methoxyestradiol was administered in mice bearing subcutaneous xenografts of LS180 colon cancer cells. The effects of chemotherapy with 5-fluorouracil were examined as a cytotoxic counterpart. Treatments were conducted for 4 days from day 8. Distribution of 99mTc-MIBI and Tc-HL91, a hypoxic marker, was observed on days 8 and 12. Oxygen tension (PO2) in tumours was measured by a microelectrode. Cellular uptake of tracers was examined in vitro in normoxic and hypoxic conditions.
  
  
  RESULTS
  99mTc-MIBI accumulation decreased with increasing tumour weight when no treatment was conducted. Tumour growth was suppressed by anti-angiogenic therapy and chemotherapy. 99mTc-MIBI accumulation in tumours decreased after chemotherapy as compared to pre-therapeutic values, whereas accumulation of 99mTc-HL91 increased. In contrast, accumulation of tracers did not significantly change after anti-angiogenic therapy as compared to that observed pre-therapeutically. Tumour PO2 decreased with increasing tumour volume when no treatment was conducted. Chemotherapy reduced PO2 in tumours. PO2 in tumours treated with anti-angiogenic therapy was as high as that observed before treatment. 2-Methoxyestradiol or 5-fluorouracil did not significantly affect tracer accumulation in cells under both normoxic and hypoxic conditions in vitro.
  
  
  CONCLUSIONS
  These findings indicate that scintigraphic assessment of therapeutic efficacy of anti-angiogenic therapy should be performed from a perspective distinct from that of cytotoxic treatment.
authors.affiliation: Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan. kinuya@med.kanazawa-u.ac.jp
authors.forename: Seigo
authors.initials: S
authors.lastname: Kinuya
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
authors.forename: Naoto
authors.initials: N
authors.lastname: Watanabe
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shuke
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Michigishi
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tonami
mesh_terms: D000077584:2-Methoxyestradiol; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia; D007700:Kinetics; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010091:Oximes / Q000493:pharmacokinetics*; D010100:Oxygen / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D015609:Organotechnetium Compounds; D010091:Oximes; D019275:Radiopharmaceuticals; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime; D004958:Estradiol; D000077584:2-Methoxyestradiol; D017256:Technetium Tc 99m Sestamibi; D010100:Oxygen; D005472:Fluorouracil