title: 5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction: an autoradiographic study in the rat.
abstract: This study was conducted to test if tumour drug uptake could be increased in experimental colorectal cancer peritoneal metastases, by using pretreatment with peritoneal vasoconstriction or radioimmunotherapy. A total of 29 nude rats with peritoneal metastases were injected intraperitoneally (i.p.) with 14C-labelled 5-FU. The animals were randomly allocated to 5 groups. Six days prior to 5-FU, group I (control) received i.p. NaCl, group II was subjected to i.p. radioimmunotherapy (RIT) 131I-labelled anti-CEA monoclonal antibody (150 MBq) and group III received i.p. Norbormide 10 minutes before 5-FU. Two days prior to 5-FU group IV and V received i.p. NaCl (control) and RIT, respectively. 5-FU uptake was visualised with autoradiography and quantified by computer-based image analysis. Tumours in group III showed a higher uptake (mean+/-SD, 21.4+/-17) than in group I (11.8+/-10, p=0.04). This was also true when the analysis was restricted to larger tumours (> or = median 627 pixels) group III (23.2+/-19) vs. group I (11.8+/-7, p=0.002). Peritoneal tumours in group II were of smaller size (median area 308 pixels) than in group I (619 pixels), in group III (901 pixels), in group IV (769 pixels) and in group V (808 pixels). RIT decreased the tumour size whereas it did not affect 5-FU uptake. The uptake of 5-FU was potentiated by pretreating the animals with Norbormide. These results demonstrate that 5-FU uptake in experimental peritoneal metastases is increased when the peritoneal absorption of the drug is blocked using pretreatment with a vasoconstrictive agent. This principle may also be relevant when treating patients with colorectal cancer peritoneal metastases.
authors.affiliation: Department of Surgery, Uppsala University Hospital, Uppsala, Sweden. Haile.Mahteme@Surgsci.uu.se
authors.forename: Haile
authors.initials: H
authors.lastname: Mahteme
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.forename: Bengt
authors.initials: B
authors.lastname: Larsson
authors.forename: Harry
authors.initials: H
authors.lastname: Khamis
authors.forename: Kiril
authors.initials: K
authors.lastname: Arow
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Graf
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D001345:Autoradiography; D002250:Carbon Radioisotopes; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D009636:Norbornanes / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000098:blood supply*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary*; D016499:Radioimmunotherapy; D011897:Random Allocation; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D002250:Carbon Radioisotopes; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D009636:Norbornanes; C005321:norbormide; D005472:Fluorouracil