5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction: an autoradiographic study in the rat.
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.
Mahteme
Haile
H
Department of Surgery, Uppsala University Hospital, Uppsala, Sweden. Haile.Mahteme@Surgsci.uu.se
Sundin
Anders
A
Larsson
Bengt
B
Khamis
Harry
H
Arow
Kiril
K
Graf
Wilhelm
W
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
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D002250:Carbon Radioisotopes; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D009636:Norbornanes; C005321:norbormide; D005472:Fluorouracil