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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Adenocarcinoma/drug therapy/*metabolism/radiotherapy/*secondary

Animals

Antibodies; Monoclonal/immunology/pharmacology

Antimetabolites; Antineoplastic/*pharmacokinetics

Autoradiography

Carbon Radioisotopes/diagnostic use

Carcinoembryonic Antigen/immunology/pharmacology

Colonic Neoplasms/pathology

Female

Fluorouracil/*pharmacokinetics

Humans

Immunotoxins/*pharmacology

Iodine Radioisotopes/therapeutic use

Male

Norbornanes/*pharmacology

Peritoneal Cavity/*blood supply

Peritoneal Neoplasms/drug therapy/*metabolism/radiotherapy/*secondary

Radioimmunotherapy

Random Allocation

Rats

Research Support; Non-U.S. Gov't

Vasoconstriction/drug effects

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)