title: Histamine but neither angiotensin nor vasopressin increases antibody uptake into xenograft colorectal liver metastases.
abstract: Although the majority of colorectal carcinomas express carcino-embryonic antigen (CEA), systemic anti-CEA antibody administration is an ineffective treatment for colorectal liver metastasis. A xenograft model of human colorectal carcinoma in the rat was used to determine anti-CEA antibody uptake into liver metastases. The influence of systemic (iliolumbar vein) or regional (gastroduodenal artery) delivery and effects of regional delivery of histamine, angiotensin II and vasopressin on anti-CEA antibody uptake by metastases were examined. Systemic antibody delivery achieved a median tumour:liver antibody uptake ratio of 1.60 (interquartile range (i.q.r.) 1.02-2.51). Regional delivery resulted in a similar median ratio of 1.61 (i.q.r. 1.22-2.46). Histamine and antibody delivered regionally produced a median tumour:liver ratio of 3.15 (i.q.r. 2.50-4.27), which was significantly greater than that obtained with systemic delivery (P = 0.004). Regional infusion of angiotensin resulted in a median (i.q.r.) ratio of 2.23 (1.58-2.49) and vasopressin in 2.15 (1.41-2.60), values that were not significantly different from those found with systemic or regional delivery alone. When both angiotensin and histamine were infused with antibody, the median tumour:liver ratio was 3.09 (i.q.r. 2.22-4.31), significantly greater than for systemic delivery (P = 0.01) but not significantly different from that obtained following the addition of histamine alone (P = 0.94). Histamine significantly increases antibody uptake in a model of liver metastasis and may improve the effectiveness of targeted immunotherapy in the treatment of colorectal liver metastasis.
authors.affiliation: Department of Surgery, Charing Cross and Westminster Medical School, London, UK.
authors.forename: T W
authors.initials: TW
authors.lastname: Hennigan
authors.forename: R H
authors.initials: RH
authors.lastname: Begent
authors.forename: T G
authors.initials: TG
authors.lastname: Allen-Mersh
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D009368:Neoplasm Transplantation; D051381:Rats; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D014667:Vasopressins; D006632:Histamine