UNSPECIFIED (1991) EFFECT OF HIGH-DOSE, HIGH-AFFINITY ANTIBODY AND DEXAMETHASONE ON ANTIBODY UPTAKE BY COLORECTAL-CANCER - RESULTS OF A PILOT-STUDY. In: 3RD CONF ON RADIOIMMUNODETECTION AND RADIOIMMUNOTHERAPY OF CANCER, NOV 14-17, 1990, PRINCETON, NJ.

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Abstract

Antibody targeting of tumours holds great potential for diagnosis and therapy but has been limited by poor uptake efficiency. we have developed a mathematical compartmental model to analyse antibody distribution between body compartments after intravenous injection. This suggested two fundamental requirements to improve uptake: very high antibody affinity and a large injected dose. This was tested in 6 patients with primary colorectal tumours using a high affinity (10(10)M-1) technetium labelled anti-CEA monoclonal antibody (BW431/26). Each patient was scanned after 1 mg of antibody and again after a higher dose (1mg labelled;12-30mg cold antibody). Tumour uptake ratios following the higher dose were significantly increased. Fitting the model parameters to patient data including plasma clearance, uptake ratios from SPECT and planar scans and tumour CEA levels, showed that measured:available tumour antigen ratios were around 10:1. Therefore in an attempt to increase antigen accessibility, 3 patients with recurrent colorectal cancer (8 tumour Bites), were given a 24 hour course of dexamethasone (to increase tumour blood flow) between 2 high dose (20mg) scans. This resulted in an average increase in uptake ratio of 60%. In addition, lesions not seen prior to steroid administration were visualised. The results of this pilot study indicate that high doses of high affinity antibody and increased antigen access can improve antibody targeting of colorectal cancer.

Item Type:	Conference Item (UNSPECIFIED)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine
Journal or Publication Title:	ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS
Publisher:	MARY ANN LIEBERT INC PUBL
ISSN:	0892-7049
Date:	1991
Volume:	4
Number:	4
Number of Pages:	6
Page Range:	pp. 871-876
Publication Status:	Published
Title of Event:	3RD CONF ON RADIOIMMUNODETECTION AND RADIOIMMUNOTHERAPY OF CANCER
Location of Event:	PRINCETON, NJ
Date(s) of Event:	NOV 14-17, 1990
URI:	http://wrap.warwick.ac.uk/id/eprint/22063

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