Relationship between tumour morphology, antigen and antibody distribution measured by fusion of digital phosphor and photographic images.
Antibody-directed cancer therapy has achieved encouraging responses despite poor localisation in tumour. This discrepancy may be attributed to heterogeneity of antibody delivery within tumours: preferential localisation in the better perfused and more radio- and chemosensitive areas provides a therapeutic advantage. Antibody distribution depends upon the interactions of many complex mechanisms. We have started to investigate this by studying the single and combined influence of two tumour-associated parameters, morphology and antigen, on antibody distribution. Tumours were taken from mice at 24 and 48 h after 125I-labeled anti-CEA antibody injection. Images of antibody distribution, antigen distribution and tumour morphology were acquired by radioluminography, radioimmunoluminography and digitisation of morphology, respectively. Image registration allowed correlation of pixel values of antibody distribution with corresponding values of antigen distribution and morphology. At 24 h there was little correlation between antibody and antigen distribution, but strong positive correlation between antibody distribution and morphology, with preferential localisation in viable tumour areas. Correlation between antibody distribution and morphology fell significantly between 24 and 48 h, while that between antibody and antigen distribution remained low. However, the combination of morphology and antigen distribution showed the largest influence on antibody distribution. This novel technique demonstrates potential for combining multi-factor information in order to provide a greater understanding of antibody distribution in tumours, facilitating the optimisation of clinical treatments.
Flynn
A A
AA
Department of Oncology, Royal Free and University College Medical School, London, UK.
Boxer
G M
GM
Begent
R H
RH
Pedley
R B
RB
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000032:analysis* / Q000276:immunology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D012815:Signal Processing, Computer-Assisted; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes